ObjectiveTo decipher the mechanism by which Zuoguiwan （ZGW） treat hyperthyroidism in rats with kidney-Yin deficiency based on the dopamine receptor D4 （DRD4）/nicotinamide adenine dinucleotide phosphate （NADPH） oxidase 4 （NOX4） signaling pathway. MethodsThe rat model of kidney-Yin deficiency was induced by unilateral intramuscular injection of dexamethasone （0.35 mg·kg^-1）. After successful modeling， the rats were randomized into model， methimazole （positive control， 5 mg·kg^-1）， low-， medium-， and high-dose （1.85， 3.70， 7.40 g·kg^-1， respectively） ZGW， and normal control groups. After 21 days of continuous gavage， the behavioral indexes and body weight changes of rats were evaluated. The pathological changes of the renal tissue were observed by hematoxylin-eosin staining. The serum levels of thyroid hormones ［triiodothyronine （T₃）， thyroxine （T₄）， thyroid-stimulating hormone （TSH）］， renal function indexes ［serum creatine （Scr） and blood urea nitrogen （BUN）］， energy metabolism markers ［cyclic adenosine monophosphate （cAMP） and cyclic guanosine monophosphate （cGMP）］， and oxidative stress-related factors ［superoxide dismutase （SOD）， malondialdehyde （MDA）， and NADPH）］ were measured by enzyme-linked immunosorbent assay （ELISA）. Western blot was employed to analyze the expression of DRD4， NOX4， mitochondrial respiratory chain complex proteins ［NADH：ubiquinone oxidoreductase subunit S4 （NDUFS4） and cytochrome C oxidase subunit 4 （COX4）］， and inflammation-related protein ［tumor necrosis factor-alpha （TNF-α）， interleukin-6 （IL-6）， p38 mitogen-activated protein kinase （MAPK）］ pathway in the renal tissue. ResultsCompared with the normal group， the model group showed mental malaise， body weight decreases （P<0.01）， inflammatory cell infiltration in the renal tissue， a few residual parotid glands in the thyroid， elevations in serum levels of T₃， T₄， Scr， BUN， cAMP， cAMP/cGMP， MDA， and NADPH （P<0.01）， down-regulation in protein levels of TSH， SOD， and DRD4 （P<0.05， P<0.01）， and up-regulation in expression of NOX4， p-p38 MAPK/p38 MAPK， and inflammatory factors （P<0.01）. Compared with the model group， ZGW increased the body weight （P<0.05， P<0.01）， reduced the infiltration of renal interstitial inflammatory cells， restored the thyroid structure and follicle size， lowered the serum levels of T₃， T₄， Scr， BUN， cAMP， cAMP/cGMP， MDA and NADPH （P<0.05， P<0.01）， up-regulated the expression of TSH， SOD and DRD4 （P<0.05， P<0.01）， and down-regulated the expression of NOX4， p-p38 MAPK/p38 MAPK， and inflammatory factors （P<0.05， P<0.01）. Moreover， high-dose ZGW outperformed methimazole （P<0.05）. ConclusionBy activating DRD4， ZGW can inhibit the expression of NOX4 mediated by the p38 MAPK pathway， reduce oxidative stress and inflammatory response， thereby ameliorating the pathological state of hyperthyroidism due to kidney-Yin deficiency. This study provides new molecular mechanism support for the clinical application of ZGW.

Objective: To investigate the distribution frequency and molecular mechanism of the rare blood type Lu(a-b-) in Shenzhen, and to compare the polymorphisms of the Lutheran blood group system encoding gene LU and the In (Lu) phenotype-related gene KLF1 among Han Chinese, Indian, and Uyghur populations in Xinjiang. Methods: Serological methods were used to screen the Lu(a-b-) phenotype of blood donors in Shenzhen. Third-generation sequencing was employed to sequence the full-length of the LU and KLF1 genes in Lu (a-b-) phenotype samples as well as the samples from the Han Chinese, Indians, and Uyghur population, followed by analysis of gene haplotypes frequencies. Results: Ten individuals with the Lu(a-b-) phenotype were screened out of 14 367 blood donors in Shenzhen, yielding a frequency of approximately 0.07%. Only 2 cases showed mutations in the coding region of the LU gene, while all individuals showed heterozygous mutations in the coding region of the KLF1 gene. The highest mutation frequencies of the LU and KLF1 genes were observed in the Uyghur population in Xinjiang and the Han Chinese in Shenzhen, respectively. Conclusion: All Lu(a-b-) phenotypes are of the In (Lu) type, and their formation mechanism is mainly related to KLF1 gene mutations. Both the LU and KLF1 genes exhibit significant polymorphism in the Han Chinese, Indians, and Uyghur populations.

BackgroundAnxiety exhibits a rising prevalence among college students. Investigating the mechanisms through which family function relates to anxiety and examining the moderating role of emotion regulation strategies within this context hold substantial implications for promoting mental health among college students. However， existing research has not sufficiently elucidated the complex interplay among family function， emotion regulation， and anxiety among college students. Further research is warranted to clarify the underlying mechanisms linking family function to anxiety outcomes and to examine the potential moderating role of emotion regulation strategies in this causal pathway. ObjectiveTo explore the relationship between family function and anxiety among lower-grade college students， and to validate the moderating role of emotion regulation strategies in this relationship， thereby offering evidence-based insights for anxiety reduction interventions in this population. MethodsIn March 2023， a total of 1 980 first- and second-year students from a comprehensive university in Shanghai were selected using the cluster sampling method. A self-designed demographic questionnaire， the Emotion Regulation Questionnaire （ERQ）， the Family Adaptability and Cohesion Evaluation Scale Ⅱ-Chinese Version （FACES Ⅱ-CV）， and the Symptom Checklist-90 （SCL-90） were utilized for assessment. Pearson correlation analysis and Spearman correlation analysis were employed to test the correlations of each variable. Hierarchical linear regression analysis was conducted to certify the moderating role of emotion regulation strategies in the relationship between family function and anxiety. ResultsCompared with female students， male students scored significantly lower on ERQ cognitive reappraisal （t=-5.793， P<0.01） but significantly higher on ERQ expressive suppression （t=8.359， P<0.01）. For lower-grade college students， scores on adaptability and cohesion subscales of FACES Ⅱ-CV showed a positive association with cognitive reappraisal in ERQ （r=0.251， 0.302， P<0.01）， while simultaneously displaying negative correlations with both expressive suppression in ERQ （r=-0.113， -0.154， P<0.01） and anxiety in SCL-90 （r=-0.243， -0.202， P<0.01）. Notably， anxiety scores in SCL-90 were inversely related to cognitive reappraisal scores in ERQ （r=-0.159， P<0.01） but directly associated with expressive suppression scores in ERQ （r=0.171， P<0.01）. Hierarchical regression analysis indicated that cognitive reappraisal significantly moderated the relationship between family cohesion and anxiety （β=-0.421， P<0.01）. ConclusionThe cognitive reappraisal strategy serves as a moderator in the relationship between family cohesion and anxiety， potentially mitigating the escalation of anxiety levels associated with family dysfunction. ［Funded by Science and Technology Development Fund of Shanghai Pudong New Area （number， PKJ2023-Y21）］

Objective To analyze the effect of releasing the lower pulmonary ligament on right residual lung expansion after right upper lobe resection under different body mass index (BMI) levels. Methods The clinical data of patients who underwent thoracoscopic right upper lobe resection in the First Affiliated Hospital with Nanjing Medical University from 2021 to 2022 were retrospectively analyzed. Patients were divided into a group A (17 kg/m2＜BMI≤23 kg/m2), a group B (23 kg/m2＜BMI≤29 kg/m2) and a group C (BMI＞29 kg/m2) according to BMI. The presence of residual cavity was judged by chest X-ray at 7-10 days after operation, the degree of compensation change of the right main bronchus angle was measured, and the changes in lung volume were determined by CT three-dimensional reconstruction. Results A total of 157 patients who underwent thoracoscopic right upper lobe resection were included, including 71 males and 86 females, with an average age of (59.7±11.2) years. There were 50 patients in the group A, 75 patients in the group B, and 32 patients in the group C. In the group A, compared with those without releasing the lower pulmonary ligament, patients with releasing had a lower incidence of postoperative residual cavity (P=0.016), greater changes in bronchus angle (P<0.001), and smaller changes in lung volume (P<0.001). In the group B and C, there was no significant effect of releasing the lower pulmonary ligament on postoperative residual cavity, bronchus angle, and lung volume changes (P>0.05). Conclusion For patients with thin and long body shape and low BMI, releasing the lower pulmonary ligament is helpful to promote the expansion of the residual lung after right upper lobe resection and reduce the occurrence of postoperative residual cavity in patients.

ObjectiveTo investigate the protective effect of α-ketoglutarate （α-KG） on hepatic lipid deposition in offspring caused by arsenic exposure during pregnancy. Methods8-week-old institute of cancer research （ICR） mice were mated in a ratio of 2∶1 between females and males， and the detection of vaginal plugs confirmed pregnant. A total of 32 pregnant mice were randomly divided into four groups： control group， arsenic group， α-KG group， arsenic+α-KG group. On gestational day 0-16 （GD0-GD16）， the arsenic and arsenic+α-KG groups were exposed to sodium arsenite （NaAsO₂ ，15 mg/L） in drinking water everyday， and the α-KG and arsenic+α-KG groups were gavaged with α-KG （2 g/kg） everyday. On GD16， pregnant mice were euthanized to collect fetal liver， and fetal body weight and crown-rump length were measured. Gene expression differences between the control group and the arsenic group were analyzed by transcriptome. The total triglycerides （TGs） and subtypes in fetal liver were detected by liquid chromatography tandem mass spectrometry （LC-MS/MS）. Oil red O staining was used to observe the histopathological changes in the liver. Quantitative polymerase chain reaction （qPCR） was used to detect the expression level of genes related to lipid synthesis， transport， and degradation， and phosphatidylinositol 3' -kinase/ protein kinase B （PI3K/AKT） in the liver of fetus. ResultsTranscriptomics analysis showed that 2 144 genes were downregulated and 1 675 genes were upregulated in the arsenic exposed fetal liver； body weight and crown-rump length were reduced （P_TuKey<0.05）； the level of hepatic TGs was elevated in arsenic group （P_TuKey<0.05）； oil-red O staining showed a significant increase in lipid droplets in arsenic group （P_TuKey<0.01）； the expression of lipid synthesis-related genes were significantly upregulated （P_TuKey<0.05）； the expression of β-oxidation-related genes and lipid degradation-related genes were downregulated （P_TuKey<0.05）； the expression of PI3K， AKT decreased（P_TuKey<0.05）. Compared with the arsenic group， the body weight and crown-rump length of fetus increased in the arsenic+α-KG group （P_TuKey<0.05）； the level of hepatic TGs decreased in the arsenic+α-KG group （P_TuKey<0.05）； oil red O staining showed lipid droplets significantly decreased （P_TuKey<0.01）； the expression of lipid synthesis-related genes were downregulated （P_TuKey<0.05）， the expression of β-oxidation-related genes and lipid degradation-related genes were upregulated （P_TuKey<0.05）； the expression levels of PI3K and AKT increased （P_TuKey<0.05）. Conclusionα-KG alleviated hepatic lipid deposition in offspring exposed to arsenic during pregnancy through activating PI3K/AKT signaling pathway.

In recent years， repetitive transcranial magnetic stimulation （rTMS） has garnered significant attention as a therapeutic approach for sleep disorders in the elderly. However， the prevailing rTMS protocols are predominantly developed based on normative neurophysiological data derived from young adults and fail to incorporate individualized parameters tailored to the brain characteristics of the elderly. To address this gap， the consensus development group synthesized the latest evidence from 2010 to 2025 and established a standardized rTMS protocol specifically for elderly patients with sleep disorders. Adhering to the Appraisal of Guidelines for Research and Evaluation II （AGREE II） framework， systematically screened randomized controlled trials （RCTs） and systematic reviews regarding rTMS in the treatment of sleep disorders across various conditions. Meanwhile， the Grading of Recommendations Assessment， Development and Evaluation （GRADE） system was employed to rigorously grade the quality of evidence and the strength of recommendations. This consensus guideline delineates precise rTMS protocols for the management of sleep disorders in the elderly， highlights the adjustment of stimulation intensity according to scalp-cortex distance recommends either MRI‑guided neuronavigation or the Beam F3/F4 heuristic approach for accurate target localization， thereby providing precise rTMS intervention protocol for sleep disorders in the elderly， aiming to enhance clinical efficacy while ensuring treatment safety. ［Funded by National Key Research and Development Program （number， 2023YFC3603200）； General Program of Shenzhen Science and Technology Innovation Commission （number， JCYJ20240813112859008， JCYJ20240813112900002）； Youth Program of Shenzhen Kangning Hospital （number， KN2023A004）； www.guidelines-registry.cn number， PREPARE-2026CN530］

To address the constrains imposed by insufficient hydrogen peroxide (H2O2) and high glutathione (GSH) expression in tumor cells on the efficacy of chemodynamic therapy (CDT), zeolitic imidazolate framework-8 (ZIF-8) loaded with disulfiram (DSF) and 3-amino-1,2,4-triazole (3-AT) was synthesized via a one-pot approach. Subsequently, hyaluronic acid (HA)-modified cupric peroxide (CuO2) was in-situ grown on its surface through biomineralization to construct a multifunctional copper-based nanozyme ADZCH (3-AT/DSF@ZIF-8@CuO2-HA). This nanoplatform disrupts the intratumoral H2O2 homeostasis, depletes GSH, and synchronously delivers DSF and Cu2+ via cascade catalysis, thereby enhancing CDT and sensitizing tumors to DSF-based chemotherapy. The results of physicochemical characterization indicated that ADZCH presented a uniform core-shell structure with favorable dispersibility. Its particle size and Zeta potential were 196.5 nm and −19.5 mV, respectively. It possessed a microporous structure with a specific surface area of 81.8600 m2/g, and demonstrated efficient loading capacity for DSF and 3-AT, achieving drug loading efficiencies of 5.91% and 45.07%, respectively. Moreover, ADZCH can continuously and slowly release drugs in an acidic environment and maintain good stability under diverse physiological conditions. In vitro functional assays verified that ADZCH catalytically generated H2O2 and hydroxyl radicals while concurrently depleting GSH in a concentration- and incubation time-dependent manner. Cellular uptake experiments showed that HA modification significantly improved the uptake of nanoparticles by 4T1 cells. Cytotoxicity tests showed that 80 μg/mL ADZCH had a significant cytotoxic effect on 4T1 cells but no significant toxicity on L929 cells. DCFH-DA probe detection indicated that ADZCH could significantly induce intracellular reactive oxygen species (ROS) generation, thereby enhancing CDT efficacy. Live/dead staining experiments showed that ADZCH efficiently induced apoptosis, with the proportion of dead cells reaching 94.74%, demonstrating its promising potential for anti-tumor applications.This study provides new research ideas and experimental basis for overcoming the tumor microenvironment barrier and enhancing the anti-tumor effect of CDT combined with chemotherapy.

Introduction: Diabetic ketoacidosis (DKA) is a life-threatening complication associated with significant morbidity and healthcare burden. Despite advances in diabetes care, recurrent DKA remains common, often reflecting gaps in treatment adherence and patient education. Identifying predictors of recurrence is crucial for risk stratification and targeted intervention. Methodology: We conducted a retrospective observational study of all adult DKA admissions to a tertiary centre between 2001 and 2025. Electronic medical records were reviewed for demographic data, biochemical parameters, precipitating factors, and clinical outcomes. DKA was defined using standard biochemical criteria. Recurrent DKA was defined as ≥2 admissions during the study period. Factors associated with recurrent DKA admissions were analyzed. Patients under the age of 18 years and those with missing vital information were excluded. Results: A total of 667 DKA admissions, comprising 566 patients, were identified, of which 101 admissions (15.1%) were recurrent, involving 65 patients. Among recurrent DKA episodes, the most common precipitating factors were infection (64.4%) and insulin omission (62.4%). After multivariate analyses, patients with type 1 diabetes mellitus (T1DM) were more likely to develop recurrent DKA compared to those with type 2 diabetes mellitus (aOR 4.16; 95% confidence interval [CI] 2.58–6.70; p <0.001). Insulin omission was strongly associated with recurrent DKA (aOR 2.29; 95% CI 1.46–3.60; p <0.001). In contrast, baseline glycated hemoglobin and chronic kidney disease were not significantly associated with recurrence. Diabetic counseling during the first DKA admission did not reduce recurrent DKA. There were no significant differences in mortality (3.9% vs 6.2%, p = 0.524) or critical care admission rates (40.6% vs 38.7%, p = 0.718) between recurrent and first DKA episodes. Conclusion Recurrent DKA accounts for a substantial proportion of DKA admissions and is strongly associated with insulin omission and T1DM. Our findings suggest that recurrent DKA is driven predominantly by behavioral and adherencerelated factors, indicating the need for multidisciplinary interventions beyond standard inpatient counseling.
Diabetic Ketoacidosis ; Retrospective Studies

Introduction: The rising incidence of diabetic ketoacidosis (DKA) in type 2 diabetes mellitus (T2DM) represents a paradigm shift from its traditional recognition as a hallmark complication of type 1 diabetes mellitus (T1DM). However, contemporary data comparing clinical presentation, precipitating factors, and outcomes between these two populations remain limited. Methodology: In this retrospective observational study, all adult DKA admissions with T1DM or T2DM at a tertiary centre between 2001 and 2025 were studied. DKA was defined according to standard biochemical criteria. Electronic medical records were reviewed to extract demographic data, biochemical parameters, precipitating factors, management details, and clinical outcomes of all adult DKA admission in T1DM and T2DM. Patients aged <18 years or those with incomplete data were excluded. Results: A total of 601 DKA episodes were analyzed, comprising 130 (21.6%) in patients with T1DM and 471 (78.4%) in those with T2DM. Mean age was 26.9 ± 0.71 years for T1DM and 52.1 ± 0.7 years for T2DM. Gender distribution was balanced (male 48.3%, female 51.7%). Mean hemoglobin A1c (HbA1c) was 11.3 ± 0.3% in T1DM and 12.1 ± 0.2% in T2DM. Infection was the most common precipitating factor overall (69.0%), occurring more frequently in T2DM than in T1DM (74.7% vs. 56.2%), followed by medication non-adherence (62.4% vs. 43.8%). Significant differences were observed between groups in admission pH, bicarbonate (both p <0.001), blood ketones (p = 0.028), and HbA1c (p = 0.010), whereas anion gap (p = 0.056) and blood glucose levels (p = 0.755) did not differ significantly. Clinical outcomes were comparable with respect to intensive care unit (ICU) admission rates (40.0% in T1DM vs. 39.0% in T2DM, p = 0.779) and median resolution time (p = 0.462). However, the median length of hospital stay was significantly longer in T2DM (8.2 ± 0.32 vs. 5.4 ± 0.4 days; p <0.001). Overall mortality was 6.0%, with substantially higher mortality in T2DM compared to T1DM (7.4% vs. 0.8%, p = 0.013). Conclusion In this large regional series of adult DKA, most episodes occurred in T2DM. Despite similar ICU admission rates and time to resolution, T2DM was associated with more frequent infection-related precipitants, longer hospital stays, and higher mortality, underscoring the need for targeted preventive strategies in this population.
Adult ; Diabetes Mellitus, Type 1 ; Diabetic Ketoacidosis ; Diabetes Mellitus, Type 2

Introduction: Diabetic ketoacidosis (DKA) in pregnancy is an uncommon yet life-threatening emergency, with disproportionate risks to both mother and fetus. Pregnancy-specific physiological changes predispose patients to rapid metabolic decompensation, often with atypical presentations. Despite this, local data remain limited. We describe the clinical profile, precipitating factors, and outcomes of DKA in pregnancy in a tertiary centre, with emphasis on potentially preventable triggers. Cases: Nine pregnant patients with DKA were identified from a retrospective review of all cases admitted for DKA from 2002 to 2025. Mean age was 31.67 ± 5.20 years; all were Malay. The majority had type 2 diabetes mellitus (55.6%), followed by type 1 diabetes (33.3%) and latent autoimmune diabetes in adults (11.1%). The mean period of amenorrhea was 19.67 ± 12.62 weeks. Infection was the leading precipitant (44.4%), with additional triggers including insulin omission (22.2%), hyperemesis gravidarum, preterm labor, steroid exposure, and perioperative fasting. Most diagnoses were made in the emergency department (55.6%). Biochemical parameters reflected significant severity (mean bicarbonate 7.89 ± 2.98 mmol/L; anion gap 25.00 ± 5.81), with 88.9% classified as severe DKA. Intensive Care Unit (ICU) care was required in 77.8% of cases. The majority (77.8%) were admitted to the ICU unit, with a median time to resolution of 13.00 ± 12.00 hours (interquartile range [IQR]), and the median hospital length of stay was 7.00 ± 5.00 days (IQR). Complications during treatment included hypokalemia (33.3%), acute kidney injury (22.2%), and hypoglycemia (11.1%). Rebound DKA occurred in one-third of patients. All patients were discharged clinically stable. Outcome data demonstrated pregnancy loss in three cases and one preterm birth. Conclusion DKA in pregnancy remains a severe and resource-intensive condition. This series highlights missed opportunities in prevention, with modifiable precipitants such as infection and insulin omission commonly identified. The high severity at presentation suggests delays in recognition. Early detection, optimized metabolic care, and targeted preventive strategies are crucial to improving maternal and fetal outcomes.
Female ; Pregnancy ; Diabetic Ketoacidosis