Objective To systematically evaluate toxicities of nifedipine in pregnant women with hypertension, and provide references for nifedipine’s clinical safety application. Methods Study was conducted with data from US food and drug administration adverse event reporting system（FARES） database from January 1, 2015, to March 31, 2021. Information component （IC） and reporting odds ratio（ROR）methods were applied for signal mining. Results Finally, a total of 539278 records of pregnant women with hypertension were selected for analysis, and 70 positive adverse drug event signals were detected. Premature delivery （IC₀₂₅=2.87，ROR₀₂₅=9.52）, pre-eclampsia （IC₀₂₅=1.82，ROR₀₂₅=3.82） and fetal growth restriction （IC₀₂₅=2.37，ROR₀₂₅=5.69）were positive adverse events with higher frequency. Polydactyly（IC₀₂₅=3.13， ROR₀₂₅=10.05）, fetal death（IC₀₂₅=2.93，ROR₀₂₅=8.57）and premature delivery（IC₀₂₅=2.87，ROR₀₂₅=9.52）were positive adverse events with higher intensity. Vascular resistance systemic increased, small for dates baby and fetal death corresponded to higher death rates. Conclusion Nifedipine-associated drug toxicities were detected in pregnant women with hypertension, and some adverse events with high frequency and high death rate were deserved further attention by medical staffs.

Objective:To analyze the main chemical components of Lanqin Granules based on UPLC-Q-TOF-MS/MS; To explore the potential targets, core components and related pathways of Lanqin Granules in the treatment of respiratory tract infection through network pharmacology.Methods:Using UPLC-Q-TOF-MS/MS secondary fragment cleavage information, combined with literature and database, the chemical components of Lanqin Granules were analyzed; the related action targets of Lanqin Granules were obtained by PharmMapper; The related targets of respiratory tract infection were obtained from GeneCards and OMIM databases, and the common targets were selected by intersection with the relevant action targets of Lanqin Granules. The common targets were imported into string database, and the protein interaction data were downloaded and input into Cytoscape 3.7.2 software to obtain hub gene; Go function and KEGG pathway enrichment analysis were carried out on DAVID platform, and chemical components closely related to hub gene were obtained by using the Network Anlyzer plug-in.Results:53 chemical constituents of Lanqin Granules were obtained, including 11 alkaloids, 20 flavonoids, 5 terpenoids, 7 organic esters, 2 amino acids and 8 other compounds. 28 hub genes and 38 related core components were obtained. The results of GO analysis showed that the treatment of respiratory tract infection with Lanqin Granules was related to neutrophil degranulation, negative regulation of apoptosis, protein hydrolysis and other biological processes; extracellular exosomes, cytoplasm, extracellular components and other cellular components; the same protein binding, RNA polymerase Ⅱtranscription factor activity, ligand activated sequence specific DNA binding, protein serine/ threonine/ tyrosine kinase activity and other molecular processes. KEGG analysis results mainly involved cancer pathway, lipid and atherosclerosis, metabolic pathway and other signaling pathways.Conclusion:Lanqin Granules can treat respiratory tract infection through multi-component, multi-target and multi-channel, and play the role of anti-inflammatory, antibacterial and anti-virus.

Foot ulcer prevention plays a crucial role in reducing the amputation rate among diabetic patients. With regard to the prevention of diabetic foot ulcers, the 2023 guidelines of the International Working Group of Diabetic Foot(IWGDF) were different from the 2019 counterpart. The most notable change is the addition of high-level evidence to support recommendations, primarily derived from randomized controlled studies. The 2023 guidelines also advocate for local skin temperature measurement, participation in ankle exercise training, and psychological intervention for foot ulcer prevention. This article conducts a comparative analysis of the two guidelines across six key dimensions: identification of high-risk feet, regular examination of high-risk feet, health education, ensuring appropriate daily footwear, addressing ulcer risk factors, and comprehensive foot care. Drawing from clinical insights, the application and prospective implications of the 2023 guidelines in China are also examined.

Objective: To investigate the effects of after school exercise service (referred to as the "after school ES") on physical health, so as to provide evidence for possible beneficial effect of after school ES. Methods: Students in the fourth grade of primary school were recruited from September 2021 to July 2022 in Changsha City and divided into the control group ( n =220) and the after school ES group ( n =220). The control group only participated in the regular physical education activities of the school. The after school ES group received after school ES for one academic year, 4 times a week, 40-50 minutes per time, for a total of 32 weeks. Body shape indicators such as height, weight and percentage of body fat, as well as physical fitness indicators such as 50 meter running, grip strength and progressive aerobic cardiovascular endurance run (PACER) were measured in September to October 2021 and June to July 2022, respectively. Independent sample t-test, Chi square test and two factors repeated measurement analysis of variance were used for statistical analysis of the data. Results: After one academic year, compared with the control group [(13.52±2.30)kg], muscle mass of primary school students in the after school ES group [(13.76±2.32)kg] significantly increased, while waist to hip ratio [(0.95±0.16)] and percentage of body fat [(20.17±7.43)%] significantly decreased compared to the control group [(1.01±0.21), (22.02±12.34)%]( F=330.70, 6.85, 4.33, P <0.05). The proportion of overweight and obesity in after school ES group decreased significantly from 19.5% to 12.3% ( χ 2=4.35, P <0.05). Compared with the control group, the scores of 50 meter running [(10.00±1.06, 10.21±0.83)s], 1 minute sit up [(33.25±8.24, 30.76±9.34)times], sitting and flexion [(14.53±7.50, 8.59±6.32)cm], 1 minute rope skipping [(125.01±30.50, 115.97±32.09)times], eyes closed and single legged standing [(30.00±34.72, 25.72±23.82)s], selective response time [(635.66±91.72, 652.79±120.42)ms] and VO 2max [(45.31± 1.02 , 43.67±0.85)mL/(kg〖 ·min)] in the after school ES group were significantly improved, with statistical significance ( F= 5.32 , 443.14, 97.23, 814.07, 36.49, 6.11, 396.91, P <0.05). Conclusions After school ES can improve body shape of primary school students, reduce the risk of overweight and obesity and enhance physical fitness. It is recommended that schools should appropriately increase after school ES to promote physical fitness of students.

ObjectiveTo explore the therapeutic effect and mechanism of the Danhe granules on hypercholesterolemia rats by observing the changes in the efficacy indicators and the levels of proteins related to the cholesterol metabolism pathway in the rats under the intervention of Danhe granules. MethodSD rats were randomly assigned to either the blank group or the model group based on their body weight. The blank group had normal chow diets， while the model group was fed high-fat diets for seven weeks. One week after the establishment of the model， the content of the serum total cholesterol （TC） in the model rats was detected. According to the TC value， the model group was further randomly divided into a control group， pravastatin sodium tablet group（4.02 mg·kg^-1）， Xuezhikang capsule group（0.12 g·kg^-1）， high-dose， middle-dose， and low-dose groups of Danhe granules（4.536， 2.268， 1.134 g·kg^-1）. After grouping the model groups， each treatment group received continuous oral gavage for six weeks， with weekly measurements of body weight and food intake （the difference between feed intake and feed surplus）. Six weeks later， the levels of serum TC， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， and high-density lipoprotein cholesterol （HDL-C） were measured. The liver pathology and lipid droplet distribution were evaluated by hematoxylin-eosin （HE） staining and oil red O staining， with scoring and calculation conducted. Rat liver tissue was collected， and western blot and immunohistochemistry （IHC） were used to detect the expression levels of cholesterol metabolism-related proteins namely phosphorylated adenosine 5'-monophosphate （AMP）-activated protein kinase （p-AMPK）， AMPK， 3-hydroxy-3-methyl glutaryl coenzyme A reductase （HMGCR）， low-density lipoprotein receptor （LDLR）， cholesterol 7α-hydroxylase （CYP7A1）， Acyl-coenzyme A： cholesterol acyltransferase 2 （ACAT2）， and apolipoprotein B （ApoB） in hypercholesterolemia rats. ResultCompared with the blank group， the model group showed a significantly higher level of serum TC （P<0.01）. The TG level had no significant change， and the HDL-C level was significantly decreased （P<0.05）. The liver index， steatosis score， total score of pathological state， and the positive area ratio of oil red O staining were significantly increased （P<0.01）， and the protein expression levels of p-AMPK， p-AMPK/AMPK， LDLR， and CYP7A1 were significantly decreased （P<0.05， P<0.01）， while the protein expression levels of AMPK， HMGCR， and ACAT2 were significantly increased （P<0.05， P<0.01）. Compared with the model group， the TC level in each dose group of Danhe granules was significantly decreased （P<0.05）， and the positive area ratio of oil red O staining in the pravastatin sodium tablet group and medium-dose group of Danhe granules was significantly decreased （P<0.05）. In each administration group， the protein expression levels of p-AMPK and p-AMPK/AMPK were significantly increased （P<0.05， P<0.01）， and the levels of HMGCR and ACAT2 were significantly decreased （P<0.01）. The ApoB level showed a downward trend. The CYP7A1 level in the pravastatin sodium tablet group and each dose group of Danhe granules was significantly increased （P<0.05， P<0.01）， and the LDLR level in the pravastatin sodium tablet group， Xuezhikang capsule group， and high-dose and medium-dose groups of Danhe granules was significantly increased （P<0.05， P<0.01）. ConclusionDanhe granules can reduce serum TC levels and improve hepatic steatosis. It may activate AMPK， down-regulate the expression of HMGCR， and inhibit cholesterol synthesis. It can also up-regulate the expression of LDLR and CYP7A1， promote cholesterol uptake and excretion， down-regulate the expression of ACAT2 and ApoB， reduce cholesterol absorption and assembly of LDL and other lipoproteins， and thus play a role in the treatment of hypercholesterolemia.

Objective:To retrospectively analyze the clinical phenotype and pathogenic variants in patients with Progressive myoclonus epilepsy (PME).Methods:Clinical data and results of genetic testing for 11 patients diagnosed with PME at the Department of Neurology, the First Affiliated Hospital of Zhejiang University School of Medicine from June 2017 to December 2022 were collected and analyzed.Results:All of the patients, including 4 males and 7 females, had predominant action myoclonus. Three patients had myoclonus as the initial manifestation, whilst eight were diagnosed through genetic testing, including three cases with NEU1 gene variants, two with EPM2A gene variants (1 was novel), one with MT- TK gene variant, one with ATN1 gene variant, and one with CSTB gene variant. No pathogenic variant was identified in the remaining three cases. Among the eight patients with a genetic diagnosis, three were diagnosed with sialidosis, two with Lafora disease, one with Dentatorubral-pallidoluysian atrophy (DRPLA), one with Unverricht-Lundborg disease (ULD), and one with Myoclonic epilepsy with ragging red fibers (MERRF). Conclusion:Compared with pediatric patients, adult patients with PME represent a distinct subtype with slower progression and milder cognitive impairment.

Objective To analyze the characteristics of time in range(TIR)and its relationship with oxidative stress(OS)and insulin resistance status(HOMA-IR)in patients with type 2 diabetes mellitus(T2DM)and sleep apnea-hypopnea syndrome(OSAHS).Methods According to apnea-hypopnea index(AHI),165 T2DM in patients were divided into simple T2DM group(AHI<5 times/h,n=43),T2DM combine OSAHS mild group(OSAHS-G,5≤AHI<15 times/h,n=51),T2DM combined OSAHS moderate group(OSAHS-M,15≤AHI≤30 times/h,n=40)and T2DM combine OSAHS severe group(OSAHS-S,AHI>30 times/h,n=31).TIR was calculated by dynamic blood glucose monitoring.Superoxide dismutase(SOD),glutathione peroxidase(GSH-Px)and other indexes were detected and analyzed.Results Compared with simple T2DM group,the levels of HOMA-IR,8-iso-PGF2a and Ox-LDL were higher in T2DM combined OSAHS-G,OSAHS-M or OSAHS-S group,while the levels of TIR,SOD and GSH-Px were lower(P<0.05).Pearson correlation analysis showed that TIR was positively correlated with the levels of SOD and GSH-Px(P<0.05 or P<0.01),and negatively correlated with the levels of 8-iso-PGF2a,Ox-LDL,HbA1c,HOMA-IR and the severity of OSAHS(P<0.01).Logistic regression analysis showed that TIR,SOD and GSH-Px were protective factors for severe OSAHS in T2DM patients,while 8-iso-PGE2a and Ox-LDL were the risk factors for severe OSAHS.Conclusions The glucose level fluctuates greatly in patients with T2DM and OSAHS.Insulin resistance and oxidative stress are factors that affect the normalization of TIR.

Fibroblast activation protein inhibitors(FAPI)can specifically bind to fibroblast activation protein,which is highly expressed in tumor stroma,and 68Ga-FAPI do not get involved into the procedure of glucose metabolism in tumor cells.68Ga-FAPI PET/CT and PET/MR can be used for displaying malignant tumors at various sites and play a unique role for diagnosis and differential diagnosis.The research progresses of 68 Ga-FAPI-based PET/CT and PET/MR for diagnosing malignant tumors were reviewed in this article.

The medicinal history of Zanthoxyli Radix is long,and it is recorded in the Shen Nong Ben Cao Jing under the name of Manjiao.Modern pharmacological research has proven that Zanthoxyli Radix has anti-tumor,antibacterial,antioxidant,and hemostatic effects.This article reviewed the pharmacological effects of Zanthoxyli Radix based on its functional indications.Based on the basic requirements of TCM quality markers(Q-markers),this article predicted and analyzed the Q-markers of Zanthoxyli Radix from the perspectives of plant phylogeny and chemical component specificity,chemical component and pharmacological correlation,and chemical component testability.It is proposed to select alkaloids,flavonoids,and lignans as the Q-markers for the general classification of Zanthoxyli Radix.The candidate components for Q-marker were identified,including chloramphenicol,white croaker alkaloid,magnolian alkaloid,taro alkaloid,vanillin,hesperidin,L-sesamin and L-asarone,providing a reference for further research on the quality standards of Zanthoxyli Radix.

Objective:To investigate the expression of anaplastic lymphoma kinase (ALK), tropomyosin receptor kinase (TRK), and recombinant C-Ros oncogene 1, receptor tyrosine kinase (ROS1) in Spitz tumors, and to analyze their associations with clinical and histopathological features of Spitz tumors.Methods:Clinical and histopathological characteristics, as well as follow-up data, were collected from patients with Spitz tumors at Department of Pathology, Hospital of Dermatology, Chinese Academy of Medical Sciences from January 2017 to August 2023, and retrospectively analyzed. Immunohistochemical staining for ALK, pan-TRK, and ROS1 was performed on skin tissues, and associations between the expression of these kinase proteins and clinicopathological features were analyzed.Results:A total of 57 patients with Spitz tumors were collected, including 36 females and 21 males. Immunohistochemical staining showed that 30 (52.6%) patients were positive for ALK, 4 (7.0%) were positive for ROS1, only 2 (3.5%) were positive for TRK, and 21 (36.8%) were negative for the three kinase proteins. Among the 30 ALK-positive patients, the median age was 9.5 years, 21 (70.0%) were females, and 15 (50.0%) presented with lesions on the face, which mainly manifested as papules or nodules; histologically, 29 (96.7%) patients had hypopigmented tumors with an exophytic growth pattern, and the tumor cells were mainly large and long spindle cells arranged in long cord-like, plexiform or fascicular patterns. Among the 4 ROS1-positive patients, there were 3 females and 1 male, presenting with exophytic papules or polyps; histologically, tumor cells were mostly arranged in small nests, without obvious clefts around cell nests. Two TRK-positive patients were both males aged 20 and 50 years respectively, and presented with brown and skin-colored flat papules, respectively; histologically, the tumors were located superficially with a flat base, and tumor cells spread in a pagetoid pattern in the epidermis, with some epithelioid cells and small cell nests. Among the 21 patients negative for the 3 kinase proteins, 9 were males and 12 were females, and they clinically presented with macules, papules and polypoid lesions; histologically, most tumors were located superficially, consisting of a mixture of epithelioid cells and spindle cells, with rare cytological atypia and mitotic figures, and 2 cases showed mild tissue structural and cellular atypia. Fifty-seven patients were followed up for 2 - 83.3 months, with a median follow-up of 19.2 months. Only 1 ALK-positive child experienced a recurrence, and no recurrence or lymph node metastasis was observed in the other cases.Conclusions:Among the three kinase proteins, ALK showed the highest positive rate in Spitz tumors in this study, while TRK- and ROS1-positive cases were sporadic. Histopathologically, ALK-positive Spitz tumor cells were mainly long spindle cells arranged in long cord-like or plexiform patterns, while TRK- and ROS1-positive Spitz tumors tended to have small cell nests. Both the kinase protein-positive and -negative Spitz tumors mostly had a good prognosis.