OBJECTIVE To provide a reference for the pharmaceutical care of a patient with type 2 diabetes mellitus （T2DM） and limb-girdle muscular dystrophy （LGMD） who developed euglycemic diabetic ketoacidosis （euDKA） after taking empagliflozin. METHODS Clinical pharmacists provided pharmaceutical care for a patient with T2DM and LGMD who developed euDKA after taking empagliflozin. According to the patient’s recent use of medications and his conditions， clinical pharmacists assessed the correlation between euDKA and empagliflozin as “very likely”. As to euDKA， clinical pharmacists suggested discontinuing empagliflozin and metformin， and giving intravenous infusion of 10% Glucose injection instead of 5% Glucose injection for fluid resuscitation. Clinical pharmacists monitored the patient’s laboratory indicators such as arterial blood gas analysis， blood/urine ketones and electrolytes. They assisted physicians to decide when to stop intravenous supplements of liquid and insulin. Clinical pharmacists also assisted physicians to adjust the antidiabetic drugs and educated the patient to avoid empagliflozin or other sodium- glucose linked transporter 2 inhibitors （SGLT2i）. RESULTS Physicians adopted the suggestions of clinical pharmacists. After treatment， the patient’s condition improved， and he was allowed to be discharged with medication. CONCLUSIONS euDKA is a relatively rare and serious adverse reaction associated with SGLT2i， and the patients with LGMD are susceptible to euDKA. Clinical pharmacists assist physicians in developing personalized medication plans by evaluating the association between euDKA and empagliflozin， adjusting medication regimens，conducting pharmaceutical monitoring，and other pharmaceutical services. Meanwhile， they provide medication education to patients to ensure their medication safety.

OBJECTIVE To provide a reference for the pharmaceutical care of a patient with type 2 diabetes mellitus （T2DM） and limb-girdle muscular dystrophy （LGMD） who developed euglycemic diabetic ketoacidosis （euDKA） after taking empagliflozin. METHODS Clinical pharmacists provided pharmaceutical care for a patient with T2DM and LGMD who developed euDKA after taking empagliflozin. According to the patient’s recent use of medications and his conditions， clinical pharmacists assessed the correlation between euDKA and empagliflozin as “very likely”. As to euDKA， clinical pharmacists suggested discontinuing empagliflozin and metformin， and giving intravenous infusion of 10% Glucose injection instead of 5% Glucose injection for fluid resuscitation. Clinical pharmacists monitored the patient’s laboratory indicators such as arterial blood gas analysis， blood/urine ketones and electrolytes. They assisted physicians to decide when to stop intravenous supplements of liquid and insulin. Clinical pharmacists also assisted physicians to adjust the antidiabetic drugs and educated the patient to avoid empagliflozin or other sodium- glucose linked transporter 2 inhibitors （SGLT2i）. RESULTS Physicians adopted the suggestions of clinical pharmacists. After treatment， the patient’s condition improved， and he was allowed to be discharged with medication. CONCLUSIONS euDKA is a relatively rare and serious adverse reaction associated with SGLT2i， and the patients with LGMD are susceptible to euDKA. Clinical pharmacists assist physicians in developing personalized medication plans by evaluating the association between euDKA and empagliflozin， adjusting medication regimens，conducting pharmaceutical monitoring，and other pharmaceutical services. Meanwhile， they provide medication education to patients to ensure their medication safety.

Depression is a common mental disorder in clinical practice， and it falls under the category of depression syndrome in traditional Chinese medicine （TCM）. In TCM， Qi depression is considered as the root cause of all depression syndromes. Qi depression can lead to blood stasis， which is a key cause of diseases due to depression syndrome. Therefore， treating stasis is an important therapeutic approach for depression syndrome. Salviae Miltiorrhizae Radix et Rhizoma， a representative herbal medicine for activating blood and removing stasis， is effective in activating blood， removing stasis， dredging meridians， and alleviating pain. Currently， it is primarily used in clinical practice to treat cardiovascular and cerebrovascular diseases， such as neurasthenia， coronary heart disease， insomnia， and palpitations. The active components of Salviae Miltiorrhizae Radix et Rhizoma are complex and exhibit a variety of pharmacological effects. These components include water-soluble salvianolic acids and lipid-soluble tanshinones. Modern pharmacological studies have proven that Salviae Miltiorrhizae Radix et Rhizoma and its active components possess antioxidant， anti-inflammatory， anti-tumor， anti-fibrosis， and neuroprotective properties. In recent years， increasing attention has been paid to the pharmacological effects and mechanisms of Salviae Miltiorrhizae Radix et Rhizoma and its active components in treating depression. This paper systematically reviews the antidepressant mechanisms of Salviae Miltiorrhizae Radix et Rhizoma and its main active components from the regulation of monoamine neurotransmitters， the hypothalamic-pituitary-adrenal axis， neurotrophic factors， and neuroinflammation. In addition， this paper summarizes the clinical applications of the prescriptions containing Salviae Miltiorrhizae Radix et Rhizoma in the treatment of depression， providing new insights for further research on the pharmacological mechanisms of Salviae Miltiorrhizae Radix et Rhizoma in treating depression.

Objective To analyze the spatial and temporal distribution characteristics of hand-foot-mouth disease (HFMD) in Zibo City, to explore the key incidence areas, and to find a suitable prediction model, so as to provide reference for the prevention and control of HFMD. Methods The spatiotemporal clustering characteristics of HFMD in Zibo City from 2018 to 2023 were analyzed by using SaTScan 10.0.2 software and ArcGIS 10.7 software. A combination model of ARIMA and SVM was established, and the prediction results were verified and compared. Results Spatial clustering analysis showed that there was spatial clustering of the incidence of HFMD in various townships of Zibo City from 2020 to 2022. The high-high clustering areas and Getis-Ord hot spot areas were mainly concentrated in some main urban areas of Zhangdian District, Zichuan District, and Huantai County. A total of 2-5 aggregation areas were detected by spatiotemporal scanning analysis. The first-type aggregation areas were mainly concentrated in the towns of Zhangdian District, Huantai County, Linzi District, Zhoucun District and Gaoxin District. The aggregation months were July, August, September and November. The model prediction results showed that the ARIMA-SVM combined model was more accurate than the traditional ARIMA model. Conclusion There is a spatiotemporal clustering of hand-foot-mouth disease in Zibo City. The ARIMA-SVM combined model can be used to predict the incidence of hand-foot-mouth disease in Zibo City, and to strengthen health education and disease monitoring in high-risk areas and populations during the epidemic months.

AIM: To analyze the reasons and clinical outcomes of intraocular lens(IOL)exchange.METHODS:This retrospective case series study included 47 patients(53 eyes)who underwent IOL exchange surgery at the Department of Ophthalmology, the First Affiliated Hospital of Zhengzhou University, between April 2020 and May 2024, aged from 5 to 87(44.8±3.6)years old. Patients' demographics, surgical indications, surgical techniques, preoperative and postoperative uncorrected visual acuity(UCVA)and best-corrected visual acuity(BCVA), as well as postoperative complications were recorded.RESULTS:The reasons for IOL exchange included refractive error(18 cases, 23 eyes, 43%), IOL dislocation(12 cases, 13 eyes, 25%), IOL opacification(12 cases, 12 eyes, 23%), neuroadaptation failure(3 cases, 3 eyes, 6%), and patient dissatisfaction with visual quality(2 cases, 2 eyes, 4%). The surgical techniques for IOL exchange included in-the-bag IOL fixation(16 eyes, 30%), ciliary sulcus fixation(27 eyes, 51%), and scleral suture fixation(10 eyes, 19%). There was statistical significant difference between preoperative UCVA(LogMAR)and UCVA(LogMAR)at 1 d postoperatively(1.03±0.64 vs 0.50±0.46, P<0.05), and there was statistical significant difference between preoperative BCVA(LogMAR)and BCVA(LogMAR)at 1 mo postoperatively(0.41±0.37 vs 0.17±0.21, P<0.05). Postoperative complications included posterior capsule opacification in 2 eyes and IOL dislocation in 1 eye.CONCLUSION:Refractive error, IOL dislocation, and IOL opacification were the three most common reasons for IOL exchange. Although less frequent, factors such as neuroadaptation issues associated with multifocal IOLs and patient-reported visual quality dissatisfaction reflect growing expectations for improved visual outcomes. IOL exchange surgery, though technically challenging, demonstrates favorable clinical efficacy and a low complication rate, representing an effective intervention for managing postoperative IOL-related issues following cataract surgery.

Spermatogenesis is a fundamental process that requires a tightly controlled epigenetic event in spermatogonial stem cells (SSCs). The mechanisms underlying the transition from SSCs to sperm are largely unknown. Most studies utilize gene knockout mice to explain the mechanisms. However, the production of genetically engineered mice is costly and time-consuming. In this study, we presented a convenient research strategy using an RNA interference (RNAi) and testicular transplantation approach. Histone H3 lysine 9 (H3K9) methylation was dynamically regulated during spermatogenesis. As Jumonji domain-containing protein 1A (JMJD1A) and Jumonji domain-containing protein 2C (JMJD2C) demethylases catalyze histone H3 lysine 9 dimethylation (H3K9me2), we firstly analyzed the expression profile of the two demethylases and then investigated their function. Using the convenient research strategy, we showed that normal spermatogenesis is disrupted due to the downregulated expression of both demethylases. These results suggest that this strategy might be a simple and alternative approach for analyzing spermatogenesis relative to the gene knockout mice strategy.
Spermatogenesis/physiology* ; Animals ; Male ; Mice ; Epigenesis, Genetic ; Jumonji Domain-Containing Histone Demethylases/metabolism* ; Histones/metabolism* ; RNA Interference ; Testis/metabolism* ; Methylation ; Mice, Knockout ; Histone Demethylases

OBJECTIVES: To elucidate the underlying mechanisms of macrophage-mediated inflammation and tissue injury in diabetic foot ulcer (DFU). METHODS: Skin tissue samples were collected from patients with DFU and with non-DFU. A total of 79 272 high-quality cell transcriptomes were obtained using single-cell RNA sequencing. An unbiased clustering approach was employed to identify cell subpopulations. Seurat functions were used to identify differentially expressed genes between DFU and non-DFU groups, and gene ontology (GO) enrichment analysis was used to reveal gene function. Furthermore, cell-cell communication network construction and ligand-receptor interaction analysis were performed to reveal the mechanisms underlying cellular interactions and signaling regulation in the DFU microenvironment from multiple perspectives. RESULTS: The results revealed a significant expansion of myeloid cells in DFU tissues, alongside a marked reduction in structural cells such as endothelial cells, epithelial cells, and smooth muscle cells. Major cell types underwent functional reprogramming, characterized by immune activation and impaired tissue remodeling. Specifically, macrophages in DFU skin tissues exhibited a shift toward a pro-inflammatory M1 phenotype, with upregulation of genes associated with inflammation and oxidative stress. Cell communication analysis further demonstrated that M1 macrophages served as both primary signal receivers and influencers in the COMPLEMENT pathway mediated communication network, and as key signal senders and mediators in the secreted phosphoprotein 1 (SPP1) pathway mediated communication network, actively shaping the inflammatory microenvironment. Key ligand-receptor interactions driving macrophage signaling were identified, including C3-(ITGAM+ITGB2) and SPP1-CD44. CONCLUSIONS This study establishes a comprehensive single-cell atlas of DFU, revealing the role of macrophage-driven cellular networks in chronic inflammation and impaired healing. These findings may offer potential novel therapeutic targets for DFU treatment.
Humans ; Macrophages/immunology* ; Diabetic Foot/pathology* ; Single-Cell Analysis ; Transcriptome ; Gene Expression Profiling ; Inflammation ; Skin ; Cell Communication ; Signal Transduction ; Cellular Reprogramming

OBJECTIVE To investigate the impact of evodiamine on the proliferation， migration and invasion abilities of trophoblastic cells induced by high glucose and its potential mechanism based on advanced glycation end products （AGE）/receptor for advanced glycation end products （RAGE） signaling pathway. METHODS Human trophoblastic cells HTR-8/SVneo were divided into control group， high glucose group， evodiamine low-dose group （2 μmol/L）， evodiamine high-dose group （4 μmol/L）， pc-NC group （transfected with pc-NC plasmid+4 μmol/L evodiamine）， and pc-RAGE group （transfected with pc-RAGE plasmid+ 4 μmol/L evodiamine）. Cells in all groups except for the control group were cultured in a high sugar （25 mmol/L glucose） environment， and cells in all groups except for the control group and the model group were transfected with the corresponding plasmids and/or received the corresponding drug interventions. The survival rate， apoptotic rate， scratch healing rate， and invasion number， as well as the protein and mRNA expressions of AGE， RAGE， nuclear factor- κB p65 （NF- κB p65）， matrix metalloproteinase-2 （MMP-2）， and MMP-9 were examined in each group. RESULTS Compared with the control group， the cell survival rate， scratch healing rate， invasions number， and the mRNA and protein expressions of MMP-2 and MMP-9 in the high glucose group significantly decreased （P＜0.05）， while the apoptotic rate， the mRNA and protein expressions of AGE and RAGE， the mRNA expression of NF-κB p65， and the phosphorylation level of NF-κB p65 protein significantly increased （P＜0.05）； compared with the high glucose group， the above indexes of cells in evodiamine low-dose and high-dose groups were significantly improved， and the effect of the high-dose group was significantly better than that of the low-dose group （P＜0.05）； overexpression of RAGE attenuated the ameliorative effect of evodiamine onthe above indexes in high glucose-induced trophoblast cells （except for AGE mRNA and protein） （P＜0.05）. CONCLUSIONS Evodiamine can promote the proliferation， migration and invasion of high glucose-induced trophoblast cells and ameliorate their functional impairment， and the above effects are associated with the inhibition of the AGE/RAGE signaling pathway.

Objective: To compare the effects of aerobic exercise, resistance training, and a combination of aerobic exercise and resistance training (combined exercise) with dietary restrictions on inflammatory factors and gut microbiota in obese children, so as to provide the reference for improving the health level of obese children. Methods: From August to September 2022, a total of 70 obese children aged 10-12 from the Affiliated Experimental Primary School of Minjiang Normal University were recruited through online notifications and WeChat distribution through parent groups. Participants were divided into dietary restriction (DR, n=18) group, aerobic exercise combined with dietary restriction (AE+DR, n=18) group, resistance training combined with dietary restriction (RT+DR, n=17) group and combined exercise combined with dietary restriction (ART+DR, n=17) group,through random number table method. From September to November 2022, each group received different interventions.The daily dietary intake of calories in the DR group was determined according to resting energy consumption. The AE+DR group intervention mainly included skipping rope, aerobics exercises, jogging and sports games, and were maintained for each session lasting 50 minutes. For RT+DR group, the exercise intensity of resistance training was (65%-85%) maximum strength, with a total of 10 actions. The ART+DR group included resistance training (20 minutes), aerobic exercise (20 minutes), preparation and relaxation phases for 5 minutes each. The DR and exercise intervention was administered for 8 weeks (4 times a week for Monday, Tuesday, Thursday and Friday). Before and after different intervention methods, serum inflammatory factors were detected by enzymelinked immunosorbent assay (ELISA) and intestinal flora was calculated by plate colony counting method. Results: Compared to those before intervention, the levels of serum TNF-α, IL-6 and CRP, and the contents of enterococcus and escherichia coli in the faeces significantly decreased, while the contents of lactobacillus and bifidobacterium in the faeces significantly increased after intervention (t=7.19，7.15，4.57，5.42，5.15，-3.51，-7.30；5.14，3.64，3.02，3.27，5.00，-3.09，-3.75；7.10，10.86，7.74，10.92，9.26，-6.63，-6.33，P<0.05) in AE+DR, RT+DR and ART+DR groups. The levels of serum TNF-α and CRP and enterococcus decreased significantly, and the contents of lactobacillus and bifidobacterium in the faeces increased significantly after intervention (t=2.74, 2.22, 2.14, -2.21, -2.81, P<0.05) in the DR Group. After 8 weeks of intervention with different methods, the change differences of enterococcus, escherichia coli, lactobacillus, bifidobacterium in the faeces, and serum TNF-α, IL-6 and CRP levels were statistically significantin the four groups of obese children (H=22.22, 23.75, 13.44, 28.33, 18.02, 33.64, 25.14, P<0.01). In addition, the decreases of enterococcus in the faeces and serum TNF-α, IL-6, CRP levels, and the increases of lactobacillus in the faeces were significantly higher than those in the other three groups. Conclusions Dietary restriction alone or combined with different exercises bring beneficial changes in the inflammatory factors and gut microbiota indicators in obese children. Combined exercise,as well as aerobic exercise combined with dietary restrictions are more reasonable and effective in obese children.