With global warming, the threat of high temperatures is increasing, and the incidence of heat stroke has reached new highs. As a systemic disease of multiple organ dysfunction caused by a failure of thermoregulation, acute liver failure is one of the most severe manifestations of heat stroke and has an extremely high fatality. Heat stroke is usually treated with supportive therapy, and most patients improve after such treatment. However, some patients still face death. Therefore, acute liver failure caused by heat stroke has been recognized internationally as one of the super-urgent conditions of liver transplantation. There are some reports of successful liver transplantation for heat stroke, but due to the lack of clear indications and timing for surgery, as well as the consensus recommendations of “ten early actions and one prohibition” in China, the situation is somewhat difficult. This article reviews the definition, diagnosis and pathophysiological mechanisms of heat stroke, summarizes the current status of liver transplantation for heat stroke, and discusses the indications and timing for liver transplantation in the treatment of heat stroke.

The translation of genetic findings from genome-wide association studies into actionable therapeutics persists as a critical challenge in Alzheimer's disease (AD) research. Here, we present PI4AD, a computational medicine framework that integrates multi-omics data, systems biology, and artificial neural networks for therapeutic discovery. This framework leverages multi-omic and network evidence to deliver three core functionalities: clinical target prioritisation; self-organising prioritisation map construction, distinguishing AD-specific targets from those linked to neuropsychiatric disorders; and pathway crosstalk-informed therapeutic discovery. PI4AD successfully recovers clinically validated targets like APP and ESR1, confirming its prioritisation efficacy. Its artificial neural network component identifies disease-specific molecular signatures, while pathway crosstalk analysis reveals critical nodal genes (e.g., HRAS and MAPK1), drug repurposing candidates, and clinically relevant network modules. By validating targets, elucidating disease-specific therapeutic potentials, and exploring crosstalk mechanisms, PI4AD bridges genetic insights with pathway-level biology, establishing a systems genetics foundation for rational therapeutic development. Importantly, its emphasis on Ras-centred pathways-implicated in synaptic dysfunction and neuroinflammation-provides a strategy to disrupt AD progression, complementing conventional amyloid/tau-focused paradigms, with the future potential to redefine treatment strategies in conjunction with mRNA therapeutics and thereby advance translational medicine in neurodegeneration.

Objective:To analyze the effects and mechanisms of ginseng polysaccharide in myocardial fibrosis and endothelial function in coronary heart disease model rats based on mitogen activated extracellular signal regulated kinase (MEK) and extracellular signal regulated kinase (ERK) signaling pathways.Methods:Totally 60 SD rats were divided into control group (10 rats) and model group (50 rats). A coronary heart disease model was established in modeling rats. The successfully modeled rats were divided into model group, drug control group, ginseng polysaccharide high- and low-dosage groups, with 10 rats in each group. The drug control group was orally administered with 2 mg/kg Lipitor solution, while the ginseng polysaccharide low- and high-dosage groups were orally administered with 100 and 200 mg/kg ginseng polysaccharide solution. The control group and model group were orally administered with equal volumes of physiological saline solution once a day for one week. HE staining and Masson staining were used to observe the morphological changes and pathological morphology of myocardial tissue. ELISA was used to detect the levels of NO, eNOS, ET-1, ADMA, TNF-α, CRP, and IL-6. Immunochemiluminescence was used to detect the expression levels of CK-MB and cTnl. Real time fluorescence quantification was used to identify the expression of MEK and ERK. Western blot was used to detect the expression of MEK, ERK, p-MEK, and p-ERK in myocardial tissue.Results:Compared with the model group, the levels of serum NO and eNOS increased in the drug control group and ginseng polysaccharide low- and high-dosage groups ( P<0.05), while the levels of ET-1, ADMA, TNF-α, CRP, IL-6, CK-MB, and cTnl decreased ( P<0.05), and the mRNA and protein expressions of MEK and ERK in myocardial tissue decreased ( P<0.05). Conclusions:Ginseng polysaccharides can improve the degree of myocardial fibrosis in rats, alleviate endothelial function and myocardial injury. Its mechanism may be related to the inhibition of the MEK/ERK signaling pathway.

Objective To investigate the expression and clinical significance of serum C-C motif chemokine ligand 11(CCL11)and phosphorylated neurofilament heavy chain(pNF-H)in diabetic peripheral neuropathy(DPN).Methods A total of 174 patients with type 2 diabetes mellitus(T2DM)were enrolled as T2DM group,and 87 healthy volunteers who underwent physical examina-tions during the same period were selected as control group.The T2DM patients were divided into DPN group and non-DPN group based on the occurrence of DPN.According to the disease severity[assessed by the Toronto Clinical Scoring System(TCSS)],DPN patients were further classified into mild DPN group,moderate DPN group and severe DPN group.Enzyme-linked immunosorbent assay was used to measure the levels of CCL11 and pNF-H.Pearson correlation analysis was employed to examine the correlations of serum CCL11 and pNF-H levels with TCSS scores in DPN patients.Multivariate uncon-ditional logistic regression analysis was conducted to screen for influencing factors of DPN in T2DM pa-tients.Receiver operating characteristic(ROC)curves were plotted to evaluate the predictive value of serum CCL11 and pNF-H levels for the development of DPN in T2DM patients.Results The serum levels of CCL11 and pNF-H in the T2DM group were significantly higher than those in the control group(P＜0.05).The incidence of DPN in the T2DM group was 47.13％(82/174).The age of the DPN group was significantly older,the disease course was significantly longer,and the levels of fasting blood glucose,HbA1c,CCL11 and pNF-H were significantly higher than those of the non-DPN group(P＜0.05).The serum levels of CCL11 and pNF-H increased sequentially from the mild DPN group to the moderate DPN group and then to the severe DPN group,with statistically sig-nificant differences(P＜0.05).Serum CCL11 and pNF-H levels in DPN patients were positively correlated with TCSS scores(r=0.661 and 0.619;P＜0.001).A prolonged disease duration,high glycated hemoglobin levels,high CCL11 levels and high pNF-H levels were independent risk factors for DPN in T2DM patients(P＜0.05).Thearea under the ROC curve for the combined pre-diction of DPN in T2DM patients by serum CCL11 and pNF-H levels was 0.861,which was greater than those for the individual indicators by serum CCL11(0.751)and pNF-H(0.765)levels(P＜0.05).After 1,000-time bootstrap internal validation through self-sampling,the C-index for the combined prediction was 0.861.Conclusion Elevated serum levels of CCL11 and pNF-H are in-dependently associated with the development of DPN in T2DM patients and increase with the worse-ning of DPN.The combination of these two markers has a high predictive value for DPN in T2DM patients.

ObjectiveTo evaluate the efficacy and safety of topical Bisaitong （鼻塞通） in treating moderate-to-severe allergic rhinitis （AR）. MethodsA randomized， positive-controlled， non-inferiority clinical trial design was adopted. Totally， 108 cases of moderate-to-severe AR were randomly divided into Bisaitong group and mometasone furoate group，with 54 cases in each group. The Bisaitong group was treated with Bisaitong smeared at the nasal cavity twice a day， and the mometasone furoate group received inhalation of mometasone furoate nasal spray 100 μg in each nostril， once a day. Both groups were treated for 4 weeks and followed up after additional 4 weeks. Both groups were compared on the rhinoconjunctivitis quality of life questionnaire （RQLQ）， rhinoconjunctivitis total symptom score （RTSS）， visual analogue score （VAS） of sneezing， runny nose， nasal itching， nasal congestion degree， days of AR episodes at enrollment， after 2- and 4-week， and at follow-up. The peripheral blood eosinophil （EOS） count and percentage （EOS%）， serum eosinophil cationic protein （ECP）， serum dust mite， dermatophagoides farinae， and cockroach allergen-specific IgE （sIgE） levels were compared between groups at enrollment and after 4-week treatment. Drug overuse rate was calculated， and the safety was evaluated. The analysis of all efficacy outcomes was based on both full analysis set （FAS） and per-protocol set （PPS）. ResultsThe lower limit of the 95% confidence interval for the differences in RQLQ scores were greater than -0.6 measured after 2- and 4-week treatment and at follow-up compared to that measured at the enrollment in both groups， indicating of the Bisaitong group being non-inferior to the mometasone furoate group. There was no statistically significant difference between groups on RTSS score， VAS scores of sneezing， runny nose， nasal itching， nasal congestion degree and days of episodes at all timepoints （P＞0.05）， but each outcome changed significantly over time in both groups （P＜0.01）. The differences between groups in EOS count， EOS%， ECP levels， serum dust mite， dermatophagoides farinae， cockroach sIgE levels， and drug overuse rate were not statistically significant at enrollment and after 4-week treatment （P＞0.05）. Adverse events occurred in eight cases （15.10%） in the Bisaitong group and five cases （9.30%） in the mometasone furoate group， showing no significant difference between groups （P＞0.05）. ConclusionTopical Bisaitong is non-inferior to mometasone furoate nasal spray in the treatment of moderate to severe AR in terms of clinical symptom relief，reduction in the episodes， improvement of quality of life， and sound safety.

Objective:To explore the prognostic value of tumor deposits (TD) by number and anatomical distribution in gastric cancer (GC) patients without lymph node metastasis.Methods:From Aug 2012 to Aug 2018 all 91 GC patients undergoing radical gastrectomy and without nodal metastasis at Yijishan Hospital of Wannan Medical College were enrolled in this study. Patients were divided into L1, L2, and L3 groups according to the number of TD and into Q1 and Q2 groups according to the anatomical regions of the TD.Results:The 3-year overall survival (OS) rates of groups L1, L2, and L3 were 58.9%, 52.1%, and 31.5%, respectively ( χ2=9.769, P=0.008). The 3-year OS rates of groups Q1 and Q2 were 58.9% and 7.1% ( χ2=46.310, P<0.001). The number of TD, their distribution, neural invasion, vascular invasion, tumor size, and pT stage were all related to prognosis by univariate analysis (all P<0.05). Tumor size>4 cm ( HR=2.460, 95% CI:1.307-4.629, P=0.005), distribution of TD (non-perigastric)( HR=3.959, 95% CI:2.077-7.545, P<0.001), neural invasion ( HR=4.299,95% CI:1.953-9.461, P<0.001), and pT 4 stage ( HR=2.283, 95% CI:1.250-4.171, P=0.007) were independent risk factors for prognosis by multivariate analysis. Conclusion:The distribution of TD (non-perigastric) is an independent risk factor for poor prognosis in gastric cancer patients after radical gastrectomy and with negative lymph node metastasis.

Objective:To explore the risk factors for the occurrence of thrombocytopenia (TCP) within 2 weeks after pediatric liver transplantation (LT) and examine the relationship between the occurrence of TCP and prognosis.Methods:From January 2021 to November 2021, clinical data were retrospectively reviewed for 162 pediatric LT recipients aged under 4 years at Organ Transplantation Center of Tianjin First Central Hospital.Based upon the lowest value of platelet count at Week 2 post-operation, they were assigned into two groups of TCP (n=90) and non-TCP (n=72). General preoperative profiles, intraoperative findings, postoperative complications, types of commonly used antibiotics, anticoagulant dosing and prognosis of two groups were compared.Univariate and multivariate analyses were utilized for examining the independent risk factors for TCP.Receiver operating characteristic (ROC) curve was plotted for examining the cut-off value of independent risk factors for diagnosing TCP.Results:Among them, 90 (55.56%) developed TCP within 2 weeks post-operation and 25(15.43%) developed TCP at Day 1 post-operation.The median preoperative platelet count was 178×10 9/L and the lowest value was 65×10 9/L at Day 3(1-4) post-operation with a declining rate of 63.5% and platelet count of recipient normalized at Day 6(4-7.25) post-operation.The results of univariate analysis showed statistically significant inter-group differences in operative duration[(574.43±80.53)min vs.(526.75±72.42)min], intraoperative blood loss[400(300, 550)ml vs.320(300, 400)ml], red blood cell transfusion[2(2, 3)U vs.2(1.5, 2.0)U], preoperative platelet count[178.5(141.75, 242.5)×10 9/L vs.257 (209.75, 357)×10 9/L], postoperative infection rate[27.8%(25/90)vs.13.9%(10/72)] and dosing rates of piperacillin sodium and tazobactam sodium[8.9%(8/90)vs.25.0%(18/72)] ( P<0.05). Multivariate Logistic regression analysis revealed statistically significant inter-group differences in operative duration( P=0.008), red blood cell transfusion( P=0.01), preoperative platelet count( P<0.01) and postoperative infection rate ( P=0.02). The results of ROC curve analysis showed that the cut-off values of operative duration, red blood cell transfusion and preoperative platelet count were 535 min, 2.75 U and 183.5×10 9/L respectively.Length of ICU stay was higher in TCP group than that in non-TCP group, and the difference was statistically significant [4(3, 5) vs.3(3, 4) day, P=0.006]. Conclusions:LT children aged under 4 years with intraoperative red blood cell transfusion>2.75 U, operative duration>535 min and preoperative platelet count<183.5×10 9/L are more likely to develop post-transplantation TCP.And occurrence of TCP prolongs the length of ICU stay in pediatric recipients.

Malfunction of the ventral subiculum (vSub), the main subregion controlling the output connections from the hippocampus, is associated with major depressive disorder (MDD). Although the vSub receives cholinergic innervation from the medial septum and diagonal band of Broca (MSDB), whether and how the MSDB-to-vSub cholinergic circuit is involved in MDD is elusive. Here, we found that chronic unpredictable mild stress (CUMS) induced depression-like behaviors with hyperactivation of vSub neurons, measured by c-fos staining and whole-cell patch-clamp recording. By retrograde and anterograde tracing, we confirmed the dense MSDB cholinergic innervation of the vSub. In addition, transient restraint stress in CUMS increased the level of ACh in the vSub. Furthermore, chemogenetic stimulation of this MSDB-vSub innervation in ChAT-Cre mice induced hyperactivation of vSub pyramidal neurons along with depression-like behaviors; and local infusion of atropine, a muscarinic receptor antagonist, into the vSub attenuated the depression-like behaviors induced by chemogenetic stimulation of this pathway and CUMS. Together, these findings suggest that activating the MSDB-vSub cholinergic pathway induces hyperactivation of vSub pyramidal neurons and depression-like behaviors, revealing a novel circuit underlying vSub pyramidal neuronal hyperactivation and its associated depression.
Rats ; Mice ; Animals ; Rats, Sprague-Dawley ; Depressive Disorder, Major/metabolism* ; Basal Forebrain ; Depression ; Hippocampus/metabolism* ; Cholinergic Agents

Objective: To compare the efficacy and safety of combining diosmin with Jiuhua hemorrhoid suppository versus diosmin alone for the treatment of hemorrhoid hemorrhage. Methods: The Jiuhua hemorrhoid suppository study was conducted in 10 medical centers across China from April 1, 2019 to June 30, 2020. Patients with hemorrhoid bleeding were randomized in a ratio of 1 : 1 to either receive Jiuhua hemorrhoid suppository and diosmin tablets (the study group) or diosmin tablets alone (the control group). The suppository was used once a day after defecation or at bedtime after rinsing the anus with warm water. Diosmin tablets were administered only once a day (0.9 g). The primary endpoint of the study was the assessment of hemorrhoid bleeding relief 7 ± 2 days after treatment, classified as “very effective” “effective” and “ineffective”. The secondary endpoint included the evaluation of pain alleviation using the visual analogue scale (VAS, with scores ranging from 0 to 10) and edema (with scores ranging from 0 to 3). The safety of the two treatment regimens was evaluated 14 ± 2 days after drug administration. Results: The full analysis set (FAS) comprised 107 participants in the study group and 111 in the control group, while the per-protocol set (PPS) included 106 participants in the study group and 111 in the control group. In terms of hemorrhoid bleeding, the proportion of very effective and effective cases in the study group were significantly higher than that in the control group [106 (99.06%) vs. 91 (81.98%), P < 0.0001] in the FAS, and the PPS results [105 (99.06%) vs. 91 (81.98%), P < 0.0001] were comparable to the FAS results. The pain VAS scores at day 7 after treatment were comparable between the two groups (0.80 ± 1.17 vs. 0.80 ± 1.20, P = 0.2177). The majority of the participants in both groups had an edema score of 0 at day 7 after treatment [96 (89.72%) vs. 99 (91.67%), P = 0.370 5]. Adverse events (AEs) occurred in 9 patients (8.4%) in the study group and 3 patients (2.7%) in the control group. In addition, 5 AEs in the study group and 1 AE in the control group were possibly in association with the study drug. Conclusion Compared with the administration of diosmin oral tablets alone, the addition of Jiuhua hemorrhoid suppository to the tablets demonstrates enhanced efficacy in addressing hemorrhoid bleeding, with satisfactory patient adherence and acceptable safety.

Objective:To investigate the effect of centrosome protein 55 (CEP55) on the proliferation of bladder cancer cells and its related molecular mechanism.Methods:Western blot was used to detect the expression of CEP55 and H3K9me3 in normal bladder tissue cells (SV-HUC-1) and bladder cancer cells (T24) . The bladder cancer cells T24 were divided into experimental group and control group. The experimental group cells were transfected with siRNA-CEP55, and the control group cells were transfected with siRNA-MOCK. The expression levels of CEP55, H3K9 and H3K9me3 in each group of cells were detected by Western blot. The proliferation ability of each group of cells was detected by CCK8 assay.Results:Western blot assay showed that the expression of CEP55 and H3K9me3 in T24 cells was 0.83±0.15 and 1.01±0.19 respectively. The expressions of CEP55 and H3K9me3 in bladder epithelial SV-HUC-1 cells were 0.35±0.09 and 0.44±0.10 respectively. The expressions of CEP55 and H3K9me3 in bladder cancer cells were higher than those in normal bladder cells (all P<0.05) . siRNA-CEP55 successfully reduced the expression of T24 CEP55 in bladder cancer cells. The absorbance of T24 cells in the experimental group was 1.109±0.105, which was significantly lower than that in the control group (2.208±0.104) . Low expression of CEP55 reduced the proliferation ability of T24 cells ( P<0.05) . Western blot results showed that H3K9 was not significantly changed in T24 cells in the experimental group, and H3K9me3 expression decreased significantly ( P<0.05) . Conclusion:CEP55 can inhibit the proliferation of bladder cancer cells by reducing the trimethylation of H3K9.