1.Strategies to Overcome Immunotherapy Resistance in Non-Small Cell Lung Cancer: Targeting Non-Cancer Cells
Runzhi CHEN ; Chang XUE ; Xiaoyu LI ; Yuanxiang LI ; Sheng HU
Cancer Research on Prevention and Treatment 2025;52(11):926-936
One of the key mechanisms underlying resistance against immunotherapy is the reduction in the abundance and functional capacity of immune cells within the tumor microenvironment (TME). Accordingly, the development of novel antibodies and small-molecule agents that target multiple co-inhibitory molecules—whether employed as monotherapies or in combination—holds promise for reinvigorating exhausted T cells and restoring antitumor immune responses. In addition, exploring agonists targeting co-stimulatory molecules represents a promising strategy to enhance the secondary signals necessary for T cell activation and thereby facilitates tumor eradication. However, careful attention must be given to potential toxicities associated with these agents. Furthermore, this review highlights the emerging therapeutic potential of cancer vaccines, oncolytic viruses, diverse cellular therapies, and other innovative strategies designed to augment the efficacy of immunotherapy in non-small cell lung cancer (NSCLC). Moreover, we discuss therapeutic strategies targeting non-proliferating TME components, including cancer-associated fibroblasts (CAFs) and the extracellular matrix (ECM), and hypoxia-alleviating agents and immune homeostasis-supporting probiotics, all aimed at enhancing anti-tumor immunity. In summary, this article emphasizes the critical importance of integrating therapeutics with complementary mechanisms of action while maintaining the balance between efficacy and tolerability in the advancement of precise and effective immunotherapy in NSCLC to an unprecedented level.
2.Clinical analysis of 29 cases of postsurgical gastroparesis syndrome after laparoscopic radical resection of right-side colon cancer
Yang LI ; Tao LIU ; Lipeng ZENG ; Yuanxiang HU
Journal of Clinical Surgery 2024;32(2):196-198
Objective To investigate the influencing factors of postoperative gastroparesis syndrome(PSG)after laparoscopic right hemicolon cancer resection.Methods A total of 1070 patients with laparoscopic right hemicolon cancer resection(complete right hemicolon mesoresection)were selected from Wuhan General Hospital of Yangtze River Shipping and Wuhan Union Hospital Cancer Department from December 2012 to June 2022.According to whether the patients got postoperative gastroparesis,were divided into the postoperative gastroparesis syndrome(PSG)group or the normal control group.Univariate and multivariate Logistic regression analysis were used to analyze the risk factors of PGS after right hemicolon resection.Results There were 29 patients in the gastroparesis group and 1041 patients in the normal control group.Univariate analysis showed that age,perioperative blood glucose level,surgical resection range,and surgical approach were related to the occurrence of PGS(P<0.05).Multivariate Logistic analysis showed that age,high perioperative blood glucose level,caudal approach plus combined approach,and large surgical resection range were independent influencing factors of PGS(P<0.05).Conclusions Age,high perioperative blood glucose level,caudal approach plus combined approach,and large surgical resection range are influencing factors of PGS.
3.Predictive value of myocardial contrast echocardiography in evaluating myocardial perfusion and prognosis after percutaneous coronary intervention in patients with acute myocardial infarction
Longhe ZHONG ; Yanfang SU ; Jianqin ZHANG ; Ying TANG ; Shasha LI ; Yanru XU ; Jian LIU ; Yuanxiang ZHANG ; Tiangang ZHU ; Juefei WU
Chinese Journal of Cardiology 2024;52(10):1186-1192
Objective:To evaluate myocardial microcirculation perfusion with myocardial contrast echocardiography (MCE) in patients with acute myocardial infarction after percutaneous coronary intervention (PCI), and to explore the prognostic value of different types of myocardial microcirculation perfusion.Methods:This is a prospective cohort study. Patients with acute myocardial infarction who underwent successful PCI in Nanfang Hospital of Southern Medical University and Kanghua Hospital of Dongguan City from October 2019 to June 2021 were selected. All the enrolled patients completed MCE examination within 72 hours after PCI. According to the examination results, the patients were divided into normal microcirculation perfusion group, delayed microcirculation perfusion group, and blocked microcirculation perfusion group. Adverse cardiovascular events including all-cause death, cardiovascular death, and angina re-hospitalization were followed up, and left ventricular ejection fraction (LVEF) review results were collected at six months to one year after surgery. Kaplan-Meier survival curve was used to investigate the difference in the incidence of adverse cardiovascular events in different myocardial perfusion groups, and Cox regression analysis was used to evaluate the effect of myocardial perfusion on adverse cardiovascular events.Results:A total of 113 patients with acute myocardial infarction were included, aged (56.3±11.5) years, with 88(78%) males. There were 31 cases in the normal microcirculation perfusion group, 43 cases in the delayed microcirculation perfusion group and 39 cases in the blocked microcirculation perfusion group. LVEF was reviewed in 49 patients, and LVEF in the delayed microcirculation perfusion group was significantly improved compared with baseline at follow-up ((63.3±1.2) % vs. (58.6±1.8) %, P=0.043), and there was no statistically significant difference between the other two groups (all P>0.05). The median follow-up time was 473 days, during follow-up period 30 adverse cardiovascular events occurred. Kaplan-Meier survival curve analysis showed that there was a statistically significant difference in the incidence of adverse cardiovascular events among the three groups ( Plog-rank=0.029). Cox regression analysis showed that abnormal microcirculation perfusion (defined as delayed and blocked microcirculation perfusion) was an independent predictor of adverse cardiovascular events in patients with acute myocardial infarction after PCI ( HR=1.90, 95% CI1.16-3.12, P=0.011). Conclusions:Microcirculatory perfusion decrease or lost is common in patients with acute myocardial infarction after PCI. Timely restoration of blood flow reconstruction can save heart function when microcirculatory perfusion decreases. Microcirculatory perfusion is a predictor of adverse cardiovascular events in patients with acute myocardial infarction, and patients with poor myocardial perfusion are more likely to experience adverse cardiovascular events.
4.Safety and feasibility of day surgery management model under ERAS concept for gynecologic laparoscopic surgery
Huaying LIU ; Ling LI ; Yuanxiang SHI ; Xin RONG ; Xiaolong LIANG ; Yanzhou WANG ; Zhimin WU
Journal of Army Medical University 2024;46(14):1658-1665
Objective To explore the safety and feasibility of the application of day surgery management model under enhanced recovery after surgery(ERAS)concept in patients undergoing gynecologic laparoscopic surgery.Methods A non-randomized concurrent control trial was conducted on the patients who underwent laparoscopic surgery in our department from January to August 2021.A total of 92 patients admitted on odd date were assigned into Ward B of our department and served as the control group,and another 96 patients hospitalized on even date were subjected into Ward A and served as the observation group.The control group was given the routine treatment schedule,including the relevant examinations after admission and general operation procedure during hospitalization.The observation group was under a day surgery management model based on the concept of ERAS,with aid of a day surgery team and optimized perioperative management measures,including pre-hospital rehabilitation,shortening water fasting before surgery,multi-mode analgesia,preventive antiemesis,intraoperative warmth,prevention of deep vein thrombosis,immediate postoperative eating and activity,and follow-up after discharge.Postoperative subjective comfort,intestinal function recovery,social and economic benefits,postoperative complications and inflammatory indicators were compared between the 2 groups.Results In 0~6,7~12 and 13~24 h after operation,the scores of thirst,hunger,nausea,pain,abdominal distension and pharyngeal discomfort were significantly lower in the observation group than the control group(P<0.01).The observation group had obviously shorter length of hospital stay and ealier bowel sound recovery and first anal exhaust than the control group(P<0.01).No postoperative complication,such as fall,unplanned secondary operation or wound infection was observed in both groups.The postoperative inflammatory indicators,including procalcitonin(PCT),neutrophil percentage(Neu%)and white blood cell count(WBC)were all in the normal ranges in the 2 groups at 24 h and 3 and 7 d after surgery.Statistical differences were found in firstly postoperative mobilization,length of hospital stay,hospitalization cost and patient satisfaction between the 2 groups(P<0.01).Conclusion ERAS-based day surgery management model has the advantages of shortening hospital stay,reducing medical costs,promoting postoperative rehabilitation,and improving the comfort and satisfaction in patients undergoing gynecologic laparoscopic surgery.
5.A Self-Developed Mobility Augmented Reality System Versus Conventional X-rays for Spine Positioning in Intraspinal Tumor Surgery: A Case-Control Study
Wenyao HONG ; Xiaohua HUANG ; Tian LI ; Juntao LUO ; Yuqing LIU ; Shengyue HUANG ; Zhongyi CHEN ; Bingwei HE ; Yuxing WEN ; Yuanxiang LIN
Neurospine 2024;21(3):984-993
Objective:
To evaluate the efficacy of a self-developed mobile augmented reality navigation system (MARNS) in guiding spinal level positioning during intraspinal tumor surgery based on a dual-error theory.
Methods:
This retrospective study enrolled patients diagnosed with intraspinal tumors admitted to Fujian Provincial Hospital between May and November 2023. The participants were divided into conventional x-rays and self-developed MARNS groups according to the localization methods they received. Position time, length of intraoperative incision variation, and location accuracy were systematically compared.
Results:
A total of 41 patients (19 males) with intraspinal tumors were included, and MARNS was applied to 21 patients. MARNS achieved successful lesion localization in all patients with an error of 0.38±0.12 cm. Compared to x-rays, MARNS significantly reduced positioning time (129.00±13.03 seconds vs. 365.00±60.43 seconds, p<0.001) and length of intraoperative incision variation (0.14 cm vs. 0.67 cm, p=0.009).
Conclusion
The self-developed MARNS, based on augmented reality technology for lesion visualization and perpendicular projection, offers a radiation-free complement to conventional x-rays.
6.A Self-Developed Mobility Augmented Reality System Versus Conventional X-rays for Spine Positioning in Intraspinal Tumor Surgery: A Case-Control Study
Wenyao HONG ; Xiaohua HUANG ; Tian LI ; Juntao LUO ; Yuqing LIU ; Shengyue HUANG ; Zhongyi CHEN ; Bingwei HE ; Yuxing WEN ; Yuanxiang LIN
Neurospine 2024;21(3):984-993
Objective:
To evaluate the efficacy of a self-developed mobile augmented reality navigation system (MARNS) in guiding spinal level positioning during intraspinal tumor surgery based on a dual-error theory.
Methods:
This retrospective study enrolled patients diagnosed with intraspinal tumors admitted to Fujian Provincial Hospital between May and November 2023. The participants were divided into conventional x-rays and self-developed MARNS groups according to the localization methods they received. Position time, length of intraoperative incision variation, and location accuracy were systematically compared.
Results:
A total of 41 patients (19 males) with intraspinal tumors were included, and MARNS was applied to 21 patients. MARNS achieved successful lesion localization in all patients with an error of 0.38±0.12 cm. Compared to x-rays, MARNS significantly reduced positioning time (129.00±13.03 seconds vs. 365.00±60.43 seconds, p<0.001) and length of intraoperative incision variation (0.14 cm vs. 0.67 cm, p=0.009).
Conclusion
The self-developed MARNS, based on augmented reality technology for lesion visualization and perpendicular projection, offers a radiation-free complement to conventional x-rays.
7.A Self-Developed Mobility Augmented Reality System Versus Conventional X-rays for Spine Positioning in Intraspinal Tumor Surgery: A Case-Control Study
Wenyao HONG ; Xiaohua HUANG ; Tian LI ; Juntao LUO ; Yuqing LIU ; Shengyue HUANG ; Zhongyi CHEN ; Bingwei HE ; Yuxing WEN ; Yuanxiang LIN
Neurospine 2024;21(3):984-993
Objective:
To evaluate the efficacy of a self-developed mobile augmented reality navigation system (MARNS) in guiding spinal level positioning during intraspinal tumor surgery based on a dual-error theory.
Methods:
This retrospective study enrolled patients diagnosed with intraspinal tumors admitted to Fujian Provincial Hospital between May and November 2023. The participants were divided into conventional x-rays and self-developed MARNS groups according to the localization methods they received. Position time, length of intraoperative incision variation, and location accuracy were systematically compared.
Results:
A total of 41 patients (19 males) with intraspinal tumors were included, and MARNS was applied to 21 patients. MARNS achieved successful lesion localization in all patients with an error of 0.38±0.12 cm. Compared to x-rays, MARNS significantly reduced positioning time (129.00±13.03 seconds vs. 365.00±60.43 seconds, p<0.001) and length of intraoperative incision variation (0.14 cm vs. 0.67 cm, p=0.009).
Conclusion
The self-developed MARNS, based on augmented reality technology for lesion visualization and perpendicular projection, offers a radiation-free complement to conventional x-rays.
8.A Self-Developed Mobility Augmented Reality System Versus Conventional X-rays for Spine Positioning in Intraspinal Tumor Surgery: A Case-Control Study
Wenyao HONG ; Xiaohua HUANG ; Tian LI ; Juntao LUO ; Yuqing LIU ; Shengyue HUANG ; Zhongyi CHEN ; Bingwei HE ; Yuxing WEN ; Yuanxiang LIN
Neurospine 2024;21(3):984-993
Objective:
To evaluate the efficacy of a self-developed mobile augmented reality navigation system (MARNS) in guiding spinal level positioning during intraspinal tumor surgery based on a dual-error theory.
Methods:
This retrospective study enrolled patients diagnosed with intraspinal tumors admitted to Fujian Provincial Hospital between May and November 2023. The participants were divided into conventional x-rays and self-developed MARNS groups according to the localization methods they received. Position time, length of intraoperative incision variation, and location accuracy were systematically compared.
Results:
A total of 41 patients (19 males) with intraspinal tumors were included, and MARNS was applied to 21 patients. MARNS achieved successful lesion localization in all patients with an error of 0.38±0.12 cm. Compared to x-rays, MARNS significantly reduced positioning time (129.00±13.03 seconds vs. 365.00±60.43 seconds, p<0.001) and length of intraoperative incision variation (0.14 cm vs. 0.67 cm, p=0.009).
Conclusion
The self-developed MARNS, based on augmented reality technology for lesion visualization and perpendicular projection, offers a radiation-free complement to conventional x-rays.
9.A Self-Developed Mobility Augmented Reality System Versus Conventional X-rays for Spine Positioning in Intraspinal Tumor Surgery: A Case-Control Study
Wenyao HONG ; Xiaohua HUANG ; Tian LI ; Juntao LUO ; Yuqing LIU ; Shengyue HUANG ; Zhongyi CHEN ; Bingwei HE ; Yuxing WEN ; Yuanxiang LIN
Neurospine 2024;21(3):984-993
Objective:
To evaluate the efficacy of a self-developed mobile augmented reality navigation system (MARNS) in guiding spinal level positioning during intraspinal tumor surgery based on a dual-error theory.
Methods:
This retrospective study enrolled patients diagnosed with intraspinal tumors admitted to Fujian Provincial Hospital between May and November 2023. The participants were divided into conventional x-rays and self-developed MARNS groups according to the localization methods they received. Position time, length of intraoperative incision variation, and location accuracy were systematically compared.
Results:
A total of 41 patients (19 males) with intraspinal tumors were included, and MARNS was applied to 21 patients. MARNS achieved successful lesion localization in all patients with an error of 0.38±0.12 cm. Compared to x-rays, MARNS significantly reduced positioning time (129.00±13.03 seconds vs. 365.00±60.43 seconds, p<0.001) and length of intraoperative incision variation (0.14 cm vs. 0.67 cm, p=0.009).
Conclusion
The self-developed MARNS, based on augmented reality technology for lesion visualization and perpendicular projection, offers a radiation-free complement to conventional x-rays.
10.Optimization of SARS-CoV-2 spike protein receptor binding domain expression in Pichia pastoris and evaluation of its immunogenicity
Dongdong HU ; Jiaduo SUN ; Ziyan WANG ; Haitao LIU ; Yiran SUN ; Dawei QIAN ; Dong LI ; Rongjun CHEN ; Jiao AN ; Chenliang ZHOU ; Ge LIU ; Jiang FAN ; Yuanxiang JIANG
Chinese Journal of Microbiology and Immunology 2022;42(7):520-526
Objective:To effectively express the receptor binding domain (RBD) of SARS-CoV-2 spike protein in Pichia pastoris and to evaluate its immunogenicity. Methods:The gene encoding the RBD protein was synthesized and cloned into the pPICZαA plasmid. After linearization, the plasmid was transferred and integrated into the genome of Pichia pastoris. The expressed RBD protein in culture supernatant was analyzed by Western blot and Biolayer interferometry. After screening, a single clone expressing the RBD protein was selected. The high-level expression of RBD protein was achieved by optimizing the fermentation process, including the salt concentration adjusting of the medium and induction condition optimization (pH, temperature and duration). The immunogenicity of the expressed RBD protein was evaluated in a mouse model. Results:A single clone with a high expression level of RBD protein was obtained and named RBD-X33. The expression level of RBD protein in the fermentation supernatant reached up to 240 mg/L after optimization of the induction condition (HBSM medium, pH=6.5±0.3, 22℃ and 120 h). In the mouse experiment, the recombinant RBD protein was formulated with Alum+ CpG dual adjuvant and injected into mice. The binding IgG antibody levels were up to 2.7×10 6 tested by ELISA and the neutralizing antibody levels were up to 726.8 tested by live virus neutralizing antibody assay (prototype). Conclusions:The RBD protein could be efficiently expressed in Pichia pastoris and induce stronger immune response in animals. This study suggested that the recombinant SARS-CoV-2 RBD protein expressed in Pichia pastoris could serve as a candidate antigen in the development of SARS-CoV-2 vaccine.

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