Objective To analyze the main causes and risk factors of unplanned reoperation after liver transplantation. Methods The clinical data of 242 liver transplant recipients in the First Affiliated Hospital of Anhui Medical University from January 2015 to December 2024 were retrospectively analyzed. According to whether unplanned reoperation was performed during the same hospitalization after surgery, the recipients were divided into the reoperation group (n=36) and the non-reoperation group (n=206). The preoperative, intraoperative and postoperative data of the two groups, as well as donor and graft-related data, were compared to analyze the risk factors of unplanned reoperation after liver transplantation and the survival status of the two groups. Results Among the 242 liver transplant recipients, 36 underwent unplanned reoperations, with a total of 54 procedures including various laparotomies, endoscopic and interventional surgeries, among which there were 20 laparotomies, 18 endoscopic surgeries and 16 interventional surgeries. The most common cause of unplanned reoperation was biliary complications (20 times), followed by vascular complications (17 times). Compared with the non-reoperation group, the reoperation group had longer graft cold ischemia time, higher postoperative fatality rate of recipients, longer length of stay in the intensive care unit and postoperative hospital stay, and higher total hospitalization costs (all P<0.05). The incidence of unplanned reoperation was higher in recipients who underwent split liver transplantation (P<0.05). Multivariate analysis showed that intraoperative blood loss ≥1 000 mL, positive culture of graft perfusate and split liver transplantation were independent risk factors for unplanned reoperation (all P<0.05). The postoperative 7-day, 1-month, 3-month and 6-month survival rates of recipients in the reoperation group and the non-reoperation group were 100% vs. 98.1%, 88.9% vs. 94.2%, 69.4% vs. 90.8% and 66.7% vs. 90.8%, respectively, and the postoperative survival rate of recipients in the reoperation group was lower than that in the non-reoperation group (P<0.05). Conclusions The main causes of unplanned reoperation after liver transplantation are biliary complications, vascular complications, abdominal incision infection and intra-abdominal hemorrhage. Intraoperative massive blood loss, positive culture of graft perfusate and split liver transplantation are the risk factors associated with unplanned reoperation after liver transplantation.

Background: and Purpose Vertebrobasilar fusiform aneurysms (VBFAs) carry substantial morbidity and mortality, but optimal management for unruptured VBFAs remains unclear. We compared the safety and efficacy of conservative management (CM), stent-assisted coiling (SAC), and flow diverters (FDs) in patients with unruptured VBFAs, focusing on long-term prognosis. Methods: This study included data from a nationwide Chinese cohort of patients with vertebrobasilar dissecting aneurysms. Inverse probability of treatment weighting (IPTW) balanced confounders across groups. The primary outcome was poor prognosis (modified Rankin Scale score >2). Secondary outcomes included aneurysm rupture, ischemic stroke, compression symptoms, and VBFA-related deaths. Logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CIs). Subgroup and sensitivity analyses were performed. Results: Among 1,115 patients with unruptured VBFAs, 838 (median age, 54 years; 655 men) were included. After IPTW, baseline characteristics were balanced. Median follow-up was 54 months. FD was associated with a lower risk of poor prognosis than CM (OR, 0.48 [95% CI, 0.30 to 0.77]; p=0.002), with no difference between CM and SAC. FD also reduced aneurysm rupture (OR, 0.20 [95% CI, 0.07 to 0.60]; p=0.004) and compression symptoms (OR, 0.30 [95% CI, 0.13 to 0.68]; p=0.004) versus CM. Time-to-event analyses further revealed significant differences in vertebral artery lesions and Type I–II VBFAs, whereas no significant differences were observed in basilar or vertebrobasilar junction lesions or in Type III–IV VBFAs. Conclusions Compared with CM, FD was associated with improved long-term outcomes in unruptured VBFAs, particularly in vertebral artery lesions and Type I–II VBFAs, although residual confounding cannot be excluded.

ObjectiveNon-invasive magnetic stimulation technology has been widely used in the treatment of Alzheimer’s disease (AD), but there is a lack of convenient and timely methods for evaluating and providing feedback on the effectiveness of the stimulation, which can be used to guide the adjustment of the stimulation protocol. This study aims to explore the possibility of heart rate variability (HRV) in diagnosing AD and guiding AD magnetic stimulation intervention techniques. MethodsIn this study, we used a 40 Hz, 10 mT pulsed magnetic field to expose AD mouse models to whole-body exposure for 18 d, and detected the behavioral and electroencephalographic signals before and after exposure, as well as the instant electrocardiographic signals after exposure every day. ResultsUsing one-way ANOVA and Pearson correlation coefficient analysis, we found that some HRV indicators could identify AD mouse models as accurately as behavioral and electroencephalogram(EEG) changes (P<0.05) and significantly distinguish the severity of the disease (P<0.05), including rMSSD, pNN6, LF/HF, SD1/SD2, and entropy arrangement. These HRV indicators showed good correlation and statistical significance with behavioral and EEG changes (r>0.3, P<0.05); HRV indicators were significantly modulated by the magnetic field exposure before and after the exposure, both of which were observed in the continuous changes of electrocardiogram (ECG) (P<0.05), and the trend of the stimulation effect was more accurately observed in the continuous changes of ECG. ConclusionHRV can accurately reflect the pathophysiological changes and disease degree, quickly evaluate the effect of magnetic stimulation, and has the potential to guide the pattern of magnetic exposure, providing a new idea for the study of personalized electromagnetic neuroregulation technology for brain diseases.

Background/Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a significant risk factor for gallstone formation, but mechanisms underlying MASH-related gallstone formation remain unclear. Golgi membrane protein 1 (GOLM1) participates in hepatic cholesterol metabolism and is upregulated in MASH. Here, we aimed to explore the role of GOLM1 in MASH-related gallstone formation. Methods: The UK Biobank cohort was used for etiological analysis. GOLM1 knockout (GOLM1-/-) and wild-type (WT) mice were fed with a high-fat diet (HFD). Livers were excised for histology and immunohistochemistry analysis. Gallbladders were collected to calculate incidence of cholesterol gallstones (CGSs). Biles were collected for biliary lipid analysis. HepG2 cells were used to explore underlying mechanisms. Human liver samples were used for clinical validation. Results: MASH patients had a greater risk of cholelithiasis. All HFD-fed mice developed MASH, and the incidence of gallstones was 16.7% and 75.0% in GOLM1-/- and WT mice, respectively. GOLM1-/- decreased biliary cholesterol concentration and output. In vivo and in vitro assays confirmed that GOLM1 facilitated cholesterol efflux through upregulating ATP binding cassette transporter subfamily G member 5 (ABCG5). Mechanistically, GOLM1 translocated into nucleus to promote osteopontin (OPN) transcription, thus stimulating ABCG5-mediated cholesterol efflux. Moreover, GOLM1 was upregulated by interleukin-1β (IL-1β) in a dose-dependent manner. Finally, we confirmed that IL-1β, GOLM1, OPN, and ABCG5 were enhanced in livers of MASH patients with CGSs. Conclusions In MASH livers, upregulation of GOLM1 by IL-1β increases ABCG5-mediated cholesterol efflux in an OPN-dependent manner, promoting CGS formation. GOLM1 has the potential to be a molecular hub interconnecting MASH and CGSs.

ObjectiveTo explore the clinical characteristics and risk factors for 30-day mortality in hospitalized patients with bloodstream infections (BSI) caused by carbapenem-resistant Klebsiella pneumoniae (CRKP). MethodsData were obtained retrospectively from the electronic medical records of inpatients at a tertiary A-grade hospital in Shanghai from January 2016 to December 2023. The collected variables included age, gender, department, surgical treatment, empirical antibiotic therapy, Pitt Bacteremia score (PBS), Charlson comorbidity index (CCI), INCREMENT-CPE score (ICS), length of hospital stay, the time from CRKP-BSI to discharge and, etc. The follow-up period ended upon discharge, with the follow-up outcomes defined as in-hospital mortality or discharge. The endpoint was defined as death within 30 days (including day 30) caused by CRKP-BSI or infection-related complications. Patients who survived within 30 days after CRKP-BSI were classified into the survival group, while those who died within 30 days were classified into the death group. Independent risk factors for 30-day mortality in patients with CRKP-BSI were analyzed using univariate and multivariate Cox regression analysis. ResultsA total of 71 hospitalized patients with CRKP-BSI, comprising 51 males and 20 females, with an average age of (65.12±18.25) years, were included during the study period. The M (P₂₅, P₇₅) of hospital stay were 37.00 (24.00, 56.00) days, and M (P₂₅, P₇₅) of the duration from CRKP-BSI to discharge or death were 18.00 (7.00, 35.00) days. There were 20 deaths (28.17%) in the death group and 51 survivors (71.83%) in the survival group. The results of multivariate Cox regression analysis showed that the ICS as an independent risk factor for 30-day mortality in CRKP-BSI patients (HR=1.379, 95%CI: 1.137‒1.671, P=0.001). Each 1-point increase in the ICS was associated with a 37.9% increase in the risk of mortality. ConclusionThe ICS is found to be a risk factor for 30-day mortality in patients with CRKP-BSI, which may facilitate the prediction for the risk of 30-day mortality and thereby support clinical decision-making for patients with CRKP-BSI.

At present,the main reason for the lagging development of emotional disease theory and the backward development of targeted drugs is the lack of suitable and effective animal models,and model evaluation is the key and difficult point in the preparation of emotional disease animal models.The theory of syndrome element differentiation in traditional Chinese medicine is closely matched with the theory of behavioral elements in animal behavior,which is expected to bring theoretical changes and methodological progress in related fields.Based on this background,this paper systematically sorted out and clarified the theoretical conception of animal model e-valuation of emotional diseases:guided by the thinking mode of syndrome differentiation theory of TCM,an attempt was made to estab-lish a complete model evaluation system.It also pointed out the realization path of animal model evaluation of emotional disease based on syndrome element differentiation theory:collection of behavioral elements in natural state and analysis of time sequence,phenotypic identification of abnormal behaviors under stress state,and equivalent transformation of model animal syndrome discrimination.

BACKGROUND:Linagliptin exhibits the capacity to regulate macrophage polarization,shifting them from the pro-inflammatory M1 phenotype towards the anti-inflammatory M2 phenotype. This alteration results in a dampened release of inflammatory mediators,thereby mitigating local inflammation.OBJECTIVE:To explore the effects of linagliptin on macrophage polarization,osteoclast activation,and inflammatory osteolysis elicited by wear particles.METHODS:(1) Cell experiments:For macrophage polarization,RAW264.7 cells were cultured and divided into four groups:the control group received high-glucose culture medium;the M1-induced group received M1-inducing culture medium (high-glucose culture medium containing 100 ng/mL lipopolysaccharide and 20 ng/mL interferon-γ) to simulate an inflammatory environment;the low-and high-dose linagliptin groups were treated with 50 and 200 nmol/L linagliptin,respectively,for 4 hours before exposure to M1-inducing culture medium. After 24 hours of macrophage polarization induction,immunofluorescence staining and RT-PCR were performed. For osteoclast activation,RAW264.7 cells were cultured and divided into four groups:the control group was cultured with high-glucose culture medium,the osteoclast-induced group and low-and high-dose linagliptin groups were subjected to osteoclast induction. After osteoclast formation,cells were treated with linagliptin (50 and 200 nmol/L) for 3 days. Subsequently,cell tartrate-resistant acid phosphatase staining and RT-PCR were performed. (2) Animal experiments:Twenty-four male C57BL/6J mice were randomly divided into four groups:sham operation group,model group,low-dose linagliptin group,and high-dose linagliptin group. The model group,low-dose linagliptin group,and high-dose linagliptin group were induced to establish a cranial bone resorption model by injecting titanium particle suspension onto the surface of the skull. Starting from the 2nd day after modeling,the low-and high-dose linagliptin groups were orally administered linagliptin (2 and 10 mg/kg,respectively) once daily. After modeling for 3 weeks,serum macrophage polarization marker protein and inflammatory factor levels were detected;skull samples were collected for micro-CT scanning,bone parameter analysis,and hematoxylin-eosin staining to evaluate osteolysis and morphological changes.RESULTS AND CONCLUSION:(1) Cell experiments:Both low and high doses of linagliptin significantly suppressed M1 polarization while promoting M2 polarization compared to the M1-induced group (P<0.01). Notably,the high-dose group exhibited a more pronounced inhibitory effect (P<0.01). Inflammatory factor mRNA expression was elevated in the M1-induced group compared with the control group (P<0.01),whereas inflammatory factor mRNA expression was significantly lower in the low-and high-dose linagliptin groups compared with the M1-induced group (P<0.01). There was a significant upregulation of mRNA expression of osteoclast functional markers in the osteoclast-induced group compared with the control group (P<0.01). Conversely,both low and high doses of linagliptin led to a substantial downregulation of mRNA expression of these markers compared with the osteoclast-induced group (P<0.01),with the high-dose group exhibiting a more pronounced reduction. (2) Animal experiments:Titanium particle implantation induced cranial bone resorption damage in mice. Treatment with linagliptin effectively mitigated this bone resorption,with the high-dose group showing superior efficacy. To conclude,linagliptin has been shown to modulate macrophage polarization,inhibit osteoclast activation,and have a protective effect on the skeletal system.

Alzheimer's disease (AD) is a progressively worsening neurodegenerative disorder primarily characterized by cognitive dysfunction, which increasingly impairs patients' quality of life as the condition worsened.Recent studies have found that the cerebellum not only plays a crucial role in motor coordination but also is key in learning, memory and executive functions.However, the mechanisms of the cerebellum influences cognitive function in AD patients remain unclear, and further research is needed to elucidate these processes in greater depth.This article reviews the latest research advances on the cerebellum and AD-related cognitive dysfunction, and explores the role of the cerebellum in the pathogenesis, clinical manifestations, and potential treatment strategies for AD, in order to provide valuable insights for future investigations into the pathological mechanisms and clinical therapies of AD.

Objective To analyze the effect of diltiazem on blood concentration of tacrolimus(TAC)retrospectively,and to provide reference for individual administration of tacrolimus in patients with nephrotic syndrome(NS).Methods The patients with NS who were treated in the outpatient/inpatient department of our hospital from January 2018 to December 2022 were collected,and the general information,combined drug use,blood drug concentration and other information of the patients were recorded.The patients were divided into two groups according to whether diltiazem was used or not:TAC group alone and TAC group combined with diltiazem.The effect of diltiazem on tacrolimus concentration was analyzed.Results A total of 45 patients with NS were included in this study,and 21 patients in the TAC group were treated with TAC alone.The mean blood concentration of TAC after medication was(5.77±2.87)ng·mL-1,which reached the effective therapeutic concentration range.The average blood concentration of TAC+Diltiazem group in the 24 patients was(2.90±1.29)ng·mL-1 before combined treatment,and increased to(5.74±2.46)ng·mL-1 after combined with diltiazem,with a growth rate of(127.34±119.57)％.The increase range was from 10％to 288％,and there was significant difference(P＜0.05).According to the observation within 6 months after the combination of the two drugs,the average blood concentration of TAC continued to increase,especially in the 5th month after the administration of TAC,and the concentration tended to be stable after 5 months.By compare with the effect of diltiazem dosage on the blood concentration of TAC,90 mg·d-1 and 180 mg·d-1 had little difference in improving the blood concentration of TAC.At the same time,the combination of the two drugs did not cause adverse reactions.Conclusion A daily dose of 90 mg of Diltiazem can significantly increase the TAC blood concentration in patients with NS who cannot reach the effective therapeutic concentration with conventional doses.It can reach the effective clinical therapeutic concentration without increasing the dose of tacrolimus.The combination of the two drugs were generally safe and effective.

Objective To explore the effect of transcutaneous auricular vagus nerve stimulation(taVNS)on postoperative recovery of gastrointestinal function in gynecological laparoscopic surgery patients.Methods Ninety-six patients who underwent elective laparoscopic total hysterectomy were selected.According to the random number table method,patients were divided into the taVNS group(group T)and the sham stimulation group(group F)with 48 patients in each group.The conventional general anesthesia method was used in both groups.The group T received taVNS once before surgery and once in the anaesthesia recovery room with 30 min per stimulation,while the group F was given sham stimulation for 30 min each.Postoperative recovery time of anal gas and defecation,the I-FEED scores on the 1st,2nd and 3rd postoperative days,the GSRS score on the 3rd postoperative day were recorded.The NRS scores on the 1st and 2nd postoperative days,postoperative remedial analgesia,occurrence of postoperative adverse effects and duration of postoperative hospitalization were recorded.Results Compared with the group F,the time to first postoperative anal exhaust and defecation was significantly shorter in the group T.The I-FEED scores on the 1st,2nd and 3rd postoperative days,and the GSRS score on 3rd postoperative day were significantly decreased in the group T.The proportion of patients with postoperative gastrointestinal intolerance and postoperative gastrointestinal dysfunction were reduced in the group T(P＜0.05).NRS scores at postoperative days 1,and 2 were decreased and the incidence of postoperative nausea was lower(P＜0.05).There were no significant differences in postoperative remedial analgesia,the occurrence of postoperative vomiting,dizziness,bradycardia and hypotension,and duration of postoperative hospitalization in the two groups of patients(P＞0.05).Conclusion taVNS can improve the recovery of postoperative gastrointestinal function,reduce postoperative nausea and alleviate postoperative pain in laparoscopic total hysterectomy patients.