In Situ Evolution of Ionic Sites at Clay Mineral Interfaces Facilitates Fluoride and Phosphorus Mineralization.

Soil minerals influence the biogeochemical cycles of fluoride (F) and phosphorus (P), impacting soil quality and bioavailability to plants. However, the cooperative mechanisms of soil minerals in governing F and P in the soil environment remain a grand challenge. Here, we reveal the essential role of a typical soil mineral, montmorillonite (Mt), in the cycling and fate of F and P. The results show that the enrichment of metal sites on the Mt surface promotes the mineralization of F to the fluorapatite (FAP) phase, thereby remaining stable in the environment, simultaneously promoting P release. This differential behavior leads to a reduction in the level of F pollution and an enhancement of P availability. Moreover, solid-state NMR and HRTEM observations confirm the existence of metastable F-Ca-F intermediates, emphasizing the pivotal role of Mt surface sites in regulating crystallization pathways and crystal growth of FAP. Furthermore, the in situ atomic force microscopy and theoretical calculations reveal molecular fractionation mechanisms and adsorption processes. It is observed that a competitive relationship exists between F and P at the Mt interface, highlighting the thermodynamically advantageous pathway of forming metastable intermediates, thereby governing the activity of F and P in the soil environment at a molecular level. This work paves the way to reveal the important role of clay minerals as a mineralization matrix for soil quality management and offers new strategies for modulating F and P dynamics in soil ecosystems.

Review of the therapeutic effects of traditional Chinese medicine in sepsis-associated encephalopathy.

ETHNOPHARMACOLOGICAL RELEVANCE: Sepsis-associated encephalopathy (SAE) is a common and serious complication during the acute phase of and after recovery from sepsis that seriously affects the quality of life of patients. Traditional Chinese medicine (TCM) has been widely used in modern medicine for neurological anomalies and has become a therapeutic tool for the treatment of SAE due to its multitargeting effects and low toxicity and side effects. AIMS OF THE STUDY: This review provides insights into the pathogenesis and treatments of SAE, focusing on the clinical and experimental impacts of TCM formulations and their single components. METHODS: Several known databases such as PubMed, Web of Science, Google Scholar, China National Knowledge Infrastructure (CNKI), and others were extensively explored with keywords and phrases such as "sepsis-associated encephalopathy", "traditional Chinese medicine", "herbs", "SAE", "sepsis", "cerebral" or other relevant terms to obtain literature between 2018 and 2024. RESULTS: Extensive evidence indicated that TCM could decrease mortality and normalize neurological function in patients with sepsis; these effects might be associated with factors such as reduced oxidative stress and downregulated expression of inflammatory factors. CONCLUSIONS: TCM shows notable efficacy in treating SAE, warranting deeper mechanistic studies to optimize its clinical application.

Comparative effects of different posterior decompression techniques for lumbar spinal stenosis: a systematic review and Bayesian network meta-analysis.

STUDY DESIGN: A systematic review and Bayesian network meta-analysis (NMA). OBJECTIVE: To compare the effectiveness and safety of different posterior decompression techniques for LSS. Lumbar spinal stenosis (LSS) is one of the most common degenerative spinal diseases that result in claudication, back and leg pain, and disability. Currently, posterior decompression techniques are widely used as an effective treatment for LSS. METHODS: An electronic literature search was performed using the EMBASE, Web of Science, PubMed, and Cochrane Library databases. Two authors independently performed data extraction and quality assessment. A Bayesian random effects model was constructed to incorporate the estimates of direct and indirect treatment comparisons and rank the interventions in order. RESULTS: In all, 14 eligible studies comprising 1,260 patients with LSS were included. Five interventions were identified, namely, spinal processes osteotomy (SPO), conventional laminotomy/laminectomy (CL), unilateral laminotomy/laminectomy (UL), bilateral laminotomy/ laminectomy (BL), and spinous process-splitting laminotomy/laminectomy (SPSL). Among these, SPO was the most promising surgical option for decreasing back and leg pain and for lowering the Oswestry Disability Index (ODI). SSPL had the shortest operation time, while SPSL was associated with maximum blood loss. SPO and UL were superior to other posterior decompression techniques concerning lesser blood loss and shorter length of hospital stay, respectively. Patients who underwent BL had the lowest postoperative complication rates. CONCLUSION: Overall, SPO was found to be a good surgical choice for patients with LSS.

Targeting TANK-binding kinase 1 attenuates painful diabetic neuropathy via inhibiting microglia pyroptosis.

BACKGROUND: Painful diabetic neuropathy (PDN) is closely linked to inflammation, which has been demonstrated to be associated with pyroptosis. Emerging evidence has implicated TANK-binding kinase 1 (TBK1) in various inflammatory diseases. However, it remains unknown whether activated TBK1 causes hyperalgesia via pyroptosis. METHODS: PDN mice model of type 1 or type 2 diabetic was induced by C57BL/6J or BKS-DB mice with Lepr gene mutation. For type 2 diabetes PDN model, TBK1-siRNA, Caspase-1 inhibitor Ac-YVAD-cmk or TBK1 inhibitor amlexanox (AMX) were delivered by intrathecal injection or intragastric administration. The pain threshold and plantar skin blood perfusion were evaluated through animal experiments. The assessments of spinal cord, dorsal root ganglion, sciatic nerve, plantar skin and serum included western blotting, immunofluorescence, ELISA, and transmission electron microscopy. RESULTS: In the PDN mouse model, we found that TBK1 was significantly activated in the spinal dorsal horn (SDH) and mainly located in microglia, and intrathecal injection of chemically modified TBK1-siRNA could improve hyperalgesia. Herein, we described the mechanism that TBK1 could activate the noncanonical nuclear factor κB (NF-κB) pathway, mediate the activation of NLRP3 inflammasome, trigger microglia pyroptosis, and ultimately induce PDN, which could be reversed following TBK1-siRNA injection. We also found that systemic administration of AMX, a TBK1 inhibitor, could effectively improve peripheral nerve injury. These results revealed the key role of TBK1 in PDN and that TBK1 inhibitor AMX could be a potential strategy for treating PDN. CONCLUSIONS: Our findings revealed a novel causal role of TBK1 in pathogenesis of PDN, which raises the possibility of applying amlexanox to selectively target TBK1 as a potential therapeutic strategy for PDN.

Corrigendum: Dynamic evolution of left ventricular strain and microvascular perfusion assessed by speckle tracking echocardiography and myocardial contrast echocardiography in diabetic rats: effect of dapagliflozin.

[This corrects the article DOI: 10.3389/fcvm.2023.1109946.].

Chiral inversion induced by aromatic interactions in short peptide assembly.

Although hydrophobic interactions provide the main driving force for initial peptide aggregation, their role in regulating suprastructure handedness of higher-order architectures remains largely unknown. We here interrogate the effects of hydrophobic amino acids on handedness at various assembly stages of peptide amphiphiles. Our studies reveal that relative to aliphatic side chains, aromatic side chains set the twisting directions of single ß-strands due to their strong steric repulsion to the backbone, and upon packing into multi-stranded ß-sheets, the side-chain aromatic interactions between strands form the aromatic ladders with a directional preference. This ordering not only leads to parallel ß-sheet arrangements but also induces the chiral flipping over of single ß-strands within a ß-sheet. In contrast, the lack of orientational hydrophobic interactions in the assembly of aliphatic peptides implies no chiral inversion upon packing into ß-sheets. This study opens an avenue to harness peptide aggregates with targeted handedness via aromatic side-chain interactions.

Structural and functional abnormalities and cognitive profiles in older adults with early-onset and late-onset focal epilepsy.

This study aimed to determine the patterns of changes in structure, function, and cognitive ability in early-onset and late-onset older adults with focal epilepsy (OFE). This study first utilized the deformation-based morphometry analysis to identify structural abnormalities, which were used as the seed region to investigate the functional connectivity with the whole brain. Next, a correlation analysis was performed between the altered imaging findings and neuropsychiatry assessments. Finally, the potential role of structural-functional abnormalities in the diagnosis of epilepsy was further explored by using mediation analysis. Compared with healthy controls (n = 28), the area of reduced structural volume was concentrated in the bilateral cerebellum, right thalamus, and right middle cingulate cortex, with frontal, temporal, and occipital lobes also affected in early-onset focal epilepsy (n = 26), while late-onset patients (n = 31) displayed cerebellar, thalamic, and cingulate atrophy. Furthermore, correlation analyses suggest an association between structural abnormalities and cognitive assessments. Dysfunctional connectivity in the cerebellum, cingulate cortex, and frontal gyrus partially mediates the relationship between structural abnormalities and the diagnosis of early-onset focal epilepsy. This study identified structural and functional abnormalities in early-onset and late-onset focal epilepsy and explored characters in cognitive performance. Structural-functional coupling may play a potential role in the diagnosis of epilepsy.

Primary leiomyosarcoma of epididymis: a case report.

BACKGROUND: Leiomyosarcoma is a tumor that can develop in any organ that contains smooth muscles. Although leiomyosarcoma is common, its epididymal localization is quite rare. CASE PRESENTATION: A 79-year-old male Chinese Han patient presented with mild pain in the right groin and scrotum for 3 years concomitant with right scrotal swelling. Ultrasonography and magnetic resonance imaging of the scrotum showed a irregular and heterogeneous mass that was extratesticular. Right high orchiectomy was performed, and pathological examination of the resected specimen confirmed the diagnosis of leiomyosarcoma of the epididymis with surgical margins clear of tumor. CONCLUSION: Epididymal leiomyosarcoma is rare and difficult to diagnose preoperatively. The final diagnosis of epididymal leiomyosarcoma requires histologic examination. Resection must be extensive and complete. The effect of chemotherapy and radiation on the epididymal leiomyosarcoma remains unclear. Recurrence is common, so follow-up is necessary.

Desmoid tumors of rectus abdominis: A case report and literature review.

RATIONALE: Desmoid tumor (DT) is a rare soft tissue tumor that can occur anywhere in the body. Abdominal wall DT presents unique clinical challenges due to its distinctive manifestations, treatment modalities, and the lack of biomarkers for diagnosis and recurrence prediction, making clinical decisions exceedingly complex. PATIENT CONCERNS: A 32-year-old female who underwent radical resection combined with patch reinforcement for rectus abdominis DT, successfully alleviating abdominal discomfort, with no recurrence during the 6-month follow-up after surgery. DIAGNOSES: Based on the imaging studies and medical history, the patient underwent radical surgical resection. Histopathology reveals that the tumor cells predominantly composed of proliferative fibroblasts with local collagen deposition. The lesional cells show positive staining for ß-catenin, indicating a diagnosis of DT. INTERVENTIONS: The patient underwent radical surgical resection with patch reinforcement to repair the abdominal wall defect. Pathology confirmed negative margins, achieving an R0 resection, and genetic testing identified a T41A mutation in CTNNB1. Consequently, no additional adjuvant therapy was administered postoperatively. OUTCOMES: The patient was discharged with the incision healing well after 3 days postoperation. Upon reexamination 6 months later, no recurrence or adverse complications were observed. LESSONS: Abdominal wall DT treatment requires personalized plans from multidisciplinary team discussions. Genetic testing plays a crucial role in identifying novel biomarkers for abdominal wall DT. We have once again demonstrated the significant clinical significance of CTNNB1 mutations in the diagnosis and progression of abdominal wall DT. Additionally, genes such as CCND1, CYP3A4, SLIT1, RRM1, STIM1, ESR2, UGT1A1, among others, may also be closely associated with the progression of abdominal wall DT. Future research should delve deeper into and systematically evaluate the precise impact of these genetic mutations on treatment selection and prognosis for abdominal wall DT, in order to better guide patient management and treatment decisions.

Classification and Regression Machine Learning Models for Predicting the Combined Toxicity and Interactions of Antibiotics and Fungicides Mixtures.

Antibiotics and triazole fungicides coexist in varying concentrations in natural aquatic environments, resulting in complex mixtures. These mixtures can potentially affect aquatic ecosystems. Accurately distinguishing synergistic and antagonistic mixtures and predicting mixture toxicity are crucial for effective mixture risk assessment. We tested the toxicities of 75 binary mixtures of antibiotics and fungicides against Auxenochlorella pyrenoidosa. Both regression and classification models for these mixtures were developed using machine learning models: random forest (RF), k-nearest neighbors (KNN), and kernel k-nearest neighbors (KKNN). The KKNN model emerged as the best regression model with high values of determination coefficient (R2 = 0.977), explained variance in prediction leave-one-out (Q2LOO = 0.894), and explained variance in external prediction (Q2F1 = 0.929, Q2F2 = 0.929, and Q2F3 = 0.923). The RF model, the leading classifier, exhibited high accuracy (accuracy = 1 for the training set and 0.905 for the test set) in distinguishing the synergistic and antagonistic mixtures. These results provide crucial value for the risk assessment of mixtures.

Microscale Normal Compression Behaviors of Clay Aggregates: A Coarse-Grained Molecular Dynamics Study.

Given the limitations of micromechanical experiments and molecular dynamics simulations, the normal compression process of clay aggregates was simulated under different vertical pressures (P), numbers of particles, loading methods, and environments by a Gay-Berne potential model. On the basis of the variations of particle orientation and the distribution of stacks, the evolution of deformation and stresses was elucidated. The results showed that the effects of the pressure level and loading environment on the deformation were significant. In the range of 0.1-10 MPa, the changes in the void ratio were essentially the evolution of the distribution of stacks determined by attractive short-range van der Waals interactions. The deformation under constant pressure was larger than that under step loading. Because the interactions between clay particles were mainly controlled by mechanical force when in the range of 40-100 MPa, the void ratios under various loading conditions were consistent. It was also found that changes in three-dimensional stresses during compression were dependent on those of the distribution of stacks. In the vacuum environment, owing to the lateral movement of interlocked small stacks, the horizontal stress decreased. The lateral pressure coefficients (k) were greater in an atmospheric environment because the anisotropic particle orientation was relatively less obvious. In the range of 10-100 MPa, when the loading path became longer, k was similar in vacuum but became smaller in an atmosphere. If the initial loading pressure was increased, the number of large stacks sharply increased and the anisotropy was significant in a vacuum environment, which was less prone to lateral expansion. In contrast, more consistent particle arrangements were maintained in an atmosphere. This work will be conducive to explaining experimental observations of long-term ripening.

High-Intensity Focused Ultrasound Ablation Combined With Pharmacogenomic-Guided Chemotherapy for Advanced Pancreatic Cancer: Initial Experience.

OBJECTIVE: To investigate the safety and efficacy of high-intensity focused ultrasound (HIFU) ablation combined with pharmacogenomic-guided chemotherapy in treating patients with advanced pancreatic cancer (PC). METHODS: Thirty-one patients with unresectable PC (stage III 17, stage IV 14) were enrolled in this study. The patients were divided into group A (pharmacogenomic-guided chemotherapy following HIFU treatment, n = 13) and group B (traditional chemotherapy following HIFU treatment, n = 18). Contrast-enhanced computed tomography and magnetic resonance imaging were used to evaluate tumor response. Pain intensity was assessed using the numerical rating scale. The Kaplan-Meier method and log-rank test were used to analyze survival. RESULTS: The mean pain intensity score in 18 patients decreased from 6.6 ± 2.2 before HIFU to 3.3 ± 1.0 after HIFU (p = 0.000). The mean duration of pain relief was 5.2 ± 3.2 mo in group A and 2.4 ± 1.3 mo in group B (p = 0.026). There was no significant difference of the non-perfused volume ratio (83.5% ± 22.3% in group A and 85.3% ± 16.8% in group B) between the two groups. The median survival time was 14 mo in group A and 5 mo in group B. The 6 and 12-mo survival rates were 74.1% and 59.3% in group A, and 32.4% and 19.4% in group B, respectively. The difference in survival between the two groups was significant (p = 0.04). No severe complications (≥grade 3) related to HIFU were observed. Bone marrow depression was the main adverse reaction related to chemotherapy, with grade 3 bone marrow depression observed 2 (15.4%) patients in group A and 7 (38.9%) patients in group B. CONCLUSION: HIFU combined with pharmacogenomic-guided chemotherapy is safe and effective in treating patients with advanced PC. It provides better clinical outcomes in pain relief, quality of life and survival benefits for patients with advanced PC compared to HIFU combined with traditional chemotherapy. This combined approach may have the potential to become an important supplement to the treatment of advanced PC.

Expanding the Structural Diversity of Tubulin-Targeting Agents: Development of Highly Potent Benzimidazoles for Treating Fungal Diseases.

Benzimidazoles, the representative pharmacophore of fungicides, have excellent antifungal potency, but their simple structure and single site of action have hindered their wider application in agriculture. In order to extend the structural diversity of tubulin-targeted benzimidazoles, novel benzimidazole derivatives were prepared by introducing the attractive pyrimidine pharmacophore. 2-((6-(4-(trifluoromethyl)phenoxy)pyrimidin-4-yl)thio)-1H-benzo[d]imidazole (A25) exhibited optimal antifungal activity against Sclerotinia sclerotiorum (S. s.), affording an excellent half-maximal effective concentration (EC50) of 0.158 µg/mL, which was higher than that of the reference agent carbendazim (EC50 = 0.594 µg/mL). Pot experiments revealed that compound A25 (200 µg/mL) had acceptable protective activity (84.7%) and curative activity (78.1%), which were comparable with that of carbendazim (protective activity: 90.8%; curative activity: 69.9%). Molecular docking displayed that multiple hydrogen bonds and π-π interactions could be formed between A25 and ß-tubulin, resulting in a stronger bonding effect than carbendazim. Fluorescence imaging revealed that the structure of intracellular microtubules can be changed significantly after A25 treatment. Overall, these remarkable antifungal profiles of constructed novel benzimidazole derivatives could facilitate the application of novel microtubule-targeting agents.

Comprehensive investigation in oncogenic functions and immunological roles of NCBP2 and its validation in prostate cancer.

BACKGROUND: Nuclear cap-binding protein 2 (NCBP2), as the component of the cap-binding complex, participates in a number of biological processes, including pre-mRNA splicing, transcript export, translation regulation and other gene expression steps. However, the role of NCBP2 on the tumor cells and immune microenvironment remains unclear. To systematically analyze and validate functions of NCBP2, we performed a pan-cancer analysis using multiple approaches. METHODS: The data in this study were derived from sequencing, mutation, and methylation data in the TCGA cohort, normal sample sequencing data in the GTEx project, and cell line expression profile data in the CCLE database. RESULTS: Survival analyses including the Cox proportional-hazards model and log-rank test revealed the poor prognostic role of NCBP2 in multiple tumors. We further validated the oncogenic ability of NCBP2 in prostate cancer cell lines, organoids and tumor-bearing mice. A negative correlation was observed between NCBP2 expression and immune score by the ESTIMATE algorithm. Simultaneously, the NCBP2-induced immunosuppressive microenvironment might be related to the decline in CD8+T cells and the increase in regulatory T cells and neutrophils, examined by flow cytometry experiments for NCBP2 overexpressed tumor-bearing mice. CONCLUSION: This research offered strong proof supporting NCBP2 as the prognostic marker and the therapeutic target in the future.

Versatile Framework for Drug-Target Interaction Prediction by Considering Domain-Specific Features.

Predicting drug-target interactions (DTIs) is one of the crucial tasks in drug discovery, but traditional wet-lab experiments are costly and time-consuming. Recently, deep learning has emerged as a promising tool for accelerating DTI prediction due to its powerful performance. However, the models trained on limited known DTI data struggle to generalize effectively to novel drug-target pairs. In this work, we propose a strategy to train an ensemble of models by capturing both domain-generic and domain-specific features (E-DIS) to learn diverse domain features and adapt them to out-of-distribution data. Multiple experts were trained on different domains to capture and align domain-specific information from various distributions without accessing any data from unseen domains. E-DIS provides a comprehensive representation of proteins and ligands by capturing diverse features. Experimental results on four benchmark data sets in both in-domain and cross-domain settings demonstrated that E-DIS significantly improved model performance and domain generalization compared to existing methods. Our approach presents a significant advancement in DTI prediction by combining domain-generic and domain-specific features, enhancing the generalization ability of the DTI prediction model.

Integrated analysis of methylation and transcriptome identifies a novel risk model for diagnosis, prognosis, and immune characteristics in head and neck squamous cell carcinoma.

BACKGROUND: DNA methylation is an important epigenetic modification that plays a crucial role in the development and progression of various tumors. However, the association between methylation­driven genes and diagnosis, prognosis, and immune characteristics of head and neck squamous cell carcinoma (HNSCC) remains unclear. METHODS: We obtained transcriptome, methylation, and clinical data from HNSCC patients in TCGA database, and used MethylMix algorithm to identify methylation-driven genes. A methylation driven gene-related risk model was constructed using Lasso regression analysis, and validated using data from GEO database. Immune infiltration and immune function analysis of the expression profiles were conducted using ssGSEA. Differences in immune checkpoint-related genes were analyzed, and the efficacy of immunotherapy was evaluated using TCIA database. Finally, a series of cell functional experiments were conducted to validate the results. RESULTS: Five methylation-driven genes were identified and utilized to construct a prognostic risk model. Based on the median risk score, all patients were categorized into high-risk and low-risk groups. The K-M analysis revealed that patients in the high-risk group have a worse prognosis. Additionally, the risk model demonstrated better prognostic predictive value as indicated by ROC analysis. GSEA enrichment analysis indicated that gene sets in the high and low-risk groups were primarily enriched in pathways associated with tumor immunity and metabolism. Our subsequent investigations showed that high-risk patients exhibited more immunosuppressive phenotypes, while low-risk patients were more likely to respond positively to immunotherapy. CONCLUSION: These findings of our research have the potential to improve patient stratification, guide treatment decisions, and advance the development of personalized therapies for HNSCC.

Prediction of tumor regression grade in far-advanced gastric cancer after preoperative immuno-chemotherapy using dual-energy CT-derived extracellular volume fraction.

OBJECTIVES: This study examines the effectiveness of dual-energy CT (DECT) delayed-phase extracellular volume (ECV) fraction in predicting tumor regression grade (TRG) in far-advanced gastric cancer (FAGC) patients receiving preoperative immuno-chemotherapy. MATERIALS AND METHODS: A retrospective analysis was performed on far-advanced gastric adenocarcinoma patients treated with preoperative immuno-chemotherapy at our institution from August 2019 to March 2023. Patients were categorized based on their TRG into pathological complete response (pCR) and non-pCR groups. ECV was determined using the delayed-phase iodine maps. In addition, tumor iodine densities and standardized iodine ratios were meticulously analyzed using the triple-phase enhanced iodine maps. Univariate analysis with five-fold cross-validation and Spearman correlation determined DECT parameters and clinical indicators association with pCR. The predictive accuracy of these parameters for pCR was evaluated using a weighted logistic regression model with five-fold cross-validation. RESULTS: Of the 88 patients enrolled (mean age 60.8 ± 11.1 years, 63 males), 21 (23.9%) achieved pCR. Univariate analysis indicated ECV's significant role in differentiating between pCR and non-pCR groups (average p value = 0.021). In the logistic regression model, ECV independently predicted pCR with an average odds ratio of 0.911 (95% confidence interval, 0.798-0.994). The model, incorporating ECV, tumor area, and IDAV (the relative change rate of iodine density from venous phase to arterial phase), showed an average area under curves (AUCs) of 0.780 (0.770-0.791) and 0.766 (0.731-0.800) for the training and validation sets, respectively, in predicting pCR. CONCLUSION: DECT-derived ECV fraction is a valuable predictor of TRG in FAGC patients undergoing preoperative immuno-chemotherapy. CLINICAL RELEVANCE STATEMENT: This study demonstrates that DECT-derived extracellular volume fraction is a reliable predictor for pathological complete response in far-advanced gastric cancer patients receiving preoperative immuno-chemotherapy, offering a noninvasive tool for identifying potential treatment beneficiaries.

Active on-site calibration technology of current transformer based on non-rated frequency current injection.

This paper proposes an active on-site calibration method through background current cancellation and non-rated current injection. It can measure the error of the current transformer in service from 1% to 120% rated current percentage without power supply interruption. In order to establish the error relationship between rated frequency and arbitrary frequency, a theoretical analysis of current transformer calibration at the arbitrary frequency has been developed by means of the equivalent circuit. It describes a method to determine the phase angle and ratio errors of the measuring transformers at arbitrary frequencies on the basis of the calibrated error values at rated frequency. To prove the theoretical analysis, an experimental validation was carried out. The experimental results demonstrate that this active onsite calibration is a valid tool for the evaluation of current transformer performances. The calibration results showed that, for both cases (non-rated frequency calibration and mixing frequency calibration), the difference between mean ratio error and rated frequency ratio error was lower than 0.01%, and the difference between mean phase error and rated frequency phase error was lower than 1', which meets the requirement of the 0.2 accuracy class calibration.

Comparison of the therapeutic effects of three minimally invasive approaches for laparoscopic cholecystectomy combined with common bile duct exploration-- a 5-year retrospective analysis.

OBJECTIVE: The aim of this retrospective study was to explore the indications for three minimally invasive approaches-T-tube external drainage, double J-tube internal drainage, and primary closure-in laparoscopic cholecystectomy combined with common bile duct exploration. METHODS: Three hundred eighty-nine patients with common bile duct stones who were treated at the Second People's Hospital of Hefei between February 2018 and January 2023 were retrospectively included. Patients were divided into three groups based on the surgical approach used: the T-tube drainage group, the double J-tube internal drainage group, and the primary closure group. General data, including sex, age, and BMI, were compared among the three groups preoperatively. Surgical time, length of hospital stay, pain scores, and other aspects were compared among the three groups. Differences in liver function, inflammatory factors, and postoperative complications were also compared among the three groups. RESULTS: There were no significant differences among the three groups in terms of sex, age, BMI, or other general data preoperatively (P > 0.05). There were significant differences between the primary closure group and the T-tube drainage group in terms of surgical time and pain scores (P < 0.05). The primary closure group and double J-tube drainage group differed from the T-tube drainage group in terms of length of hospital stay, hospitalization expenses, and time to passage of gas (P <0.05). Among the three groups, there were no statistically significant differences in inflammatory factors or liver function, TBIL, AST, ALP, ALT, GGT, CRP, or IL-6, before surgery or on the third day after surgery (P > 0.05). However, on the third day after surgery, liver function in all three groups was significantly lower than that before surgery (P<0.05). In all three groups, the levels of CRP and IL-6 were significantly lower than their preoperative levels. The primary closure group had significantly lower CRP and IL-6 levels than did the T-tube drainage group (P < 0.05). The primary closure group differed from the T-tube drainage group in terms of the incidences of bile leakage and electrolyte imbalance (P < 0.05). The double J-tube drainage group differed from the T-tube drainage group in terms of the tube dislodgement rate (P < 0.05). CONCLUSION: Although primary closure of the bile ducts has clear advantages in terms of length of hospital stay and hospitalization expenses, it is associated with a higher incidence of postoperative complications, particularly bile leakage. T-tube drainage and double J-tube internal drainage also have their own advantages. The specific surgical approach should be selected based on the preoperative assessment, indications, and other factors to reduce the occurrence of postoperative complications.

The effect of rifaximin and lactulose treatments to chronic hepatic encephalopathy rats: An [18F]PBR146 in-vivo neuroinflammation imaging study.

INTRODUCTION: Hepatic encephalopathy (HE) is a severe neuropsychiatric complication of liver diseases characterized by neuroinflammation. The efficacies of nonabsorbable rifaximin (RIF) and lactulose (LAC) have been well documented in the treatment of HE. [18F]PBR146 is a translocator protein (TSPO) radiotracer used for in vivo neuroinflammation imaging. This study investigated anti-neuroinflammation effect of RIF or/and LAC in chronic HE rats by [18F]PBR146 micro-PET/CT. METHODS: Bile duct ligation (BDL) operation induced chronic HE models, and this study included Sham+normal saline (NS), BDL+NS, BDL+RIF, BDL+LAC, and BDL+RIF+LAC groups. Behavioral assessment was performed to analyze the motor function, and fecal samples were collected after successfully established the chronic HE model (more than 28 days post-surgery). In addition, fecal samples collection and micro-PET/CT scans were performed sequentially. And we also collected the blood plasma, liver, intestinal, and brain samples after sacrificing the rats for further biochemical and pathological analyses. RESULTS: The RIF- and/or LAC-treated BDL rats showed similar behavioral results with Sham+NS group, while the treatment could not reverse the biliary obstruction resulting in sustained liver injury. The RIF or/and LAC treatments can inhibit IFN-γ and IL-10 productions. The global brain uptake values of [18F]PBR146 in BDL+NS group was significantly higher than other groups (p < .0001). The brain regions analysis showed that the basal ganglia, hippocampus, and cingulate cortex had radiotracer uptake differences among groups (all p < .05), which were consistent with the brain immunohistochemistry results. Sham+NS group was mainly enriched in Christensenella, Coprobacillus, and Pseudoflavonifractor. BDL+NS group was mainly enriched in Barnesiella, Alloprevotella, Enterococcus, and Enterorhabdus. BDL+RIF+LAC group was enriched in Parabacteroides, Bacteroides, Allobaculum, Bifidobacterium, and Parasutterella. CONCLUSIONS: RIF or/and LAC had anti-neuroinflammation in BDL-induced chronic HE rats with gut microbiota alterations. The [18F]PBR146 could be used for monitoring RIF or/and LAC treatment efficacy of chronic HE rats.