1.Prodrug-based combinational nanomedicine remodels lipid metabolism for reinforced ferroptosis and immune activation.
Ling LIN ; Zaixiang FANG ; Guohao LIU ; Yiwei LIU ; Zhiqian LI ; Dayi PAN ; Yunkun LI ; Hemi KANG ; Xiaoding SHEN ; Jingyao ZHANG ; Qiyong GONG ; Kui LUO ; Jing JING
Acta Pharmaceutica Sinica B 2025;15(5):2746-2763
Ferroptosis is a form of programmed cell death characterized by overwhelmed lipid oxidation, and it has emerged as a promising strategy for cancer therapy. Enhanced ferroptosis could overcome the limitations of conventional therapeutic modalities, particularly in difficult-to-treat tumors. In this study, we developed a dual-modality therapy in nanomedicine by combining paclitaxel (PTX) chemotherapy and pyropheophorbide-a (Ppa) phototherapy. Heparin (HP) was grafted with poly(N-(2'-hydroxy) propyl methacrylamide) (pHPMA) using reversible addition-fragmentation chain transfer polymerization to form HP-pHPMA (HH), which was utilized to deliver Ppa and PTX, yielding HP-pHPMA-Ppa (HH-Ppa) and HP-pHPMA-PTX (HH-PTX), respectively. The prodrug-based combinational nanomedicine (HH-PP) was formed by co-assembly of HH-PTX and HH-Ppa. It was found that HH-PP treatment significantly disrupted lipid metabolism in triple-negative breast cancer (TNBC) cells, induced extensive lipid oxidation, and promoted ferroptosis. In vivo, HH-PP intervention achieved a tumor growth inhibition rate of 86.63% and activated adaptive immunity with an elevated CD8+ cytotoxic T cell infiltration level. This combinational nanomedicine offers a promising platform for co-delivery of multiple therapeutic agents. It exerts a promising anti-tumor effect via enhanced ferroptosis and ferroptosis-induced immune activation by disrupting lipid metabolism in TNBC cancer cells.
2.Study on the mechanism of Qiangjin Zhuanggu Capsules in promoting bone formation in postmenopausal osteoporosis mice
Han LIU ; Jiapeng WANG ; Yunle RUAN ; Zaixiang ZHANG ; Yao JIAO ; Xia LEI
International Journal of Traditional Chinese Medicine 2025;47(7):952-958
Objective:To investigate the effects and mechanism of Qiangjin Zhuanggu Capsules in bone remodeling in ovariectomized osteoporotic mice.Methods:Totally 75 8-week-old C57BL/6 female mice were divided into a sham-operation group of 15 mice and a modeling group of 60 mice. The model was created using bilateral ovariectomy (OVX) to replicate a postmenopausal osteoporosis mouse model. The successfully modeled mice were divided into model group, estradiol group, and Qiangjin Zhuanggu Capsules low-, medium-, and high-dosage groups using a random number table method, with 10 mice in each group. The estradiol group was given a 0.013 mg/ml solution of estradiol valerate tablets by gavage; Qiangjin Zhuanggu Capsules low-, medium-, and high-dosage groups were orally administered with Qiangjin Zhuanggu Capsule solution at dosages of 46.0, 92.0, and 184.0 mg/ml. The sham-operation group and model group were orally administered with equal volumes of physiological saline once a day for 8 consecutive weeks. After the intervention, the femoral trabecular bone structure, bone mineral density (BMD), bone volume/total volume (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), bone surface area/bone volume (BS/BV), and trabecular separation (Tb.Sp) were assessed using Micro-CT. Serum levels of bone metabolism markers such as calcium (Ca), phosphorus (P), bone alkaline phosphatase (BALP), osteocalcin (OCN), and cathepsin K (CTSK) were measured by ELISA. Hematoxylin and eosin (HE) and Masson staining were used to observe the morphological changes in femoral trabecular bone structure and collagen fibers. Western blot analysis was employed to detect the protein expression of Runt-related transcription factor 2 (Runx2), alkaline phosphatase (ALP), and bone morphogenetic protein-2 (BMP-2), .Results:Compared with the model group, the levels of BMD, BV/TV, Tb. N, and Tb.Th ( P<0.01 or P<0.05) in estradiol group and Qiangjin Zhuanggu Capsule medium- and high-dosage groups increased ( P<0.01, P<0.05), and BS/BV and Tb.Sp decreased ( P<0.01, P<0.05)serum levels of Ca, P, BALP, and OCN were elevated ( P<0.01, P<0.05), while CTSK was reduced ( P<0.01); the expression of Runx2, ALP and BMP-2 proteins significantly increased ( P<0.01, P<0.05). Conclusion:Qiangjin Zhuanggu Capsules exhibit preventive and therapeutic effects on postmenopausal osteoporosis, potentially through the regulation of Runx2, ALP and BMP-2.
3.Screening and clinical significance of intestinal colonization of carbapenem-resistant Enterobacteriaceae (CRE) in patients before haploidentical hematopoietic stem cell transplantation
Wenqi WU ; Yuqi ZHANG ; Jie XU ; Zaixiang TANG ; Shijia LI ; Xiya WEI ; Ling LI ; Heqing WU ; Xiao MA ; Jisheng LIU ; Depei WU ; Xiaojin WU
Chinese Journal of Blood Transfusion 2023;36(6):496-500
【Objective】 To investigate the situation of carbapenem-resistant Enterobacteriaceae(CRE) colonization in patients undergoing haploidentical hematopoietic stem cell transplantation (haplo-HSCT). 【Methods】 A total of 241 consecutive patients who underwent haplo-HSCT in the First Affiliated Hospital of Soochow University from June 1, 2021 to June 1, 2022 were enrolled. Anal swab screening was performed within 48 hours of admission and blood cultures were taken when the patient developed fever. Univariate and multivariate analysis were used to analyze the colonization rate, distribution, risk factors and the correlation between CRE colonization and post-transplant bloodstream infection(BSI). 【Results】 Among 241 patients with haplo-HSCT, there were 90 cases in CRE colonization positive group, with a colonization rate of 37.3% (90/241). Multivariate logistic regression analysis showed that sex (OR 2.42, 95% CI 1.38-4.22, P<0.05) and history of infection within 30 days before transplantation (OR 3.37, 95% CI 1.59-7.17, P<0.05) may be independent risk factors for CRE intestinal colonization. Of the 95 CRE strains, the top five species were carbapenem-resistant Klebsiella pneumoniae (38/95, 40.0%), carbapenem-resistant Escherichia coli (29/95, 30.5%), carbapenem-resistant Enterobacter cloacae (13/95, 13.6%), carbapenem-resistant Klebsiella acidophilus (6/95, 6.3%) and carbapenem-resistant Proteus mirabilis (3/95, 3.1%). The incidence of post-transplant BSI was 12.0% (29/241) in the CRE-colonized group and 3.3% (8/241) in the non-colonized group. In the colonization group, 100% of the pathogens of BSI were identical with those of CRE colonization. 【Conclusion】 Bacterial culture of anal swab during haplo-HSCT is helpful for detection of CRE colonization in intestinal tract, which provides some clinical basis for active monitoring of key flora, prevention and control of infection.
4.Multiple linear regression analysis of hip function and vitamin D levels before and after hip arthroplasty
Wei ZHANG ; Zaixiang TANG ; Dechun GENG ; Feng ZHU ; Hanqing DONG ; Yijun WANG ; Yaozeng XU
Chinese Journal of Tissue Engineering Research 2016;20(44):6557-6563
BACKGROUND:The incidence of low serum level of vitamin D in patients undergoing hip arthroplasty and its impact has not been reported in China, indicating that it has not been brought to the forefront. OBJECTIVE:To determine the prevalence of low serum level of vitamin D in patients before total hip arthroplasty and its relationship with the hip function scores. METHODS:Forty-eight hips from 48 patients undergoing primary hip arthroplasty from July 2013 to August 2014 in the First Affiliated Hospital of Suzhou University were enrol ed. According to the serum level of vitamin D, patients were assigned to low-level (<20μg/L) and high-level (20≥μg/L) groups. The general information of patients, the hip function scores before and after replacement at the last fol ow-up in the two groups were observed and compared. The relationship between the serum level of vitamin D and the hip function scores before and after replacement was analyzed by multiple linear regression analysis. And the average fol ow-up was 12 months (11-14 months). RESULTS AND CONCLUSION:(1) The incidence of low vitamin D level was 82%(20 ng/mL serving as standard). (2) Compared with patients with high vitamin D level, patients with low level of vitamin D had lower preoperative Harris scores and Merle D′Aubigne-Postel score (P<0.05), and also at the last fol ow-up (P<0.05. (3) Based on the preoperative and postoperative Harris, the multiple linear regression analysis showed that there was a positive correlation between the level of vitamin D and Harris score both preoperatively and postoperatively (P<0.05). (4) These results suggest that there is a higher incidence of low level of vitamin D in patients undergoing arthroplasty, and hip function scores before and after replacement in patients with low level of vitamin D are lower than the high level patients. Moreover, there is a positive correlation between the level of vitamin D and the hip joint function scores. Therefore, it is advisable to supplement vitamin D and calcium preoperatively, and the level of vitamin D wil be helpful for disease assessment and prognosis.
5.The application of pulse indication contour cardiac output to early fluid resuscitation in patients with septic shock
Jiaqiong LI ; Maoqin LI ; Jiyuan XU ; Zaixiang SHI ; Zhou ZHANG ; Lin LI ; Fei LU ; Xun MO ; Yanjun XU
Chinese Journal of Emergency Medicine 2011;20(1):30-34
Objective To explore the use of pulse indication contour cardiac output (PiCCO) as a guidance for fluid resuscitation and vasopressors employment in patients with septic shock in order to find out the efficacy of this resuscitation strategy in the respect of outcome of patients. Mtthod A total of 30 patients with septic shock were treated with the EDGT fluid treatment protocol as the conventional treatment group from December 2006 to June 2008; and another 26 patients were given fluid treatment under the guidance of PiCCO as PiCCO group from July 2008 to October 2009. Exclusion criteria included patients with history of heart and lung diseases, and liver and kidney dysfunction. The mean arterial blood pressure was maintained above or equal to 65mmHg in PiCCO group,and fluid resuscitation was concluded when global end-diastolic volume index reached 600~750 mL·-2 with the stroke volume variation in < 10% and without auricular fibrillation. Nor-epinephrine was administrated to adiust the systemic peripheral vascular resistance index during 1300~1500 d·s·cm-5·m-2.Dobutamine was empoyed when global ejection fraction was compromised. The options of liquid and diuretics depend upon the presence d extra-vascular lung water. Central venous oxygen saturation and the level of lactate were observed 6hours after resuscitation. The liquid equilibrium for 3 days and the dosage of vasopressors were also recorded. The rate of survival, the time taken for weaning from mechanical ventilation, the days of ICU stay and rate of intact organ function within 28 days were compared between two groups. Results The demphics of patients of two goups were similar. There were no significant difference between PiCCO and the conventional group in values of central venous oxygen saturation and lactate 6 hours after admission to ICU (P > 0.05). And 6 h and 1d after fluid resuscitation, the dosages of dobutamine and the dosages of nor-epinephrine used in PiCCO group were significantly higher than those in conventional group in which the dosages of dobutamine in two groups were [(145.4±24.5)mg vs. (104.2 ± 46.3) mg and (330.2 ± 30.3) mg vs. (202.4 ± 40.3) mg], respectively, and the dosages of nor-epinephrine [(14.5±3.8) mgvs. (10.2±5.6) mgand (38.2±4.2) rng vs.(20.1±6.2) mg], respectively. However, the dosages of vasopressors were similar between two groups 2 d and 3 d later. The amounts of liquid administered to get equilibrium in 6 h and the 3 d in PiCCO group were significantly less than those in conventional group [(2121±578) mL vs. (2910±987) mL and (3845±435) mL vs. (4545 ± 765) mL and (2467±510) mLvs. (2867±618) mL and (951±332) mLvs. (1472±533) mL], respectively. The days required to get free from mechanical ventilation within 28d were significantly longer in PiCGO group[(19.7 ± 8.3) d vs.(15.1±9.1) d], but the days of ICU stay were significantly shorter in PiCCO group [(7.5 ± 3.5) d vs. (9.5±3.2) d] (P<0.05). The rates of survival and days free from organ failure within 28 days of two groups were similar(P>0.05). Conclusions When the early fluid management guided with PiCCO in septic shock patients,the fluid management can be implement more safely and precisely. It can shorten the days of ICU stay and days of mechanical ventilation support with avoidance of fluid resuscitation.
6.The Study on Method of Evaluatiing Medical Students' Occupation Quality
Zaixiang WANG ; Naizheng ZHANG
Chinese Medical Ethics 1995;0(02):-
The well-liking medical occupation personality is a hardcore of medical students' occupation quality and it is very important to synthetically evaluate medical students' occupation quality. The fuzzy evaluation method can sufficiently combine quality and quantity,and get a valuation grade, and make the qualitative evaluation have an objective basis. And it can get a synthetic quantitative index by a proper method combining uneasy quantitative factors and easy quantitative factors, and promote the medical students' synthetic development.

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