ObjectiveThis study aims to investigate the therapeutic effects of Wenweishu granule （WWSG） on functional dyspepsia （FD） with spleen-stomach deficiency cold syndrome in rats by integrating network pharmacology， molecular docking， and animal experiments. MethodsActive components and corresponding targets of WWSG were collected from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and the Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine （BATMAN-TCM）. Disease-related targets for FD with spleen-stomach deficiency cold syndrome were screened using GeneCards and the Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine （TCMIP）. Core therapeutic targets were identified via Cytoscape and validated by molecular docking. A rat model of FD with spleen-stomach deficiency cold syndrome was established using vinegar gavage combined with tail-clamping. The rats were randomly divided into a model group， low-， medium-， and high-dose WWSG groups （2.0， 4.0， 8.0 g·kg^-1）， a domperidone group （3.0 mg·kg^-1）， a Fuzi Lizhong pillwan （0.8 g·kg^-1）， and a normal control group （n=10 per group）. Drugs were administered once daily by gavage for 14 consecutive days. After treatment， body weight， symptom scores， and gastrointestinal motility indices were recorded. Gastric and duodenal pathologies changes were observed via hematoxylin-eosin （HE） staining. Brain-gut peptides were measured in serum and tissue using enzyme-linked immunosorbent assay （ELISA）. Immunohistochemistry and Western blot were performed to assess stem cell factor （SCF） and receptor tyrosine kinase （c-Kit） protein expression in gastric tissues. ResultsA total of 305 drug targets， 1 140 disease targets， and 116 overlapping targets were identified. Cytoscape analysis revealed 104 core targets. Enrichment analysis indicated that the SCF/c-Kit signaling pathway was the key mechanism. Molecular docking confirmed a strong binding affinity between active components of WWSG and SCF/c-Kit proteins （binding energy<-5.1 kcal·mol^-1）. Compared with the normal group， model rats exhibited slower weight gain （P<0.05）， reduced gastric emptying and intestinal propulsion （P<0.01）， mild gastric mucosal shedding， duodenal inflammatory cell infiltration， decreased levels of gastrin （GAS）， 5-hydroxytryptamine （5-HT）， and vasoactive intestinal peptide （VIP） （P<0.05， P<0.01）， and elevated somatostatin （SS） expression （P<0.05， P<0.01）. WWSG treatment ameliorated weight gain， symptom scores， and low-grade inflammation in gastric/duodenal tissues. High-dose WWSG significantly improved gastric emptying and intestinal propulsion， upregulated GAS， 5-HT， and VIP， and downregulated SS expression in serum and tissues （P<0.05， P<0.01）. Immunohistochemistry and Western blot demonstrated that SCF and c-Kit protein expression was decreased in the model group （P<0.05， P<0.01）， which was reversed by WWSG intervention （P<0.05）. ConclusionWWSG exerts therapeutic effects on FD with spleen-stomach deficiency cold syndrome in rats， potentially by regulating the SCF/c-Kit signaling pathway to enhance gastrointestinal motility.

Objective To explore the longitudinal associations of body roundness index (BRI), visceral adiposity index (VAI), and metabolic score for visceral fat (METS-VF) with the risk of new-onset atrial fibrillation (AF). Methods This study included participants from the UK Biobank who were free of AF or pregnancy at baseline and completed the first and second assessments of BRI, VAI, and METS-VF. The changes in BRI, VAI, and METS-VF were classified using K-means clustering analyses, and the cumulative adiposity indices were also calculated. The primary outcome was new-onset AF. Three Cox regression models were employed to investigate the longitudinal associations of the BRI, VAI, and METS-VF changes with the risk of incident new-onset AF. The results were presented as hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs). Restricted cubic spline analyses were performed to explore potential non-linear associations between baseline or cumulative adiposity indices and the risk of new-onset AF. C-index analyses were conducted to evaluate the predictive value of BRI, VAI, and METS-VF for new-onset AF. Subgroup analyses were performed according to age, gender, race, smoking status, alcohol consumption, and physical activity. Polygenic risk scores were applied to account for genetic susceptibility and investigate potential interactions between adiposity indices and genetic risk. Univariate linear regression analyses were performed to evaluate the relationships of cumulative adiposity indices and magnetic resonance imaging and dual X-ray absorptiometry parameters, including visceral adipose tissue (VAT) volume, VAT mass, trunk fat volume, and trunk fat mass. We further applied the eXtreme Gradient Boosting (XGBoost) algorithm, with the feature importance being measured to evaluate the predictive value of each adiposity index for imaging parameters. Mendelian randomization analysis was further conducted to investigate the potential causal relationship between trunk fat mass and AF. Results A total of 12 776 participants were included. Over a median follow-up of 9.60 years, 761 (5.96%) new-onset AF events were recorded. Participants were divided into four classes based on the changes in adiposity indices. In the fully adjusted model, compared to participants in Class 1 of BRI, those in Class 3 (HR＝1.30, 95%CI 1.04-1.63, P＝0.023) and Class 4 (HR＝2.17, 95%CI 1.61-2.93, P＜0.001) were associated with significantly higher risks of new-onset AF. Regarding METS-VF, participants in Class 4 of METS-VF also demonstrated a significantly higher risk of new-onset AF compared to those in Class 1 (HR＝1.66, 95%CI 1.15-2.39, P＝0.007). However, no significant association was observed between different classes of VAI and the risk of new-onset AF. For every 1 standard deviation increase in cumulative BRI, VAI, and METS-VF, the fully adjusted HRs of new-onset AF were 1.23 (95%CI 1.13-1.35), 1.02 (95%CI 0.94-1.10), and 1.23 (95%CI 1.12-1.35), respectively. Cumulative adiposity indices (BRI, VAI, and METS-VF) were divided into quartiles. Using the first quartile as reference, participants in the highest quartiles of BRI (HR＝1.40, 95%CI 1.10-1.79, P＝0.007) and METS-VF (HR＝1.44, 95%CI 1.13-1.83, P＝0.003) both exerted a significantly higher risk of new-onset AF. Regarding VAI, no significant association was observed (HR＝1.00, 95%CI 0.81-1.23, P＝0.988). Restricted cubic spline analyses revealed non-linear relationships between cumulative BRI, baseline/cumulative VAI, and baseline/cumulative METS-VF with new-onset AF risk (all P_overall＜0.05, P_non-linear＜0.05). In the C-index analysis, BRI demonstrated the highest predictive performance for new-onset AF, followed by METS-VF and VAI. Subgroup analysis indicated a stronger association between METS-VF and the risk of new-onset AF amongst participants younger than 60 years (P_interaction＝0.008). Polygenic risk score analysis stratified by genetic risk demonstrated a synergistic effect between BRI and genetic risk with new-onset AF, with the overall risk of new-onset AF increasing as both BRI and genetic risk increased. Linear regression analysis revealed a positive correlation between cumulative BRI with VAT volume, VAT mass, trunk fat volume, and trunk fat mass. The feature importance plot derived from the XGBoost algorithm indicated that cumulative BRI had the greatest predictive value on VAT volume, VAT mass, trunk fat volume, and trunk fat mass. Mendelian randomization analysis confirmed a significant causal relationship between trunk fat mass and AF. Conclusions There are significant non-linear associations between BRI, METS-VF, and VAI with new-onset AF. Higher BRI and METS-VF are significantly associated with a higher risk of new-onset AF, whereas no significant association is observed for the VAI. BRI exhibits a positive correlation with VAT and trunk fat, and demonstrates superior performance in predicting new-onset AF compared to VAI and METS-VF. Monitoring and managing BRI may be important in the early detection and intervention of AF.

Objective:To explore the role of ductular reaction in assessing the efficacy of liver transplantation.Method:From January 2015 to December 2020, he relevant clinical data were retrospectively reviewed for 100 recipients and their corresponding donors at Shulan (Hangzhou) Hospital. They were assigned into two groups of hepatic steatosis (HS group, 65 cases) and non-hepatic steatosis (non-HS group, 35 cases) according to whether or not receiving steatosis donated liver. Furthermore, based upon the occurrence of early allograft dysfunction (EAD), the participants were categorized into two groups of EAD (33 cases) and non-EAD (67 cases). The degree of bile duct reaction ductular reaction was defined by the percentage of staining area occupied by cytokeratin 19 (CK19) -positive bile duct cells in immunohistochemical-stained specimens. Donor of ductular reaction were compared between HS/non-HS and EAD/non-EAD groups. The risk factors for EAD were identified by univariate and multivariate Logistic regression analysis. Subgroup analysis was conducted based upon the level of ductular reaction (DR number) in donors (DR=0.4 as a threshold) and whether or not donors exhibited steatosis. The impact of DR was examined on the incidence of EAD and survival post-liver transplantation in steatosis donors.Result:The level of DR was higher in steatosis donor than that in non-steatosis donor [ (0.59%±0.385%) vs. (0.32%±0.194%), P<0.01]. And it was higher in EAD group than that in non-EAD group [ (0.72%±0.449%) vs. (0.38%±0.226%), P<0.01]. Multivariate logistic regression analysis showed that a high level of ductular reaction was an independent risk factor for EAD post-liver transplantation in donor. Subgroup analysis revealed that receiving a steatosis donor with low ductular reaction (DR<0.4%) had comparable levels of EAD occurrence and overall survival rate to receiving a non-steatosis donor. Conclusion:Steatosis with low ductular reaction donor may be safely applied for liver transplantation. And assessing donor injury based upon ductular reaction can effectively expand the clinical application of steatosis donors.

Objective:To investigate the relationship and assess the value of serum polyadenosine diphosphate ribose polymerase 1 (PARP1) and forkhead box transcription factor O1 (FOXO1) with cerebral neurological function in patients with severe craniocerebral injury (SCI).Methods:The clinical data of 100 patients with SCI from February 2021 to October 2022 in Baoji High-Tech Hospital were retrospectively analyzed. The Glasgow coma score (GCS) on admission was recorded. According to the modified Rankin score (mRS) 3 months after discharge, the patients were divided into good recovery group (mRS 0 to 2 scores, 62 cases) and poor recovery group (mRS 3 to 5 scores, 38 cases). In addition, 50 individuals who underwent physical examinations in Baoji High-Tech Hospital during the same period were selected as the control group. The serum levels of PARP1 and FOXO1 were measured by enzyme-linked immunosorbent assay. Correlation analysis was performed using Spearman method. Multifactor Logistic regression was used to analyze the independent risk factors for poor cerebral neurological recovery in patients with SCI. The efficacy of PARP1 and FOXO1 in predicting the poor cerebral neurological recovery in patients with SCI was evaluated by the receiver operating characteristic (ROC) curve.Results:The PARP1 and FOXO1 in good recovery group and poor recovery group were significantly higher than those in control group: (4.14 ± 1.19) and (5.98 ± 1.02) μg/L vs. (2.13 ± 0.71) μg/L, (5.83 ± 1.22) and (7.57 ± 3.12) μg/L vs. (4.23 ± 1.34) μg/L, the indexes in poor recovery group were significantly higher than those in good recovery group, and there were statistical differences ( P<0.05). The mRS in poor recovery group was significantly higher than that in good recovery group: (3.92 ± 0.87) scores vs. (1.03 ± 0.80) scores, and there was statistical difference ( P<0.05). Spearman correlation analysis result showed that PARP1 and FOXO1 were positively correlated with mRS score in patients with SCI ( r = 0.673 and 0.646, P<0.05). Multifactor Logistic regression analysis result showed that the GCS, mRS, PARP1 and FOXO1 were independent risk factors for poor neurological recovery in patients with SCI ( HR = 1.039, 1.286, 1.439 and 1.389; 95% CI 1.003 to 1.076, 1.011 to 1.637, 1.029 to 2.012 and 1.009 to 1.912; P<0.05). ROC curve analysis result showed that the area under the curve (AUC) of PARP1 combination with FOXO1 in assessing poor cerebral neurological recovery in patients with SCI was significantly greater than the PARP1 and FOXO1 alone: 0.953 (95% CI 0.918 to 0.988) vs. 0.866 (95% CI 0.796 to 0.936) and 0.859 (95% CI 0.783 to 0.935), Z = 2.162 and 2.188, P = 0.031 and 0.029. Conclusions:The serum PARP1 and FOXO1 levels in patients with SCI are positively correlated with cerebral neurological recovery, and they have predictive value for cerebral neurological recovery status.

Traumatic supraorbital fissure syndrome (TSOFS) is a symptom complex caused by nerve entrapment in the supraorbital fissure after skull base trauma. If the compressed cranial nerve in the supraorbital fissure is not decompressed surgically, ptosis, diplopia and eye movement disorder may exist for a long time and seriously affect the patients′ quality of life. Since its overall incidence is not high, it is not familiarized with the majority of neurosurgeons and some TSOFS may be complicated with skull base vascular injury. If the supraorbital fissure surgery is performed without treatment of vascular injury, it may cause massive hemorrhage, and disability and even life-threatening in severe cases. At present, there is no consensus or guideline on the diagnosis and treatment of TSOFS that can be referred to both domestically and internationally. To improve the understanding of TSOFS among clinical physicians and establish standardized diagnosis and treatment plans, the Skull Base Trauma Group of the Neurorepair Professional Committee of the Chinese Medical Doctor Association, Neurotrauma Group of the Neurosurgery Branch of the Chinese Medical Association, Neurotrauma Group of the Traumatology Branch of the Chinese Medical Association, and Editorial Committee of Chinese Journal of Trauma organized relevant experts to formulate Chinese expert consensus on the diagnosis and treatment of traumatic supraorbital fissure syndrome ( version 2024) based on evidence of evidence-based medicine and clinical experience of diagnosis and treatment. This consensus puts forward 12 recommendations on the diagnosis, classification, treatment, efficacy evaluation and follow-up of TSOFS, aiming to provide references for neurosurgeons from hospitals of all levels to standardize the diagnosis and treatment of TSOFS.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Background The benchmark dose (BMD) method calculates the dose associated with a specific change in response based on a specific dose-response relationship. Compared with the traditional no observed adverse effect level (NOAEL) method, the BMD method has many advantages, and the 95% lower confidence limit of benchmark dose lower limit (BMDL) is recommended to replace NOAEL in deriving biological exposure limits. No authority has yet published any health-based guideline for rare earth elements. Objective To evaluate genotoxicity threshold induced by acute exposure to neodymium nitrate in mice using BMD modeling through micronucleus test and comet assay. Methods SPF grade mice (n=90) were randomly divided into nine groups, including seven neodymium nitrate exposure groups, one control group (distilled water), and one positive control group (200 mg·kg⁻¹ ethyl methanesulfonate), 10 mice in each group, half male and half female. The seven dose groups were fed by gavage with different concentrations of neodymium nitrate solution (male: 14, 27, 39, 55, 77, 109, and 219 mg·kg⁻¹; female: 24, 49, 69, 97, 138, 195, and 389 mg·kg⁻¹) twice at an interval of 21 h. Three hours after the last exposure, the animals were neutralized by cervical dislocation. The bone marrow of mice femur was taken to calculate the micronucleus rate of bone marrow cells, and the liver and stomach were taken for comet test. Results The best fitting models for the increase of polychromatophil micronucleus rate in bone marrow of female and male mice induced by neodymium nitrate were the exponential 4 model and the hill model, respectively. The BMD and the BMDL of female mice were calculated to be 31.37 mg·kg⁻¹ and 21.90 mg·kg⁻¹, and those of male mice were calculated to be 58.62 mg·kg⁻¹ and 54.31 mg·kg⁻¹, respectively. The best fitting models for DNA damage induced by neodymium nitrate in female and male mouse hepatocytes were the exponential 5 model and the exponential 4 model, respectively, and the calculated BMD and BMDL were 27.15 mg·kg⁻¹ and 11.99 mg·kg⁻¹ for female mice, and 16.28 mg·kg⁻¹ and 10.47 mg·kg⁻¹ for male mice, respectively. The hill model was the best fitting model for DNA damage of gastric adenocytes in both female and male mice, and the calculated BMD and BMDL were 36.73 mg·kg⁻¹ and 19.92 mg·kg⁻¹ for female mice, and 24.74 mg·kg⁻¹ and 14.08 mg·kg⁻¹ for male mice, respectively. Conclusion Taken the micronucleus rate of bone marrow cells, DNA damage of liver cells and gastric gland cells as the end points of genotoxicity, the BMDL of neodymium nitrate is 10.47 mg·kg⁻¹, which can be used as the threshold of genotoxic effects induced by acute exposure to neodymium nitrate in mice.

Objective:To design a specialized ultrasound therapeutic device for rabbit urethral scars and to verify its applicability and effectiveness.Methods:New Zealand male rabbits were used as the experimental objects, and the ultrasound therapeutic instrument was customized according to the structure and size of the rabbit penises. The ultrasound therapeutic instrument included the ultrasound pulse emission and control system, the final-stage amplifier, and the ultrasound probe. Firstly, the ultrasound probe was designed according to the size and structure of rabbit penises, and the parameters of the ultrasound probe were determined by COMSOL finite element simulation and actual testing of the sound field distribution. Secondly, the driving circuit of the ultrasound probe was designed according to the parameters of the elements. Then the ultrasound pulse emission and control system based on the field-programmable gate array (FPGA) and the serial screen were designed. Subsequently, the ultrasound therapeutic instrument was subjected to a performance test and a safety test. The ultrasound therapeutic instrument was constructed to include the ultrasound amplifier and the ultrasound probe. Finally, a rabbit urethra reconstruction model was constructed, and eight white rabbits were randomly divided into a model group and an experimental group. The rabbits in the experimental group received the ultrasound therapeutic instrument for treatment of the urethra immediately, with an ultrasound frequency of 2 MHz, a pulse interval of 10 ms, and an output sound intensity of 0.73 W/cm 2. The treatment was performed twice a week (on Tuesday and Thursday), with 10 min of irradiation each time, lasting for four weeks. The rabbits in the model group did not receive any treatment. The area percentage of transforming growth factor-β1 (TGF-β1), matrix metalloproteinase-2 (MMP-2), and tumor necrosis factor-α (TNF-α) staining-positive areas in rabbit urethral tissues were quantitatively analyzed, and the urethral circumference was calculated using Image J software. Results:Due to the addition of sound-absorbing materials, the sound pressure distribution in the treatment chamber was more uniform, and the average value of the standing wave ratio was 1.11, indicating that the structural design met the design requirements. In the overall performance test, the natural focal position of the three ultrasonic transducers was 10 mm, and the consistency of the sound field distribution meet the experimental requirements. The relationship between the peak sound pressure of each transducer and the power supply voltage was close to linear. The output sound intensity ranged from 0.35 to 0.74 W/cm 2, which met the experimental requirements. With the ultrasound output, the temperature of the test point increased slowly, and this experiment could increase the temperature of the tissue by up to 3.3 ℃, which would not lead to thermal damage to the tissue. Animal experiment results showed that the immunopositive area fraction of TGF-β1 in the urethral tissues of rabbits in the experimental group [(4.21 ± 1.32)%] was smaller than that of the model group [(8.53 ± 3.43)%] ( t = ?4.24, P < 0.001). The immunopositive area fraction of TNF-α in the urethral tissues of rabbits in the experimental group [(5.14 ± 2.72)%] was smaller than that of the model group [(7.23 ± 1.57)%] ( t = ?3.37, P < 0.05). The MMP-2 level in the urethral tissue of rabbits in the experimental group [(10.65 ± 2.24)%] was higher than that of the model group[(6.98 ± 2.74)%] ( t = 2.19, P < 0.05). The urethral circumference [(12 209 ± 2 743) μm] was higher than that of the model group [(10 127 ± 2 237) μm] ( t = 15.46, P < 0.05). Conclusions:An ultrasound therapeutic instrument dedicated to rabbit urethral scars has been successfully designed and can be used for the study of ultrasound treatment of rabbit urethral scars.

Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) functions as a key regulator in inflammation and cell death and is involved in mediating a variety of inflammatory or degenerative diseases. A number of allosteric RIPK1 inhibitors (RIPK1i) have been developed, and some of them have already advanced into clinical evaluation. Recently, selective RIPK1i that interact with both the allosteric pocket and the ATP-binding site of RIPK1 have started to emerge. Here, we report the rational development of a new series of type-II RIPK1i based on the rediscovery of a reported but mechanistically atypical RIPK3i. We also describe the structure-guided lead optimization of a potent, selective, and orally bioavailable RIPK1i, 62, which exhibits extraordinary efficacies in mouse models of acute or chronic inflammatory diseases. Collectively, 62 provides a useful tool for evaluating RIPK1 in animal disease models and a promising lead for further drug development.

This paper provided a comprehensive review of the concept, current situation and influencing factors of survivors returning to work after hematopoietic stem cell transplantation, both in domestic and international contexts. The research analyzed and elaborates on four aspects of individual factors, disease-related factors, occupational factors, and social support, in order to provide references for constructing an intervention program for the return to work of hematopoietic stem cell transplantation survivors based on the cultural background in China.