OBJECTIVE To investigate the effect and mechanism of modified Lichong decoction （MLCD） on the apoptosis of transplanted tumor cells in nude mice. METHODS Human gastric cancer AGS cells were cultured， and a nude mice transplanted tumor model was established. The nude mice were divided into the model group and MLCD low-， medium- and high-dose groups （150， 300， 600 mg/kg）. They were given distilled water or the corresponding drug solution by gavage once daily for four consecutive weeks. The size of transplanted tumors in nude mice was measured every six days， and the tumor volume was calculated. After the medication， the nude mice were sacrificed， and the transplanted tumor tissues were isolated. The contents of lactate dehydrogenase （LDH） and reactive oxygen species （ROS） in the transplanted tumor tissues were detected， and the changes in mitochondrial membrane potential were assessed. The pathological morphological changes were observed. The enzymatic activities of caspase-3， caspase-8， and caspase-9， as well as protein expressions of Fas and FasL and mRNA expressions of caspase-3， caspase-8， caspase-9， Fas and FasL in the transplanted tumor tissues， were detected. RESULTS Compared with the model group， the volume of transplanted tumors in nude mice from all MLCD dose groups was reduced to varying degrees. The contents of LDH and ROS， as well as the enzymatic activities of caspase-3， caspase-8 and caspase-9， were significantly increased/enhanced. The mitochondrial membrane potential was significantly decreased. The protein expressions of Fas and FasL， and the mRNA expressions of caspase-3， caspase-8， caspase-9， Fas and FasL were significantly up-regulated. Most of these differences were statistically significant （ P ＜0.05 or P ＜0.01）. Pathological results showed that with increasing doses of MLCD， the cellular density in the transplanted tumor tissues gradually decreased， and typical morphological features of apoptosis， such as loosening and increasing fragmentation， became more prominent. CONCLUSIONS MLCD can induce apoptosis in transplanted tumor cells of nude mice， and its mechanism may be related to the activation of the Fas/FasL pathway and the caspase apoptotic pathway.

Objective To explore the related risk factors of osteosarcopenia (OS) in elderly patients with type 2 diabetes mellitus (T2DM) and to evaluate their predictive value. Methods We selected 409 elderly patients with T2DM from our hospital between June 2021 and December 2024 as the study subjects, and divided them into an OS occurrence group and a non-occurrence group based on whether they were diagnosed with OS. Results Among the 409 elderly patients with T2DM included, 93 were diagnosed with OS, yielding a prevalence rate of 22.73%. Spearman correlation analysis revealed a significant association between lumbar spine BMD and T-scores with age, history of previous fractures, fasting plasma glucose (FPG), procollagen type I N-terminal propeptide (PINP), osteocalcin (OC), and 25-hydroxyvitamin D (25(OH)D). Gender (OR=0.193), Body Mass Index (BMI) (OR=0.254), history of previous fractures (OR=8.883), FPG (OR=0.543), Total Cholesterol (TC) (OR=3.684), High-Density Lipoprotein Cholesterol (HDL-C) (OR=86.024), PINP (OR=0.818), and OC (OR=0.526) are identified as influential factors for the occurrence of OS in elderly patients with T2DM. The combined prediction of these variables yields a sensitivity of 96.5%, a specificity of 97.8%, and an area under the curve (AUC) of 0.992 for the occurrence of OS in elderly patients with T2DM, indicating an excellent predictive performance. Conclusion The following factors—gender, BMI, history of previous fractures, FPG, TC, HDL-C, PINP, and OC—are influential in the occurrence of OS among elderly patients with T2DM. Formulating intervention measures based on these influencing factors can provide assistance in preventing and treating the occurrence of OS.

Purpose: In this study, the neural communication patterns between hypothalamic structures and cortical areas in girls diagnosed with central precocious puberty (CPP) were explored. Endocrine profiles were incorporated to clarify the pathophysiological interactions between cerebral networks and hormonal regulation. The hypothalamus was designated as the key focus area for connectivity analysis. Methods: Fifty-seven girls (37 CPP, 20 non-CPP) were recruited from the Pediatric Development Clinic at the Second Affiliated Hospital of Anhui Medical University. The collected data included demographic information, gonadotropin-releasing hormone stimulation tests, and magnetic resonance imaging scans. Hypothalamic functional connectivity (FC) was analyzed using predefined region of interest coordinates, and correlations between hormone levels and FC values were assessed. Results: Compared to the non-CPP group, the CPP group exhibited elevated baseline follicle-stimulating hormone (FSH), baseline luteinizing hormone (LH), peak FSH, peak LH, and peak LH/FSH ratios. Patients with CPP exhibited enhanced neural synchronization linking the right lateral hypothalamic effector zone to the right superior frontal gyrus (displaying a borderline significant correlation with peak LH concentrations), concurrent with diminished functional coupling of the right lateral hypothalamic efferent to the right fusiform/supramarginal gyri. The left lateral hypothalamic projections demonstrated amplified connectivity with the right cuneus. No FC differences were observed in the medial hypothalamus. Conclusion Abnormal lateral hypothalamus FC patterns were identified in CPP girls and were particularly linked to peak LH levels. The findings offer novel insights into the neuroendocrine mechanisms underlying CPP.

Alzheimer's disease (AD) is the major form of dementia in the elderly and is closely related to the toxic effects of microglia sustained activation. In AD, sustained microglial activation triggers impaired synaptic pruning, neuroinflammation, neurotoxicity, and cognitive deficits. Accumulating evidence has demonstrated that aberrant expression of deubiquitinating enzymes is associated with regulating microglia function. Here, we use RNA sequencing to identify a deubiquitinase YOD1 as a regulator of microglial function and AD pathology. Further study showed that YOD1 knockout significantly improved the migration, phagocytosis, and inflammatory response of microglia, thereby improving the cognitive impairment of AD model mice. Through LC-MS/MS analysis combined with Co-IP, we found that Myosin heavy chain 9 (MYH9), a key regulator maintaining microglia homeostasis, is an interacting protein of YOD1. Mechanistically, YOD1 binds to MYH9 and maintains its stability by removing the K48 ubiquitin chain from MYH9, thereby mediating the microglia polarization signaling pathway to mediate microglia homeostasis. Taken together, our study reveals a specific role of microglial YOD1 in mediating microglia homeostasis and AD pathology, which provides a potential strategy for targeting microglia to treat AD.

Gelsemium elegans (G. elegans) is an extremely poisonous plant that is widely distributed in southern China and southeastern Asia. G. elegans poisoning events occur frequently in southern China, and are therefore an urgent public health problem requiring multidisciplinary action. However, the toxic components and toxicological mechanisms remain unclear. Here, we describe a systematic investigation on the toxic components of G. elegans, resulting in the isolation and identification of 120 alkaloids. Based on acute toxicity screening, the structure-toxicity relationship of Gelsemium alkaloids was proposed for the first time. Moreover, gelsedine- and humantenine-type alkaloids were detected in the clinical blood sample, and were confirmed to be causative in the poisoning. The most toxic compound, gelsenicine (1), had selective inhibitory effects toward ventral respiratory group (VRG) neurons in the medulla, which is the main brain region controlling respiration in the central nervous system. Gelsenicine (1) strongly inhibited the firing of action potentials in VRG neurons through its ability to stimulate GABA_A receptors, the main receptors involved in inhibitory neurotransmission. Application of GABA_A receptor antagonists successively reversed action potential firing in gelsenicine (1)-treated VRG neurons. Importantly, the GABA_A receptor antagonists securinine and flumazenil significantly increased the survival of poisoned animals. Our findings provide insight into the components and mechanisms of G. elegans toxicity, and should assist the development of effective emergency treatments for G. elegans poisoning.

With the growing emphasis on maternal and child oral health, the significance of managing oral health across preconception, pregnancy, and infancy stages has become increasingly apparent. Oral health challenges extend beyond affecting maternal well-being, exerting profound influences on fetal and neonatal oral development as well as immune system maturation. This expert consensus paper, developed using a modified Delphi method, reviews current research and provides recommendations on maternal and child oral health management. It underscores the critical role of comprehensive oral assessments prior to conception, diligent oral health management throughout pregnancy, and meticulous oral hygiene practices during infancy. Effective strategies should be seamlessly integrated across the life course, encompassing preconception oral assessments, systematic dental care during pregnancy, and routine infant oral hygiene. Collaborative efforts among pediatric dentists, maternal and child health workers, and obstetricians are crucial to improving outcomes and fostering clinical research, contributing to evidence-based health management strategies.
Humans ; Pregnancy ; Female ; Infant ; Consensus ; Mouth Diseases/therapy* ; Pregnancy Complications/therapy* ; Oral Health ; Infant, Newborn ; Delphi Technique ; Oral Hygiene

Ulcerative colitis (UC) is an idiopathic, relapsing, and etiologically complicated chronic inflammatory bowel disease. Despite substantial progress in the management of UC, the outcomes of mucosal barrier repair are unsatisfactory. In this study, phillygenin (PHI) treatment alleviated the symptoms of chronic colitis in mice, including body weight loss, severe disease activity index scores, colon shortening, splenomegaly, oxidative stress, and inflammatory response. In particular, PHI treatment ameliorated the tight junction proteins (TJs) reduction, fibrosis, apoptosis, and intestinal stem cell activity, indicating that PHI exerted beneficial effects on the intestinal mucosal barrier in mice with chronic colitis. In the NCM460 cells damage model, dextran sulfate sodium triggered the sequential induction of TJs reduction, fibrosis, and apoptosis. Takeda G protein-coupled receptor-5 (TGR5) dysfunction mediated NCM460 cell injury. Moreover, PHI treatment enhanced TJs and suppressed fibrosis and apoptosis to maintain NCM460 cell function, depending on TGR5 activation. PHI promoted TGR5 activation and elevated intracellular cyclic adenosine monophosphate levels in HEK 293T cells transfected with TGR5 expression plasmids. Cellular thermal shift assay and molecular docking studies confirmed that PHI directly binds to TGR5, indicating that PHI is an agonist of TGR5. The process of PERK-eIF2α pathway-mediated endoplasmic reticulum Ca²⁺ release was involved in NCM460 cell injury as well, which was associated with TGR5 dysfunction. When NCM460 cells were pretreated with PHI, the PERK-eIF2α pathway and elevated Ca²⁺ levels were blocked. In conclusion, our study demonstrated a novel mechanism that PHI inhibited the PERK-eIF2α-Ca²⁺ pathway through TGR5 activation to against DSS-induced TJs reduction, fibrosis, and apoptosis.

OBJECTIVE: To evaluate the impact of critical care warning platform (CWP) on clinical outcomes of patients transferred from internal medical ward to intensive care unit (ICU) based on real-world data. METHODS: A retrospective cohort study was conducted. The patients transferred from internal medical ward to ICU of Zhongda Hospital, Southeast University, between January 2022 and October 2024, were enrolled. They were divided into critical care warning group and conventional treatment group based on whether they were connected to the CWP. The patients in the critical care warning group were connected to the CWP, which collected real-time vital signs and treatment data. The platform automatically calculated severity scores, generated individualized risk assessments, and triggered warning alerts, allowing clinicians to adjust treatment plans accordingly. The patients in the conventional treatment group were not connected to the CWP and relied on conventional clinical judgment and nursing measures for treatment management. Baseline characteristics [gender, age, body mass index (BMI), admission type, severity score of illness, underlying diseases, and disease type at ICU admission], primary clinical outcome (in-hospital mortality), and secondary clinical outcomes [ICU mortality, length of ICU stay, total length of hospital stay, and mechanical ventilation and continuous renal replacement therapy (CRRT) status] were collected. Multivariate Logistic regression was used to analyze the impact of CWP on in-hospital death, and subgroup analyses were performed based on different patient characteristics. RESULTS: A total of 1 281 patients were enrolled, with 768 in the critical care warning group and 513 in the conventional treatment group. Compared with the conventional treatment group, the proportion of patients in the critical care warning group with underlying diseases of diabetes and malignancy and transferred to ICU due to sepsis was lowered, however, there were no statistically significant differences in other baseline characteristics between the two groups. Regarding the primary clinical outcome, the in-hospital mortality in the critical care warning group was significantly lower than that in the conventional treatment group [17.6% (135/768) vs. 25.7% (132/513), P < 0.01]. For secondary clinical outcomes, compared with the conventional treatment group, the patients in the critical care warning group had significantly fewer days of mechanical ventilation within 28 days [days: 2 (1, 6) vs. 2 (1, 8), P < 0.05], significantly shorter length of ICU stay [days: 3 (2, 8) vs. 4 (2, 10), P < 0.01], and significantly lower ICU mortality [15.1% (116/768) vs. 21.4% (110/513), P < 0.01]. Multivariate Logistic regression analysis showed that, after adjusting for age and underlying diseases, the use of CWP was significantly associated with a reduction of in-hospital mortality among patients transferred from internal medical ward to ICU [odds ratio (OR) = 0.670, 95% confidence interval (95%CI) was 0.502-0.894, P = 0.006]. Further subgroup analysis revealed that, among patients transferred to ICU due to sepsis, the use of CWP significantly reduced in-hospital mortality (OR = 0.514, 95%CI was 0.367-0.722, P < 0.001). In patients aged ≥ 70 years old (OR = 0.587, 95%CI was 0.415-0.831, P = 0.003) and those with underlying diseases of malignancy (OR = 0.124, 95%CI was 0.046-0.330, P < 0.001), CWP also showed significant protective effects on in-hospital prognosis. CONCLUSION The use of CWP is significantly associated with a reduction in in-hospital mortality among patients transferred from internal medical ward to ICU, demonstrating its potential in assessing the deterioration of hospitalized patients.
Humans ; Intensive Care Units ; Retrospective Studies ; Hospital Mortality ; Prognosis ; Critical Care ; Male ; Female ; Patient Transfer ; Middle Aged ; Aged ; Cohort Studies

Anterior cruciate ligament (ACL) reconstruction yields favorable outcomes for restoring anteroposterior stability of the knee joint in patients with ACL tears. However, some patients still exhibit positive knee pivot shift after ACL reconstruction. Currently, combined ACL and anterolateral ligament(ALL) reconstruction has been accepted by most scholars. This surgical technique can restore the rotational stability of the knee joint in patients postoperatively and facilitate the early besumption of sports training after surgery. This article reviews the anatomical research, isometry-like point research, and reconstruction indications of the anterolateral ligament, as well as the surgical approaches, graft tunnel convergence, and reconstruction outcomes of combined anterior cruciate ligament and anterolateral ligament reconstruction.

Objective To assess the effects of “dual low” scanning technology in conjunction with an individualized injection protocol in enhancing the quality of abdominal contrast-enhanced CT images. Methods A total of 200 patients who underwent abdominal contrast-enhanced CT examinations at the Hainan Western Central Hospital between January 2022 and January 2024 were selected for the study. Using a random number table, participants were randomly assigned to either a control group (n = 100, sub-hypertonic contrast agent + conventional tube voltage + individualized injection protocol) or an observation group (n = 100, isotonic contrast agent + tube voltage of 100 kV + individualized injection protocol). The study compared the impact of these two methodologies on the quality of abdominal contrast-enhanced CT images. Results During the arterial phase, the CT value of the abdominal aorta was significantly higher in the observation group than that in the control group (P < 0.05), suggesting that isotonic contrast agent and low tube voltage more effectively enhanced vascular signal. During the portal vein phase, the CT value was higher and the liver parenchymal noise was lower in the observation group those in the control group (P < 0.05), further validating the advantages of the “dual low” approach during the portal venous phase. The radiation dose was significantly lower in the observation group than that in the control group (P < 0.05), indicating that the “dual low” protocol effectively reduced radiation dose while enhancing patient safety. During the arterial phase, both the abdominal aorta noise and liver parenchymal noise were lower in the observation group than those in the control group (P < 0.05), demonstrating that the “dual low” strategy effectively reduced image noise and enhanced image clarity. The image quality scores were significantly higher in the observation group than in the control group (P < 0.05), indicating that high image quality could be achieved even at reduced radiation doses and contrast agent concentrations. Conclusion The “dual low” scanning technology, combined with an individualized injection protocol, not only effectively enhances the contrast of arteries and veins, reduces image noise, and improves the overall image quality, but also decreases radiation dose and enhances patient safety. Therefore, this technology is worth being widely promoted.