1.Analysis of Toxicity Characteristics and Rational Drug Use of Polygoni Multiflori Radix
Qiongyi FU ; Yupu QI ; Yu HUAN ; Yagang SONG ; Xiangxiang WU ; Mingsan MIAO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):222-231
ObjectivePolygoni Multiflori Radix is a commonly used tonic traditional Chinese medicine (TCM) in clinical practice, but liver injury has often been reported in recent years. Some related preparations containing Polygoni Multiflori Radix have been reported by the National Medical Products Administration many times for the risk of liver injury. This has caused extensive discussion on the potential toxicity of TCM in China and abroad, which has limited the clinical use of Polygoni Multiflori Radix to some extent. To understand the adverse reactions of Polygoni Multiflori Radix, the safe and rational use of Polygoni Multiflori Radix in clinical practice was discussed. MethodsThe pharmacovigilance thought of modern Chinese medicine and the TCM pharmacovigilance system framework of ''identification of poison, use of poison, anti-poison, and detoxification'' were employed to mine the relevant toxicity records, usage and dosage, processing compatibility, and contraindication of taking Polygoni Multiflori Radix in ancient books. The drug safety information of Polygoni Multiflori Radix was summarized by comparing with modern reports. ResultsA total of 74 ancient books related to Polygoni Multiflori Radix were included, suggesting that the toxicity of Polygoni Multiflori Radix was recognized in ancient times. The main chemical components of Polygoni Multiflori Radix had both efficacy and toxicity, and the adverse reactions may be related to long-term use, excessive use, and individual differences. The results showed that the toxic components of Polygoni Multiflori Radix could be reduced by peeling, steaming with black beans, and processing without iron tools. The toxic effects of Polygoni Multiflori Radix could be reduced by the compatibility of Polygoni Multiflori Radix with Poria, Psoraleae Fructus, and Cistanches Herba. ConclusionReasonable dosage, standard processing, correct compatibility, and syndrome differentiation are the key points to standardize the use of Polygoni Multiflori Radix and reduce the incidence of adverse reactions. Clinically, the toxicity classification of TCM should be strengthened, and the susceptible population should be prioritized. The detection indicators and early warning mechanisms should be improved, and precise drug dosage and course of treatment should be guaranteed. These measures can ensure the safe use of Polygoni Multiflori Radix.
2.Analysis of Toxicity Characteristics and Rational Drug Use of Polygoni Multiflori Radix
Qiongyi FU ; Yupu QI ; Yu HUAN ; Yagang SONG ; Xiangxiang WU ; Mingsan MIAO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):222-231
ObjectivePolygoni Multiflori Radix is a commonly used tonic traditional Chinese medicine (TCM) in clinical practice, but liver injury has often been reported in recent years. Some related preparations containing Polygoni Multiflori Radix have been reported by the National Medical Products Administration many times for the risk of liver injury. This has caused extensive discussion on the potential toxicity of TCM in China and abroad, which has limited the clinical use of Polygoni Multiflori Radix to some extent. To understand the adverse reactions of Polygoni Multiflori Radix, the safe and rational use of Polygoni Multiflori Radix in clinical practice was discussed. MethodsThe pharmacovigilance thought of modern Chinese medicine and the TCM pharmacovigilance system framework of ''identification of poison, use of poison, anti-poison, and detoxification'' were employed to mine the relevant toxicity records, usage and dosage, processing compatibility, and contraindication of taking Polygoni Multiflori Radix in ancient books. The drug safety information of Polygoni Multiflori Radix was summarized by comparing with modern reports. ResultsA total of 74 ancient books related to Polygoni Multiflori Radix were included, suggesting that the toxicity of Polygoni Multiflori Radix was recognized in ancient times. The main chemical components of Polygoni Multiflori Radix had both efficacy and toxicity, and the adverse reactions may be related to long-term use, excessive use, and individual differences. The results showed that the toxic components of Polygoni Multiflori Radix could be reduced by peeling, steaming with black beans, and processing without iron tools. The toxic effects of Polygoni Multiflori Radix could be reduced by the compatibility of Polygoni Multiflori Radix with Poria, Psoraleae Fructus, and Cistanches Herba. ConclusionReasonable dosage, standard processing, correct compatibility, and syndrome differentiation are the key points to standardize the use of Polygoni Multiflori Radix and reduce the incidence of adverse reactions. Clinically, the toxicity classification of TCM should be strengthened, and the susceptible population should be prioritized. The detection indicators and early warning mechanisms should be improved, and precise drug dosage and course of treatment should be guaranteed. These measures can ensure the safe use of Polygoni Multiflori Radix.
3.Eupatilin Inhibits Proliferation, Invasion, and Metastasis of Non-small Cell Lung Cancer via EZH2/H3K27me3 Signaling Pathway
Bo XU ; Yihan YU ; Linling HU ; Bo JIANG ; Yu QI ; Shasha YUAN ; Yiling FAN ; Jixian ZHANG ; Qing MIAO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(10):58-69
ObjectiveTo investigate the mechanisms by which eupatilin (Eup) inhibits proliferation, invasion, and metastasis of non-small cell lung cancer (NSCLC) through the enhancer of zeste homolog 2/histone H3 lysine 27 trimethylation (EZH2/H3K27me3) signaling pathway. MethodsIn vivo, a subcutaneous xenograft tumor model was established in nude mice using H1299 cells to evaluate the anti-NSCLC effects of Eup. Immunohistochemistry (IHC-P) was used to detect the expression of proliferation- and invasion/metastasis-related proteins, including proliferating cell nuclear antigen (PCNA), matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), and vascular endothelial growth factor A (VEGFA). In vitro, cell counting kit-8 (CCK-8) assays were performed to determine the viability of H1299 cells treated with different concentrations of Eup (0-200 μmol·L-1) and to select appropriate concentrations. Colony formation and 5-ethynyl-2′-deoxyuridine (EdU) assays were used to evaluate cell proliferation. Wound healing and invasion assays were conducted to assess cell migration and invasion. Human umbilical vein endothelial cell (HUVEC) angiogenesis assays were used to evaluate the effects of Eup on angiogenesis. Transcriptomic analysis was performed to identify the targets of Eup in H1299 cells and to explore its major functions. Molecular docking and molecular dynamics simulations were conducted to predict the binding affinity and interaction stability between Eup and its target proteins. Western blot was used to detect the effects of Eup on the expression levels of EZH2/H3K27me3 pathway-related proteins and proliferation- and invasion/metastasis-related proteins, including PCNA, MMP-2, MMP-9, and VEGFA. ResultsIn the subcutaneous xenograft model, compared with the model group, Eup treatment dose-dependently inhibited the growth of H1299 xenograft tumors, and the tumor inhibition rate was significantly increased (P<0.05). IHC-P results showed that, compared with the model group, high-dose Eup significantly reduced the expression levels of PCNA, MMP-2, MMP-9, and VEGFA in vivo (P<0.05). In vitro, compared with the control group, Eup inhibited the proliferation, invasion, and metastasis of NSCLC cells in a concentration-dependent manner. Transcriptomic analysis further showed that, compared with the control group, Eup significantly downregulated EZH2 expression, and its functional effects were associated with inhibition of tumor metastasis. Molecular docking and molecular dynamics simulations indicated that Eup exhibited strong binding affinity with EZH2 and stable interactions. Western blot results demonstrated that, compared with the model group, Eup significantly inhibited, in a dose-dependent manner, the expression levels of EZH2, H3K27me3, and proliferation- and invasion/metastasis-related proteins (PCNA, MMP-2, MMP-9, and VEGFA) in both in vivo and in vitro experiments (P<0.05). In vitro, compared with the control group, overexpression of EZH2 via plasmid transfection partially reversed the inhibitory effects of Eup on the expression of key proteins involved in proliferation and invasion/metastasis in H1299 cells. ConclusionEup effectively inhibits the proliferation, migration, and invasion of H1299 cells both in vivo and in vitro. The underlying mechanism may be related to inhibition of the EZH2/H3K27me3 signaling pathway and downregulation of proliferation- and invasion/metastasis-related proteins, including PCNA, MMP-2, MMP-9, and VEGFA. Eup may serve as a potential therapeutic agent for suppressing proliferation and invasion/metastasis in NSCLC.
4.Anti-lung Cancer Mechanisms of Yang-warming Herbs and Formulas: A Review
Bo XU ; Yu QI ; Jixian ZHANG ; Linling HU ; Bo JIANG ; Yilong ZOU ; Cunyu FAN ; Yiling FAN ; Qing MIAO ; Yihan YU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(10):70-79
Lung cancer, particularly non-small cell lung cancer (NSCLC), is the malignant tumor with the highest incidence and mortality in China and worldwide. In 2022, the global number of deaths reached 1.8 million, accounting for 18.7% of all cancer-related deaths, seriously threatening human health and life, and posing a severe challenge for prevention and treatment. Although treatment strategies for lung cancer have been continuously enriched in recent years, and progress has been made in targeted therapy and immunotherapy, long-term survival benefits remain limited due to primary or acquired drug resistance, low immune responsiveness, and chemotherapy-related toxicities. Therefore, there is an urgent need to explore safe and effective adjunctive therapeutic strategies. Traditional Chinese medicine (TCM), with its advantages of holistic regulation and individualized syndrome differentiation, has played an increasingly prominent role in comprehensive cancer treatment. TCM holds that "Yang deficiency leads to accumulation" is a key pathogenesis of tumors. Based on the theory that "Yang transforms Qi, while Yin forms substance", deficiency of Yang Qi results in impaired warming and transformation functions, leading to internal accumulation of Yin-cold. This is closely related to dysregulation of the immune microenvironment, "cold tumor" characteristics, and dysfunction of the neuroendocrine system in modern medicine. Accordingly, the therapeutic strategy of "warming Yang, supporting healthy Qi, and combating cancer" has gained increasing attention. In recent years, commonly used Yang-warming Chinese herbs, including Aconiti Lateralis Radix Praeparata, Zingiberis Rhizoma, Cinnamomi Cortex, Epimedii Folium, and Psoraleae Fructus, as well as their active constituents, have achieved notable progress in anti-lung cancer research by regulating multiple signaling pathways, inducing apoptosis, inhibiting metastasis, and reversing drug resistance. In addition, Yang-warming formulae such as Sini Tang and Yanghe Tang have shown promising effects in alleviating myelosuppression, improving cancer-related fatigue, managing malignant pleural effusion, and relieving cancer pain. These therapies exhibit toxicity-reducing and efficacy-enhancing effects, significantly improving patients' quality of life and survival benefits. To systematically summarize the roles and mechanisms of Yang-warming Chinese herbal medicines and compound formulae in lung cancer, this paper provides a comprehensive review of recent advances, aiming to offer insights for the clinical practice of TCM in the prevention and treatment of lung cancer.
5.Eupatilin Inhibits Proliferation, Invasion, and Metastasis of Non-small Cell Lung Cancer via EZH2/H3K27me3 Signaling Pathway
Bo XU ; Yihan YU ; Linling HU ; Bo JIANG ; Yu QI ; Shasha YUAN ; Yiling FAN ; Jixian ZHANG ; Qing MIAO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(10):58-69
ObjectiveTo investigate the mechanisms by which eupatilin (Eup) inhibits proliferation, invasion, and metastasis of non-small cell lung cancer (NSCLC) through the enhancer of zeste homolog 2/histone H3 lysine 27 trimethylation (EZH2/H3K27me3) signaling pathway. MethodsIn vivo, a subcutaneous xenograft tumor model was established in nude mice using H1299 cells to evaluate the anti-NSCLC effects of Eup. Immunohistochemistry (IHC-P) was used to detect the expression of proliferation- and invasion/metastasis-related proteins, including proliferating cell nuclear antigen (PCNA), matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), and vascular endothelial growth factor A (VEGFA). In vitro, cell counting kit-8 (CCK-8) assays were performed to determine the viability of H1299 cells treated with different concentrations of Eup (0-200 μmol·L-1) and to select appropriate concentrations. Colony formation and 5-ethynyl-2′-deoxyuridine (EdU) assays were used to evaluate cell proliferation. Wound healing and invasion assays were conducted to assess cell migration and invasion. Human umbilical vein endothelial cell (HUVEC) angiogenesis assays were used to evaluate the effects of Eup on angiogenesis. Transcriptomic analysis was performed to identify the targets of Eup in H1299 cells and to explore its major functions. Molecular docking and molecular dynamics simulations were conducted to predict the binding affinity and interaction stability between Eup and its target proteins. Western blot was used to detect the effects of Eup on the expression levels of EZH2/H3K27me3 pathway-related proteins and proliferation- and invasion/metastasis-related proteins, including PCNA, MMP-2, MMP-9, and VEGFA. ResultsIn the subcutaneous xenograft model, compared with the model group, Eup treatment dose-dependently inhibited the growth of H1299 xenograft tumors, and the tumor inhibition rate was significantly increased (P<0.05). IHC-P results showed that, compared with the model group, high-dose Eup significantly reduced the expression levels of PCNA, MMP-2, MMP-9, and VEGFA in vivo (P<0.05). In vitro, compared with the control group, Eup inhibited the proliferation, invasion, and metastasis of NSCLC cells in a concentration-dependent manner. Transcriptomic analysis further showed that, compared with the control group, Eup significantly downregulated EZH2 expression, and its functional effects were associated with inhibition of tumor metastasis. Molecular docking and molecular dynamics simulations indicated that Eup exhibited strong binding affinity with EZH2 and stable interactions. Western blot results demonstrated that, compared with the model group, Eup significantly inhibited, in a dose-dependent manner, the expression levels of EZH2, H3K27me3, and proliferation- and invasion/metastasis-related proteins (PCNA, MMP-2, MMP-9, and VEGFA) in both in vivo and in vitro experiments (P<0.05). In vitro, compared with the control group, overexpression of EZH2 via plasmid transfection partially reversed the inhibitory effects of Eup on the expression of key proteins involved in proliferation and invasion/metastasis in H1299 cells. ConclusionEup effectively inhibits the proliferation, migration, and invasion of H1299 cells both in vivo and in vitro. The underlying mechanism may be related to inhibition of the EZH2/H3K27me3 signaling pathway and downregulation of proliferation- and invasion/metastasis-related proteins, including PCNA, MMP-2, MMP-9, and VEGFA. Eup may serve as a potential therapeutic agent for suppressing proliferation and invasion/metastasis in NSCLC.
6.Anti-lung Cancer Mechanisms of Yang-warming Herbs and Formulas: A Review
Bo XU ; Yu QI ; Jixian ZHANG ; Linling HU ; Bo JIANG ; Yilong ZOU ; Cunyu FAN ; Yiling FAN ; Qing MIAO ; Yihan YU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(10):70-79
Lung cancer, particularly non-small cell lung cancer (NSCLC), is the malignant tumor with the highest incidence and mortality in China and worldwide. In 2022, the global number of deaths reached 1.8 million, accounting for 18.7% of all cancer-related deaths, seriously threatening human health and life, and posing a severe challenge for prevention and treatment. Although treatment strategies for lung cancer have been continuously enriched in recent years, and progress has been made in targeted therapy and immunotherapy, long-term survival benefits remain limited due to primary or acquired drug resistance, low immune responsiveness, and chemotherapy-related toxicities. Therefore, there is an urgent need to explore safe and effective adjunctive therapeutic strategies. Traditional Chinese medicine (TCM), with its advantages of holistic regulation and individualized syndrome differentiation, has played an increasingly prominent role in comprehensive cancer treatment. TCM holds that "Yang deficiency leads to accumulation" is a key pathogenesis of tumors. Based on the theory that "Yang transforms Qi, while Yin forms substance", deficiency of Yang Qi results in impaired warming and transformation functions, leading to internal accumulation of Yin-cold. This is closely related to dysregulation of the immune microenvironment, "cold tumor" characteristics, and dysfunction of the neuroendocrine system in modern medicine. Accordingly, the therapeutic strategy of "warming Yang, supporting healthy Qi, and combating cancer" has gained increasing attention. In recent years, commonly used Yang-warming Chinese herbs, including Aconiti Lateralis Radix Praeparata, Zingiberis Rhizoma, Cinnamomi Cortex, Epimedii Folium, and Psoraleae Fructus, as well as their active constituents, have achieved notable progress in anti-lung cancer research by regulating multiple signaling pathways, inducing apoptosis, inhibiting metastasis, and reversing drug resistance. In addition, Yang-warming formulae such as Sini Tang and Yanghe Tang have shown promising effects in alleviating myelosuppression, improving cancer-related fatigue, managing malignant pleural effusion, and relieving cancer pain. These therapies exhibit toxicity-reducing and efficacy-enhancing effects, significantly improving patients' quality of life and survival benefits. To systematically summarize the roles and mechanisms of Yang-warming Chinese herbal medicines and compound formulae in lung cancer, this paper provides a comprehensive review of recent advances, aiming to offer insights for the clinical practice of TCM in the prevention and treatment of lung cancer.
7.Shengmai Yin alleviates myocardial ischemia/reperfusion injury via inhibiting Calpains expression
Rong MIAO ; Jing-wen GUO ; Ming HUANG ; Hai-shuo REN ; Rui LIU ; Xiao-yu SUN ; Opoku Bonsu FRANCIS ; Qi-long WANG ; Shi-ming FANG ; Ling LENG
Chinese Pharmacological Bulletin 2025;41(8):1569-1577
Aim To investigate the protective effect of Shengmai Yin on myocardial ischemia/reperfusion in-jury(MI/RI)in vitro and in vivo and to unravel the underlying mechanism.Methods SD rats were divid-ed into the sham group,model group,and Shengmai Yin group(SM).Rat MI/RI model was established.Cardiac function,infarct area,pathological changes,cardiomyocyte apoptosis,macrophage infiltration,and serum cTnT and CK-MB levels were measured.The mRNA and protein expressions of Calpain-1 and Cal-pain-2 were assessed.The hypoxia/reoxygenation(H/R)model was constructed in H9c2 cells.The active ingredients of Shengmai Yin were screened using net-work pharmacology and verified by CCK-8.In the car-diomyocytes H/R model,Fluo-4 AM staining was used to detect the changes of Ca2+levels.Results Com-pared with model group,LVEF and LVFS of Shengmai Yin-treated rats increased,myocardial infarction area was reduced,while myocardial tissue injury was allevi-ated.Myocardial apoptosis rate and the number of macrophages were reduced.Similarly,cTnT and CK-MB levels decreased.In addition,the expression lev-els of Calpain-1 and Calpain-2 mRNA and protein de-creased in the SM treatment group.Under the H/R model,all the active ingredients of Shengmai decoction had protective effects on cardiomyocytes,and the treat-ment could reduce the level of Ca2+in cardiomyocytes.Conclusions Shengmai Yin has protective effects on MI/RI in rats.This effect may be related to the de-crease in Ca2+levels,as well as Calpain-1 and Calap-in-2 mRNA and protein expression.
8.Effect of ultrasound-guided superior laryngeal nerve block in endotracheal intubation during geriatric general anesthesia surgery
Cui-wen LI ; Yu-qi MIAO ; Hui-wen WANG
Journal of Regional Anatomy and Operative Surgery 2025;34(3):219-223
Objective To evaluate the effect of ultrasound-guided superior laryngeal nerve block(SLNB)in endotracheal intubation during geriatric general anesthesia surgery.Methods A total of 40 elderly patients scheduled for elective general anesthesia surgery were selected,and randomly divided into the observation group(with ultrasound-guided SLNB)and the control group(without any local anesthesia).The mean arterial pressure(MAP),heart rate(HR),blood glucose,and concentrations of epinephrine,norepinephrine,and cortisol before intubation(T0),and 1 minute(T1),5 minutes(T2),and 15 minutes(T3)after intubation were compared between the two groups.The incidences of sore throat and hoarseness 30 minutes and 24 hours after extubation were compared between the two groups.Results The MAP and HR at T1,T2,and T3 of the observation group were significantly lower than those of the control group(P<0.05).The blood glucose and cortisol at T1 of the observation group were significantly lower than those of the control group(P<0.05).The serum concentrations of epinephrine and norepinephrine at T1,T2 and T3 in the observation group were lower than those in the control group(P<0.05).The incidences of sore throat 30 minutes and 24 hours after extubation in the observation group were lower than those in the control group(P<0.05).The incidence of hoarseness 30 minutes after extubation in the observation group was higher than that in the control group(P<0.05);the incidence of hoarseness 24 hours after extubation in the observation group was lower than that in the control group(P<0.05).Conclusion Ultrasound-guided SLNB has good clinical effect,which can effectively improve the stress response caused by endotracheal intubation and reduce intubation-related complications.
9.Effect of ultrasound-guided superior laryngeal nerve block in endotracheal intubation during geriatric general anesthesia surgery
Cui-wen LI ; Yu-qi MIAO ; Hui-wen WANG
Journal of Regional Anatomy and Operative Surgery 2025;34(3):219-223
Objective To evaluate the effect of ultrasound-guided superior laryngeal nerve block(SLNB)in endotracheal intubation during geriatric general anesthesia surgery.Methods A total of 40 elderly patients scheduled for elective general anesthesia surgery were selected,and randomly divided into the observation group(with ultrasound-guided SLNB)and the control group(without any local anesthesia).The mean arterial pressure(MAP),heart rate(HR),blood glucose,and concentrations of epinephrine,norepinephrine,and cortisol before intubation(T0),and 1 minute(T1),5 minutes(T2),and 15 minutes(T3)after intubation were compared between the two groups.The incidences of sore throat and hoarseness 30 minutes and 24 hours after extubation were compared between the two groups.Results The MAP and HR at T1,T2,and T3 of the observation group were significantly lower than those of the control group(P<0.05).The blood glucose and cortisol at T1 of the observation group were significantly lower than those of the control group(P<0.05).The serum concentrations of epinephrine and norepinephrine at T1,T2 and T3 in the observation group were lower than those in the control group(P<0.05).The incidences of sore throat 30 minutes and 24 hours after extubation in the observation group were lower than those in the control group(P<0.05).The incidence of hoarseness 30 minutes after extubation in the observation group was higher than that in the control group(P<0.05);the incidence of hoarseness 24 hours after extubation in the observation group was lower than that in the control group(P<0.05).Conclusion Ultrasound-guided SLNB has good clinical effect,which can effectively improve the stress response caused by endotracheal intubation and reduce intubation-related complications.
10.Coverage of National Immunization Program vaccines and vaccination information consistency rate among children born during 2020-2021 in 3 provinces in China
Wenqi HUANG ; Miao XU ; Xiaohua QI ; Qing WANG ; Jing CHEN ; Ming GUANG ; Yu LIU ; Xu CHEN ; Fangfang ZENG ; Dan LIU ; Xiaofeng LIANG
Chinese Journal of Epidemiology 2025;46(8):1393-1399
Objective:To understand the coverage and information consistency rate of National Immunization Program (NIP) vaccines among children born during 2020-2021 in Zhejiang Province, Chongqing City, and Shanxi Province (3 provinces) of China .Methods:A simple random sampling method was used to randomly select 3 counties (districts) from each of the 3 provinces, 5 townships from each county (district), and 5 villages from each township. Vaccination information for seven NIP vaccines was collected for children born between 2020 and 2021 in each village. The vaccination coverage, timely coverage, and consistency rates between the survey data and the Immunization Planning Information System data were analyzed.Results:A total of 1 117 children were investigated. The vaccination coverage for each dose of NIP vaccine ranged from 99.10% to 100.00%, with those in Zhejiang Province, Chongqing City, and Shanxi Province ranging from 99.19% to 100.00%, 98.92% to 100.00%, and 99.20% to 100.00%, respectively. The timely coverage of each dose of NIP vaccine ranged from 89.79% to 99.82%, with those in Zhejiang Province, Chongqing City, and Shanxi Province ranging from 94.09% to 99.73%, 89.52% to 99.73%, and 78.55% to 100.00%, respectively. The consistency rate of information on each dose of NIP vaccine ranged from 94.36% to 99.91%, with those in Zhejiang Province, Chongqing City, and Shanxi Province ranging from 97.85% to 99.73%, 98.92% to 100.00%, and 86.06% to 100.00%, respectively.Conclusions:Coverage of NIP vaccines was generally high among children born during 2020-2021 in the 3 provinces of China, but there were regional differences in the timely coverage of some vaccine doses and the vaccination information consistency rate. It is necessary to strengthen the timely vaccination of children's vaccine booster doses and optimize the management of vaccination services.

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