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.

In-depth interviews were conducted with medical doctoral students engaged in animal experiments， animal laboratory management personnel， and ethics committee members， exploring the current status， challenges， and countermeasures regarding animal welfare protection after medical experiments based on NVivo 12 software. The study found that some laboratory animals still meet the conditions for continued breeding after the experiments， but face multiple challenges such as physiological health， psychological stress， adoption and placement， as well as ethical and legal issues. On this basis， this paper proposed countermeasures such as establishing adoption mechanisms， enhancing public awareness， and improving the ethical review system. This aimed to achieve a balance between the development of medical science and animal welfare， thereby ensuring that laboratory animals receive due respect and care after contributing to the cause of human health.

ObjectiveTo systematically analyze the evolution characteristics and practical dilemmas of China’s scientific research integrity policies from 2004 to 2025， and to provide a reference for improving the governance system of science and technology ethics. MethodsBased on 53 policy documents retrieved from authoritative sources， such as the State Council policy document database， this study employed a three-stage coding process with NVivo 14， combined with word frequency analysis and policy metrology. ResultsThe policy evolution progressed through three phases regarding “partial exploration， system construction， and technological governance.” It demonstrated three characteristics， including systematic top-level design， rigid disciplinary mechanisms， and technologized supervision means. Nevertheless， the current governance system was still confronted with dilemmas such as biased institutional incentives， insufficient deterrence of disciplinary measures， and lagging technological supervision means. ConclusionThe study attempts to build a closed-loop governance paradigm of “institution-technology-culture，” deepen institutional reform to rectify incentive biases， adopt technology empowerment to promote full-process evidence preservation， and reshape academic culture to foster conscious integrity. This can systematically solve the problems of scientific research integrity anomie， thereby providing strong support for the high-quality development of scientific and technological innovation and the improvement of human well-being.

Objective: To investigate the effect of auricular therapy on sleep improvement and the GABAergic system pathway in a rat model of insomnia and to explore its possible mechanism. Methods: According to the random number table, 60 male SD rats were randomly divided into blank control, model, auricular point sticking, auricular bloodletting, and auricular bloodletting combined with sticking groups, with 12 rats per group. Insomnia was induced by intraperitoneal injection of p-chlorophenylalanine. After establishing the insomnia model, 36 rats were treated once a day with auricular point sticking or bloodletting for 5 consecutive days. After the intervention, the general condition and body weight of rats were observed; the righting reflex test was used to detect the sleep latency and duration; HE staining was used to observe the morphology of hypothalamic neuron cells; and an enzyme-linked immunosorbent assay was used to detect the GABA and glutamate content in rat serum. Immunohistochemistry(IHC) and real-time fluorescence quantitative PCR were used to detect GABA ARα1 and GABA ARγ2 protein and mRNA expression in the hypothalamus of rats, and Western blotting(WB) was used to detect GABA ARα1, GABA ARγ2, GAD65/67, GAT-1, and GABA-T protein expression in the hypothalamus of rats. Results: Compared with the blank control group, the model group had a lower body weight, a significantly shorter sleep duration (P<0.05), severe damage to the morphological structure of hypothalamic neurons with disordered cell arrangement, larger intercellular gaps, enlarged cell bodies, and a vacuolated appearance. All the intervention groups had significantly higher body weight and longer sleep duration than the model group (P<0.05). Compared with the other intervention groups, the auricular point sticking group had a longer sleep duration (P<0.05), and the hypothalamic neuron cells in all intervention groups improved, with the auricular point sticking group showing more apparent improvement. The model group had a lower GABA and higher glutamate contents, and GABA ARα1, GABA ARγ2, and GAD65/67 protein expression in the hypothalamus were lower than in the blank control group. In contrast, GAT-1 and GABA-T protein expression was higher, and GABA ARα1 and GABA ARγ2 mRNA expression was lower (P<0.05). The serum GABA content in the auricular point sticking and auricular bloodletting groups was higher, and the serum glutamate content in the auricular point sticking and auricular bloodletting combined sticking groups was lower than in the model group. GABA ARα1 mRNA expression in the hypothalamus of each intervention group was significantly increased, and GABA ARγ2 mRNA expression in the hypothalamus of the auricular point sticking and auricular bloodletting combined sticking groups increased. GABA ARα1(IHC, WB), GABA ARγ2(WB), and GAD65/67 protein expression in the hypothalamus of the auricular point sticking group increased, whereas GAT-1 and GABA-T protein expression decreased. GABA ARα1 and GABA ARγ2 protein expression(IHC, WB) in the hypothalamus of the auricular bloodletting group increased, whereas GABA-T protein expression decreased. GABA ARγ1(IHC) and GABA ARγ2(WB) protein expression in the hypothalamus of the auricular bloodletting combined sticking group increased, whereas GAT-1 and GABA-T protein expression decreased (P<0.05). Compared with in the inventation groups, the serum GABA content in the auricular point sticking group increased, the serum glutamate content decreased, GABA ARα1 and GABA ARγ2 mRNA expression in the hypothalamus increased, and GABA ARα1(IHC), GAD65/67 protein expression increased. In contrast, GABA-T protein expression decreased (P<0.05), and GABA ARγ2 protein expression(IHC) in the hypothalamus of the auricular bloodletting group increased (P<0.05). Conclusion Auricular therapy, particularly auricular point sticking, may have modulated the GABAergic system pathway by upregulating hypothalamic GABA ARα1, GABA ARγ2, and GAD65/67 protein expression while downregulating GAT-1 and GABA-T protein expression to alleviate symptoms in an insomnia rat model.

ObjectiveTo investigate the effect of high-definition transcranial direct current stimulation (HD-tDCS) combined with upper limb robot on upper limb dysfunction in patients with ischemic stroke. MethodsFrom January, 2023 to March, 2024, 56 inpatients with upper limb dysfunction after ischemic stroke were selected from Zhejiang Rehabilitation Medical Center, and divided into control group (n = 28) and experimental group (n = 28) randomly. All the patients received comprehensive treatment and upper limb robot training, while the control group received sham HD-tDCS and the experimental group received HD-tDCS, for four weeks. They were assessed with Fugl-Meyer Assessment-Upper Extremities (FMA-UE), Wolf Motor Function Test (WMFT) and modified Barthel Index (MBI) before and after treatment. The cortical amplitude, cortical latency and central motor conduction time (CMCT) of transcranial magnetic stimulation motor-evoked potential (MEP) were recorded, and a correlation analysis was conducted. ResultsThe scores of FMA-UE, WMFT and MBI, and MEP cortical amplitude, cortical latency and CMCT improved in both groups after treatment (t > 3.177, P < 0.01), and they were better in the experimental group than in the control group (t > 3.610, P < 0.01). The scores of FMA-UE and WMFT negatively correlated with MEP cortical latency and CMCT, and positively correlated with MEP cortical amplitude (|r| > 0.448, P < 0.001). ConclusionHD-tDCS is effective on upper limb motor function and activities of daily living for patients with ischemic stroke, and can improve corticospinal motor conduction.

HDAC7, a member of class IIa HDACs, plays a pivotal regulatory role in tumor, immune, fibrosis, and angiogenesis, rendering it a potential therapeutic target. Nevertheless, due to the high similarity in the enzyme active sites of class IIa HDACs, inhibitors encounter challenges in discerning differences among them. Furthermore, the substitution of key residue in the active pocket of class IIa HDACs renders them pseudo-enzymes, leading to a limited impact of enzymatic inhibitors on their function. In this study, proteolysis targeting chimera (PROTAC) technology was employed to develop HDAC7 drugs. We developed an exceedingly selective HDAC7 PROTAC degrader B14 which showcased superior inhibitory effects on cell proliferation compared to TMP269 in various diffuse large B cell lymphoma (DLBCL) and acute myeloid leukemia (AML) cells. Subsequent investigations unveiled that B14 disrupts BCL6 forming a transcriptional inhibition complex by degrading HDAC7, thereby exerting proliferative inhibition in DLBCL. Our study broadened the understanding of the non-enzymatic functions of HDAC7 and underscored the importance of HDAC7 in the treatment of hematologic malignancies, particularly in DLBCL and AML.

Environmental toxicants have been linked to aging and age-related diseases. The emerging evidence has shown that the enhancement of detoxification gene expression is a common transcriptome marker of long-lived mice, Drosophila melanogaster, and Caenorhabditis elegans. Meanwhile, the resistance to toxicants was increased in long-lived animals. Here, we show that farnesoid X receptor (FXR) agonist obeticholic acid (OCA), a marketed drug for the treatment of cholestasis, may extend the lifespan and healthspan both in C. elegans and chemical-induced early senescent mice. Furthermore, OCA increased the resistance of worms to toxicants and activated the expression of detoxification genes in both mice and C. elegans. The longevity effects of OCA were attenuated in Fxr ^-/- mice and Fxr homologous nhr-8 and daf-12 mutant C. elegans. In addition, metabolome analysis revealed that OCA increased the endogenous agonist levels of the pregnane X receptor (PXR), a major nuclear receptor for detoxification regulation, in the liver of mice. Together, our findings suggest that OCA has the potential to lengthen lifespan and healthspan by activating nuclear receptor-mediated detoxification functions, thus, targeting FXR may offer to promote longevity.

Several types of arthritis share the common feature that the generation of inflammatory mediators leads to joint cartilage degradation. However, the shared mechanism is largely unknown. H2BK120ub1 was reportedly involved in various inflammatory diseases but its role in the shared mechanism in inflammatory joint conditions remains elusive. The present study demonstrated that levels of cartilage degradation, H2BK120ub1, and its regulator WW domain-containing adapter protein with coiled-coil (WAC) were increased in cartilage in human rheumatoid arthritis (RA) and osteoarthritis (OA) patients as well as in experimental RA and OA mice. By regulating H2BK120ub1 and H3K27me3, WAC regulated the secretion of inflammatory and cartilage-degrading factors. WAC influenced the level of H3K27me3 by regulating nuclear entry of the H3K27 demethylase KDM6B, and acted as a key factor of the crosstalk between H2BK120ub1 and H3K27me3. The cartilage-specific knockout of WAC demonstrated the ability to alleviate cartilage degradation in collagen-induced arthritis (CIA) and collagenase-induced osteoarthritis (CIOA) mice. Through molecular docking and dynamic simulation, doxercalciferol was found to inhibit WAC and the development of cartilage degradation in the CIA and CIOA models. Our study demonstrated that WAC is a key factor of cartilage degradation in arthritis, and targeting WAC by doxercalciferol could be a viable therapeutic strategy for treating cartilage destruction in several types of arthritis.

Anxiety disorder is a major symptom of autism spectrum disorder (ASD) with a comorbidity rate of ~40%. However, the neural mechanisms of the emergence of anxiety in ASD remain unclear. In our study, we found that hyperactivity of basolateral amygdala (BLA) pyramidal neurons (PNs) in Shank3 InsG3680 knock-in (InsG3680^+/+) mice is involved in the development of anxiety. Electrophysiological results also showed increased excitatory input and decreased inhibitory input in BLA PNs. Chemogenetic inhibition of the excitability of PNs in the BLA rescued the anxiety phenotype of InsG3680^+/+ mice. Further study found that the diminished control of the BLA by medial prefrontal cortex (mPFC) and optogenetic activation of the mPFC-BLA pathway also had a rescue effect, which increased the feedforward inhibition of the BLA. Taken together, our results suggest that hyperactivity of the BLA and alteration of the mPFC-BLA circuitry are involved in anxiety in InsG3680^+/+ mice.
Animals ; Prefrontal Cortex/metabolism* ; Basolateral Nuclear Complex/metabolism* ; Mice ; Anxiety/metabolism* ; Nerve Tissue Proteins/genetics* ; Male ; Gene Knock-In Techniques ; Pyramidal Cells/physiology* ; Mice, Transgenic ; Neural Pathways/physiopathology* ; Mice, Inbred C57BL ; Microfilament Proteins

OBJECTIVE: To investigate the clinical characteristics and related risk factors of Clostridium difficile infection (CDI) in intensive care unit (ICU). METHODS: A retrospective study was conducted. Patients with diarrhea admitted to the ICU of the General Hospital of Ningxia Medical University from May 1 to August 30, 2023 were selected. Patients were divided into CDI group and non-CDI group based on the presence or absence of CDI. Clinical data from two groups of patients meeting the criteria were collected and compared, including gender, age, acute physiology and chronic health evaluation II (APACHE II), length of hospital stay, serum lactic acid, parenteral nutrition time, white blood cell count (WBC), procalcitonin (PCT), C-reactive protein (CRP), coagulation indicators, albumin, antibiotic exposure, etc. Multivariate Logistic regression analysis was performed to analyze the risk factors for CDI in ICU diarrhea patients. Receiver operator characteristic curve (ROC curve) was drawn to analyze the predictive value of each index for CDI in diarrhea patients. RESULTS: A total of 24 patients with diarrhea were enrolled, including 9 patients in the CDI group and 15 patients in the non-CDI group. The time of parenteral nutrition in the CDI group was significantly longer than that in the non-CDI group [days: 18.0 (13.5, 19.5) vs. 10.0 (4.0, 18.0)], the serum lactic acid level [mmol/L: 4.40 (3.00, 15.25) vs. 2.50 (1.90, 3.20)] and the ratio of serum lactic acid > 3.9 mmol/L [66.67% (6/9) vs. 6.67% (1/15)] were significantly higher than those in the non-CDI group, with statistical significance (all P < 0.05). Multivariate binary Logistic regression analysis showed that the serum lactic acid level of the patients was an independent risk factor for CDI [odds ratio (OR) = 3.193, 95% confidence interval (95%CI) was 1.011-10.080, P = 0.048]. ROC curve showed that serum lactic acid level had a high predictive value for CDI in ICU patients with diarrhea, and the area under the curve (AUC) was 0.815, respectively. When the cut-off value of serum lactic acid was 3.9 mmol/L, the sensitivity was 66.7% and the specificity was 93.3%. CONCLUSION Patients with diarrhea who have higher serum lactate levels (> 3.9 mmol/L) on admission are at increased risk of developing CDI.
Humans ; Retrospective Studies ; Risk Factors ; Intensive Care Units ; Clostridium Infections ; Clostridioides difficile ; Male ; Female ; Middle Aged ; Aged ; Diarrhea/microbiology* ; Logistic Models ; ROC Curve ; Adult