Traditional treatment for type 1 diabetes mellitus （T1DM） primarily involves insulin replacement， yet some patients encounter issues such as significant blood glucose fluctuations， high risk of hypoglycemia， and weight gain. In recent years， the adjuvant therapeutic role of non-insulin hypoglycemic drugs in T1DM has gradually gained attention. This article reviews the mechanisms of action and clinical research progress of five types of non-insulin hypoglycemic drugs in the treatment of T1DM： amylin analogues （pramlintide）， biguanides （metformin）， sodium-glucose co-transporter 2 inhibitor， dipeptidyl peptidase-4 inhibitor， and glucagon-like peptide-1 receptor agonist. It is found that these drugs can enhance clinical benefits for T1DM patients by improving insulin sensitivity， delaying gastric emptying， promoting urinary glucose excretion， and regulating incretin levels， thereby reducing glycated hemoglobin levels， decreasing insulin dosage， and managing body weight. Simultaneously， these drugs also present limitations such as low patient compliance due to complex dosing regimens， increased risk of diabetic ketoacidosis， and heterogeneity in glycemic control. Future research could focus on developing individualized treatment strategies， combining pharmacogenomics with novel biomarkers to precisely identify subpopulations of patients who may benefit， and delving into the potential value of these drugs in delaying diabetic vascular complications and improving patients’ quality of life.

Parkinson's disease (PD) is a kind of prevalent neurodegenerative disorders characterized by motor symptoms such as bradykinesia, tremor and muscle rigidity, as well as non-motor symptoms such as neuropsychiatric symptoms, autonomic dysfunction and sleep-wake disorders; these symptoms seriously affect the quality of life of patients. The current diagnosis and treatment as well as long-term management still face some deficiencies, such as lack of highly sensitive biomarkers for early diagnosis, relatively subjective clinical comprehensive assessment, individualized treatment strategies mainly formulated based on subjective cognition and clinical experience of physicians, and absence of long-term management data. In recent years, with the rapid development of artificial intelligence (AI), it has demonstrated significant application potential and value in diagnosis, treatment, and long-term management of PD. This article reviews the recent advances of AI in the above-mentioned fields of PD, with the aim of providing references for improving clinical diagnosis, treatment, and long-term management of PD.

Objective To investigate the medication law of Professor Wang Xuefeng in the treatment of transient tic disorders in children using data mining techniques;To clarify clinical thoughts and academic experience in the treatment of this disease.Methods The outpatient medical records of Professor Wang Xuefeng treated children with transient tic disorder in Affiliated Hospital of Liaoning University of Traditional Chinese Medicine from September 2021 to September 2024 were collected,and the prescriptions for patients'first visit were input after screening and sorting.Excel 2019 was used to establish the database.SPSS Modeler 18.0 was used to analyze the association rules of high-frequency drugs.SPSS Statistics 27.0 was used for clustering analysis.Gephi 0.10.1 was used for complex network analysis,and medication law was summarized.Results A total of 223 TCM prescriptions meeting the standard were included,involving 116 kinds of Chinese materia medica,with a total frequency of 3 668,and 30 high-frequency drugs were screened.The properties were mainly cold,neutral,and warm and the tastes were mainly pungent,bitter and sweet.The meridians were mainly liver,lung and heart meridians.The efficacy was mainly for suppressing hyperactive liver for calming endogenous wind,relieving surface and clearing heat;the results of association rules analysis showed that the drug combination with the highest correlation was Paeoniae Radix alba-Glycyrrhizae Radix et Rhizoma Praeparata cum Melle-Acori Tatarinowii Rhizoma;the high-frequency drugs were grouped into 9 categories by clustering analysis;a core drug combination consisting of 10 kinds of highly correlated Chinese materia medica was obtained by complex network analysis.Conclusion Professor Wang Xuefeng believes that transient tic disorders is mainly in the lung and liver,the etiology is due to the wind and phlegm,the pathogenesis is the external pathogens invading the lung,the pathogenic qi is reluctant to leave,the five viscera are disharmonious,the producing phlegm and turbid,the internal and external connection,the wind phlegm consolidation,the flowing meridians,thus causing twitching.It is necessary to take into account the whole process of disease development,with clear medication,fewer tastes,refined prescription and special efficacy.

A 64-year-old male patient with hemophilia A was scheduled for the surgical removal of a pulmonary mass. Preoperative evaluation revealed that the coagulation factor Ⅷ (FⅧ) activity was 0.5%, with an F Ⅷ inhibitor level of 32 BU/ml; the R value could not be detected on the thromboelastogram. Thoracoscopic lobectomy was successfully completed. On the day of the operation and the first day after the operation, 6 mg of recombinant activated coagulation factor Ⅶ (rFⅦa) was intravenously administered every 6 h. On postoperative day 1, the patient’s blood pressure dropped and the HGB gradually declined from 102 g/L to 65 g/L. Chest X-ray revealed a large amount of pleural effusion on the left side, and urgent thoracoscopic thoracic exploration was performed. A total of 3200 mL fresh blood was cleared, and a thoracic drainage tube was placed. On postoperative day 2, the rFⅦa dose was increased to 6 mg, which was intravenously administered every 4 h, and concentrated red cells were intermittently infused to correct anemia. Four days later, due to the inability to obtain rFⅦa, PCC (50 IU/kg every 8 hours) was administered. Additionally, treatment with methylprednisolone (40 mg/d) and cyclophosphamide (200 mg, every 2 weeks) was initiated to remove FⅧ inhibitors. The thoracic drainage tube was removed on postoperative day 9, and the patient was successfully discharged 3 weeks later.

Objective To investigate the correlation between the eosinophil percentage and prognosis in patients with sepsis after intensive care unit(ICU)admission.Methods A retrospec-tive cohort study design was employed,data from adult patients with sepsis or septic shock who were hospitalized for the first time and admitted to the ICU for the first time from the MIMIC-Ⅳ database(version 2.2)were selected.Patients were grouped according to differed eosinophil percentage(＜0.4％and≥0.4％),and the correlation between eosinophil percentage＜0.4％and prognostic out-comes was analyzed.Results A total of 616 patients were included.On the first day after ICU ad-mission,an eosinophil percentage＜0.4％was not significantly associated with prognosis;on the sec-ond day after ICU admission,patients with an eosinophil percentage＜0.4％exhibited a significantly increased 28-day mortality rate(HR=1.572,95％CI,1.119 to 2.208)and in-hospital mortality rate(HR=1.634,95％CI,1.137 to 2.349);on the third day after ICU admission,patients with an eosinophil percentage＜0.4％demonstrated significantly increased 28-day mortality rate(HR=2.072,95％CI,1.482 to 2.896),ICU mortality rate(HR=2.033,95％CI,1.296 to 3.188),and in-hospital mortality rate(HR=2.193,95％CI,1.533 to 3.136).Patients with eosinophil percentages＜0.4％on both the second day and the third day after ICU admission had the worst prog-nosis,with a significantly increased 28-day mortality rate(HR=2.271,95％CI,1.393 to 3.785).Conclusion The eosinophil percentages on the second day and the third day after ICU admission in patients with sepsis are closely correlated with prognosis,particularly aneosinophil percentage＜0.4％on the third day,which is significantly associated with a higher mortality rate.

Long-term hypertension causes excessive vascular remodeling and leads to adverse cardiovascular events. Balance of ubiquitination and deubiquitination has been linked to several chronic conditions, including pathological vascular remodeling. In this study, we discovered that the expression of ubiquitin-specific protease 25 (USP25) is significantly up-regulated in angiotensin II (Ang II)-challenged mouse aorta. Knockout of Usp25 augments Ang II-induced vascular injury such as fibrosis and endothelial to mesenchymal transition (EndMT). Mechanistically, we found that USP25 interacts directly with Forkhead box O3 (FOXO3) and removes the K63-linked ubiquitin chain on the K258 site of FOXO3. We also showed that this USP25-mediated deubiquitination of FOXO3 increases its binding to light chain 3 beta isoform and autophagosomic-lysosomal degradation of FOXO3. In addition, we further validated the biological function of USP25 by overexpressing USP25 in the mouse aorta with AAV9 vectors. Our studies identified FOXO3 as a new substrate of USP25 and showed that USP25 may be a potential therapeutic target for excessive vascular remodeling-associated diseases.

This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*

Objective To explore the time-varying pattern of potential symptoms in breast cancer patient before and after chemotherapy,and further analyze its influencing factors,aims to provide reference for clinical nursing practice.Methods 233 cases of breast cancer in a tertiary A hospital in Ningxia from June to October,2023 were selected as the research subjects.By the general information questionnaire and the Chinese version of Anderson Symptom Assessment Scale,the potential change of symptoms of breast cancer patients undergoing chemotherapy 1-3 days before the first chemotherapy(T1,233 cases)and 7-14 days after the third or fourth chemotherapy(T2,225 cases)was analyzed.Results 225 cases of breast cancer patients completed 2 surveys,and their symptom characteristics before and after chemotherapy can be divided into 2 categories:a high symptom troubled group and a low symptom troubled group.The high-symptom troubled group has strong stability,and the probability of maintaining the original group is 85.20％,while the low-symptom troubled group is more inclined to change to the high-symptom troubled group,and the transition probability is 26.60％.Logistic regression analysis showed that the mass was located on the left side,and the patients who obtained disease knowledge mainly through the Internet were more likely to change from the high symptom troubled group to the low symptom troubled group,while the patients who were employed,with unsatisfactory sleep at night,and never exercised were more likely to change from the low symptom troubled group to the high symptom troubled group.Conclusion The symptoms of breast cancer patients before and after chemotherapy are heterogeneous.Patients who are on the job,have unsatisfied sleep at night and never exercise are more likely to change from the low-symptom troubled group to the high-symptom troubled group,which suggests that medical staff should identify potential high-risk groups at an early stage,and make full use of the predictive function of symptom characteristics to carry out individualized management based on the dynamic monitoring of symptoms according to different types of population characteristics,so as to reduce the burden of symptoms and improve their quality of life.

OBJECTIVE To explore the effect and mechanism of Zhiqiao gancao decoction （ZQGCD） on pathological angiogenesis of degenerative intervertebral disc. METHODS The rats were randomly divided into sham operation group （normal saline）， model group （normal saline）， hypoxia inducible factor-1α （HIF-1α） inhibitor （YC-1） group [2 mg/（kg·d）， tail vein injection]， and ZQGCD low-dose， medium-dose and high-dose groups [3.06， 6.12， 12.24 g/（kg·d）]， with 8 rats in each group. Except for sham operation group， lumbar disc degeneration model of rat was constructed in all other groups. After modeling， they were given relevant medicine once a day， for consecutive 3 weeks. After the last medication， pathological changes and angiogenesis of the intervertebral disc tissue in rats were observed； the levels of inflammatory factors [interleukin-1β （IL-1β）， IL-6， tumor necrosis factor-α （TNF-α）] and the expressions of angiogenesis-related proteins [HIF-1α， vascular endothelial growth factor （VEGF）， VEGF receptor 2 （VEGFR2）， angiotensin 1（Ang 1）， Ang 2] in the com intervertebral disc tissue in rats were all determined. In cell experiment， the primary nucleus pulposus cells were isolated and cultured from rats， and cellular degeneration was induced using 50 ng/mL TNF-α. The cells were divided into blank control group （10% blank control serum）， TNF-α group （10% blank control serum）， YC-1 group （10% blank control serum+0.2 mmol/L YC-1）， and 5%， 10%， 15% drug-containing serum group （5%， 10%， 15% drug-containing serum）. After 24 hours of intervention， the nucleus pulposus cells were co-cultured with HUVEC. The expressions of Collagen Ⅱ， matrix metalloproteinase-3 （MMP-3） in nucleus pulposus cells were detected. HUVEC proliferation， migration and tube forming ability were detected， and the expression levels of the HIF-1α/VEGF/Ang signal axis and angiogenesis- related proteins （add MMP-2， MMP-9） in HUVEC were detected. RESULTS Animal experiments had shown that compared with model group， the positive expression of CD31 in the intervertebral disc tissues of rats in each drug group was down-regulated （P＜ 0.05）， the levels of inflammatory factors and angiogenesis-related proteins were decreased significantly （P＜0.05）， and the pathological changes in the intervertebral disc were alleviated. Cell experiments had shown that compared with TNF-α group， the expression of Collagen Ⅱ in nucleus pulposus cells of all drug groups was significantly up-regulated （P＜0.05）， and the expression of MMP-3 was significantly down-regulated （P＜0.05）； the proliferation， migration and tubulogenesis of HUVEC were significantly weakened （P＜0.05）. The mRNA and protein expressions of HIF-1α， VEGF， Ang 2 as well as the expression of angiogenesis-related proteins （except for the expression of Ang 2 mRNA and HIF-1α， VEGFR2， Ang 2 protein in 5% drug- containing serum group） were significantly down-regulated （P＜0.05）. CONCLUSIONS ZQGCD may inhibit the HIF-1α/VEGF/ Ang signal axis to weaken the angiogenic ability of vascular endothelial cells， improve pathological angiogenesis in the intervertebral disc， and delay the degeneration of the intervertebral disc.

Objective:To explore the genotype and the clinical phenotype of SCN2A-related developmental delay in children. Methods:A case series study was adopted. Collect clinical data from 10 cases of children with SCN2A gene variants diagnosed with global developmental delay/intellectual disability who were admitted to the Children′s Hospital between July 2019 and March 2023. Summarize the clinical phenotype and genotype based on clinical data such as general information, clinical manifestations, imaging examinations, laboratory tests, genetic testing results, and comprehensive pediatric neuropsychological development assessment. Results:A total of 10 patients were recruited, including 7 males and 3 females, with an age range of 27 days to 5 years and 9 months. 9 patients underwent children′s neuropsychological and behavioral assessments, and the results were consistent with global developmental delay, including 2 mild cases, 4 moderate cases, and 3 severe cases. 3 cases had autism spectrum disorder, and 2 cases had epilepsy. 6 patients underwent complete head MRI examination, and 4 of them showed abnormalities, including delayed myelination, widening of the local extra brain space in the frontal lobe, and abnormal frontal lobe morphology. All 10 cases had point variants. Among them, 9 cases are de novo and 1 case is maternal inheritance. Out of 10 cases, there were 5 cases with copy number variations, but all of them were of unknown significance. Among the 10 variants, 8 have been reported and 2 have not been reported, namely c.4145A>T(p.N1382I) and c.4937T>A(p.I1646N). In this study, 4 out of 10 patients with SCN2A variants had variation sites located in the S4 segment of domain which constitute Nav1.2, the sodium ion channel encoded by SCN2A. The developmental quotient level was lower when the variation sites were located in the S4 segment of domain, and the difference was statistically significant ( t=-3.101, P=0.017), indicating that the severity of developmental delay may be related to the localization of amino acids corresponding to variant sites within the protein domain. Conclusion:SCN2A mutations are strongly associated with diverse neurodevelopmental disorders. In this study, the phenotypic spectrum of SCN2A variants encompassed epilepsy, global developmental delay, and autism spectrum disorder. Affected individuals exhibited early-onset developmental delays, predominantly moderate to severe in severity. Voltage-sensing domain dysfunction in sodium channels may constitute a critical pathomechanism underlying neurodevelopmental impairments. Further electrophysiological characterization and molecular mechanistic studies are warranted todelineate the genotype-phenotype correlations between specific variant loci and clinical severity.