1.Evaluation of the efficacy,safety and cost-effectiveness of different formulations of short-acting rhGH in the treatment of patients with short stature
Zhuoting ZHENG ; Yilong LIU ; Xiaomao QIN ; Zhen ZENG ; Run YAN ; Enwu LONG
China Pharmacy 2025;36(9):1111-1116
OBJECTIVE To compare the efficacy, safety, and cost-effectiveness of two different formulations of short-acting recombinant human growth hormone (rhGH) in the treatment of patients with short stature. METHODS Data from patients with short stature treated with short-acting rhGH at the Leshan People’s Hospital from August 2016 to June 2023 were collected. Patients were divided into powder formulation group and aqueous formulation group based on the rhGH formulation used. The changes in growth-related efficacy indicators and the occurrence of adverse drug reactions were compared between two groups after 12 months of treatment; cost-effectiveness analysis and sensitivity analysis were used to compare the cost per unit of effect achieved; subgroup analysis was performed by dividing the patients into growth hormone deficiency (GHD) subgroup and idiopathic short stature (ISS) subgroup based on clinical diagnosis. RESULTS After 12 months of treatment, the height and the levels of insulin-like growth factor-1 and insulin-like growth factor binding protein-3 in serum in aqueous formulation group and powder formulation group were significantly increased compared to before treatment (P<0.001), but there was no statistically significant difference in the changes of the above indicators between the two groups(P>0.05). The analysis results of GHD and ISS subgroups were consistent with the overall population. In the overall population, the cost-effectiveness ratio of powder formulation group (2 582 yuan/cm) was significantly better than that of aqueous formulation group (6 729 yuan/cm), with a statistically significant difference (P<0.001), and the result was consistent in the GHD and ISS subgroups as well as in the sensitivity analysis. No serious adverse drug reactions occurred in either powder formulation or aqueous formulation group, and there was no statistically significant difference in the incidence of various adverse reactions between two groups (P>0.05). CONCLUSIONS Short-acting rhGH powder and aqueous formulations have equivalent efficacy and safety, but the powder formulation has greater economic advantages.
2.Herbal Textual Research on Zanthoxylum armatum and Zanthoxyli Radix in Famous Classical Formulas
Zhen ZENG ; Yanmeng LIU ; Yihan WANG ; Yapeng WANG ; Erwei HAO ; Chun YAO ; Zhilai ZHAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):252-262
This article systematically analyzes the historical evolution of the name, origin, medicinal parts, harvesting and processing, and other aspects of Manjiao and Zanthoxyli Radix by referring to the herbal medicine, medical books, prescription books and other documents of the past dynasties, combined with the relevant modern research materials, in order to provide a basis for the development of famous classical formulas containing the two medicinal materials. According to the herbal textual research, Manjiao was first recorded in Shennong Bencaojing of the Han dynasty with aliases such as Zhujiao, Goujiao and Zhijiao. Throughout history, Manjiao was sourced from the stems and roots of Zanthoxylum armatum in the Rutaceae family, and its leaves and fruits can also be used in medicine. The traditional recorded production area was mainly in Yunzhong(now Tuoketuo region in Inner Mongolia), with mentions in Zhejiang, Hunan, Fujian, Guangdong, Guangxi, Yunnan, Taiwan, and other provinces. Presently, this species is distributed from the south of Shandong, to Hainan, Taiwan, Tibet and other regions. The roots can be harvested year-round, while the fruits are harvested in autumn after maturity. In ancient times, the roots and stems were mostly used for brewing or soaking in wine, whereas nowadays, the roots are often sliced and then used as a raw material in traditional Chinese medicine, and the fruits should be stir-fried before use. Manjiao has a bitter taste and warm property, and was historically used to treat wind-cold dampness, joint pain, limb numbness, and knee pain. Modern researches have summarized its effects as dispelling wind, dispersing cold, promoting circulation, and relieving pain, and it is used for treating rheumatoid arthritis, toothache, bruises, as well as an anthelmintic. Zanthoxyli Radix initially known as Rudi Jinniugen, recorded in Bencao Qiuyuan of the Qing dynasty, with the alternate name of Liangbianzhen. In recent times, it is more commonly referred to as Liangmianzhen, sourced from the dried roots of Z. nitidum of the Rutaceae family, mainly produced in Guangxi and Guangdong. It can be harvested throughout the year, cleaned, sliced, and dried after harvesting. Zanthoxyli Radix is pungent, bitter, warm and slightly toxic, with the functions of promoting blood circulation, removing stasis, relieving pain, dispelling wind, and resolving swelling. Based on the results of herbal textual research, it is clarified that the ancient Manjiao and the modern Zanthoxyli Radix are not the same species. This article corrects the mistaken belief of by previous scholars that Zanthoxyli Radix is the same as ancient Manjiao, and suggests that formulas described as Manjiao should use Z. armatum as the medicinal herb, while those described as Liangmianzhen or Rudi Jinniu should use Z. nitidum. The processing was performed according to the processing requirements prescribed in the formulas, otherwise, the raw products are recommended for use.
3.Herbal Textual Research on Zanthoxylum armatum and Zanthoxyli Radix in Famous Classical Formulas
Zhen ZENG ; Yanmeng LIU ; Yihan WANG ; Yapeng WANG ; Erwei HAO ; Chun YAO ; Zhilai ZHAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):252-262
This article systematically analyzes the historical evolution of the name, origin, medicinal parts, harvesting and processing, and other aspects of Manjiao and Zanthoxyli Radix by referring to the herbal medicine, medical books, prescription books and other documents of the past dynasties, combined with the relevant modern research materials, in order to provide a basis for the development of famous classical formulas containing the two medicinal materials. According to the herbal textual research, Manjiao was first recorded in Shennong Bencaojing of the Han dynasty with aliases such as Zhujiao, Goujiao and Zhijiao. Throughout history, Manjiao was sourced from the stems and roots of Zanthoxylum armatum in the Rutaceae family, and its leaves and fruits can also be used in medicine. The traditional recorded production area was mainly in Yunzhong(now Tuoketuo region in Inner Mongolia), with mentions in Zhejiang, Hunan, Fujian, Guangdong, Guangxi, Yunnan, Taiwan, and other provinces. Presently, this species is distributed from the south of Shandong, to Hainan, Taiwan, Tibet and other regions. The roots can be harvested year-round, while the fruits are harvested in autumn after maturity. In ancient times, the roots and stems were mostly used for brewing or soaking in wine, whereas nowadays, the roots are often sliced and then used as a raw material in traditional Chinese medicine, and the fruits should be stir-fried before use. Manjiao has a bitter taste and warm property, and was historically used to treat wind-cold dampness, joint pain, limb numbness, and knee pain. Modern researches have summarized its effects as dispelling wind, dispersing cold, promoting circulation, and relieving pain, and it is used for treating rheumatoid arthritis, toothache, bruises, as well as an anthelmintic. Zanthoxyli Radix initially known as Rudi Jinniugen, recorded in Bencao Qiuyuan of the Qing dynasty, with the alternate name of Liangbianzhen. In recent times, it is more commonly referred to as Liangmianzhen, sourced from the dried roots of Z. nitidum of the Rutaceae family, mainly produced in Guangxi and Guangdong. It can be harvested throughout the year, cleaned, sliced, and dried after harvesting. Zanthoxyli Radix is pungent, bitter, warm and slightly toxic, with the functions of promoting blood circulation, removing stasis, relieving pain, dispelling wind, and resolving swelling. Based on the results of herbal textual research, it is clarified that the ancient Manjiao and the modern Zanthoxyli Radix are not the same species. This article corrects the mistaken belief of by previous scholars that Zanthoxyli Radix is the same as ancient Manjiao, and suggests that formulas described as Manjiao should use Z. armatum as the medicinal herb, while those described as Liangmianzhen or Rudi Jinniu should use Z. nitidum. The processing was performed according to the processing requirements prescribed in the formulas, otherwise, the raw products are recommended for use.
4.Herbal Textual Research on Abri Herba and Abri Mollis Herba in Famous Classical Formulas
Zhen ZENG ; Yanmeng LIU ; Yihan WANG ; Erwei HAO ; Chun YAO ; Zhilai ZHAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(17):193-201
This article systematically analyzes the historical evolution of the name, origin, academic name, medicinal parts, origin, harvesting, processing and other aspects of Abri Herba and Abri Mollis Herba by referring to the herbal medicine, medical books, prescription books and other documents of the past dynasties, combined with the modern literature, so as to provide a basis for the development of famous classical formulas containing this type of medicinal materials. According to the herbal textual research, Abri Herba was first recorded in Lingnan Caiyaolu, with other aliases such as Huangtoucao and Xiye Longlincao. It originates from the dried whole plant of Abrus cantoniensis, a Fabaceae plant, which can be used medicinally except for its fruits. Currently, this species is mainly distributed in Guangdong and Guangxi, and also found in Hunan and Thailand, it can be harvested throughout the year, mainly in spring and autumn. The roots, stems, and leaves can be used for medicinal purposes, but the pods are toxic and need to be removed. After harvesting, impurities and pods are removed, and it is dried and processed for medicinal use. Abri Herba has a sweet and slightly bitter taste, is cool in nature, and is associated with the liver and stomach meridians, it is used for clearing heat and relieving dampness, dispersing blood stasis and relieving pain, and is mainly used to treat jaundice-type hepatitis, stomach pain, rheumatic bone pain, contusion and ecchymosis pain, and mastitis. Abri Mollis Herba was first recorded in the 1982 edition of Zhongyaozhi as another origin for Abri Herba, and was singled out in some monographs such as Xinhua Bencao Gangyao in 1988 for use, while some other monographs use it as a local habitual products or confused products of Abri Herba with aliases such as Daye Jigucao, Qingtingteng, and Maoxiangsi. It comes from the dried whole herb of A. mollis without pods, and is mainly produced in Guangxi and Guangdong, and occasionally found in Hong Kong, Hainan and Fujian. The collection and processing are similar to Abri Herba, after harvesting, impurities and pods are removed, and it is dried and cut for medicinal use. Abri Mollis Herba has a sweet and light taste, is cool in nature, and is associated with the liver and stomach meridians, with the efficacy of clearing heat and detoxifying, and promoting dampness, it is mainly used to treat infectious hepatitis, mastitis, furuncles, burns and scalds, and pediatric malnutrition. Based on the research, A. mollis was first recorded to be used as a medicine in the same origin as A. cantoniensis, and as plants of the same genus, have similar morphological characteristics, and their medicinal parts, collection and processing, properties and flavors, and meridian affiliations are consistent. And in the folk, Abri Mollis Herba is often used as Abri Herba, which has been used for a long time and is now dominated by the cultivation of A. mollis. So it is recommended that the subsequent version of Chinese Pharmacopoeia should include A. mollis in the origin of Abri Herba, and it is also recommended that in famous classical formulas refered to Jiguccao can use A. cantoniensis and A. mollis as the sources of the herb, refered to Mao Jiguccao can use A. mollis as the sources of the herb. Processing is carried out according to the requirements specified in the original formulas, and raw products are recommended to be included in the medicine if there are no requirements.
5.Herbal Textual Research on Abri Herba and Abri Mollis Herba in Famous Classical Formulas
Zhen ZENG ; Yanmeng LIU ; Yihan WANG ; Erwei HAO ; Chun YAO ; Zhilai ZHAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(17):193-201
This article systematically analyzes the historical evolution of the name, origin, academic name, medicinal parts, origin, harvesting, processing and other aspects of Abri Herba and Abri Mollis Herba by referring to the herbal medicine, medical books, prescription books and other documents of the past dynasties, combined with the modern literature, so as to provide a basis for the development of famous classical formulas containing this type of medicinal materials. According to the herbal textual research, Abri Herba was first recorded in Lingnan Caiyaolu, with other aliases such as Huangtoucao and Xiye Longlincao. It originates from the dried whole plant of Abrus cantoniensis, a Fabaceae plant, which can be used medicinally except for its fruits. Currently, this species is mainly distributed in Guangdong and Guangxi, and also found in Hunan and Thailand, it can be harvested throughout the year, mainly in spring and autumn. The roots, stems, and leaves can be used for medicinal purposes, but the pods are toxic and need to be removed. After harvesting, impurities and pods are removed, and it is dried and processed for medicinal use. Abri Herba has a sweet and slightly bitter taste, is cool in nature, and is associated with the liver and stomach meridians, it is used for clearing heat and relieving dampness, dispersing blood stasis and relieving pain, and is mainly used to treat jaundice-type hepatitis, stomach pain, rheumatic bone pain, contusion and ecchymosis pain, and mastitis. Abri Mollis Herba was first recorded in the 1982 edition of Zhongyaozhi as another origin for Abri Herba, and was singled out in some monographs such as Xinhua Bencao Gangyao in 1988 for use, while some other monographs use it as a local habitual products or confused products of Abri Herba with aliases such as Daye Jigucao, Qingtingteng, and Maoxiangsi. It comes from the dried whole herb of A. mollis without pods, and is mainly produced in Guangxi and Guangdong, and occasionally found in Hong Kong, Hainan and Fujian. The collection and processing are similar to Abri Herba, after harvesting, impurities and pods are removed, and it is dried and cut for medicinal use. Abri Mollis Herba has a sweet and light taste, is cool in nature, and is associated with the liver and stomach meridians, with the efficacy of clearing heat and detoxifying, and promoting dampness, it is mainly used to treat infectious hepatitis, mastitis, furuncles, burns and scalds, and pediatric malnutrition. Based on the research, A. mollis was first recorded to be used as a medicine in the same origin as A. cantoniensis, and as plants of the same genus, have similar morphological characteristics, and their medicinal parts, collection and processing, properties and flavors, and meridian affiliations are consistent. And in the folk, Abri Mollis Herba is often used as Abri Herba, which has been used for a long time and is now dominated by the cultivation of A. mollis. So it is recommended that the subsequent version of Chinese Pharmacopoeia should include A. mollis in the origin of Abri Herba, and it is also recommended that in famous classical formulas refered to Jiguccao can use A. cantoniensis and A. mollis as the sources of the herb, refered to Mao Jiguccao can use A. mollis as the sources of the herb. Processing is carried out according to the requirements specified in the original formulas, and raw products are recommended to be included in the medicine if there are no requirements.
6.tRF Prospect: tRNA-derived Fragment Target Prediction Based on Neural Network Learning
Dai-Xi REN ; Jian-Yong YI ; Yong-Zhen MO ; Mei YANG ; Wei XIONG ; Zhao-Yang ZENG ; Lei SHI
Progress in Biochemistry and Biophysics 2025;52(9):2428-2438
ObjectiveTransfer RNA-derived fragments (tRFs) are a recently characterized and rapidly expanding class of small non-coding RNAs, typically ranging from 13 to 50 nucleotides in length. They are derived from mature or precursor tRNA molecules through specific cleavage events and have been implicated in a wide range of cellular processes. Increasing evidence indicates that tRFs play important regulatory roles in gene expression, primarily by interacting with target messenger RNAs (mRNAs) to induce transcript degradation, in a manner partially analogous to microRNAs (miRNAs). However, despite their emerging biological relevance and potential roles in disease mechanisms, there remains a significant lack of computational tools capable of systematically predicting the interaction landscape between tRFs and their target mRNAs. Existing databases often rely on limited interaction features and lack the flexibility to accommodate novel or user-defined tRF sequences. The primary goal of this study was to develop a machine learning based prediction algorithm that enables high-throughput, accurate identification of tRF:mRNA binding events, thereby facilitating the functional analysis of tRF regulatory networks. MethodsWe began by assembling a manually curated dataset of 38 687 experimentally verified tRF:mRNA interaction pairs and extracting seven biologically informed features for each pair: (1) AU content of the binding site, (2) site pairing status, (3) binding region location, (4) number of binding sites per mRNA, (5) length of the longest consecutive complementary stretch, (6) total binding region length, and (7) seed sequence complementarity. Using this dataset and feature set, we trained 4 distinct machine learning classifiers—logistic regression, random forest, decision tree, and a multilayer perceptron (MLP)—to compare their ability to discriminate true interactions from non-interactions. Each model’s performance was evaluated using overall accuracy, receiver operating characteristic (ROC) curves, and the corresponding area under the ROC curve (AUC). The MLP consistently achieved the highest AUC among the four, and was therefore selected as the backbone of our prediction framework, which we named tRF Prospect. For biological validation, we retrieved 3 high-throughput RNA-seq datasets from the gene expression omnibus (GEO) in which individual tRFs were overexpressed: AS-tDR-007333 (GSE184690), tRF-3004b (GSE197091), and tRF-20-S998LO9D (GSE208381). Differential expression analysis of each dataset identified genes downregulated upon tRF overexpression, which we designated as putative targets. We then compared the predictions generated by tRF Prospect against those from three established tools—tRFTar, tRForest, and tRFTarget—by quantifying the number of predicted targets for each tRF and assessing concordance with the experimentally derived gene sets. ResultsThe proposed algorithm achieved high predictive accuracy, with an AUC of 0.934. Functional validation was conducted using transcriptome-wide RNA-seq datasets from cells overexpressing specific tRFs, confirming the model’s ability to accurately predict biologically relevant downregulation of mRNA targets. When benchmarked against established tools such as tRFTar, tRForest, and tRFTarget, tRF Prospect consistently demonstrated superior performance, both in terms of predictive precision and sensitivity, as well as in identifying a higher number of true-positive interactions. Moreover, unlike static databases that are limited to precomputed results, tRF Prospect supports real-time prediction for any user-defined tRF sequence, enhancing its applicability in exploratory and hypothesis-driven research. ConclusionThis study introduces tRF Prospect as a powerful and flexible computational tool for investigating tRF:mRNA interactions. By leveraging the predictive strength of deep learning and incorporating a broad spectrum of interaction-relevant features, it addresses key limitations of existing platforms. Specifically, tRF Prospect: (1) expands the range of detectable tRF and target types; (2) improves prediction accuracy through multilayer perceptron model; and (3) allows for dynamic, user-driven analysis beyond database constraints. Although the current version emphasizes miRNA-like repression mechanisms and faces challenges in accurately capturing 5'UTR-associated binding events, it nonetheless provides a critical foundation for future studies aiming to unravel the complex roles of tRFs in gene regulation, cellular function, and disease pathogenesis.
7.Trend in incidence of pulmonary tuberculosis in Wenzhou City from 2010 to 2024
LI Jun ; ZENG Zhen ; WANG Juejin ; WANG yunfeng
Journal of Preventive Medicine 2025;37(11):1140-1144,1150
Objective:
To investigate the epidemic characteristics and trends in incidence of pulmonary tuberculosis (PTB) in Wenzhou City, Zhejiang Province from 2010 to 2024, so as to provide the basis for improving PTB prevention and control strategies.
Methods:
The PTB data in Wenzhou City from 2010 to 2024 were captured from the Surveillance System of China Information System for Disease Control and Prevention. Descriptive epidemiological methods were applied to analyze the characteristics across different genders, age, and regions. The average annual percent change (AAPC) was used to evaluate the trend in PTB incidence.
Results:
A total of 73 706 PTB cases were reported in Wenzhou City from 2010 to 2024, with an average annual reported incidence of 52.92/100 000. The reported incidence of PTB decreased from 75.33/100 000 in 2010 to 35.47/100 000 in 2024, showing a significant overall downward trend (AAPC=-5 .287%, P<0.05). The average annual reported incidence of PTB was higher in males than in females (70.45/100 000vs. 33.41/100 000, P<0.05). The trends in reported incidence for both males and females were generally consistent with the overall population, showing declining trends (AAPC=-4.992% and -6.112%, both P<0.05). The group aged ≥65 years had the highest average annual reported incidence of PTB at 91.73/100 000. From 2010 to 2024, significant declining trends were observed in the groups aged 15-<25, 25-<35, 35-<45, and 45-<55 years (AAPC=-8.599%, -7.975%, -9.007%, and -5.104%, all P<0.05). The average annual reported incidences of PTB in Taishun County, Longwan District, and Yongjia County were higher, at 81.08/100 000, 75.31/100 000, and 64.68/100 000, respectively. Except for Dongtou District, Pingyang County, and Taishun County, the reported incidences in all other counties (cities, districts) showed declining trends from 2010 to 2024, with AAPC values ranging from -9.056% to -3.791% (all P<0.05).
Conclusions
The reported incidence of PTB in Wenzhou City from 2010 to 2024 showed an overall declining trend, varying in genders, age, and regions. Males and individuals aged ≥65 years were the key populations for prevention and control. Taishun County, Longwan District, and Yongjia County were high-incidence areas.
8.Herbal Textual Research on Chrysanthemum indicum in Famous Classical Formulas
Jing WANG ; Zhen ZENG ; Yanmeng LIU ; Yihan WANG ; Qing MA ; Zhilai ZHAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(24):190-199
This article systematically analyzes the historical evolution of the name, origin, medicinal parts, harvesting, processing and others of Chrysanthemi Indici by referring to the herbal medicine, medical books, prescription books and other documents of the past dynasties, combined with the relevant modern research materials, in order to provide a basis for the development of famous classical formulas containing this medicinal herb. According to the research, Chrysanthemi Indici was first recorded under the name Kuyi in Bencao Jingjizhu, with aliases such as Yeshanju, Huangjuzai and Lubianju. The botanical source of Chrysanthemi Indici throughout history was Chrysanthemum indicum of the Asteraceae family. It is now distributed in most areas of China, and since the Qing dynasty, the product from Suichang, Zhejiang has been highly regarded. The whole plant can be used as medicine. According to the natural growth laws, the roots were collected in the first lunar month, leaves in the third, stems in the fifth, flowers in the ninth, and fruits in the eleventh, all of which were dried in the shade. In modern times, Chrysanthemi Indici is harvested during their initial blooming in autumn and winter. Since Bencao Gangmu listed Chrysanthemi Indici as a single medicinal material and clarified that all parts have medicinal value, ancient herbal texts began to record the independent medicinal use of Chrysanthemi Indici Flos, and the use of flowers as medicine has become mainstream. In modern times, the quality of Chrysanthemi Indici Flos is summarized to be best when they are dry, yellow, complete, and fragrant. Because Chrysanthemi Indici has a bitter and pungent taste, and is warm, it can eliminate and disperse, often using the power of alcohol to reach and ascend, and is commonly used to treat carbuncles, boils, and scrofula, with consistent properties and effects throughout ancient and modern times. Based on the research results, it is suggested that Chrysanthemi Indici involved in the formulas can be used as C. indicum, which can be used according to the medicinal parts labeled in the original formulas and the requirements of processing, while those without clear medicinal parts and requirements of processing should be used as the whole plant of the dried raw products.
9.Effects of phillyrin on lung injury in rats with influenza virus pneumonia by regulating the SphK1/S1P/S1PR1 signal pathway
Hai-Yan LIU ; Ming-Yue FU ; Hai-Zhen SUN ; Yu-Ying ZENG
The Chinese Journal of Clinical Pharmacology 2024;40(3):378-382
Objective To explore the effect of phillyrin(KD-1)on lung injury in rats with influenza virus pneumonia and its regulatory mechanism on the sphingosine kinases 1(SphK1)/sphingosine 1-phosphate(S1P)/S1P receptors 1(S1PR1)signal pathway.Methods Wistar male rats were divided into control group(gavage with equal amount of 0.9%NaCl),model group(gavage with equal amount of 0.9%NaCl),positive drug group(gavage with 0.02 g·kg-1 ribaverin),PF-543 group(gavage with 10 mg·kg-1 SphK1 inhibitor PF-543 Citrate)and experimental-L,-H groups(gavage with 6.5,13 mg·kg-1 KD-1,respectively).Except the control group,the other rats were treated with influenza virus nasal drip to establish influenza virus infection pneumonia model.The lung index of rats was measured;Hematoxylin-eosin(HE)staining was applied to observe the pathological damage of lung tissue in rats;the contents of interleukin 1β(IL-1β),tumor necrosis factor α(TNF-α)and IL-6 in bronchoalveolar lavage fluid(BALF)were detected by enzyme linked immunosorbent assay(ELISA);Western blot was applied to detect the expression levels of SphK1,S1P and S1PR1 proteins in rat lung tissue.Results The lung indices of experimental-L,-H groups,PF-543 group,positive drug group,model group and control group were(7.62±0.51),(5.34±0.46),(6.53±0.52),(5.48±0.43),(12.46±0.87)and(4.41±0.32)mg·g-1;IL-1β content were(47.26±2.05),(25.18±1.58),(35.75±1.50),(27.31±1.67),(62.37±2.51)and(13.28±1.04)ng·L-1;the contents of TNF-α were(76.58±4.73),(51.82±3.90),(64.81±4.15),(53.06±3.86),(98.47±4.92)and(42.71±3.52)ng·L-1;IL-6 content were(57.62±4.29),(39.06±3.86),(48.75±3.83),(41.23±3.61),(76.92±5.24)and(28.56±3.17)ng·L-1;SphK1 protein expression were 1.07±0.08,0.51±0.04,0.65±0.05,0.53±0.04,1.28±0.09 and 0.36±0.03;S1P protein expression were 1.21±0.10,0.57±0.05,0.73±0.06,0.58±0.05,1.39±0.11 and 0.39±0.03;S1PR1 protein expression were 0.45±0.03,0.83±0.07,0.64±0.05,0.81±0.07,0.28±0.02 and 1.03±0.07,respectively.Compared with the control group,the above indexes in the model group had statistical significance(all P<0.05);compared with the model group,the above indexes in experimental-L,-H groups,PF-543 group and positive drug group had statistical significance(all P<0.05).Conclusion KD-1 may alleviate lung injury in rats with influenza virus pneumonia by inhibiting the SphK1/S1 P/S1 PR1 signal pathway.
10.Stability study of umbilical cord mesenchymal stem cells formulation in large-scale production
Wang-long CHU ; Tong-jing LI ; Yan SHANGGUAN ; Fang-tao HE ; Jian-fu WU ; Xiu-ping ZENG ; Tao GUO ; Qing-fang WANG ; Fen ZHANG ; Zhen-zhong ZHONG ; Xiao LIANG ; Jun-yuan HU ; Mu-yun LIU
Acta Pharmaceutica Sinica 2024;59(3):743-750
Umbilical cord mesenchymal stem cells (UC-MSCs) have been widely used in regenerative medicine, but there is limited research on the stability of UC-MSCs formulation during production. This study aims to assess the stability of the cell stock solution and intermediate product throughout the production process, as well as the final product following reconstitution, in order to offer guidance for the manufacturing process and serve as a reference for formulation reconstitution methods. Three batches of cell formulation were produced and stored under low temperature (2-8 ℃) and room temperature (20-26 ℃) during cell stock solution and intermediate product stages. The storage time intervals for cell stock solution were 0, 2, 4, and 6 h, while for intermediate products, the intervals were 0, 1, 2, and 3 h. The evaluation items included visual inspection, viable cell concentration, cell viability, cell surface markers, lymphocyte proliferation inhibition rate, and sterility. Additionally, dilution and culture stability studies were performed after reconstitution of the cell product. The reconstitution diluents included 0.9% sodium chloride injection, 0.9% sodium chloride injection + 1% human serum albumin, and 0.9% sodium chloride injection + 2% human serum albumin, with dilution ratios of 10-fold and 40-fold. The storage time intervals after dilution were 0, 1, 2, 3, and 4 h. The reconstitution culture media included DMEM medium, DMEM + 2% platelet lysate, 0.9% sodium chloride injection, and 0.9% sodium chloride injection + 1% human serum albumin, and the culture duration was 24 h. The evaluation items were viable cell concentration and cell viability. The results showed that the cell stock solution remained stable for up to 6 h under both low temperature (2-8 ℃) and room temperature (20-26 ℃) conditions, while the intermediate product remained stable for up to 3 h under the same conditions. After formulation reconstitution, using sodium chloride injection diluted with 1% or 2% human serum albumin maintained a viability of over 80% within 4 h. It was observed that different dilution factors had an impact on cell viability. After formulation reconstitution, cultivation in medium with 2% platelet lysate resulted in a cell viability of over 80% after 24 h. In conclusion, the stability of cell stock solution within 6 h and intermediate product within 3 h meets the requirements. The addition of 1% or 2% human serum albumin in the reconstitution diluent can better protect the post-reconstitution cell viability.


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