1.Market Access Policy for New Antimicrobial Drugs:International Experience and Inspiration
Baolong DING ; Qiang LIU ; Jingxuan WEI ; Yuyang SUN ; Wenmin DU ; Xin LI
Herald of Medicine 2025;44(3):416-421
Objective By reviewing the access policies for new antimicrobial drugs internationally,this study provides a reference for the development of China's antimicrobial drug access policy.Methods The Chinese and English databases,offi-cial websites of health agencies,and health technology assessment agencies of various countries(CNKI,PubMed,NICE in the UK,HAS in France,etc.)were searched to collect and sort out the access policies of new antibacterial drugs.Taking the antibacte-rial drug ceftazidime-avibactam and the antifungal drug esaconazole sulfate as examples,the key evidence points for the evaluation of antibacterial drugs in the market access process of medical insurance were analyzed.Finally,the author put forward suggestions for China's antibacterial drug access policy based on the opinions of experts in related fields of antibacterial drugs in China.Re-sults Access policies for antimicrobial drugs had already established in the UK,US,EU,Sweden Switzerland,and Republic of Korea.These policies included a series of measures such as evaluation approval rewards,patent extensions,additional reimburse-ment,decoupling sales revenue from sales volume,etc.,with the ultimate goal being to encourage research and development of new antibiotics while reducing resistance rates.The review found that besides evaluating the safety,economy,and cost-effectiveness,some evaluation agencies also consider the actual clinical value and social value of drugs when reviewing the evidence of two types of new antibacterial drugs in the medical insurance access link.Conclusion China can draw upon international framework principles while considering unique demands such as national antibiotic management policy or national healthcare negotiation re-quirements to provide certain policy support throughout the market access process for new antimicrobials due to their unique val-ues so that it can encourage research & development while curbing antibiotic resistance.
2.Effects of electroacupuncture for muscle regeneration and the secretion of exosomes around acupoints in a model of erector spinae muscle injury
Xiaolin XU ; Ying CHEN ; Zongze LYU ; Zhibin HUANG ; Dilin WANG ; Wenmin LI ; Miao XIE ; Yunqing GU ; Hui WANG ; Tong LIU
Journal of Beijing University of Traditional Chinese Medicine 2025;48(7):1000-1010
Objective To investigate the effects of electroacupuncture for the restoration of muscle regeneration and the secretion of exosomes around acupoints in a model of erector spinae muscle injury.Methods Forty SPF-grade male SD rats were randomly divided into blank group,model group,electroacupuncture group,and electroacupuncture+exosome inhibitor group,with 10 rats per group.Except for the blank group,the erector spinae muscle injury models were established in other groups by intramuscular injection of 0.5%bupivacaine.The blank control group received no treatment,whereas the rats in the electroacupuncture and electroacupuncture+exosome inhibitor groups were treated with electroacupuncture at"Weizhong"(BL40)and"Shenshu"(BL23)acupoints,respectively,stimulation was applied daily for 7 consecutive days,with each session lasting 20 minutes.The parameters used were a sparse-dense wave waveform,a frequency of 2/10 Hz,and a current intensity of 1 mA.The exosome inhibitor GW4869(3 g/L,50 μL per acupoint)was injected 1 h before each electroacupuncture in the electroacupuncture+exosome inhibitor group.After intervention,the erector spinae muscles were collected and observed by HE and Masson staining for morphological changes.The expression of paired box gene 7(Pax7)and recombinant myogenic differentiation(MyoD)was detected by immunohistochemistry,while the expression of myogenin(MyoG)and myosin heavy chain(MyHC)proteins was detected by western blotting.The serum exosomes of rats in each group were extracted and identified by transmission electron microscopy and nanoparticle tracking analysis,and the expression of Alix,differentiation cluster 63(CD63),and tumor susceptibility gene 101(TSG101)proteins were detected by Western blotting.Results Compared with the blank group,the model group,the electroacupuncture group,and the electroacupuncture+exosome inhibitor group exhibited spinae muscle fiber fragmentation,degeneration,necrosis,and inflammatory cell infiltration in HE staining.The result of Masson staining showed that collagen fiber hyperplasia was increased.The model group showed increased expression of MyoD,Pax7,MyoG,MyHC,and CD63,while TSG101 expression was downregulated(P<0.05).In the electroacupuncture group,the expression of MyoD,Pax7,Alix,and TSG101 was elevated(P<0.05),and the expression of MyHC and CD63 was decreased(P<0.05).The electroacupuncture+exosome inhibitor group displayed increased expression of MyHC,Alix,and TSG101(P<0.05),and the expression of CD63 was decreased(P<0.05).Compared with the model group,the electroacupuncture group and the electroacupuncture+exosome inhibitor group showed reduced muscle fiber degeneration,necrotic areas,and inflammatory cell infiltration as observed in HE staining,along with decreased collagen fiber hyperplasia in Masson staining.Specifically,the electroacupuncture group demonstrated increased expression of MyoD,Pax7,MyoG,Alix,and TSG101(P<0.05),and the expression of CD63 was decreased(P<0.05).The electroacupuncture+exosome inhibitor group displayed downregulated expression of Pax7,MyoG,MyHC,and CD63(P<0.05),and the expression of Alix and TSG101 was regulated(P<0.05).Compared with the electroacupuncture+exosome inhibitor group,the electroacupuncture group exhibited less muscle fiber degeneration and necrosis,reduced inflammatory cell infiltration in HE staining,and decreased stained collagen fibers in Masson staining.The electroacupuncture group showed increased expression of MyoD,Pax7,MyoG,MyHC,Alix,and CD63(P<0.05).Conclusion Electroacupuncture can up-regulate the expression of Pax7 and MyoD,and promote the regeneration of erector spinae muscles,which may be related to stimulating the secretion of exosomes around the acupoint.Exosomes may be an important mediator for the efficacy of acupuncture.
3.Discovery of novel butyrylcholinesterase inhibitors for treating Alzheimer's disease.
Zhipei SANG ; Shuheng HUANG ; Wanying TAN ; Yujuan BAN ; Keren WANG ; Yufan FAN ; Hongsong CHEN ; Qiyao ZHANG ; Chanchan LIANG ; Jing MI ; Yunqi GAO ; Ya ZHANG ; Wenmin LIU ; Jianta WANG ; Wu DONG ; Zhenghuai TAN ; Lei TANG ; Haibin LUO
Acta Pharmaceutica Sinica B 2025;15(4):2134-2155
Alzheimer's disease (AD) is a common neurodegenerative disorder among the elderly, and BuChE has emerged as a potential therapeutic target. In this study, we reported the development of compound 8e, a selective reversible BuChE inhibitor (eqBuChE IC50 = 0.049 μmol/L, huBuChE IC50 = 0.066 μmol/L), identified through extensive virtual screening and lead optimization. Compound 8e demonstrated favorable blood-brain barrier permeability, good drug-likeness property and pronounced neuroprotective efficacy. Additionally, 8e exhibited significant therapeutic effects in zebrafish AD models and scopolamine-induced cognitive impairments in mice. Further, 8e significantly improved cognitive function in APP/PS1 transgenic mice. Proteomics analysis demonstrated that 8e markedly elevated the expression levels of very low-density lipoprotein receptor (VLDLR), offering valuable insights into its potential modulation of the Reelin-mediated signaling pathway. Thus, compound 8e emerges as a novel and potent BuChE inhibitor for the treatment of AD, with significant implications for further exploration into its mechanisms of action and therapeutic applications.
4.Research on the current status and influencing factors of consumer health activation index in hospitalized elderly patients with multiple chronic conditions
Yunfeng ZHAO ; Rui LIU ; Min WU ; Caijie XU ; Wenmin ZHANG ; Yue WANG ; Aihong PAN
Chinese Journal of Nursing 2025;60(14):1716-1722
Objective To explore and analyze the current situation of consumer health activation index and its influencing factors in hospitalized elderly patients with multiple chronic conditions,and to provide reference basis for clinical intervention.Methods Convenience sampling method was used to select 332 hospitalized elderly patients with multiple chronic conditions from a tertiary hospital in Hefei City from July to December 2024 as the study subjects,and general information questionnaire,Consumer Health Activation Index,Health Literacy Management Scale,Scale of the Elderly Self-neglcet(Rural),and Perceived Social Support Scale were used to investigate the current situation of consumer health activation index of hospitalized elderly patients with multiple chronic conditions.Univariate analysis and multiple linear regression analysis were employed to explore the influencing factors of consumer health activation index in patients with multiple chronic conditions.Results A total of 332 questionnaires were distributed,and 325 valid questionnaires were retrieved.The score of the consumer health activation index of hospitalized elderly patients with multiple chronic conditions was(61.68±15.12).The results of multiple linear regression showed that literacy,average monthly household income,number of chronic diseases,medication frequency,self-care ability,health literacy management,perceived social support and self-neglect were the influencing factors for the positivity of hospitalized elderly patients with multiple chronic conditions(P<0.05),which could explain 59.9%of the variance of the consumer health activation index of hospitalized elderly patients with multiple chronic conditions.Conclusion The consumer health activation index of hospitalized elderly patients with multiple chronic conditions is at a low level.In the future,precise and systematic intervention measures for enhancing positive health status can be formulated by taking into account relevant influencing factors,in order to promote the transformation of patients from passive health to active health,and thereby facilitating positive aging.
5.Research on the current status and influencing factors of consumer health activation index in hospitalized elderly patients with multiple chronic conditions
Yunfeng ZHAO ; Rui LIU ; Min WU ; Caijie XU ; Wenmin ZHANG ; Yue WANG ; Aihong PAN
Chinese Journal of Nursing 2025;60(14):1716-1722
Objective To explore and analyze the current situation of consumer health activation index and its influencing factors in hospitalized elderly patients with multiple chronic conditions,and to provide reference basis for clinical intervention.Methods Convenience sampling method was used to select 332 hospitalized elderly patients with multiple chronic conditions from a tertiary hospital in Hefei City from July to December 2024 as the study subjects,and general information questionnaire,Consumer Health Activation Index,Health Literacy Management Scale,Scale of the Elderly Self-neglcet(Rural),and Perceived Social Support Scale were used to investigate the current situation of consumer health activation index of hospitalized elderly patients with multiple chronic conditions.Univariate analysis and multiple linear regression analysis were employed to explore the influencing factors of consumer health activation index in patients with multiple chronic conditions.Results A total of 332 questionnaires were distributed,and 325 valid questionnaires were retrieved.The score of the consumer health activation index of hospitalized elderly patients with multiple chronic conditions was(61.68±15.12).The results of multiple linear regression showed that literacy,average monthly household income,number of chronic diseases,medication frequency,self-care ability,health literacy management,perceived social support and self-neglect were the influencing factors for the positivity of hospitalized elderly patients with multiple chronic conditions(P<0.05),which could explain 59.9%of the variance of the consumer health activation index of hospitalized elderly patients with multiple chronic conditions.Conclusion The consumer health activation index of hospitalized elderly patients with multiple chronic conditions is at a low level.In the future,precise and systematic intervention measures for enhancing positive health status can be formulated by taking into account relevant influencing factors,in order to promote the transformation of patients from passive health to active health,and thereby facilitating positive aging.
6.Enhanced CT radiomics combined with deep learning algorithm for predicting cervical lymph node metastasis of papillary thyroid carcinoma
Yuanyuan YE ; Kewu HE ; Qifeng LIU ; Wenmin HONG
Chinese Journal of Interventional Imaging and Therapy 2025;22(3):196-200
Objective To observe the value of enhanced CT radiomics combined with deep learning(DL)algorithm for predicting cervical lymph node metastasis(CLNM)of papillary thyroid carcinoma(PTC).Methods Totally 100 patients with single PTC were retrospectively enrolled and divided into training set(n=70)and test set(n=30)at the ratio of 7∶3.The optimal radiomics features and DL features of lesions were extracted and screened based on arterial phase cervical CT,and the radiomics score(Radscore)and DL score(Deepscore)were calculated to construct radiomics model and DL model,respectively.Clinical data,routine CT findings,Radscore and Deepscore were enrolled in multivariate logistic regression analysis to screen the independent predictors of PTC CLNM,and a combined model was then constructed.The receiver operating characteristic curve was plotted,and the area under the curve(AUC)was calculated to evaluate the efficacy of each model for predicting PTC CLNM.Results Thirteen optimal radiomics features and 12 DL features were selected.Radscore(OR=1.698,P=0.002)and Deepscore(OR=1.872,P=0.021)were both independent predictors of PTC CLNM.The AUC of radiomics mode,l DL model and combined model for predicting PTC CLNM was 0.775,0.876 and 0.880 in training set,which in test set was 0.739,0.776 and 0.789,respectively.In training set,the prediction efficacy of combined model was better than that of radiomics model(Z=2.551,P=0.011).Conclusion Combined with DL algorithm could effectively increase the efficacy of enhanced CT radiomics for predict PTC CLNM.
7.Effects of electroacupuncture for muscle regeneration and the secretion of exosomes around acupoints in a model of erector spinae muscle injury
Xiaolin XU ; Ying CHEN ; Zongze LYU ; Zhibin HUANG ; Dilin WANG ; Wenmin LI ; Miao XIE ; Yunqing GU ; Hui WANG ; Tong LIU
Journal of Beijing University of Traditional Chinese Medicine 2025;48(7):1000-1010
Objective To investigate the effects of electroacupuncture for the restoration of muscle regeneration and the secretion of exosomes around acupoints in a model of erector spinae muscle injury.Methods Forty SPF-grade male SD rats were randomly divided into blank group,model group,electroacupuncture group,and electroacupuncture+exosome inhibitor group,with 10 rats per group.Except for the blank group,the erector spinae muscle injury models were established in other groups by intramuscular injection of 0.5%bupivacaine.The blank control group received no treatment,whereas the rats in the electroacupuncture and electroacupuncture+exosome inhibitor groups were treated with electroacupuncture at"Weizhong"(BL40)and"Shenshu"(BL23)acupoints,respectively,stimulation was applied daily for 7 consecutive days,with each session lasting 20 minutes.The parameters used were a sparse-dense wave waveform,a frequency of 2/10 Hz,and a current intensity of 1 mA.The exosome inhibitor GW4869(3 g/L,50 μL per acupoint)was injected 1 h before each electroacupuncture in the electroacupuncture+exosome inhibitor group.After intervention,the erector spinae muscles were collected and observed by HE and Masson staining for morphological changes.The expression of paired box gene 7(Pax7)and recombinant myogenic differentiation(MyoD)was detected by immunohistochemistry,while the expression of myogenin(MyoG)and myosin heavy chain(MyHC)proteins was detected by western blotting.The serum exosomes of rats in each group were extracted and identified by transmission electron microscopy and nanoparticle tracking analysis,and the expression of Alix,differentiation cluster 63(CD63),and tumor susceptibility gene 101(TSG101)proteins were detected by Western blotting.Results Compared with the blank group,the model group,the electroacupuncture group,and the electroacupuncture+exosome inhibitor group exhibited spinae muscle fiber fragmentation,degeneration,necrosis,and inflammatory cell infiltration in HE staining.The result of Masson staining showed that collagen fiber hyperplasia was increased.The model group showed increased expression of MyoD,Pax7,MyoG,MyHC,and CD63,while TSG101 expression was downregulated(P<0.05).In the electroacupuncture group,the expression of MyoD,Pax7,Alix,and TSG101 was elevated(P<0.05),and the expression of MyHC and CD63 was decreased(P<0.05).The electroacupuncture+exosome inhibitor group displayed increased expression of MyHC,Alix,and TSG101(P<0.05),and the expression of CD63 was decreased(P<0.05).Compared with the model group,the electroacupuncture group and the electroacupuncture+exosome inhibitor group showed reduced muscle fiber degeneration,necrotic areas,and inflammatory cell infiltration as observed in HE staining,along with decreased collagen fiber hyperplasia in Masson staining.Specifically,the electroacupuncture group demonstrated increased expression of MyoD,Pax7,MyoG,Alix,and TSG101(P<0.05),and the expression of CD63 was decreased(P<0.05).The electroacupuncture+exosome inhibitor group displayed downregulated expression of Pax7,MyoG,MyHC,and CD63(P<0.05),and the expression of Alix and TSG101 was regulated(P<0.05).Compared with the electroacupuncture+exosome inhibitor group,the electroacupuncture group exhibited less muscle fiber degeneration and necrosis,reduced inflammatory cell infiltration in HE staining,and decreased stained collagen fibers in Masson staining.The electroacupuncture group showed increased expression of MyoD,Pax7,MyoG,MyHC,Alix,and CD63(P<0.05).Conclusion Electroacupuncture can up-regulate the expression of Pax7 and MyoD,and promote the regeneration of erector spinae muscles,which may be related to stimulating the secretion of exosomes around the acupoint.Exosomes may be an important mediator for the efficacy of acupuncture.
8.Enhanced CT radiomics combined with deep learning algorithm for predicting cervical lymph node metastasis of papillary thyroid carcinoma
Yuanyuan YE ; Kewu HE ; Qifeng LIU ; Wenmin HONG
Chinese Journal of Interventional Imaging and Therapy 2025;22(3):196-200
Objective To observe the value of enhanced CT radiomics combined with deep learning(DL)algorithm for predicting cervical lymph node metastasis(CLNM)of papillary thyroid carcinoma(PTC).Methods Totally 100 patients with single PTC were retrospectively enrolled and divided into training set(n=70)and test set(n=30)at the ratio of 7∶3.The optimal radiomics features and DL features of lesions were extracted and screened based on arterial phase cervical CT,and the radiomics score(Radscore)and DL score(Deepscore)were calculated to construct radiomics model and DL model,respectively.Clinical data,routine CT findings,Radscore and Deepscore were enrolled in multivariate logistic regression analysis to screen the independent predictors of PTC CLNM,and a combined model was then constructed.The receiver operating characteristic curve was plotted,and the area under the curve(AUC)was calculated to evaluate the efficacy of each model for predicting PTC CLNM.Results Thirteen optimal radiomics features and 12 DL features were selected.Radscore(OR=1.698,P=0.002)and Deepscore(OR=1.872,P=0.021)were both independent predictors of PTC CLNM.The AUC of radiomics mode,l DL model and combined model for predicting PTC CLNM was 0.775,0.876 and 0.880 in training set,which in test set was 0.739,0.776 and 0.789,respectively.In training set,the prediction efficacy of combined model was better than that of radiomics model(Z=2.551,P=0.011).Conclusion Combined with DL algorithm could effectively increase the efficacy of enhanced CT radiomics for predict PTC CLNM.
9.Market Access Policy for New Antimicrobial Drugs:International Experience and Inspiration
Baolong DING ; Qiang LIU ; Jingxuan WEI ; Yuyang SUN ; Wenmin DU ; Xin LI
Herald of Medicine 2025;44(3):416-421
Objective By reviewing the access policies for new antimicrobial drugs internationally,this study provides a reference for the development of China's antimicrobial drug access policy.Methods The Chinese and English databases,offi-cial websites of health agencies,and health technology assessment agencies of various countries(CNKI,PubMed,NICE in the UK,HAS in France,etc.)were searched to collect and sort out the access policies of new antibacterial drugs.Taking the antibacte-rial drug ceftazidime-avibactam and the antifungal drug esaconazole sulfate as examples,the key evidence points for the evaluation of antibacterial drugs in the market access process of medical insurance were analyzed.Finally,the author put forward suggestions for China's antibacterial drug access policy based on the opinions of experts in related fields of antibacterial drugs in China.Re-sults Access policies for antimicrobial drugs had already established in the UK,US,EU,Sweden Switzerland,and Republic of Korea.These policies included a series of measures such as evaluation approval rewards,patent extensions,additional reimburse-ment,decoupling sales revenue from sales volume,etc.,with the ultimate goal being to encourage research and development of new antibiotics while reducing resistance rates.The review found that besides evaluating the safety,economy,and cost-effectiveness,some evaluation agencies also consider the actual clinical value and social value of drugs when reviewing the evidence of two types of new antibacterial drugs in the medical insurance access link.Conclusion China can draw upon international framework principles while considering unique demands such as national antibiotic management policy or national healthcare negotiation re-quirements to provide certain policy support throughout the market access process for new antimicrobials due to their unique val-ues so that it can encourage research & development while curbing antibiotic resistance.
10.Non-invasive imaging of pathological scars using a portable handheld two-photon microscope
Yang HAN ; Yuxuan SUN ; Feili YANG ; Qingwu LIU ; Wenmin FEI ; Wenzhuo QIU ; Junjie WANG ; Linshuang LI ; Xuejun ZHANG ; Aimin WANG ; Yong CUI
Chinese Medical Journal 2024;137(3):329-337
Background::Pathological scars are a disorder that can lead to various cosmetic, psychological, and functional problems, and no effective assessment methods are currently available. Assessment and treatment of pathological scars are based on cutaneous manifestations. A two-photon microscope (TPM) with the potential for real-time non-invasive assessment may help determine the under-surface pathophysiological conditions in vivo. This study used a portable handheld TPM to image epidermal cells and dermal collagen structures in pathological scars and normal skin in vivo to evaluate the effectiveness of treatment in scar patients. Methods::Fifteen patients with pathological scars and three healthy controls were recruited. Imaging was performed using a portable handheld TPM. Five indexes were extracted from two dimensional (2D) and three dimensional (3D) perspectives, including collagen depth, dermo-epidermal junction (DEJ) contour ratio, thickness, orientation, and occupation (proportion of collagen fibers in the field of view) of collagen. Two depth-dependent indexes were computed through the 3D second harmonic generation image and three morphology-related indexes from the 2D images. We assessed index differences between scar and normal skin and changes before and after treatment.Results::Pathological scars and normal skin differed markedly regarding the epidermal morphological structure and the spectral characteristics of collagen fibers. Five indexes were employed to distinguish between normal skin and scar tissue. Statistically significant differences were found in average depth ( t = 9.917, P <0.001), thickness ( t = 4.037, P <0.001), occupation ( t= 2.169, P <0.050), orientation of collagen ( t = 3.669, P <0.001), and the DEJ contour ratio ( t = 5.105, P <0.001). Conclusions::Use of portable handheld TPM can distinguish collagen from skin tissues; thus, it is more suitable for scar imaging than reflectance confocal microscopy. Thus, a TPM may be an auxiliary tool for scar treatment selection and assessing treatment efficacy.

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