ObjectiveTo establish a geographical origin identification model for Foeniculi Fructus from Haiyuan， providing a new technical reference for the protection of Haiyuan's geo-authentic medicinal materials and its designation as a national geographical indication agricultural product. MethodsSamples of Foeniculi Fructus were collected from eight producing areas， including Minqin （Gansu）， Bozhou （Anhui）， Qingdao （Shandong）， Dezhou （Shandong）， Urumqi （Xinjiang）， Nujiang （Yunnan）， Gutuo （Inner Mongolia）， and Haiyuan （Ningxia）. Gas chromatography-ion mobility spectrometry （GC-IMS） was used to detect the volatile organic compounds （VOCs） in samples from these geographic origins. VOCs were qualitatively analyzed through dual matching with the National Institute of Standards and Technology （NIST） mass spectral database and the IMS drift time database. Using the Reporter module and Gallery Plot visualization tools within the LAV analytical platform， VOC fingerprint profiles characterizing geographic origins were constructed. A non-targeted analytical strategy was adopted， and 97 VOCs detected via GC-IMS were subjected to principal component analysis （PCA） and partial least squares discriminant analysis （PLS-DA） based on their differential distribution patterns to construct an origin identification model for Foeniculi Fructus from Haiyuan region. Key discriminative markers were screened using variable importance in projection （VIP） values greater than 1. ResultsA total of 97 VOCs were identified， including alcohols， aldehydes， ketones， esters， organic acids， terpenoids， ethers， alkenes， and benzenes. The PLS-DA model， based on VOCs data obtained by GC-IMS， effectively distinguished Foeniculi Fructus in Haiyuan region from those of other origins. During cross-validation， the model achieved a prediction parameter （Q²） of 0.976 and a goodness-of-fit parameter （R²） of 0.936， with no overfitting observed in permutation testing. Twelve key flavor markers with VIP > 1 were identified as characteristic indicators of Haiyuan origin. ConclusionA stable and highly predictive origin identification model for Foeniculi Fructus from Haiyuan was successfully established using GC-IMS technology， PLS-DA， and VIP-based marker screening. This model provides a novel technical strategy for accurately distinguishing Foeniculi Fructus in Haiyuan region from other regional varieties and offers new technical support for its protection as a geo-authentic medicinal material and a nationally designated geographical indication agricultural product in China.

ObjectiveTo establish a geographical origin identification model for Foeniculi Fructus from Haiyuan， providing a new technical reference for the protection of Haiyuan's geo-authentic medicinal materials and its designation as a national geographical indication agricultural product. MethodsSamples of Foeniculi Fructus were collected from eight producing areas， including Minqin （Gansu）， Bozhou （Anhui）， Qingdao （Shandong）， Dezhou （Shandong）， Urumqi （Xinjiang）， Nujiang （Yunnan）， Gutuo （Inner Mongolia）， and Haiyuan （Ningxia）. Gas chromatography-ion mobility spectrometry （GC-IMS） was used to detect the volatile organic compounds （VOCs） in samples from these geographic origins. VOCs were qualitatively analyzed through dual matching with the National Institute of Standards and Technology （NIST） mass spectral database and the IMS drift time database. Using the Reporter module and Gallery Plot visualization tools within the LAV analytical platform， VOC fingerprint profiles characterizing geographic origins were constructed. A non-targeted analytical strategy was adopted， and 97 VOCs detected via GC-IMS were subjected to principal component analysis （PCA） and partial least squares discriminant analysis （PLS-DA） based on their differential distribution patterns to construct an origin identification model for Foeniculi Fructus from Haiyuan region. Key discriminative markers were screened using variable importance in projection （VIP） values greater than 1. ResultsA total of 97 VOCs were identified， including alcohols， aldehydes， ketones， esters， organic acids， terpenoids， ethers， alkenes， and benzenes. The PLS-DA model， based on VOCs data obtained by GC-IMS， effectively distinguished Foeniculi Fructus in Haiyuan region from those of other origins. During cross-validation， the model achieved a prediction parameter （Q²） of 0.976 and a goodness-of-fit parameter （R²） of 0.936， with no overfitting observed in permutation testing. Twelve key flavor markers with VIP > 1 were identified as characteristic indicators of Haiyuan origin. ConclusionA stable and highly predictive origin identification model for Foeniculi Fructus from Haiyuan was successfully established using GC-IMS technology， PLS-DA， and VIP-based marker screening. This model provides a novel technical strategy for accurately distinguishing Foeniculi Fructus in Haiyuan region from other regional varieties and offers new technical support for its protection as a geo-authentic medicinal material and a nationally designated geographical indication agricultural product in China.

More than 300 million people world-wide suffer from asthma,and the incidence is in-creasing year by year.As one of the most common chronic diseases,asthma is an immune-mediated inflammatory disease with complex triggering mechanisms and strong heterogeneity.With the in-depth study of physiological and pathological mech-anisms,therapeutic small molecule and hormone drugs have been introduced to control and treat most patients,but about 5％-10％of patients still suffer from various subtypes of difficult to control and treat asthma,that is,severe asthma.In the past decade,with the rapid development of bio-pharmaceutical research,protein and antibody have become the key drugs for the treatment of se-vere asthma with high efficacy,high specificity and high safety.However,biological drugs are usually administered by injection,they cannot be noninva-sive and directly delivered into the lung to quickly absorb and take effect.Therefore,there is an ur-gent need for the introduction of inhaled biologics with quick effectiveness,convenience,economy and safety in clinical.The review summarizes the existing small molecule,hormone and biological therapy drugs,and summarizes the development of inhalable biological agents of asthma,and ana-lyzes the future prospects of the inhalable biologi-cal drugs,which is designed to deepen the percep-tion of the direction of the inhalable biological drugs research,and update the information of the field,in order to provide reference for the develop-ment of more inhalable biologics.

More than 300 million people worldwide suffer from asthma, and the incidence is increasing year by year. As one of the most common chronic diseases, asthma is an immune-mediated inflammatory disease with complex triggering mechanisms and strong heterogeneity. With the in-depth study of physiological and pathological mechanisms, therapeutic small molecule and hormone drugs have been introduced to control and treat most patients, but about 5% - 10% of patients still suffer from various subtypes of difficult to control and treat asthma, that is, severe asthma. In the past decade, with the rapid development of bio-pharmaceutical research, protein and antibody have become the key drugs for the treatment of severe asthma with high efficacy, high specificity and high safety. However, biological drugs are usually administered by injection, they cannot be noninvasive and directly delivered into the lung to quickly absorb and take effect. Therefore, there is an urgent need for the introduction of inhaled biologics with quick effectiveness, convenience, economy and safety in clinical. The review summarizes the existing small molecule, hormone and biological therapy drugs, and summarizes the development of inhalable biological agents of asthma, and analyzes the future prospects of the inhalable biological drugs, which is designed to deepen the perception of the direction of the inhalable biological drugs research, and update the information of the field, in order to provide reference for the development of more inhalable biologics.

More than 300 million people world-wide suffer from asthma,and the incidence is in-creasing year by year.As one of the most common chronic diseases,asthma is an immune-mediated inflammatory disease with complex triggering mechanisms and strong heterogeneity.With the in-depth study of physiological and pathological mech-anisms,therapeutic small molecule and hormone drugs have been introduced to control and treat most patients,but about 5％-10％of patients still suffer from various subtypes of difficult to control and treat asthma,that is,severe asthma.In the past decade,with the rapid development of bio-pharmaceutical research,protein and antibody have become the key drugs for the treatment of se-vere asthma with high efficacy,high specificity and high safety.However,biological drugs are usually administered by injection,they cannot be noninva-sive and directly delivered into the lung to quickly absorb and take effect.Therefore,there is an ur-gent need for the introduction of inhaled biologics with quick effectiveness,convenience,economy and safety in clinical.The review summarizes the existing small molecule,hormone and biological therapy drugs,and summarizes the development of inhalable biological agents of asthma,and ana-lyzes the future prospects of the inhalable biologi-cal drugs,which is designed to deepen the percep-tion of the direction of the inhalable biological drugs research,and update the information of the field,in order to provide reference for the develop-ment of more inhalable biologics.

Objective:To summarize the clinical and genetic characteristics of children with β-ketothiolase deficiency (BKTD).Methods:The clinical characteristics, biochemical, markers detected by tandem mass spectrometry (MS/MS) and gas chromatography-mass spectrometry (GC/MS), as well as the variants in ACAT1 gene among 5 children with BKTD in Children′s Hospital of Chongqing Medical University between October 2018 and December 2022 were retrospectively analyzed.Results:The onset age of the disease in 5 patients (4 males and 1 female) ranged from 9.7 to 28.0 months. During the acute phase, severe metabolic acidosis was observed with a pH of 6.9-7.1, as well as hypoglycaemia (2.3-3.4 mmol/L) and positive urinary ketone bodies (+-++++). Blood levels of methylcrotonyl carnitine, methylmalonyl carnitine and malonyl carnitine were 0.03-0.42, 0.34-1.43 and 0.83-3.53 μmol/L respectively and were significantly elevated. Urinary 2-methyl-3-hydroxybutyric acid was 22-202 and 3-hydroxybutyric acid was 4-6 066, both were higher than the normal levels. Methylcrotonylglycine was mild elevated (0-29). The metabolites detected by MS/MS and GC/MS were significantly reduced after treatment. Analysis of ACAT1 gene mutation was performed in 5 children. Most variants were missense (8/9). Four previously unreported variants were identified: c.678G>T (p.Trp226Cys), c.302A>G (p.Gln101Arg), c.627_629dupTGA (p.Asn209_Glu210insAsp) and c.316C>T (p.Gln106Ter), the first 2 variants were predicted to be damaging by SIFT, PolyPhen-2 and Mutation Taster software. c.316C>T (p.Gln106Ter) is a nonsense variant.Conclusions:β-ketothiolase deficiency is relatively rare, lacks specific clinical manifestations, however severe metabolic acidosis, hypoglycemia, and ketosis during the acute onset were consistent findings. Missense mutations in the ACAT1 gene are common genetic causes of β-ketothiolase deficiency.

More than 300 million people world-wide suffer from asthma,and the incidence is in-creasing year by year.As one of the most common chronic diseases,asthma is an immune-mediated inflammatory disease with complex triggering mechanisms and strong heterogeneity.With the in-depth study of physiological and pathological mech-anisms,therapeutic small molecule and hormone drugs have been introduced to control and treat most patients,but about 5％-10％of patients still suffer from various subtypes of difficult to control and treat asthma,that is,severe asthma.In the past decade,with the rapid development of bio-pharmaceutical research,protein and antibody have become the key drugs for the treatment of se-vere asthma with high efficacy,high specificity and high safety.However,biological drugs are usually administered by injection,they cannot be noninva-sive and directly delivered into the lung to quickly absorb and take effect.Therefore,there is an ur-gent need for the introduction of inhaled biologics with quick effectiveness,convenience,economy and safety in clinical.The review summarizes the existing small molecule,hormone and biological therapy drugs,and summarizes the development of inhalable biological agents of asthma,and ana-lyzes the future prospects of the inhalable biologi-cal drugs,which is designed to deepen the percep-tion of the direction of the inhalable biological drugs research,and update the information of the field,in order to provide reference for the develop-ment of more inhalable biologics.

More than 300 million people world-wide suffer from asthma,and the incidence is in-creasing year by year.As one of the most common chronic diseases,asthma is an immune-mediated inflammatory disease with complex triggering mechanisms and strong heterogeneity.With the in-depth study of physiological and pathological mech-anisms,therapeutic small molecule and hormone drugs have been introduced to control and treat most patients,but about 5％-10％of patients still suffer from various subtypes of difficult to control and treat asthma,that is,severe asthma.In the past decade,with the rapid development of bio-pharmaceutical research,protein and antibody have become the key drugs for the treatment of se-vere asthma with high efficacy,high specificity and high safety.However,biological drugs are usually administered by injection,they cannot be noninva-sive and directly delivered into the lung to quickly absorb and take effect.Therefore,there is an ur-gent need for the introduction of inhaled biologics with quick effectiveness,convenience,economy and safety in clinical.The review summarizes the existing small molecule,hormone and biological therapy drugs,and summarizes the development of inhalable biological agents of asthma,and ana-lyzes the future prospects of the inhalable biologi-cal drugs,which is designed to deepen the percep-tion of the direction of the inhalable biological drugs research,and update the information of the field,in order to provide reference for the develop-ment of more inhalable biologics.

More than 300 million people world-wide suffer from asthma,and the incidence is in-creasing year by year.As one of the most common chronic diseases,asthma is an immune-mediated inflammatory disease with complex triggering mechanisms and strong heterogeneity.With the in-depth study of physiological and pathological mech-anisms,therapeutic small molecule and hormone drugs have been introduced to control and treat most patients,but about 5％-10％of patients still suffer from various subtypes of difficult to control and treat asthma,that is,severe asthma.In the past decade,with the rapid development of bio-pharmaceutical research,protein and antibody have become the key drugs for the treatment of se-vere asthma with high efficacy,high specificity and high safety.However,biological drugs are usually administered by injection,they cannot be noninva-sive and directly delivered into the lung to quickly absorb and take effect.Therefore,there is an ur-gent need for the introduction of inhaled biologics with quick effectiveness,convenience,economy and safety in clinical.The review summarizes the existing small molecule,hormone and biological therapy drugs,and summarizes the development of inhalable biological agents of asthma,and ana-lyzes the future prospects of the inhalable biologi-cal drugs,which is designed to deepen the percep-tion of the direction of the inhalable biological drugs research,and update the information of the field,in order to provide reference for the develop-ment of more inhalable biologics.