1.Disrupting calcium homeostasis and glycometabolism in engineered lipid-based pharmaceuticals propel cancer immunogenic death.
Qiuxia PENG ; Xiaolong LI ; Chao FANG ; Chunyan ZHU ; Taixia WANG ; Binxu YIN ; Xiulin DONG ; Huaijuan GUO ; Yang LIU ; Kun ZHANG
Acta Pharmaceutica Sinica B 2025;15(3):1255-1267
Homeostasis and energy and substance metabolism reprogramming shape various tumor microenvironment to sustain cancer stemness, self-plasticity and treatment resistance. Aiming at them, a lipid-based pharmaceutical loaded with CaO2 and glucose oxidase (GOx) (LipoCaO2/GOx, LCG) has been obtained to disrupt calcium homeostasis and interfere with glycometabolism. The loaded GOx can decompose glucose into H2O2 and gluconic acid, thus competing with anaerobic glycolysis to hamper lactic acid (LA) secretion. The obtained gluconic acid further deprives CaO2 to produce H2O2 and release Ca2+, disrupting Ca2+ homeostasis, which synergizes with GOx-mediated glycometabolism interference to deplete glutathione (GSH) and yield reactive oxygen species (ROS). Systematical experiments reveal that these sequential multifaceted events unlocked by Ca2+ homeostasis disruption and glycometabolism interference, ROS production and LA inhibition, successfully enhance cancer immunogenic deaths of breast cancer cells, hamper regulatory T cells (Tregs) infiltration and promote CD8+ T recruitment, which receives a considerably-inhibited outcome against breast cancer progression. Collectively, this calcium homeostasis disruption glycometabolism interference strategy effectively combines ion interference therapy with starvation therapy to eventually evoke an effective anti-tumor immune environment, which represents in the field of biomedical research.
2. Finite element analysis of cervical intervertebral discs after removing different ranges of uncinate processes
Yang YANG ; Jun SHI ; Kun LI ; Shao-Jie ZHANG ; Er-Fei HOU ; Jie CHEN ; Xing WANG ; Zhi-Jun LI ; Kun LI ; Yuan MA ; Shao-Jie ZHANG ; Zhi-Jun LI ; Chao-Qun WANG
Acta Anatomica Sinica 2024;55(1):88-97
Objective To study the stress change characteristics of the cervical disc after removing different ranges of the uncinate process by establishing a three⁃dimensional finite element model of the C
3.Research progress in micro/nanobubbles for ultrasound diagnosis or treatment
Qing-qing AN ; Chen-xi LI ; Shao-kun YANG ; Xiao-ming HE ; Yue-heng WANG ; Chao-xing HE ; Bai XIANG
Acta Pharmaceutica Sinica 2024;59(3):581-590
In the past few decades, microbubbles were widely used as ultrasound contrast agents in the field of tumor imaging. With the development of research, ultrasound targeted microbubble destruction technology combined with drug-loaded microbubbles can achieve precise drug release and play a therapeutic role. As a micron-scale carrier, microbubbles are difficult to penetrate the endothelial cell space of tumors, and nano-scale drug delivery system—nanobubbles came into being. The structure of the two is similar, but the difference in size highlights the unique advantages of nanobubbles in drug delivery. Based on the classification principle of shell materials, this review summarized micro/nanobubbles used for ultrasound diagnosis or treatment and discussed the possible development directions, providing references for the subsequent development.
4.Natural collapse course of ARCO Ⅱ stage osteonecrosis of the femoral head based on China-Japan Friendship Hospital classification
Rushun ZHAO ; Yangquan HAO ; Hanbo XU ; Zhi YANG ; Peng XU ; Xin ZHENG ; Kun ZHANG ; Chao LU
Chinese Journal of Tissue Engineering Research 2024;28(30):4871-4875
BACKGROUND:Osteonecrosis of the femoral head is one of the refractory diseases in orthopedic diseases.The natural collapse course of osteonecrosis of the femoral head under different stages and types affects the progression and prognosis of the disease. OBJECTIVE:To explore the progression of natural collapse within 5 years in patients under the different classifications of China-Japan Friendship Hospital(CJFH)with stage Ⅱ osteonecrosis of the International Association for Research Circulation Osseous(ARCO),and to analyze the collapse rate and collapse risk of the femoral head under the different classifications of CJFH. METHODS:A retrospective study was performed to select patients diagnosed with ARCO Ⅱ stage osteonecrosis of the femoral head without collapse in the Honghui Hospital Affiliated to Xi'an Jiaotong University from October 2016 to October 2017.According to whether it collapsed,the number of hips was divided into the collapse group(n=82)and the non-collapsed group(n=70).The collapse risk of patients with osteonecrosis of the femoral head under different CJFH classifications,as well as the collapse time,number of collapses,and collapse rate within 5 years were counted,and then the Kaplan-Meier survival curve of the femoral head under different classification of CJFH was plotted. RESULTS AND CONCLUSION:(1)A total of 97 patients with 152 hips were enrolled,and 82 hips collapsed during the follow-up period,with a total collapse rate of 53.9%,of which the collapse rates of M type,C type,L1 type,L2 type,and L3 type were 0.0%,36.7%,51.4%,72.2%,and 77.8%,respectively,and the comparison between the groups was statistically significant(P<0.05).(2)In terms of collapse risk,the collapse risk of L1 type was 1.704 times that of C-type(P>0.05),while the collapse risks of L2 type and L3 type were 3.866 times and 6.423 times that of C type(P<0.05),respectively.(3)In terms of the Kaplan-Meier survival curve,the median survival time of the femoral head of ARCO Ⅱ stage patients was 3 years,with a 95%confidence interval of 2.885-3.471 years,and the survival rates of the femoral head at the first,third and fifth years were 65.1%(99/152),50.7%(77/152),and 46.1%(70/152),respectively.(4)These findings conclude that different CJFH classifications affect the collapse rate of ARCO Ⅱ stage osteonecrosis of the femoral head patients,among which L3 type patients have the highest collapse rate,followed by L2 type and L1 type patients;C type patients have a lower collapse rate,and M type patients do not collapse,which indicates that the preservation of the lateral column of the femoral head is of great significance for the natural collapse course of osteonecrosis of the femoral head.
5.Progress of biomacromolecule drug nanodelivery systems in the treatment of rare diseases
Shu-jie WEI ; Han-xing HE ; Jin-tao HAO ; Qian-qian LV ; Ding-yang LIU ; Shao-kun YANG ; Hui-feng ZHANG ; Chao-xing HE ; Bai XIANG
Acta Pharmaceutica Sinica 2024;59(7):1952-1961
Rare diseases still lack effective treatments, and the development of drugs for rare diseases (known as orphan drugs) is an urgent medical problem. As natural active ingredients in living organisms, some biomacromolecule drugs have good biocompatibility, low immunogenicity, and high targeting. They have become one of the most promising fields in drug research and development in the 21st century. However, there are still many obstacles in terms of
6.Reliability of ICF dysfunction combination in rehabilitated inpatients
Weiwen XU ; Yang CHEN ; Chao TANG ; Kun CHEN ; Teng MA ; Dan LI ; Jie XIANG
China Modern Doctor 2024;62(8):45-50
Objective To explore the inter-rater and within-rater reliability of the 30 categories of the International Classification of Functioning Disability,and Health(ICF)dysfunction set(ICF generic-30 set)in clinical function assessment,to provide a basis for its clinical application.Methods Ninety patients from the Neurorehabilitation Department of the First People's Hospital of Suqian City were enrolled in this study.All patients were evaluated by the same functional evaluator's ICF dysfunction combination at the two time points of admission and discharge for the internal reliability analysis of the evaluator.Thirty patients in the neurorehabilitation department were randomly selected to be evaluated by two ICF function evaluators at the same time to conduct test-retest reliability analysis among evaluators.The internal consistency of the Cronbach's α coefficient test scale,and the intra-group correlation coefficient(ICC)test inter-rater reliability and within-rater reliability.Results The Cronbach's α coefficients of the combination of ICF dysfunction,physical function and activity,and participation in the two subscales were 0.941,0.717,and 0.942,respectively.The inter-rater reliability analysis showed that the ICC of the total score of the scale and the total scores of physical function and activity and participation in the two subscales were 0.998,0.971,0.999(P<0.01),and the inter-rater reliability good;the internal reliability analysis of the evaluator showed that the total score of the scale and the total scores of physical function and activity and participation in the two subscales were 0.988,0.917,0.991(P<0.01),except that b640 sexual function is not applicable,and b130 energy Harmony drive function ICC is 0.558,b280 pain ICC is 0.409,ICC of other combination items is 0.838-0.986(P<0.01),the evaluator's internal reliability is good;90 patients'ICF dysfunction combination scale has 30 categories.The comparison between admission and discharge was statistically significant except that b640 was not applicable for sexual function(P<0.05).Conclusion The combination of ICF dysfunction has good internal consistency and inter-evaluator and intra-evaluator reliability in the functional evaluation of patients in neurorehabilitation department.
7.Design of intelligent positioning system for mobile medical equipment in operating room based on Bluetooth technology
Zhi-Meng LIU ; Ya-Dong LYU ; Long-Xue QIAO ; Lin-Huai TIAN ; Kun YANG ; Kai-Yuan LI ; Ning-Bo ZHAN ; Ying-Kang WEI ; Yong CHAO
Chinese Medical Equipment Journal 2023;44(9):29-32
Objective To develop an intelligent positioning system for mobile medical equipment in the operating room based on Bluetooth technology to enhance medical equipment management efficiency.Methods The intelligent positioning system for mobile medical equipment used received signal strength indication(RSSI)algorithm and multi-gateway trajectory filtering algorithm to realize Bluetooth positioning,which was composed of Bluetooth gateways,Bluetooth beacons,Bluetooth labels and a background data processing platform.The Bluetooth gateway consisted of an active power over ethernet(POE)module,a DC power module,a CPU,a Wi-Fi module and a Bluetooth module;the Bluetooth beacon included a beacon control unit,a Bluetooth transmitter module and a Bluetooth receiver module;the Bluetooth label was made up of a microcontroller unit(MCU),a Bluetooth module,an anti-temper switch and a accelerometer;the data processing platform had the front end developed with Vue architecture and the back end with Java language.Results The system developed could accurately locate the medical equipment in the operating room without electromagnetic interference to other medical devices.Conclusion The system developed gains advantages in high positioning accuracy,low electromagnetic interference,high stability and reliability and low cost,which improves the positioning and management efficiency of medical equipment under the premise of ensuring safety.[Chinese Medical Equipment Journal,2023,44(9):29-32]
8.Effects of single-person hyperbaric chamber on hemodynamics of superior mesenteric artery in personnel rushing to extremely high altitude area
Kun WANG ; Shi-Chao LI ; Shuo YANG ; Yu-Jing WU ; Jing JIN ; Maitikasimu ALIYE ; Rui-Jing SHI ; Xi YANG
Chinese Medical Equipment Journal 2023;44(10):59-63
Objective To evaluate the effect of the single-person hyperbaric chamber on hemodynamics of superior mesenteric artery in the personnel rushing to the extremely high altitude area.Methods Sixty healthy young male subjects who traveled by car from the plains(890 m above sea level)to a very high altitude area(5 130 m above sea level)were randomly divided into a control group,a low-flow oxygen therapy group and a hyperbaric oxygen group,with 20 cases in each group.After entering the plateau area,no intervention was made in the control group;in the low-flow oxygen therapy group,low-flow oxygen therapy was performed once a day by means of nasal oxygen cannula(oxygen flow rate of 2 L/min,60 min/times);in the hyperbaric oxygen group,hyperbaric oxygen therapy was carried out once a day in a single-person hyperbaric oxygen chamber(pressuri-zation pressure of 0.25 MPa,60 min/times).The subjects in the three groups had their peak systolic velocity(PSV),resistance index(RI),and pulsation index(PI)of the main trunks of the SMAs and their grade 1 and 2 branches measured and compared using color Doppler ultrasound diagnostic instruments on days 30,60,and 90,respectively,after acute entry to the plateau.SPSS 19.0 software was used for statistical analysis.Results There were no significant differences in PSV,RI and PI of SMA and its 1 st and 2nd grade branches between the 3 groups 30 days after entry(P>0.05).Sixty days after entry,the control group had the values of PSV statistically higher than those of the other two groups(P<0.05);there were no significant differences between the low-flow oxygen therapy group and the hyperbaric oxygen group in the values of PSV(P>0.05);the three groups had no obvious differences in the values of RI and PI(P>0.05).Ninety days after entry,the control group had the values of PSV,RI and PI all significantly higher than those of the other two groups(P<0.05);the low-flow oxygen therapy group had the values of PSV statistically higher than those of the hyperbaric oxygen group(P<0.05),while the values of RI and PI not significantly different from those of the hyperbaric oxygen group(P>0.05).Conclusion Single-person hyperbaric oxygen chamber significantly improves the SMA blood flow changes due to oxygen partial pressure reduction in the plateau,and thus is of significance for preventing ischemic enteropathy of the personnel rushing to the plateau.[Chinese Medical Equipment Journal,2023,44(10):59-63]
9.The impact of amygdala glutamate receptors on cardiovascular function in rats with post-traumatic stress disorder.
Ya-Yang WU ; Kun-Yi CAI ; Yu-Jie WU ; Chao ZHENG ; Meng-Ya WANG ; Huan-Huan ZHANG
Acta Physiologica Sinica 2023;75(5):611-622
Post-traumatic stress disorder (PTSD) has been reported to be associated with a higher risk of cardiovascular disease. The amygdala may have an important role in regulating cardiovascular function. This study aims to explore the effect of amygdala glutamate receptors (GluRs) on cardiovascular activity in a rat model of PTSD. A compound stress method combining electrical stimulation and single prolonged stress was used to prepare the PTSD model, and the difference of weight gain before and after modeling and the elevated plus maze were used to assess the PTSD model. In addition, the distribution of retrogradely labeled neurons was observed using the FluoroGold (FG) retrograde tracking technique. Western blot was used to analyze the changes of amygdala GluRs content. To further investigate the effects, artificial cerebrospinal fluid (ACSF), non-selective GluR blocker kynurenic acid (KYN) and AMPA receptor blocker CNQX were microinjected into the central nucleus of the amygdala (CeA) in the PTSD rats, respectively. The changes in various indices following the injection were observed using in vivo multi-channel synchronous recording technology. The results indicated that, compared with the control group, the PTSD group exhibited significantly lower weight gain (P < 0.01) and significantly decreased ratio of open arm time (OT%) (P < 0.05). Retrograde labeling of neurons was observed in the CeA after microinjection of 0.5 µL FG in the rostral ventrolateral medulla (RVLM). The content of AMPA receptor in the PTSD group was lower than that in the control group (P < 0.05), while there was no significant differences in RVLM neuron firing frequency and heart rate (P > 0.05) following ACSF injection. However, increases in RVLM neuron firing frequency and heart rate were observed after the injection of KYN or CNQX into the CeA (P < 0.05) in the PTSD group. These findings suggest that AMPA receptors in the amygdala are engaged in the regulation of cardiovascular activity in PTSD rats, possibly by acting on inhibitory pathways.
Rats
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Animals
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Rats, Sprague-Dawley
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Stress Disorders, Post-Traumatic
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Receptors, AMPA
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6-Cyano-7-nitroquinoxaline-2,3-dione/pharmacology*
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Receptors, Glutamate/metabolism*
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Amygdala
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Weight Gain
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Medulla Oblongata/physiology*
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Blood Pressure
10.Research progress of intelligent reversible drug delivery system
Ke-xin CONG ; Xiao-dan SONG ; Ya-nan SUN ; Chao-xing HE ; Shao-kun YANG ; De-ying CAO ; Jing BAI ; Jia ZHANG ; Bai XIANG
Acta Pharmaceutica Sinica 2023;58(3):483-493
In the research on cancer theranostics, most environment-sensitive drug delivery systems can only achieve unidirectional and irreversible responsive changes under pathological conditions, thereby improving the targeting effect and drug release performance of the delivery system. However, such irreversible changes pose potential safety hazards when the dynamically distributed delivery system returns to the blood circulation or transports to the normal physiological environment. Intelligent reversible drug delivery systems can respond to normal physiological and pathological microenvironments to achieve bidirectional and reversible structural changes. This feature will help to precisely control the drug release of the delivery system, prolong the blood circulation time, improve the targeting efficiency, and avoid the potential safety hazards of the irreversible drug delivery system. In this review, we describe the research progress of intelligent reversible drug delivery system from two main aspects: controlled drug release and prolonged blood circulation time/enhanced cellular internalization of drug.

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