OBJECTIVE To explore the main factors influencing the blood concentration of duloxetine， and provide a scientific basis for the individualized use of duloxetine. METHODS Retrospective analysis was conducted on 434 inpatients with depressive disorders at the First Hospital of Hebei Medical University， who were treated with duloxetine and underwent blood concentration monitoring between January 2022 and April 2024. The study examined the impact of various factors， including gender， age， body mass index （BMI）， gene phenotypes， combined medication， drug type （original/generic）， and genotyping results of gene single nucleotide polymorphism loci， on blood concentration and the concentration-to-dose （C/D） after dose adjustment. RESULTS The blood concentration of duloxetine was 76.65 （45.57， 130.31） ng/mL， and C/D was 0.96 （0.63， 1.60） ng·d/（mL·mg）. The blood concentration of duloxetine was positively correlated with the daily dose of administration （R2＝0.253 7， P＜0.001）. Blood concentration of duloxetine in 38.94% of patients exceeded the recommended range specified in the guidelines. Gender， age， BMI， combined use of CYP2D6 enzyme inhibitors， and CYP2D6 and CYP1A2 phenotypes had significant effects on C/D of duloxetine （P＜0.05）. CONCLUSIONS The patient’s age， gender， BMI， combined medication， and genetic phenotypes are closely related to the blood concentration of duloxetine.

Objective To evaluate the performance of the artificial intelligence (AI)-enabled snail identification system for recognition of Oncomelania hupensis robertsoni and Tricula in schistosomiasis-endemic areas of Yunnan Province. Methods Fifty O. hupensis robertsoni and 50 Tricula samples were collected from Yongbei Township, Yongsheng County, Lijiang City, a schistosomiasis-endemic area in Yunnan Province in May 2024. A total of 100 snail sample images were captured with smartphones, including front-view images of 25 O. hupensis robertsoni and 25 Tricula samples (upward shell opening) and back-view images of 25 O. hupensis robertsoni and 25 Tricula samples (downward shell opening). Snail samples were identified as O. hupensis robertsoni or Tricula by schistosomiasis control experts with a deputy senior professional title and above according to image quality and morphological characteristics. A standard dataset for snail image classification was created, and served as a gold standard for recognition of snail samples. A total of 100 snail sample images were recognized with the AI-enabled intelligent snail identification system based on a WeChat mini program in smartphones. Schistosomiasis control professionals were randomly sampled from stations of schistosomisis prevention and control and centers for disease control and prevention in 18 schistosomiasis-endemic counties (districts, cities) of Yunnan Province, for artificial identification of 100 snail sample images. All professionals are assigned to two groups according the median years of snail survey experiences, and the effect of years of snail survey experiences on O. hupensis robertsoni sample image recognition was evaluated. A receiver operating characteristic (ROC) curve was plotted, and the sensitivity, specificity, accuracy, Youden’s index and the area under the curve (AUC) of the AI-enabled intelligent snail identification system and artificial identification were calculated for recognition of snail sample images. The snail sample image recognition results of AI-enabled intelligent snail identification system and artificial identification were compared with the gold standard, and the internal consistency of artificial identification results was evaluated with the Cronbach’s coefficient alpha. Results A total of 54 schistosomiasis control professionals were sampled for artificial identification of snail sample image recognition, with a response rate of 100% (54/54), and the accuracy, sensitivity, specificity, Youden’s index, and AUC of artificial identification were 90%, 86%, 94%, 0.80 and 0.90 for recognition of snail sample images, respectively. The overall Cronbach’s coefficient alpha of artificial identification was 0.768 for recognition of snail sample images, and the Cronbach’s coefficient alpha was 0.916 for recognition of O. hupensis robertsoni snail sample images and 0.925 for recognition of Tricula snail sample images. The overall accuracy of artificial identification was 90% for recognition of snail sample images, and there was no significant difference in the accuracy of artificial identification for recognition of O. hupensis robertsoni (86%) and Tricula snail sample images (94%) (χ² = 1.778, P > 0.05). There was no significant difference in the accuracy of artificial identification for recognition of snail sample images with upward (88%) and downward shell openings (92%) (χ² = 0.444, P > 0.05), and there was a significant difference in the accuracy of artificial identification for recognition of snail sample images between schistosomiasis control professionals with snail survey experiences of 6 years and less (75%) and more than 6 years (90%) (χ² = 7.792, P < 0.05). The accuracy, sensitivity, specificity and AUC of the AI-enabled intelligent snail identification system were 88%, 100%, 76% and 0.88 for recognition of O. hupensis robertsoni snail sample images, and there was no significant difference in the accuracy of recognition of O. hupensis robertsoni snail sample images between the AI-enabled intelligent snail identification system and artificial identification (χ² = 0.204, P > 0.05). In addition, there was no significant difference in the accuracy of artificial identification for recognition of snail sample images with upward (90%) and downward shell openings (86%) (χ² = 0.379, P > 0.05), and there was a significant difference in the accuracy of artificial identification for recognition of snail sample images between schistosomiasis control professionals with snail survey experiences of 6 years and less and more than 6 years (χ² = 5.604, P_adjusted < 0.025). Conclusions The accuracy of recognition of snail sample images is comparable between the AI-enabled intelligent snail identification system and artificial identification by schistosomiasis control professionals, and the AI-enabled intelligent snail identification system is feasible for recognition of O. hupensis robertsoni and Tricula in Yunnan Province.

Psoriasis is a chronic inflammatory skin disease with a polygenic genetic background. Its etiology remains unclear， and its pathogenesis is complex and refractory， collectively posing significant challenges in its treatment and greatly affecting the physical and mental health of patients. With the advantages of multi-target and multi-pathway treatment， traditional Chinese medicine has shown unique efficacy and value in the diagnosis and treatment of psoriasis. Modern doctors have a lot of discussion on psoriasis， and most of them tend to treat the disease by solving disorders of the blood system. They think that the disease is closely related to the "heat in the blood". Combining the clinical characteristics and accompanying symptoms of psoriasis， this article traced the causes of "heat in the blood" in psoriasis and believed that multiple internal and external factors have prevented the smooth circulation of Qi. Yang Qi Fuyu （stagnation） and transformation into heat and toxicity is the source of "heat in the blood" in psoriasis. Furthermore， it was proposed that "Fuyu" is the core pathogenesis of psoriasis. The etiology of "Fuyu" is complex， such as external wind and cold pathogens， emotional injuries， internal accumulation of dampness， and deficiency of healthy Qi， all of which can disrupt the ascending and descending movement of Qi， impede the circulation of Qi and fluids， close the pores and skin texture， and subsequently lead to stagnation. Based on the above understanding， "resolving stagnation" is crucial for treating the disease. Many doctors have explored the treatment ideas of psoriasis from the perspectives of dispelling wind， warming cold， regulating Qi， eliminating dampness， tonifying deficiency， and external treatment， aiming to remove the causes， promote the circulation of Qi and fluids， and resolve stagnation and heat. Clinical studies have shown that the therapies can relieve clinical symptoms， reduce recurrence rate， and improve quality of life， which also have good safety in the treatment of psoriasis. This article discussed the treatment of psoriasis from the perspective of "Fuyu"， enriching the understanding of TCM regarding the etiology and pathogenesis of psoriasis. It is aiming to serve as an effective supplement to the "treating by solving disorders of the blood system" approach and provide a reference for clinical diagnosis and treatment of psoriasis.

ObjectiveTo use bioinformatics technology to screen the molecular patterns and diagnostic biomarkers of ferroptosis closely related to psoriasis， observe the therapeutic effect of Kaixuan Jiedu core prescription on psoriasis and explore its potential mechanism through animal experiments. MethodsPsoriasis microarray data from GEO were analyzed to identify differentially expressed genes （DEGs）. Intersection with a ferroptosis gene set yielded psoriasis ferroptosis-related genes （FRGs）， which underwent correlation， consensus clustering， enrichment， and immune infiltration analyses. Core diagnostic FRGs （Hub-FRGs） were identified using random forest （RF）， support vector machine （SVM）， LASSO regression， Nomogram， and ROC analyses. In vivo， imiquimod （5% cream） induced psoriasis in mice （except controls）. Drug treatment groups received respective doses， while control and model groups received saline via daily gavage for 7 days. Back skin changes were recorded and PASI scored. Hematoxylin-eosin （HE） staining assessed histopathology. The levels of ferrous ion （Fe²⁺）， malondialdehyde （MDA）， 4-hydroxynonenal （4-HNE） and free fatty acid （FFA） in skin tissue were detected. The level of reactive oxygen species （ROS） in skin tissue was detected by immunofluorescence. Immunohistochemistry was used to detect the expression of ChaC glutathione-specific γ-glutamyl transferase 1 （CHAC1）， arachidonic acid 12-lipoxygenase β （ALOX12B）， trimotif protein 21 （TRIM21）， proliferation marker （Ki67） and nuclear transcription factor-κB （NF-κB） protein. ResultsAnalysis of GSE30999 identified 2 100 DEGs and 24 FRGs. Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment revealed 1 000 biological functions and 75 pathways. After cluster analysis， combined with three machine learning algorithms， Nomogram and ROC curve analysis， the core Hub-FRGs （CHAC1， ALOX12 B， TRIM21） were obtained. Immunoinfiltration showed inactive memory CD4⁺T cells and activated dendritic cells abundance significantly correlated with Hub-FRGs. In vivo， model group vs. control showed significantly increased PASI/Baker scores （P<0.05）， epidermal hyperkeratosis， inflammatory infiltration， and elevated levels of Fe²⁺， MDA， 4-HNE， FFA， ROS， CHAC1， ALOX12B， TRIM21， Ki67， and NF-κB （P<0.05）. Drug groups vs. model group exhibited significantly reduced scores （P<0.05）， alleviated skin lesions， and decreased levels of Fe²⁺， MDA， 4-HNE， FFA， ROS， Hub-FRGs， Ki67， and NF-κB （P<0.05）. ConclusionKaixuan Jiedu core prescription can significantly improve the skin pathological injury of psoriasis mice， showing good therapeutic and repair effects， and its mechanism may be related to regulating the expression of ferroptosis genes CHAC1， ALOX12B and TRIM21， which are closely related to the pathogenesis of psoriasis.

ObjectiveTo investigate the efficacy and safety of Kaixuan Jiedu compatibility and the decomposed prescriptions in the treatment of psoriasis. MethodsThirty Balb/c mice were randomly grouped as follows （n=6）： normal， model， Kaixuan Jiedu （KXJD， 15.21 g·kg^-1）， Kaixuan （KX， 3.08 g·kg^-1）， and Jiedu （JD， 12.13 g·kg^-1）. Except the normal group， the rest groups were modeled for psoriasis-like skin lesions by topical application of imiquimod， and samples were collected after 7 days of continuous intervention. Mice were photographed at the lesion site during modeling and before sampling and the psoriasis area and severity index （PASI） was calculated. Hematoxylin-eosin （HE） staining was used to observe pathological changes in the lesions and measure the epidermal thickness. Mice were photographed and observed for the tortuous dilation of dermal capillaries. The expression of vascular endothelial growth factor （VEGF）， platelet-endothelial cell adhesion molecule （CD31）， proliferating cell nuclear antigen （Ki67）， and cytokeratin 10 （CK10） in the epidermal tissue was detected by immunohistochemistry. Immunofluorescence assay was employed to determine the expression of Claudin-1 and Occludin. Real-time PCR was employed to determine the mRNA levels of interleukin-17A （IL-17A） and interleukin-23 （IL-23）. The spleen and thymus were photographed and weighed， and the spleen and thymus indices were calculated. The safety of the treatment was assessed by automatic biochemistry testing of the serum， liver， and kidney functions and by HE staining of the liver， kidney and spleen. ResultsCompared with that of the normal group， the skin of the model group showed erythema， infiltration， and typical psoriasis-like changes， tortuous dilation of dermal capillaries， hyperkeratosis in epidermal cells， acanthosis， massive lymphocytic infiltration in the dermis， impaired barrier function， increased expression of VEGF， CD31， Ki67， and CK10 （P<0.01）， reduced expression of Claudin-1 and Occludin （P<0.01） in the epidermis， and up-regulated mRNA levels of IL-17A and IL-23 （P<0.01）. In addition， the mice in the model group showed spleen enlargement， thymus atrophy， increased spleen index， and decreased thymus index （P<0.01）. Compared with the model group， KXJD and JD reduced psoriasis-like skin lesions， inhibited the tortuous dilation of dermal capillaries， reduced the expression of VEGF， CD31， Ki67， and CK10 （P<0.01）， increased the expression of claudin-1 （P<0.01）， and down-regulated the mRNA levels of inflammatory factors （P<0.01）. Moreover， the KXJD group outperformed the JD group. The JD group showed no significant difference from the model group regarding the spleen index， thymus index， and Occludin expression. The psoriasis indicators in the KX group were not significantly different from those in the model group. ConclusionKXJD and JD can reduce the symptoms of local skin lesions of psoriasis， which is manifested as different inhibition degrees of the proliferation and differentiation of keratin-forming cells， tortuous dilation of dermal capillaries， and inflammatory reactions， as well as the protection of the skin barrier. Moreover， KXJD outperformed JD. KX alone did not significantly reduce psoriasis lesions in mice. KXJD and the decomposed prescriptions are safe and effective， causing no obvious liver and kidney injuries.

Psoriasis is a chronic inflammatory skin disease with a polygenic genetic background. Its etiology remains unclear， and its pathogenesis is complex and refractory， collectively posing significant challenges in its treatment and greatly affecting the physical and mental health of patients. With the advantages of multi-target and multi-pathway treatment， traditional Chinese medicine has shown unique efficacy and value in the diagnosis and treatment of psoriasis. Modern doctors have a lot of discussion on psoriasis， and most of them tend to treat the disease by solving disorders of the blood system. They think that the disease is closely related to the "heat in the blood". Combining the clinical characteristics and accompanying symptoms of psoriasis， this article traced the causes of "heat in the blood" in psoriasis and believed that multiple internal and external factors have prevented the smooth circulation of Qi. Yang Qi Fuyu （stagnation） and transformation into heat and toxicity is the source of "heat in the blood" in psoriasis. Furthermore， it was proposed that "Fuyu" is the core pathogenesis of psoriasis. The etiology of "Fuyu" is complex， such as external wind and cold pathogens， emotional injuries， internal accumulation of dampness， and deficiency of healthy Qi， all of which can disrupt the ascending and descending movement of Qi， impede the circulation of Qi and fluids， close the pores and skin texture， and subsequently lead to stagnation. Based on the above understanding， "resolving stagnation" is crucial for treating the disease. Many doctors have explored the treatment ideas of psoriasis from the perspectives of dispelling wind， warming cold， regulating Qi， eliminating dampness， tonifying deficiency， and external treatment， aiming to remove the causes， promote the circulation of Qi and fluids， and resolve stagnation and heat. Clinical studies have shown that the therapies can relieve clinical symptoms， reduce recurrence rate， and improve quality of life， which also have good safety in the treatment of psoriasis. This article discussed the treatment of psoriasis from the perspective of "Fuyu"， enriching the understanding of TCM regarding the etiology and pathogenesis of psoriasis. It is aiming to serve as an effective supplement to the "treating by solving disorders of the blood system" approach and provide a reference for clinical diagnosis and treatment of psoriasis.

ObjectiveTo use bioinformatics technology to screen the molecular patterns and diagnostic biomarkers of ferroptosis closely related to psoriasis， observe the therapeutic effect of Kaixuan Jiedu core prescription on psoriasis and explore its potential mechanism through animal experiments. MethodsPsoriasis microarray data from GEO were analyzed to identify differentially expressed genes （DEGs）. Intersection with a ferroptosis gene set yielded psoriasis ferroptosis-related genes （FRGs）， which underwent correlation， consensus clustering， enrichment， and immune infiltration analyses. Core diagnostic FRGs （Hub-FRGs） were identified using random forest （RF）， support vector machine （SVM）， LASSO regression， Nomogram， and ROC analyses. In vivo， imiquimod （5% cream） induced psoriasis in mice （except controls）. Drug treatment groups received respective doses， while control and model groups received saline via daily gavage for 7 days. Back skin changes were recorded and PASI scored. Hematoxylin-eosin （HE） staining assessed histopathology. The levels of ferrous ion （Fe²⁺）， malondialdehyde （MDA）， 4-hydroxynonenal （4-HNE） and free fatty acid （FFA） in skin tissue were detected. The level of reactive oxygen species （ROS） in skin tissue was detected by immunofluorescence. Immunohistochemistry was used to detect the expression of ChaC glutathione-specific γ-glutamyl transferase 1 （CHAC1）， arachidonic acid 12-lipoxygenase β （ALOX12B）， trimotif protein 21 （TRIM21）， proliferation marker （Ki67） and nuclear transcription factor-κB （NF-κB） protein. ResultsAnalysis of GSE30999 identified 2 100 DEGs and 24 FRGs. Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment revealed 1 000 biological functions and 75 pathways. After cluster analysis， combined with three machine learning algorithms， Nomogram and ROC curve analysis， the core Hub-FRGs （CHAC1， ALOX12 B， TRIM21） were obtained. Immunoinfiltration showed inactive memory CD4⁺T cells and activated dendritic cells abundance significantly correlated with Hub-FRGs. In vivo， model group vs. control showed significantly increased PASI/Baker scores （P<0.05）， epidermal hyperkeratosis， inflammatory infiltration， and elevated levels of Fe²⁺， MDA， 4-HNE， FFA， ROS， CHAC1， ALOX12B， TRIM21， Ki67， and NF-κB （P<0.05）. Drug groups vs. model group exhibited significantly reduced scores （P<0.05）， alleviated skin lesions， and decreased levels of Fe²⁺， MDA， 4-HNE， FFA， ROS， Hub-FRGs， Ki67， and NF-κB （P<0.05）. ConclusionKaixuan Jiedu core prescription can significantly improve the skin pathological injury of psoriasis mice， showing good therapeutic and repair effects， and its mechanism may be related to regulating the expression of ferroptosis genes CHAC1， ALOX12B and TRIM21， which are closely related to the pathogenesis of psoriasis.

ObjectiveTo investigate the efficacy and safety of Kaixuan Jiedu compatibility and the decomposed prescriptions in the treatment of psoriasis. MethodsThirty Balb/c mice were randomly grouped as follows （n=6）： normal， model， Kaixuan Jiedu （KXJD， 15.21 g·kg^-1）， Kaixuan （KX， 3.08 g·kg^-1）， and Jiedu （JD， 12.13 g·kg^-1）. Except the normal group， the rest groups were modeled for psoriasis-like skin lesions by topical application of imiquimod， and samples were collected after 7 days of continuous intervention. Mice were photographed at the lesion site during modeling and before sampling and the psoriasis area and severity index （PASI） was calculated. Hematoxylin-eosin （HE） staining was used to observe pathological changes in the lesions and measure the epidermal thickness. Mice were photographed and observed for the tortuous dilation of dermal capillaries. The expression of vascular endothelial growth factor （VEGF）， platelet-endothelial cell adhesion molecule （CD31）， proliferating cell nuclear antigen （Ki67）， and cytokeratin 10 （CK10） in the epidermal tissue was detected by immunohistochemistry. Immunofluorescence assay was employed to determine the expression of Claudin-1 and Occludin. Real-time PCR was employed to determine the mRNA levels of interleukin-17A （IL-17A） and interleukin-23 （IL-23）. The spleen and thymus were photographed and weighed， and the spleen and thymus indices were calculated. The safety of the treatment was assessed by automatic biochemistry testing of the serum， liver， and kidney functions and by HE staining of the liver， kidney and spleen. ResultsCompared with that of the normal group， the skin of the model group showed erythema， infiltration， and typical psoriasis-like changes， tortuous dilation of dermal capillaries， hyperkeratosis in epidermal cells， acanthosis， massive lymphocytic infiltration in the dermis， impaired barrier function， increased expression of VEGF， CD31， Ki67， and CK10 （P<0.01）， reduced expression of Claudin-1 and Occludin （P<0.01） in the epidermis， and up-regulated mRNA levels of IL-17A and IL-23 （P<0.01）. In addition， the mice in the model group showed spleen enlargement， thymus atrophy， increased spleen index， and decreased thymus index （P<0.01）. Compared with the model group， KXJD and JD reduced psoriasis-like skin lesions， inhibited the tortuous dilation of dermal capillaries， reduced the expression of VEGF， CD31， Ki67， and CK10 （P<0.01）， increased the expression of claudin-1 （P<0.01）， and down-regulated the mRNA levels of inflammatory factors （P<0.01）. Moreover， the KXJD group outperformed the JD group. The JD group showed no significant difference from the model group regarding the spleen index， thymus index， and Occludin expression. The psoriasis indicators in the KX group were not significantly different from those in the model group. ConclusionKXJD and JD can reduce the symptoms of local skin lesions of psoriasis， which is manifested as different inhibition degrees of the proliferation and differentiation of keratin-forming cells， tortuous dilation of dermal capillaries， and inflammatory reactions， as well as the protection of the skin barrier. Moreover， KXJD outperformed JD. KX alone did not significantly reduce psoriasis lesions in mice. KXJD and the decomposed prescriptions are safe and effective， causing no obvious liver and kidney injuries.

BACKGROUND: Approximately 40% of individuals with diabetes worldwide are at risk of developing diabetic kidney disease (DKD), which is not only the leading cause of kidney failure, but also significantly increases the risk of cardiovascular disease, causing significant societal health and financial burdens. This study aimed to describe the burden of DKD and explore its cross-country epidemiological status, predict development trends, and assess its risk factors and sociodemographic transitions. METHODS: Based on the Global Burden of Diseases (GBD) Study 2021, data on DKD due to type 1 diabetes (DKD-T1DM) and type 2 diabetes (DKD-T2DM) were analyzed by sex, age, year, and location. Numbers and age-standardized rates were used to compare the disease burden between DKD-T1DM and DKD-T2DM among locations. Decomposition analysis was used to assess the potential drivers. Locally weighted scatter plot smoothing and Frontier analysis were used to estimate sociodemographic transitions of DKD disability-adjusted life years (DALYs). RESULTS: The DALYs due to DKD increased markedly from 1990 to 2021, with a 74.0% (from 2,227,518 to 3,875,628) and 173.6% (from 4,122,919 to 11,278,935) increase for DKD-T1DM and DKD-T2DM, respectively. In 2030, the estimated DALYs for DKD-T1DM surpassed 4.4 million, with that of DKD-T2DM exceeding 14.6 million. Notably, middle-sociodemographic index (SDI) quintile was responsible for the most significant DALYs. Decomposition analysis revealed that population growth and aging were major drivers for the increased DKD DALYs in most regions. Interestingly, the most pronounced effect of positive DALYs change from 1990 to 2021 was presented in high-SDI quintile, while in low-SDI quintile, DALYs for DKD-T1DM and DKD-T2DM presented a decreasing trend over the past years. Frontiers analysis revealed that there was a negative association between SDI quintiles and age-standardized DALY rates (ASDRs) in DKD-T1DM and DKD-T2DM. Countries with middle-SDI shouldered disproportionately high DKD burden. Kidney dysfunction (nearly 100.0% for DKD-T1DM and DKD-T2DM), high fasting plasma glucose (70.8% for DKD-T1DM and 87.4% for DKD-T2DM), and non-optimal temperatures (low and high, 5.0% for DKD-T1DM and 5.1% for DKD-T2DM) were common risk factors for age-standardized DALYs in T1DM-DKD and T2DM-DKD. There were other specific risk factors for DKD-T2DM such as high body mass index (38.2%), high systolic blood pressure (10.2%), dietary risks (17.8%), low physical activity (6.2%), lead exposure (1.2%), and other environmental risks. CONCLUSIONS DKD markedly increased and varied significantly across regions, contributing to a substantial disease burden, especially in middle-SDI countries. The rise in DKD is primarily driven by population growth, aging, and key risk factors such as high fasting plasma glucose and kidney dysfunction, with projections suggesting continued escalation of the burden by 2030.
Humans ; Global Burden of Disease ; Risk Factors ; Male ; Female ; Disability-Adjusted Life Years ; Diabetic Nephropathies/epidemiology* ; Middle Aged ; Diabetes Mellitus, Type 2/epidemiology* ; Adult ; Diabetes Mellitus, Type 1/complications* ; Aged ; Adolescent ; Young Adult ; Quality-Adjusted Life Years

[This corrects the article DOI: 10.1016/j.apsb.2022.05.019.].