Epimedium sagittatum is a perennial herb of Berberidaceae. Its leaves have a long history of medicinal use in China. This plant is widely used as a Chinese traditional medicine，with the main functions of tonifying kidney Yang，strengthening bones and muscles，and dispelling wind and dampness. It can be used for treating kidney Yang deficiency，impotence，spermatorrhea，flaccidity of bones and muscles，rheumatic arthralgia，numbness，and spasms. The chemical constituents of this plant include flavonoids，polysaccharides，lignans，and alkaloids. Flavonoids are the main active ingredients. These compounds show a wide range of biological activities，including cartilage repair，anti-aging，anti-fatigue，cough-relieving，blood glucose-lowering，and anti-tumor effects. Modern pharmacological research has shown that E. sagittatum has definite pharmacological effects on the reproductive system，respiratory system，nervous system，cardiovascular system，skeletal system，etc. It has remarkable effects of helping pregnancy，resisting osteoporosis，controlling diabetes，improving immunity，and inhibiting tumor. Under the background of advocating one health and Chinese medicine，E. sagittatum is widely used in health care products，serving as the main raw material of various products. It has great market potential and is a Chinese medicinal herb with great clinical application and research value. This paper reviews the main chemical constituents and pharmacological effects of E. sagittatum based on domestic and foreign reports， providing a theoretical basis for further study on E. sagittatum and its safe clinical application.

Epimedium sagittatum is a perennial herb of Berberidaceae. Its leaves have a long history of medicinal use in China. This plant is widely used as a Chinese traditional medicine，with the main functions of tonifying kidney Yang，strengthening bones and muscles，and dispelling wind and dampness. It can be used for treating kidney Yang deficiency，impotence，spermatorrhea，flaccidity of bones and muscles，rheumatic arthralgia，numbness，and spasms. The chemical constituents of this plant include flavonoids，polysaccharides，lignans，and alkaloids. Flavonoids are the main active ingredients. These compounds show a wide range of biological activities，including cartilage repair，anti-aging，anti-fatigue，cough-relieving，blood glucose-lowering，and anti-tumor effects. Modern pharmacological research has shown that E. sagittatum has definite pharmacological effects on the reproductive system，respiratory system，nervous system，cardiovascular system，skeletal system，etc. It has remarkable effects of helping pregnancy，resisting osteoporosis，controlling diabetes，improving immunity，and inhibiting tumor. Under the background of advocating one health and Chinese medicine，E. sagittatum is widely used in health care products，serving as the main raw material of various products. It has great market potential and is a Chinese medicinal herb with great clinical application and research value. This paper reviews the main chemical constituents and pharmacological effects of E. sagittatum based on domestic and foreign reports， providing a theoretical basis for further study on E. sagittatum and its safe clinical application.

OBJECTIVE: To establish venetoclax-resistant acute myeloid leukemia (AML) cell lines, assess the sensitivity of venetoclax-resistant cell lines to the BCL-2 protein family, and investigate their resistance mechanisms. METHODS: CCK-8 method was used to screen AML cell lines (MV4-11, MOLM13, OCI-AML2) that were relatively sensitive to venetoclax. Low concentrations of venetoclax continuously induced drug-resistance development in the cell lines. Changes in cell viability and apoptosis rate before and after resistance development were measured using the CCK-8 method and flow cytometry. BH3 profiling assay was performed to anayze the transform of mitochondrion-dependent apoptosis pathway as well as the sensitivity of resistant cell lines to BCL-2 family proteins and small molecule inhibitors. Real-time fluorescence quantitative PCR (RT-qPCR) was utilized to examine changes in the expression levels of BCL-2 protein family members in both venetoclax-resistant cell lines and multidrug-resistant patients. RESULTS: Venetoclax-resistant cell lines of MV4-11, MOLM13, and OCI-AML2 were successfully established, with IC₅₀ values exceeding 10-fold. Under the same concentration of venetoclax, the apoptosis rate of resistant cells decreased significantly (P < 0.05). BH3 profiling assay revealed that the drug-resistant cell lines showed increased sensitivity to many pro-apoptotic proteins (such as BIM,BID and NOXA). RT-qPCR showed significantly upregulated MCL1 and downregulated NOXA1 were detected in drug-resistant cell lines. Expression changes in MCL1 and NOXA1 in venetoclax-resistant patients were consistent with our established drug-resistant cell line results. CONCLUSION The venetoclax-resistant AML cell lines were successfully established through continuous induction with low concentrations of venetoclax. The venetoclax resistance resulted in alterations in the mitochondrial apoptosis pathway of the cells and an increased sensitivity of cells to pro-apoptotic proteins BIM, BID, and NOXA, which may be associated with the upregulation of MCL1 expression and downregulation of NOXA1 expression in the drug-resistant cells.
Humans ; Sulfonamides/pharmacology* ; Drug Resistance, Neoplasm ; Bridged Bicyclo Compounds, Heterocyclic/pharmacology* ; Leukemia, Myeloid, Acute/pathology* ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Cell Line, Tumor ; Apoptosis ; Antineoplastic Agents/pharmacology*

Physiologically based pharmacokinetic (PBPK) models have been widely used to predict various stages of drug absorption, distribution, metabolism and excretion. Models based on machine learning (ML) and artificial intelligence (AI) can provide better ideas for the construction of PBPK models, which can accelerate the prediction speed and improve the prediction quality of PBPK. ML and AL can complement the advantages of PBPK model to accelerate the progress of drug research and development. This review introduces the application of machine learning and artificial intelligence in pharmacokinetics, summarizes the research progress of physiological pharmacokinetic models based on machine learning and artificial intelligence, and analyzes the limitations of machine learning and artificial intelligence applications and their application prospects and prospects.

Objective:To analyze the external quality control assessment results of fluoride testing laboratories in endemic disease prevention and control institutions nationwide from 2006 to 2023, investigate the quality control capabilities of these laboratories in various provinces, prefectures, cities, and counties nationwide, and ensure the accuracy and reliability of surveillance data on endemic fluorosis nationwide.Methods:Using retrospective analysis, the external quality control assessment results of all participating fluoride testing laboratories of national endemic disease prevention and control institutions from 2006 to 2023 were summarized and analyzed. The assessment results from 2006 to 2008 were tested for outliers using Grubbs method, homogeneity of variance using Cochran method, excluding the assessment data of unqualified laboratories, calculating the total mean and total standard deviation, Z-score method was used to test the assessment of laboratories, and statistical analysis and judgment were done when the result of │Z│ < 3. The assessment results from 2009 - 2023 were obtained from all laboratories. In 2010, two tests were conducted in the first and second half of the year, and the Z-ratio scores of each laboratory were calculated using robust statistics. When │Z│≤2, the assessment was qualified; when 2 < │Z│ < 3, the assessment was basically qualified; when│Z│≥3, the assessment was unqualified, and the consensus value came from all participating laboratories in the assessment.Results:From the beginning of quality control operation in 2006 to 2023, the number of laboratories participated in external quality control assessments had significantly increased. The number of laboratories participated in water fluoride assessment increased from 30 in 2006 to 1 277 in 2023, and the number of laboratories participated in urine fluoride assessment increased from 29 to 497. The number of laboratories participated in the brick tea fluorine assessment had increased from 43 in 2014 to 193 in 2023. The assessment results showed that when │Z│ < 3, the total qualified rate of fluoride external quality control in fluoride testing laboratories of national endemic disease control institutions was 95.2%, with the lowest being 87.1% (27/31) in 2008 and the highest being 100.0% (394/394) in 2014. When │Z│≤2, the total feedback pass rate was 88.4%, with the lowest being 79.3% (288/363) in the first half of 2010 and the highest being 99.5% (392/394) in 2014. The assessment results showed that when │Z│ < 3, the total pass rate of urine fluoride external quality control in fluoride testing laboratories of national endemic disease control institutions was 98.0%, with the lowest being 86.2% (25/29) in 2006 and 2007, respectively, and the highest being 100.0% (68/68) in 2014. When │Z│≤2, the total qualification rate was 93.7%, with the lowest being 86.5% (64/74) in the second half of 2010 and the highest being 100.0% (68/68) in 2014. The assessment results showed that when│Z│ < 3, the total pass rate of extra-fluoride quality control of brick tea in fluoride testing laboratories of national endemic disease control institutions was 95.4%, with the lowest being 85.0% (164/193) in 2023, and the highest being 100.0% (43/43, 51/51, 79/79) in 2014, 2015 and 2016, respectively. When │Z│≤2, the total pass rate was 89.2%, with the lowest being 72.7% (32/44) in 2017 and the highest being 100.0% (43/43) in 2014. From 2009 to 2023, there were a total of 21 provincial-level laboratories that passed the water fluoride detection assessment, including 3 provinces where all prefecture level and county-level laboratories were qualified. The assessment results of urinary fluorine showed that there were 11 qualified provincial-level laboratories and 1 prefecture-level laboratory. From 2014 to 2023, the assessment results of brick-tea fluorine showed that there were 5 provincial-level laboratories that passed the tea fluorine testing assessment and no prefecture-level laboratory.Conclusions:Conclusion: From 2006 to 2023, the number of fluoride testing laboratories participating in external quality control assessment has increased year by year, and most provincial, municipal and county-level laboratories have good fluoride testing capabilities, which can meet the testing needs of endemic disease prevention and monitoring. For some laboratories with problems, targeted rectification should be carried out to improve the quality of detection, in order to provide better technical support for the monitoring of endemic fluorosis areas.

ObjectiveTo investigate the correlation among the botanical characteristics， biological characteristics， chemical composition， and medicinal properties and efficacy of traditional Chinese medicines （TCM） from latex-containing plants， so as to strengthen the theory of "identifying symptoms for qualities" and provide a reference for the development and utilization of the latex-containing plant resources. MethodStatistics on the meridians for properties and tastes， efficacy， medicinal parts， family and genus， and chemical components of TCM from latex-containing plants were carried out. A total of 53 TCM from latex-containing plants included in the 2020 edition of the Chinese Pharmacopoeia were screened by mining the Chinese Botanical Journal， Chinese Materia Medica， Dictionary of Traditional Chinese Medicines， and related literature. In addition， their meridians for properties and tastes， medicinal parts， chemical components， and TCM classifications were summarized and statistically analyzed by using Excel 2013 and ChiPlot 2023.3.31 software. ResultIt was found that latex-containing plants were mainly distributed in one kingdom， one phylum， two classes， and 20 families， and most of the TCM from latex-containing plants belonged to Dicotyledonaceae under Angiosperms. In terms of properties and tastes， plain>cold>warm>cool>hot and bitter>pungent>sweet>sour>salty. In terms of meridians， liver>lung>kidney>spleen=large intestine=stomach>heart>bladder=gallbladder=small intestines. In terms of medicinal parts， roots （root， rhizomes， tuberous root， and root bark）>resin>seed>whole herb （whole herb and above-ground part）>stem （stem and branch）>fruit>leaf>flower=skin. In terms of research on chemical components， they were mostly glycosides. In terms of TCM classification， they were mostly medicines for activating blood circulation and removing blood stasis. ConclusionThe TCM from latex-containing plants is mainly plain， with a uniform warm and cold distribution. The tastes are mainly bitter and pungent， and the major meridians are the liver and lung. The roots and resins are mainly used as medicines. The components mostly contain glycosides， alkaloids， and volatile oils， and most of them are medicines for activating blood circulation and removing blood stasis， as well as for removing heat and toxins. There is a certain degree of correlation among the growth habits， medicinal parts， chemical components， and the properties， tastes， and efficacy of the TCM from latex-containing plants. It may provide a reference for resource development and utilization of TCM from latex-containing plants.

ObjectiveThe relevant laws among the biological characteristics， medicinal parts， growth environment， and medicinal properties and efficacy of traditional Chinese medicines （TCM） from fungi were excavated， so as to strengthen the theory of distinguishing symptoms for quality and provide a reference for the development and utilization of TCM from fungi. MethodThe medicinal parts， meridians for properties and tastes， heterotrophic mode， and efficacy of commonly used TCM from fungi were summarized. By consulting the Compendium of Materia Medica， Shennong Materia Medica， Flora of China， and literature， the TCM from fungi indexed in the 2020 edition of the Chinese Pharmacopoeia and some local pharmacopeias were checked. ResultA total of 28 common TCM from fungi were selected. Different TCMs from fungi have different meridians for properties and tastes， medicinal parts， habits， and growth environments. The relevant information was counted. Among the four properties， plain>cold>warm. Among the five tastes， sweet>bitter>light>pungent=salty. In terms of medicinal parts， fruiting body>sclerotia>complex>spermia=outer skin=other. In terms of meridians， lung>liver=heart>spleen=kidney>stomach. In terms of habits， parasitism>saprophysis>symbiosis=facultative parasitism=facultative saprophysis. ConclusionTCM from fungi are mainly parasitic and saprophytic， and the plain property and sweet taste the most. The meridians are mostly lung， heart， and liver. Nourishment and diuresis are the main efficacy. There is a certain correlation between the color， habit， medicinal parts， and growth environment of TCM from fungi and their properties， tastes， and efficacy， providing comprehensive literature reference and theoretical basis for their in-depth research， clinical use， and resource development.

ObjectiveTo investigate the functions and characteristics of traditional Chinese medicine （TCM） from plant skin and their Chinese patent medicines and explore the related laws of the medicinal tissue， property， taste， efficacy， and clinical application， so as to strengthen the theory of identifying symptoms for qualities and provide references for the development and utilization of TCM from plant skin and their Chinese patent medicines. MethodBy reviewing the 2020 edition of the Chinese Pharmacopoeia and some local pharmacopeias， TCM from plant skin and their Chinese patent medicines were screened out， and the characteristics， functions， and precautions of TCM from plant skin and their Chinese patent medicines were summarized. Statistical analysis was carried out with Excel. ResultA total of 62 TCM from plant skin were found， mainly distributed in one kingdom， three phyla， and 31 families. In terms of the family genus， Rutaceae>Leguminosae>Cucurbitaceae. In terms of the medicinal tissue， bark>root bark>fruit bark>seed bark. In terms of property and taste， warm>cold>plain>cool>hot， and bitter>sweet=pungent>acidic. In terms of meridians， lung>liver>spleen>heart>colorectal>kidney>stomach=bladder. In terms of TCM classification， most of them belong to the category of heat-clearing medicines. There were 485 types of Chinese patent medicines from plant skin， with the most Chinese patent medicines containing Citri Reticulatae Pericarpium. Among the forms of administration， pills were the most predominant. In terms of the tastes of the medicines， bitter and sweet flavors predominated. In terms of functions， medicines for strengthening the body resistance were the most. For the precautions， contraindications during pregnancy were the most common. ConclusionThere is a correlation among medicinal tissue， property， taste， efficacy， and clinical application of TCM from plant skin. It is also necessary to pay attention to the contraindications of the medicines and rationally choose TCM from plant skin and their Chinese patent medicines under the guidance of TCM theory based on syndrome differentiation and treatment.

ObjectiveTo explore the correlations between botanical characteristics， biological characteristics， growth environment， and medicinal properties of common pteridophyte-derived Chinese medicinal materials， thus providing evidence for the theory of quality evaluation through morphological identification and giving insights into the extensive and reasonable application of pteridophytes in traditional Chinese medicine （TCM）. MethodThe medicine parts， habitats， natures， tastes， and effects of the commonly used pteridophyte-derived Chinese medicinal materials were summarized. The commonly used pteridophyte-derived Chinese medicinal materials were retrieved from the Pharmacopoeia of China， Dictionary of Chinese Materia Medica， and related literature. Excel 2016， ChiPlot， Cytoscape 3.7.1， SPSS 21.0， and weiciyun software were used for statistical analysis. ResultThe frequency of the habitats followed the trend of streamside wetland>tree trunk and rock crevices>sunslope>water surface. The frequency of medicinal parts presented the trend of whole plant>rhizome>leaf>dried aboveground part>spore. The frequency of natures was in the order of cool>cold>plain>warm>hot， and that of tastes was in an order of bitter>pungent>sweet>bland>salty. The frequency of meridian tropism followed the trend of liver meridian>stomach meridian>lung meridian>kidney meridian>bladder meridian>heart meridian>large intestine meridian>spleen meridian>small intestine meridian. The effects of the pteridophyte-derived Chinese medicinal materials followed a frequency trend of clearing heat and detoxifying>promoting urination and relieving stranguria>cooling blood and stopping bleeding>activating blood and resolving stasis>dispelling wind and eliminating dampness. ConclusionThe pteridophyte-derived Chinese medicinal materials mainly have a cool nature， a bitter taste， and tropism to the liver meridian. Whole plants and roots are mainly used for medicinal purposes， and most of these plants grow in the wetlands near rivers， under trees， and in tree trunk and rock crevices. The main effects of these medicinal materials are clearing heat and detoxifying， dispelling wind and removing dampness， cooling blood and stopping bleeding， activating blood and resolving stasis， and soothing meridians and dredging collaterals. There are certain correlations between the structures， habitats， medicinal parts， and effects of pteridophyte-derived Chinese medicinal materials， which provide reference for the development and utilization of pteridophyte-derived Chinese medicinal material resources.