1.Nanomedicine-driven tumor glucose metabolic reprogramming for enhanced cancer immunotherapy.
Chenwei JIANG ; Minglu TANG ; Yun SU ; Junjie XIE ; Qi SHANG ; Mingmei GUO ; Xiaoran AN ; Longfei LIN ; Ruibin WANG ; Qian HUANG ; Guangji ZHANG ; Hui LI ; Feihu WANG
Acta Pharmaceutica Sinica B 2025;15(6):2845-2866
Tumors exhibit abnormal glucose metabolism, consuming excessive glucose and excreting lactate, which constructs a tumor microenvironment that facilitates cancer progression and disrupts immunotherapeutic efficacy. Currently, tumor glucose metabolic dysregulation to reshape the immunosuppressive microenvironment and enhance immunotherapy efficacy is emerging as an innovative therapeutic strategy. However, glucose metabolism modulators lack specificity and still face significant challenges in overcoming tumor delivery barriers, microenvironmental complexity, and metabolic heterogeneity, resulting in poor clinical benefit. Nanomedicines, with their ability to selectively target tumors or immune cells, respond to the tumor microenvironment, co-deliver multiple drugs, and facilitate combinatorial therapies, hold significant promise for enhancing immunotherapy through tumor glucose metabolic reprogramming. This review explores the complex interactions between tumor glucose metabolism-specifically metabolite transport, glycolysis processes, and lactate-and the immune microenvironment. We summarize how nanomedicine-mediated reprogramming of tumor glucose metabolism can enhance immunotherapy efficacy and outline the prospects and challenges in this field.
2.The Effect of Mitochondrial Damage in Chondrocytes on Osteoarthritis
Zhen-Wei LI ; Jing-Yu HOU ; Yu-Ze LIN ; Zhi-Qi ZHANG ; Shang-Yi LIU ; Xiao-Wen LIU ; Kang-Quan SHOU
Progress in Biochemistry and Biophysics 2024;51(7):1576-1588
The pathogenesis of osteoarthritis (OA) is related to a variety of factors such as mechanical overload, metabolic dysfunction, aging, etc., and is a group of total joint diseases characterized by intra-articular chondrocyte apoptosis, cartilage fibrillations, synovial inflammation, and osteophyte formation. At present, the treatment methods for osteoarthritis include glucosamine, non-steroidal anti-inflammatory drugs, intra-articular injection of sodium hyaluronate, etc., which are difficult to take effect in a short period of time and require long-term treatment, so the patients struggle to adhere to doctor’s advice. Some methods can only provide temporary relief without chondrocyte protection, and some even increase the risk of cardiovascular disease and gastrointestinal disease. In the advanced stages of OA, patients often have to undergo joint replacement surgery due to pain and joint dysfunction. Mitochondrial dysfunction plays an important role in the development of OA. It is possible to improve mitochondrial biogenesis, quality control, autophagy balance, and oxidative stress levels, thereby exerting a protective effect on chondrocytes in OA. Therefore, compared to traditional treatments, improving mitochondrial function may be a potential treatment for OA. Here, we collected relevant literature on mitochondrial research in OA in recent years, summarized the potential pathogenic factors that affect the development of OA through mitochondrial pathways, and elaborated on relevant treatment methods, in order to provide new diagnostic and therapeutic ideas for the research field of osteoarthritis.
3.Monotropein Induced Apoptosis and Suppressed Cell Cycle Progression in Colorectal Cancer Cells.
Quan GAO ; Lin LI ; Qi-Man ZHANG ; Qin-Song SHENG ; Ji-Liang ZHANG ; Li-Jun JIN ; Rui-Yan SHANG
Chinese journal of integrative medicine 2024;30(1):25-33
OBJECTIVE:
To determine whether monotropein has an anticancer effect and explore its potential mechanisms against colorectal cancer (CRC) through network pharmacology and molecular docking combined with experimental verification.
METHODS:
Network pharmacology and molecular docking were used to predict potential targets of monotropein against CRC. Cell counting kit assay, plate monoclonal assay and microscopic observation were used to investigate the antiproliferative effects of monotropein on CRC cells HCT116, HT29 and LoVo. Flow cytometry and scratch assay were used to analyze apoptosis and cell cycle, as well as cell migration, respectively in HCT116, HT29, and LoVo cells. Western blotting was used to detect the expression of proteins related to apoptosis, cell cycle, and cell migration, and the expression of proteins key to the Akt pathway.
RESULTS:
The Gene Ontology and Reactome enrichment analyses indicated that the anticancer potential of monotropein against CRC might be involved in multiple cancer-related signaling pathways. Among these pathways, RAC-beta serine/threonine-protein kinase (Akt1, Akt2), cyclin-dependent kinase 6 (CDK6), matrix metalloproteinase-9 (MMP9), epidermal growth factor receptor (EGFR), cell division control protein 42 homolog (CDC42) were shown as the potential anticancer targets of monotropein against CRC. Molecular docking suggested that monotropein may interact with the 6 targets (Akt1, Akt2, CDK6, MMP9, EGFR, CDC42). Subsequently, cell activity of HCT116, HT29 and LoVo cell lines were significantly suppressed by monotropein (P<0.05). Furthermore, our research revealed that monotropein induced cell apoptosis by inhibiting Bcl-2 and increasing Bax, induced G1-S cycle arrest in colorectal cancer by decreasing the expressions of CyclinD1, CDK4 and CDK6, inhibited cell migration by suppressing the expressions of CDC42 and MMP9 (P<0.05), and might play an anticancer role through Akt signaling pathway.
CONCLUSION
Monotropein exerts its antitumor effects primarily by arresting the cell cycle, causing cell apoptosis, and inhibiting cell migration. This indicates a high potential for developing novel medication for treating CRC.
Humans
;
Proto-Oncogene Proteins c-akt/metabolism*
;
Cell Proliferation
;
Matrix Metalloproteinase 9
;
Molecular Docking Simulation
;
Cell Cycle
;
ErbB Receptors
;
Apoptosis
;
Colorectal Neoplasms/pathology*
;
Cell Line, Tumor
4.Sponge forceps assisted threading with Speedbridge technique for the treatment of acute closed Achilles tendon rupture
Lin SHANG ; Fuqiang MA ; Qi LI ; Yalei WANG ; Xiaolong ZHANG ; Shiqiang SUN ; Guanghui JIA ; Xiangyu WANG ; Aiguo WANG
Chinese Journal of Trauma 2023;39(3):259-264
Objective:To explore the outcome of sponge forceps assisted threading with Speedbridge technique for the treatment of acute closed Achilles tendon rupture.Methods:A retrospective case series study was conducted on 20 patients with acute closed Achilles tendon rupture treated in Zhengzhou Orthopedic Hospital from December 2019 to December 2021. There were 18 males and 2 females, with age range of 24-43 years [(29.5±7.6)years]. All patients were with unilateral injury, involving the left side in 13 patients and right side in 7. Examinations revealed a palpable defect in the Achilles tendon and positive Thompson test. A longitudinal incision was made at the medial edge of the ruptured tendon. Three nonabsorbable sutures were passed through the proximal stump with sponge forceps, bypassed the rupture site and fixed directly into the calcaneal bone. The disrupted tendon ends were aligned by the tendon-bundle technique using 4-0 absorbable sutures. The operation time and incision length were documented. The ankle joint range of motion (dorsiflexion/plantar flexion), American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot score and Achilles tendon total rupture score (ATRS) in the affected and healthy side were compared at 3, 6 and 12 months postoperatively. The wound healing and complications were observed.Results:All patients were followed up for 12-16 months [(13.2±2.5)months]. The operation time was 40-66 minutes [(52.0±10.3)minutes], with the incision length of 3-4 cm [(3.3±0.7)cm]. In the affected side at 3 and 6 months postoperatively, the ankle joint dorsiflexion [(5.6±1.5)°, (10.5±0.2)°] and plantar flexion [(28.4±3.2)°, (33.5±1.5)°] showed statistically significant difference compared with the healthy side (all P<0.05). The ankle joint dorsiflexion [(13.9±0.7)°] and plantar flexion [(38.3±4.4)°] in the affected side were not statistically different from that of the healthy side at 12 months postoperatively (all P>0.05). The AOFAS ankle-hindfoot score was (58.3±5.4)points, (84.9±7.1)points and (91.8±6.3)points at 3, 6 and 12 months postoperatively, showing a gradual rise (all P<0.05). The ATRS was (60.5±4.9)points, (85.5±9.0)points and (93.1±5.7)points at 3, 6 and 12 months postoperatively, showing a gradual rise (all P<0.05). All incisions were healed primarily. No patients had wound infection, nerve injury or re-rupture. Pain at the anchor insertion site occurred in 2 patients at 1 month after operation and relieved after active functional rehabilitation at 4 months after operation. Transient pain at the Achilles tendon insertion occurred in 1 patient at 6 months after operation, and relieved after 2 weeks of oral non-steroidal anti-inflammatory drugs treatment. Conclusion:For acute closed Achilles tendon rupture, sponge forceps assisted threading with Speedbridge technique can attain short operation time, small incision and good functional recovery, with few complications.
5.Imaging classification and analysis of the diagnosis and treatment of infected pancreatic necrosis:a report of 126 cases.
Tian Qi LU ; Li Ren SHANG ; Fan BIE ; Yi Lin XU ; Yu Hang SUI ; Guan Qun LI ; Hua CHEN ; Gang WANG ; Rui KONG ; Xue Wei BAI ; Hong Tao TAN ; Yong Wei WANG ; Bei SUN
Chinese Journal of Surgery 2023;61(1):33-40
Objective: To explore the clinical characteristics of various types of infected pancreatic necrosis(IPN) and the prognosis of different treatment methods in the imaging classification of IPN proposed. Methods: The clinical data of 126 patients with IPN admitted to the Department of Pancreatic and Biliary Surgery, the First Affiliated Hospital of Harbin Medical University from December 2018 to December 2021 were analyzed retrospectively. There were 70 males(55.6%) and 56 females(44.4%), with age(M(IQR)) of 44(17)years (range: 12 to 87 years). There were 67 cases(53.2%) of severe acute pancreatitis and 59 cases (46.8%) of moderately severe acute pancreatitis. All cases were based on the diagnostic criteria of IPN. All cases were divided into Type Ⅰ(central IPN)(n=21), Type Ⅱ(peripheral IPN)(n=23), Type Ⅲ(mixed IPN)(n=74) and Type Ⅳ(isolated IPN)(n=8) according to the different sites of infection and necrosis on CT.According to different treatment strategies,they were divided into Step-up group(n=109) and Step-jump group(n=17). The clinical indicators and prognosis of each group were observed and analyzed by ANOVA,t-test,χ2 test or Fisher exact test,respectively. Results: There was no significant difference in mortality, complication rate and complication grade in each type of IPN(all P>0.05). Compared with other types of patients, the length of stay (69(40)days vs. 19(19)days) and hospitalization expenses(323 000(419 000)yuan vs. 60 000(78 000)yuan) were significantly increased in Type Ⅳ IPN(Z=-4.041, -3.972; both P<0.01). The incidence of postoperative residual infection of Type Ⅳ IPN was significantly higher than that of other types (χ2=16.350,P<0.01). There was no significant difference in the mortality of patients with different types of IPN between different treatment groups. The length of stay and hospitalization expenses of patients in the Step-up group were significantly less than those in the Step-jump group(19(20)days vs. 33(35)days, Z=-2.052, P=0.040;59 000(80 000)yuan vs. 122 000(109 000)yuan,Z=-2.317,P=0.020). Among the patients in Type Ⅳ IPN, the hospitalization expenses of Step-up group was significantly higher than that of Step-jump group(330 000(578 000)yuan vs. 141 000 yuan,Z=-2.000,P=0.046). The incidence of postoperative residual infection of Step-up group(17.4%(19/109)) was significantly lower than that of Step-jump group(10/17)(χ2=11.980, P=0.001). Conclusions: Type Ⅳ IPN is more serious than the other three types. It causes longer length of stay and more hospitalization expenses. The step-up approach is safe and effective in the treatment of IPN. However, for infected lesions which are deep in place,difficult to reach by conventional drainage methods, or mainly exhibit "dry necrosis", choosing the step-jump approach is a more positive choice.
Male
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Female
;
Humans
;
Retrospective Studies
;
Pancreatitis, Acute Necrotizing/complications*
;
Acute Disease
;
Intraabdominal Infections/complications*
;
Necrosis/complications*
;
Treatment Outcome
6.Structural and Functional Neural Alterations in Internet Addiction: A Study Protocol for Systematic Review and Meta-Analysis
Jun-Li LIU ; Jing-Ting SUN ; Hui-Lin HU ; Hao-Yuan WANG ; Yun-Xi KANG ; Tian-Qi CHEN ; Zhu-Hong CHEN ; Yu-Xuan SHANG ; Yu-Ting LI ; Bo HU ; Rui LIU
Psychiatry Investigation 2023;20(1):69-74
A growing number of neuroimaging studies have revealed abnormal brain structural and functional alterations in subjects with internet addiction (IA), however, with conflicting conclusions. We plan to conduct a systematic review and meta-analysis on the studies of voxelbased morphometry (VBM) and resting-state functional connectivity (rsFC), to reach a consolidated conclusion and point out the future direction in this field. A comprehensive search of rsFC and VBM studies of IA will be conducted in the PubMed, Cochrane Library, and Web of Science databases to retrieve studies published from the inception dates to August 2021. If the extracted data are feasible, activation likelihood estimation and seed-based d mapping methods will be used to meta-analyze the brain structural and functional changes in IA patients. This study will hopefully reach a consolidated conclusion on the impact of IA on human brain or point out the future direction in this field.
7.Agkistrodon halys venom antitumor component-I inhibits vasculogenic mimicry in triple-negative breast cancer cells in vitro by down-regulating MMP2.
Yu GE ; Lin Ming LU ; Shu Yu TIAN ; Yu XIAO ; Shang Fu XIE ; Qi WANG ; Hui ZHI
Journal of Southern Medical University 2022;42(3):438-442
OBJECTIVE:
To investigate the inhibitory effect of agkistrodon halys venom antitumor component-I (AHVAC-I) on vasculogenic mimicry (VM) formation in triple-negative breast cancer MDA-MB-231 cells and explore its possible mechanism.
METHODS:
CCK8 assay was used to determine the optimal concentration of AHVAC-I for cell treatment based on its halfinhibitory concentration (IC50). MDA-MB-231 cells were treated with different concentrations of AHVAC-I or 5-Fu, and the changes in vasomimetic capacity of the cells were examined using Matrigel assay. The expression levels of matrix metalloproteinase-2 (MMP2) and MMP9 in the treated cells were detected using quantitative PCR and Western blotting.
RESULTS:
Compared with the control treatment with culture medium, treatment with 5, 10 and 20 μg/mL AHVAC-I significantly reduced vasomimetic ability of MDA-MB-231 cells in a dose-dependent manner (P < 0.01). MMP2 supplementation obviously restored the vasomimetic ability of the cells inhibited by AHVAC-I.
CONCLUSION
AHVAC-I inhibits VM formation in triplenegative breast cancer cells in vitro by down-regulating MMP2 production.
Agkistrodon/metabolism*
;
Animals
;
Cell Line, Tumor
;
Healthy Life Expectancy
;
Humans
;
Matrix Metalloproteinase 2/metabolism*
;
Neovascularization, Pathologic/metabolism*
;
Triple Negative Breast Neoplasms/metabolism*
;
Venoms
8.Incidence of extrauterine growth retardation and its risk factors in very preterm infants during hospitalization: a multicenter prospective study.
Wei SHEN ; Zhi ZHENG ; Xin-Zhu LIN ; Fan WU ; Qian-Xin TIAN ; Qi-Liang CUI ; Yuan YUAN ; Ling REN ; Jian MAO ; Bi-Zhen SHI ; Yu-Mei WANG ; Ling LIU ; Jing-Hui ZHANG ; Yan-Mei CHANG ; Xiao-Mei TONG ; Yan ZHU ; Rong ZHANG ; Xiu-Zhen YE ; Jing-Jing ZOU ; Huai-Yu LI ; Bao-Yin ZHAO ; Yin-Ping QIU ; Shu-Hua LIU ; Li MA ; Ying XU ; Rui CHENG ; Wen-Li ZHOU ; Hui WU ; Zhi-Yong LIU ; Dong-Mei CHEN ; Jin-Zhi GAO ; Jing LIU ; Ling CHEN ; Cong LI ; Chun-Yan YANG ; Ping XU ; Ya-Yu ZHANG ; Si-Le HU ; Hua MEI ; Zu-Ming YANG ; Zong-Tai FENG ; San-Nan WANG ; Er-Yan MENG ; Li-Hong SHANG ; Fa-Lin XU ; Shao-Ping OU ; Rong JU
Chinese Journal of Contemporary Pediatrics 2022;24(2):132-140
OBJECTIVES:
To investigate the incidence of extrauterine growth retardation (EUGR) and its risk factors in very preterm infants (VPIs) during hospitalization in China.
METHODS:
A prospective multicenter study was performed on the medical data of 2 514 VPIs who were hospitalized in the department of neonatology in 28 hospitals from 7 areas of China between September 2019 and December 2020. According to the presence or absence of EUGR based on the evaluation of body weight at the corrected gestational age of 36 weeks or at discharge, the VPIs were classified to two groups: EUGR group (n=1 189) and non-EUGR (n=1 325). The clinical features were compared between the two groups, and the incidence of EUGR and risk factors for EUGR were examined.
RESULTS:
The incidence of EUGR was 47.30% (1 189/2 514) evaluated by weight. The multivariate logistic regression analysis showed that higher weight growth velocity after regaining birth weight and higher cumulative calorie intake during the first week of hospitalization were protective factors against EUGR (P<0.05), while small-for-gestational-age birth, prolonged time to the initiation of total enteral feeding, prolonged cumulative fasting time, lower breast milk intake before starting human milk fortifiers, prolonged time to the initiation of full fortified feeding, and moderate-to-severe bronchopulmonary dysplasia were risk factors for EUGR (P<0.05).
CONCLUSIONS
It is crucial to reduce the incidence of EUGR by achieving total enteral feeding as early as possible, strengthening breastfeeding, increasing calorie intake in the first week after birth, improving the velocity of weight gain, and preventing moderate-severe bronchopulmonary dysplasia in VPIs.
Female
;
Fetal Growth Retardation
;
Gestational Age
;
Hospitalization
;
Humans
;
Incidence
;
Infant
;
Infant, Newborn
;
Infant, Premature
;
Infant, Very Low Birth Weight
;
Prospective Studies
;
Risk Factors
9. CircRNA-32011 regulates apoptosis induced by arsenic trioxide in cardiac myocytes
Wen-Jun MA ; Lin CHANG ; Ji-Chen WU ; Jia-Qi LIU ; Hui FU ; Ying WANG ; Ai-Jing SHANG ; Wen-Zheng CHENG ; Xiao-Xiang GUAN ; Hong ZHANG ; Yuan JIANG ; Chao-Qian XU
Chinese Pharmacological Bulletin 2022;38(10):1498-1504
Aim To investigate the effect of circRNA- 32011 on myocardial apoptosis induced by arsenic triox- ide (ATO).Methods Primary cardioniyocytes of suckling neonate mouse were treated with ATO ( final concentration 10 (xniol • L_1 ) for 24 h.Then cell via¬bility was measured by M IT assay.The mKNA expres¬sion levels of Bel-2/ Bax and circRNA-3201 I were de¬tected by KT-PCK.Bcl-2/Bax protein expression lev¬els were detected by Western blot.Overexpression and knock down circHNA-32011 respectively by plasmid and siHNA were used to verify its function in ATO-in- duced cardiomyocyte apoptosis.Results Myocardial cell viability decreased, Bel-2 expression significantly decreased while Bax expression increased in ATO group compared with the control group.CircKNA- 32011 was down-regulated in ATO ineuhated cardio¬niyocytes.Ovcrex press ion of circRNA-32011 in ATO- incubated cardioniyocytes increased myocardial cell vi¬ability and Bel-2 expression and decreased the expres¬sion of Bax.Knockdown of circRNA-32011 could fur¬ther reduce cardiomyoevte activity and Bel-2 expression and increase the experssion of Bax induced by ATO.Conclusions CircRNA-32011 protects cardiac myo¬cytes from apoptosis induced by arsenic trioxide, which may provide a new potential therapeutic strategy for ATO-induced myocardial injury.
10.Study on the reliability and validity of the Chinese Criteria of Health Scale for the elderly people.
Jing SHI ; Shang Xin LIU ; Jia Wei LI ; Yong Quan LIU ; Ji Xiang MA ; Jing QI ; Liang Xia CHEN ; Bai Yu ZHOU ; Shu Jun WANG ; Pu Lin YU
Chinese Journal of Preventive Medicine 2022;56(12):1809-1814
Objective: To evaluate the reliability and validity of the Chinese Criteria of Health Scale for the elderly people. Methods: A cross-sectional study was performed among older adults of Meiyuan Community in Haidian District, Beijing and Nanwangkong Village in Qingzhou City,Shandong Province during July 2021. Using a cluster sampling method, totally 667 elderly people were investigated by face-to-face interview, using the scale which was formulated after two rounds of the Delphi method and pilot study. The overall scale includes physical health, mental health and social health subscales, including 9, 52 and 15 items, respectively. Four weeks after the survey, 56 elderly people were randomly selected and repeated the survey with the same method. The test-retest reliability, split-half reliability and internal consistency reliability of the scale were evaluated, and the validity was evaluated at the same time, including construct validity and content validity. Results: A total of 710 questionnaires were distributed and 667 valid questionnaires were obtained, with a total effective rate of 93.94%. The score of the overall scale was 79.79±16.22, the scores of the physical health, mental health, social health sub-scores were 41.64±9.76, 26.82±3.92 and 11.34±5.19, respectively. The scale had excellent reliability. In the test-retest reliability, the intraclass correlation coefficient (ICC) of the overall scale and each subscale were 0.766-0.861, and the weighted Kappa values were 0.762-0.817. The Spearman-Brown coefficient of the overall scale and each subscale in the split-half reliability were 0.722-0.855 (all P<0.001). The Cronbach's α coefficients of the overall scale of internal consistency reliability and each subscale were 0.748-0.899, and the Cronbach's α coefficients of each dimension were from 0.709 to 0.963(all P<0.001). At the same time, the scale had good construct validity and content validity. The correlation coefficients between the score of each dimension and its sub-scale were larger, from 0.641 to 0.873 (all P<0.05). The cumulative variance contribution rates of the scale and three subscales were all more than 50% of the approved standard. A total of 11 common factors were extracted, and all the load values of each item on the corresponding factors were ≥0.04. Conclusion: The Chinese Criteria of Health Scale for the elderly people has good validity and excellent reliability. It can be used as a basis for the scientific division of the health status of the elderly, the formulation of relevant policies by the government and the provision of appropriate health services for the elderly.
Humans
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Aged
;
Reproducibility of Results
;
Cross-Sectional Studies
;
Pilot Projects
;
East Asian People
;
Surveys and Questionnaires
;
Psychometrics/methods*
;
China

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