1.Nucleic acid-based delivery system delivering platinum drugs cooperates with siRNA for potentiated chemo-immunotherapy by reducing phosphatidylserine exposure and activating the cGAS-STING pathway.
Jianqin YAN ; Zijian ZHAO ; Dengshuai WEI ; Huapeng ZHENG ; Bin HE ; Yong SUN
Acta Pharmaceutica Sinica B 2025;15(10):5444-5457
Chemotherapeutic drugs, such as cisplatin and phenanthriplatin (PhenPt), as STING agonists to induce DNA damage and activate the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) signaling pathway provides a potential strategy for clinical chemo-immunotherapy. However, treatment with Pt-based drugs leads to irreversible ectopia of phosphatidylserine (PS), a major component of the intracellular membrane, to the surface of the cancer cells by enzymes (Xkr8). Exposed PS can bind to immune cell receptors and inhibit the presentation of tumor antigens, leading to immunosuppression and attenuation of chemotherapy. Herein, we report a novel approach to enhance chemo-immunotherapy by constructing siRNA targeted Xkr8 (siXkr8)-mediated tetrahedral framework nucleic acid nanogel structure concurrently loaded with PhenPt (siXkr8-FNG/PhenPt) for co-delivery of siRNA and Pt-based drugs. The results showed that siXkr8-FNG/PhenPt can not only be used as an efficient delivery carrier to deliver siXkr8, block the expression of Xkr8, reduce the exposure of PS on the cancer cells surface, but also act as an immune stimulant to activate cGAS-STING pathway, effectively improve the immunosuppressive microenvironment, produce antitumor immune response, and inhibit tumor growth and metastasis. Overall, this new delivery system is important for improving the effect of Pt-based drug chemotherapy, inducing immune enhancement and nucleic acid drug delivery.
2.Visualization analysis of literature information in Organ Transplantation from 2010 to 2019 based on information metrology
Huapeng LU ; Qinling YANG ; Yi LYU ; Dinghui DONG ; Boyan TIAN ; Wenjun TAN ; Wenjie TIAN ; Xia XIN ; Xuemei ZHENG
Organ Transplantation 2020;11(6):724-
Objective To analyze the characteristics of papers published in
3.Effect of enteral nutrition via a naso-gastric(intestinal) tube vs a percutaneous endoscopic gastrostomy/jejunostomy tube in patients after liver transplantation: a Meta analysis
Huapeng LU ; Qigui XIAO ; Jing WANG ; Qinling YANG ; Xin ZHENG ; Peipei LIU ; Jin LI
Chinese Journal of Hepatobiliary Surgery 2018;24(11):751-756
Objective To systematically review the effect of enteral nutrition via a naso-gastric (intestinal) tube (NG) vs a percutaneous endoscopic gastrostomy/jejunostomy (PEG/PEJ) after liver transplantation,and provide support for the selection of proper nutrition.Methods Pub Med,web of science,Cochrane Library (Jan,2018),CNKI,VIP and Wanfang Date were search until Jan,2018.Two authors independently assessed the trials for inclusion and extracted the data.Discrepancies were resolved in consultation with a third reviewer,about the research of retrospective study for the effects of enteral nutrition via NG vs PEG/PEJ after liver transplantation was performed and supplemented.Publication bias were evaluated,and Meta-analyses were conducted with RevMan5.3.Results 4 studies were collected,involving 430 patients.The Meta-analysis showed that starting time of enteral nutrition of PEG/PEJ was earlier than NG (MD =-1.77,95% CI-1.83 to-1.70,P<0.05).The average hospitalization time of PEG/PEJ was shorter than NG (MD=-2.88,95%CI-5.19 to-0.56,P<0.05).The diarrhea incidence of PEG/PEJ was higher than NG (OR=1.66,95%CI 1.04 to 2.65,P<0.05),and gastroesophageal reflux incidence of PEG/PEJ was lower than NG (OR=0.29,95%CI 0.12 to 0.66,P<0.05).The gastric retention rate of PEG/PEJ was lower than NG (OR =0.26,95% CI 0.14 to 0.41,P<0.05).Dislocation incidence of PEG/PEJ was lower than NG (OR =0.06,95%CI 0.01 to 0.46,P<0.05).The pneumonia incidence of PEG/PEJ tube was lower than NG (OR=0.59,95%CI 0.36 to 0.99,P<0.05).There were no significant differences between PEG/PEJ and NG on indwelling time,occlusion,abdominal infection,acute renal insufficiency,and acute rejection reaction.Conclusion PEG/PEJ had earlier starting time of enteral nutrition,shorter hospitalization time,lower nutrition tube placement related complications such as gastric esophagus reflux,gastric retention,dislocation rate and lower incidence of pneumonia,but the incidence of diarrhea was higher.NG is the first choice after liver transplantation,and for patients with serious basic diseases,weak digestive function or digestive system disorders PEG/PEJ can be chosen.
4.Predictive factors associated with reversibility of post-transplantation diabetes mellitus for adult: a Meta-analysis
Huapeng LU ; Qigui XIAO ; Ying LI ; Peipei LIU ; Xin ZHENG ; Jin LI
Chinese Journal of Hepatobiliary Surgery 2017;23(12):799-804
Objective To systematically review the predictive factors associated with reversibility of post-transplantation diabetes mellitus in adults using Meta-analysis,and to provide a theoretical basis for clinical prevention and treatment of diabetes after transplantation.Methods Pub Med,Web of Science,Cochrane Library (Issue 5,2017),CNKI,VIP and WanFang Data were searched from inception until May 2017.Two authors independently assessed the trials for inclusion and extracted the data.Discrepancies were resolved in consultation with a third reviewer.Publication biases were evaluated,and the Meta-analyses were conducted with RevMan5.3.Results A total of 7 studies were analyzed which involved 979 adults.Metaanalysis showed the following significant predictive factors:male (OR =1.73,95% CI 1.19 to 2.50,P <0.05),advanced age (MD =1.73,95% CI 0.07 to 10.39,P =0.05),high FPG before transplantation (MD=5.66,95%CI 0.11 to 11.31,P=0.05),hepatitis C virus (HCV) infection (OR=1.52,95%CI 1.08 to 2.14,P < 0.05),high frequency of combination therapy with MMF (OR =0.26,95% CI 0.11 to 0.61,P < 0.05),and short time before development of PTDM (MD =-19.08,95% CI-37.08 to -1.07,P < 0.05).There was no correlation with preoperative BMI,family history of diabetes and acute rejection.Conclusion The study showed that male,advanced age,high FPG before transplantation,hepatitis C virus infection,high frequency combination therapy with MMF,short time before development of posttransplantation diabetes mellitus were the predictive factors associated with reversibility of post-transplantation diabetes mellitus.
5.Toxicology and tissue distribution of Ruthenium (II) CO-releasing molecules and its interaction with endogenous substances.
Pengpeng WANG ; Huapeng LIU ; Quanyi ZHAO ; Yonglin CHEN ; Bin LIU ; Baoping ZHANG ; Qian ZHENG
Acta Pharmaceutica Sinica 2013;48(11):1677-87
Carbon monoxide has been proved to be an important signal molecule in body. Transition metal carbonyl compounds are solidified form of carbon monoxide. Numerous studies have shown that Ruthenium carbonyl carbon monoxide releasing molecules have a strong pharmacological activity. In this paper, five Ruthenium (II) carbonyl CORMs 1-5 were synthesized and their toxicology, tissue distribution and interaction with blood endogenous substances were investigated. The results showed CORMs' IC50 to fibroblasts are ranged from 212.9 to 2089.2 micromol x L(-1). Their oral LD50 to mouse is between 800 to 1600 mg x kg(-1). After repeated administration, CORMs 1 and CORMs 5 haven't shown an obvious influence to rats' liver and kidney function, but caused the injury to liver and kidney cells. The in vivo distribution result revealed the majority of CORMs were distributed in blood, liver and kidney, only a small part of CORMs distributed in lung, heart and spleen. They could scarcely cross the blood-brain barrier and distribute to brain. The non-CO ligands in structure have an obvious relevance to their in vivo absorption and distribution. Interestingly, CORMs could enhance the fluorescence of bovine serum albumin, and this enhancement was in direct proportion with the concentration of CORMs. Under different conditions, interaction of CORMs with glutathione got different type of products, one is Ruthenium (II) tricarbonyl complexes, and Ruthenium (II) dicarbonyl complexes.
6.Changes of respiratory mechanics and central drive in sleeping patients with chronic obstructive pulmonary disease
Xin CHEN ; Jingjing ZHENG ; Rui CHEN ; Huapeng YU
Chinese Journal of Geriatrics 2012;31(9):774-777
Objective To evaluate the changes of respiratory mechanics and central drive in sleeping patients with chronic obstructive pulmonary disease (COPD).Methods A total of 14 patients with moderate to severe COPD (age 63.7± 6.4 years) and 10 healthy volunteers,admitted to our hospital from October 2010 to October 2011,were chosen in our study.After performing routine pulmonary function test,all subjects were monitored by respiratory mechanics,diaphragm electromyogram (EMGdi) and polysomnography (PSG) in waking and sleeping state.The different physiological parameters were recorded and calculated on a continuous basis in time sequence for 30 minutes.Results In sleeping state as compared with waking state,there were no differences(P>0.05) in respiratory rate(RR) and the ratio of inspiratory time to duration of one breath (Ti/Ttot),but there were reductions (P < 0.05) in the tidal volume (VT),minute ventilation (VE),mean inspiratory volume per second(VT/Ti),dynamic lung compliance(CLdyn),root mean square (RMS)and pulse oxygen saturation(SpO2).Meanwhile there were significant increases (P<0.05) in airway resistance(Raw) and pressure-time product(PTP) in COPD group.In normal group,there were no differences (P>0.05) in all above physiological parameters in sleeping state compared with waking state.Conclusions There are abnormal changes in respiratory mechanics characterized by increased airway resistance and work of breathing,meanwhile in reduced central drive and requirement of ventilation,which may be the main reasons for hypopnea and hypoxemia in sleeping COPD patients.

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