1.Discovery of a novel polymyxin adjuvant against multidrug-resistant gram-negative bacteria through oxidative stress modulation.
Taotao LU ; Hongguang HAN ; Chaohui WU ; Qian LI ; Hongyan HU ; Wenwen LIU ; Donglei SHI ; Feifei CHEN ; Lefu LAN ; Jian LI ; Shihao SONG ; Baoli LI
Acta Pharmaceutica Sinica B 2025;15(3):1680-1695
Antibiotic adjuvants offer a promising strategy for restoring antibiotic sensitivity, expanding antibacterial spectra, and reducing required dosages. Previously, compound 15 was identified as a potential adjuvant for Polymyxin B (PB) against multidrug-resistant (MDR) Pseudomonas aeruginosa DK2; however, its clinical utility was hindered by high cytotoxicity, uncertain in vivo efficacy, and an unclear synergetic mechanism. To address these challenges, we synthesized and evaluated a series of novel benzamide derivatives, with A22 emerging as a particularly promising candidate. A22 demonstrated potent synergistic activity to PB, minimal cytotoxicity, improved water solubility, and broad-spectrum synergism of polymyxins against various clinically isolated MDR Gram-negative strains. In vivo studies using Caenorhabditis elegans and mouse models further confirmed the efficacy of A22. Moreover, A22 effectively suppressed the development of PB resistance in Pseudomonas aeruginosa DK2. Mechanistic investigations revealed that A22 enhances polymyxins activity by inducing reactive oxygen species production, reducing ATP levels, increasing NOX activity, and inhibiting biofilm formation, leading to bacterial death. These findings position A22 as a highly promising candidate for the development of polymyxin adjuvants, offering a robust approach to combating MDR Gram-negative bacterial infections.
2.Prevention and Treatment Principles of Virus-Associated Malignant Tumors under the Guidance of the"Cancer Toxin"Pathogenesis Theory
Hongli ZHOU ; Luyu CHEN ; Yuanyuan QIN ; Wenting LI ; Hongguang ZHOU ; Mianhua WU
Journal of Nanjing University of Traditional Chinese Medicine 2025;41(11):1414-1428
The development of malignant tumors is influenced by multiple factors,including genetics,environment,lifestyle,and pathogen infection.Viral infection plays a significant role in tumor development and progression.This article integrates the common pathways of seven oncogenic viruses(HPV,EBV,HBV,HCV,KSHV,HTLV-1,and HIV)based on the theory of cancer toxin pathomechanism.The findings reveal that cancer toxin formation is influenced by both internal factors(healthy qi deficiency,viscus dysfunction,and qi,blood,and body fluid stagnation)and external factors(viral infection,environmental factors,and the six exogenous pathogens),driving tumor development,metastasis,and recurrence.Viral infection not only provides the material foundation for cancer toxin but also accelerates its maturation and spread through chronic inflammation and immune imbalance,forming a complex pathogen-esis of"viral toxicity-endogenous cancer toxin",which translates into a three-stage strategy of"prevention,treatment,and post-recovery prevention".This article systematically discusses the pathogenesis of major cancer toxins and their associated tumors.Inte-grating the cancer toxin theory,the article explores preventive and therapeutic strategies for virus-associated malignancies,providing a theoretical basis and practical reference for the integrated prevention and treatment of tumors using traditional Chinese and Western medicine.
3.Current Status,Advantages and Strategies of TCM in the Prevention and Treatment of Malignant Tumors
Weichen YUAN ; Hongguang ZHOU ; Wenting LI ; Li LI ; Muhan LI ; Mianhua WU
Journal of Nanjing University of Traditional Chinese Medicine 2025;41(6):707-720
This paper summarizes the current status of research on the prevention and treatment of malignant tumors with traditional Chinese medicine(TCM),and points out that TCM has the advantages of being based on the holistic view and advocating the preven-tive treatment of diseases.The strategies of TCM in preventing and treating malignant tumors are proposed:first,it is necessary to clar-ify the leading or auxiliary treatment role in different stages of tumors and give full play to its strengths and advantages;second,find the characteristics of the superior and inferior populations and microscopic markers of tumor diagnosis and treatment to promote accurate di-agnosis and treatment;third,improve the overall diagnosis and treatment level of tumors by grasping the core pathogenesis and ensure clinical efficacy;fourth,incorporate modern medical therapy factors into the TCM tumor diagnosis and treatment system in order to in-tercept the disease;fifth,add TCM psychological intervention on the basis of the four-in-one holistic syndrome differentiation view to achieve harmony between body and spirit;sixth,improve the rehabilitation and health care system of tumors combined with traditional Chinese and Western medicine through the use of multiple methods to promote the recovery of diseases.In this way,the clinical effica-cy of TCM in preventing and treating tumors can be continuously improved,and the great goal of TCM in preventing and treating tumors and benefiting all mankind can be truly realized.
4.Current Status,Advantages and Strategies of TCM in the Prevention and Treatment of Malignant Tumors
Weichen YUAN ; Hongguang ZHOU ; Wenting LI ; Li LI ; Muhan LI ; Mianhua WU
Journal of Nanjing University of Traditional Chinese Medicine 2025;41(6):707-720
This paper summarizes the current status of research on the prevention and treatment of malignant tumors with traditional Chinese medicine(TCM),and points out that TCM has the advantages of being based on the holistic view and advocating the preven-tive treatment of diseases.The strategies of TCM in preventing and treating malignant tumors are proposed:first,it is necessary to clar-ify the leading or auxiliary treatment role in different stages of tumors and give full play to its strengths and advantages;second,find the characteristics of the superior and inferior populations and microscopic markers of tumor diagnosis and treatment to promote accurate di-agnosis and treatment;third,improve the overall diagnosis and treatment level of tumors by grasping the core pathogenesis and ensure clinical efficacy;fourth,incorporate modern medical therapy factors into the TCM tumor diagnosis and treatment system in order to in-tercept the disease;fifth,add TCM psychological intervention on the basis of the four-in-one holistic syndrome differentiation view to achieve harmony between body and spirit;sixth,improve the rehabilitation and health care system of tumors combined with traditional Chinese and Western medicine through the use of multiple methods to promote the recovery of diseases.In this way,the clinical effica-cy of TCM in preventing and treating tumors can be continuously improved,and the great goal of TCM in preventing and treating tumors and benefiting all mankind can be truly realized.
5.Clinical characteristics of obstructive sleep apnea in children with Prader-Willi syndrome
Kaiping WU ; Qinghua LU ; Ailiang LIU ; Yuejie ZHENG ; Zhe SU ; Rongfei ZHENG ; Hongguang PAN ; Qin YANG
Chinese Pediatric Emergency Medicine 2025;32(8):591-596
Objective:To analyze the characteristics of obstructive sleep apnea(OSA)in children with Prader-Willi syndrome (PWS),and to improve the understanding of OSA during rapid eye movement sleep.Methods:The clinical data of 13 children with PWS aged 2-14 years admitted to Shenzhen Children's Hospital from June 2017 to June 2024 were retrospectively collected as the PWS group,and 12 children with snoring caused by adenoids,tonsil hypertrophy and/or obesity were selected as the control group.The gender,age,body mass index (BMI),obstructive apnea index (OAI),oxygen desaturation index (ODI),obstructive sleep apnea hypopnea index (OAHI),rapid eye movement period OAHI(OAHIrem),non-rapid eye movement period OAHI(OAHInrem) and OAHIrem/total sleep period OAHI ratio were compared between the two groups.Multivariate linear regression was used to assess the association between PWS and OAHIrem.Results:Among the 13 children in PWS group,there were 7 males and 6 females,with an average age of (7.63±4.05) years and an average BMI of (23.06±6.12) kg/m2.Among the 12 children in control group,there were 10 males and 2 females,with an average age of (7.28±3.92) years and an average BMI of (22.41±5.68) kg/m2.There were no statistically significant differences in age,gender,and BMI between the two groups ( P>0.05).All 13 children (100%) with PWS had OSA,with 8 cases (61.53%) of mild OSA and 5 cases (38.46%) of moderate to severe OSA.OAI and ODI in PWS group were significantly higher than those in control group ( P<0.05).OAHI and OAHInrem in PWS group were higher than those in control group,but the difference was not statistically significant ( P>0.05).OAHIrem and OAHIrem/ total sleep OAHI ratio were significantly higher than those in the control group,with statistical significance ( P<0.05).Multivariate linear regression analysis showed that PWS was significantly correlated with OAHIrem/ total sleep OAH ratio (square root) ( P=0.008). Conclusion:Children with PWS have a high incidence of OSA,with a high proportion of moderate to severe OSA.They are prone to OSA with hypoxemia during rapid eye movement sleep.It is recommended that respiratory monitoring of children with PWS during rapid eye movement sleep should be strengthened,and individualized treatment plan should be formulated according to the type and severity of OSA.
6.Prevention and Treatment Principles of Virus-Associated Malignant Tumors under the Guidance of the"Cancer Toxin"Pathogenesis Theory
Hongli ZHOU ; Luyu CHEN ; Yuanyuan QIN ; Wenting LI ; Hongguang ZHOU ; Mianhua WU
Journal of Nanjing University of Traditional Chinese Medicine 2025;41(11):1414-1428
The development of malignant tumors is influenced by multiple factors,including genetics,environment,lifestyle,and pathogen infection.Viral infection plays a significant role in tumor development and progression.This article integrates the common pathways of seven oncogenic viruses(HPV,EBV,HBV,HCV,KSHV,HTLV-1,and HIV)based on the theory of cancer toxin pathomechanism.The findings reveal that cancer toxin formation is influenced by both internal factors(healthy qi deficiency,viscus dysfunction,and qi,blood,and body fluid stagnation)and external factors(viral infection,environmental factors,and the six exogenous pathogens),driving tumor development,metastasis,and recurrence.Viral infection not only provides the material foundation for cancer toxin but also accelerates its maturation and spread through chronic inflammation and immune imbalance,forming a complex pathogen-esis of"viral toxicity-endogenous cancer toxin",which translates into a three-stage strategy of"prevention,treatment,and post-recovery prevention".This article systematically discusses the pathogenesis of major cancer toxins and their associated tumors.Inte-grating the cancer toxin theory,the article explores preventive and therapeutic strategies for virus-associated malignancies,providing a theoretical basis and practical reference for the integrated prevention and treatment of tumors using traditional Chinese and Western medicine.
7.Clinical characteristics of obstructive sleep apnea in children with Prader-Willi syndrome
Kaiping WU ; Qinghua LU ; Ailiang LIU ; Yuejie ZHENG ; Zhe SU ; Rongfei ZHENG ; Hongguang PAN ; Qin YANG
Chinese Pediatric Emergency Medicine 2025;32(8):591-596
Objective:To analyze the characteristics of obstructive sleep apnea(OSA)in children with Prader-Willi syndrome (PWS),and to improve the understanding of OSA during rapid eye movement sleep.Methods:The clinical data of 13 children with PWS aged 2-14 years admitted to Shenzhen Children's Hospital from June 2017 to June 2024 were retrospectively collected as the PWS group,and 12 children with snoring caused by adenoids,tonsil hypertrophy and/or obesity were selected as the control group.The gender,age,body mass index (BMI),obstructive apnea index (OAI),oxygen desaturation index (ODI),obstructive sleep apnea hypopnea index (OAHI),rapid eye movement period OAHI(OAHIrem),non-rapid eye movement period OAHI(OAHInrem) and OAHIrem/total sleep period OAHI ratio were compared between the two groups.Multivariate linear regression was used to assess the association between PWS and OAHIrem.Results:Among the 13 children in PWS group,there were 7 males and 6 females,with an average age of (7.63±4.05) years and an average BMI of (23.06±6.12) kg/m2.Among the 12 children in control group,there were 10 males and 2 females,with an average age of (7.28±3.92) years and an average BMI of (22.41±5.68) kg/m2.There were no statistically significant differences in age,gender,and BMI between the two groups ( P>0.05).All 13 children (100%) with PWS had OSA,with 8 cases (61.53%) of mild OSA and 5 cases (38.46%) of moderate to severe OSA.OAI and ODI in PWS group were significantly higher than those in control group ( P<0.05).OAHI and OAHInrem in PWS group were higher than those in control group,but the difference was not statistically significant ( P>0.05).OAHIrem and OAHIrem/ total sleep OAHI ratio were significantly higher than those in the control group,with statistical significance ( P<0.05).Multivariate linear regression analysis showed that PWS was significantly correlated with OAHIrem/ total sleep OAH ratio (square root) ( P=0.008). Conclusion:Children with PWS have a high incidence of OSA,with a high proportion of moderate to severe OSA.They are prone to OSA with hypoxemia during rapid eye movement sleep.It is recommended that respiratory monitoring of children with PWS during rapid eye movement sleep should be strengthened,and individualized treatment plan should be formulated according to the type and severity of OSA.
8.Construction of Detoxication Method of Warming and Nourishing under the Guidance of Compound Pathogenesis Theory of Malignant Tumor
Weichen YUAN ; Hongguang ZHOU ; Yupei ZHUANG ; Hongli ZHOU ; Mianhua WU
Journal of Nanjing University of Traditional Chinese Medicine 2024;40(6):543-549
Based on the compound pathogenesis theory of malignant tumor,this article combines the theories of positive-evil,yin-yang,and central qi theories with the theory of cancer toxin,pointing out that the deficiency of positive and excess of evil are the basis for the onset of tumors.The pathogenesis characteristics of tumors are the loss of both yin and yang,stagnation of qi,and cancer toxin deeply lurking.The paper believes that the loss of both yin and yang often originates from the spleen and kidney,stagnation of qi is first blamed on the spleen and stomach,and cancer toxin deeply lurking often accompanies multiple evil qi.Based on this,the detoxi-cation method of warming and nourishing is proposed to treat malignant tumors.It is the combination or sequential application of the three methods of warming,nourishing,and detoxification,which play the role of warming and nourishing together,harmonizing yin and yang;promoting the circulation of qi,relieving depression,and regulating emotions;eliminating cancer and toxin,and breaking the combined evil.
9.Preliminarily study of arthrocentesis combined with liquid phase concentrated growth factor injection in the treatment of unilateral temporomandibular joint osteoarthritis
Hongguang LI ; Weihua HAN ; Xun WU ; Jiling FENG ; Gang LI ; Juanhong MENG
Journal of Peking University(Health Sciences) 2024;56(2):338-344
Objective:To observe the clinical effect of arthrocentesis combined with liquid phase con-centrated growth factor(CGF)injection in the treatment of unilateral temporomandibular joint osteoarthri-tis(TMJOA),in order to provide a new treatment option for TMJOA patients.Methods:In this non-randomized controlled study,patients diagnosed with unilateral TMJOA who visited the center for tem-poromandibular joint disorder and orofacial pain of Peking University School and Hospital of Stomatology from June 2021 to January 2023 were selected as research objects.The patients were divided into experi-mental group and control group,which were selected by patients themselves.The experimental group re-ceived arthrocentesis combined with liquid phase CGF injection and the control group received arthrocen-tesis combined with HA injection.Both groups were treated 3 times,once every two weeks.The clinical effect was evaluated by the maximum mouth opening,pain value and the degree of mandibular function limitation 6 months after treatment.The change of condylar bone was evaluated by cone beam CT(CBCT)image fusion technology before and after treatment.Results:A total of 20 patients were included in the experimental group,including 3 males and 17 females,with an average age of(34.40± 8.41)years.A total of 15 patients were included in the control group,including 1 male and 14 females,with an average age of(32.20±12.00)years.There was no statistical difference in general information between the two groups(P>0.05).There were no statistical differences in the mouth opening,pain value and the degree of jaw function limitation between the two groups before treatment(P>0.05),and all of them improved 6 months after treatment compared with before treatment(P<0.05).However,the mouth opening of experimental group was significantly higher than that of control group 6 months after treatment(P<0.05),and the degree of jaw function limitation was significantly lower than that of con-trol group(P<0.05).CBCT 2D images showed that the condylar bone of both groups was smoother after treatment than before treatment,and image fusion results showed that 10 patients(50.0%)in the experimental group and 5 patients(33.3%)in the control group had reparative remodeling area of con-dylar bone,and there was no statistical difference between them(P>0.05).Except for one CGF pa-tient,the other patients in both groups had some absorption areas of condylar bone.Conclusion:The ar-throcentesis combined with liquid phase CGF injection can improve the clinical symptoms and signs of unilateral TMJOA patients in short term,and is better than HA in increasing mouth opening and impro-ving jaw function.CBCT fusion images of both patient groups show some cases of condylar bone repara-tive remodeling and its relevance to treatment plans still requires further study.
10.Targeting the chromatin structural changes of antitumor immunity
Li NIAN-NIAN ; Lun DENG-XING ; Gong NINGNING ; Meng GANG ; Du XIN-YING ; Wang HE ; Bao XIANGXIANG ; Li XIN-YANG ; Song JI-WU ; Hu KEWEI ; Li LALA ; Li SI-YING ; Liu WENBO ; Zhu WANPING ; Zhang YUNLONG ; Li JIKAI ; Yao TING ; Mou LEMING ; Han XIAOQING ; Hao FURONG ; Hu YONGCHENG ; Liu LIN ; Zhu HONGGUANG ; Wu YUYUN ; Liu BIN
Journal of Pharmaceutical Analysis 2024;14(4):460-482
Epigenomic imbalance drives abnormal transcriptional processes,promoting the onset and progression of cancer.Although defective gene regulation generally affects carcinogenesis and tumor suppression networks,tumor immunogenicity and immune cells involved in antitumor responses may also be affected by epigenomic changes,which may have significant implications for the development and application of epigenetic therapy,cancer immunotherapy,and their combinations.Herein,we focus on the impact of epigenetic regulation on tumor immune cell function and the role of key abnormal epigenetic processes,DNA methylation,histone post-translational modification,and chromatin structure in tumor immunogenicity,and introduce these epigenetic research methods.We emphasize the value of small-molecule inhibitors of epigenetic modulators in enhancing antitumor immune responses and discuss the challenges of developing treatment plans that combine epigenetic therapy and immuno-therapy through the complex interaction between cancer epigenetics and cancer immunology.

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