Primary biliary cholangitis （PBC） is an autoimmune liver disease characterized by intrahepatic cholestasis， while fatigue is a common symptom of PBC that significantly affects the quality of life of patients. The pathogenesis of fatigue is complex and may be associated with the factors such as cholestasis-induced inflammation， gut microbiota dysbiosis， brain structural and functional abnormalities， and mitochondrial dysfunction. At present， first-line therapies and liver transplantation have a limited effect in alleviating fatigue， and there is still a lack of standardized comprehensive assessment system. Emerging drugs and non-pharmaceutical interventions， including lifestyle modifications， have shown potential application prospects. This article systematically reviews the research advances in the clinical manifestations， pathogenesis， clinical assessment， and intervention of fatigue in PBC patients， in order to provide a reference for optimizing treatment strategies and promoting the research and development of new therapies.

Based on spleen deficiency-phlegm dampness as the core pathogenesis of obesity， and integrating recent advances in modern medicine regarding the key role of immune inflammation in obesity， this paper proposes a multidimensional pathogenic network of "obesity-spleen deficiency-phlegm dampness-immune imbalance". Various traditional Chinese medicine （TCM） herbs that strengthen the spleen， regulate qi， and resolve phlegm and dampness can treat obesity by improving spleen-stomach transport and transformation， promoting water-damp metabolism， and regulating immune homeostasis. This highlights immune inflammation as an important entry point to elucidate the TCM concepts of "spleen deficiency-phlegm dampness" and the therapeutic principle of "strengthening the spleen and eliminating dampness to treat obesity". By systematically analyzing the intrinsic connection between "spleen deficiency generating dampness， internal accumulation of phlegm dampness" and immune dysregulation in obesity， this paper aims to provide theoretical support for TCM treatment of obesity based on dampness.

ObjectiveTo explore the quantity-quality transfer process of medicinal materials， decoction pieces and standard decoction of Haliotidis Concha（Haliotis discus hannai） by analyzing the physical phase and compositional changes， so as to provide references for the effective control of its quality. MethodsA total of 20 batches of Haliotidis Concha（H. discus hannai） from different habitats were collected and prepared into corresponding calcined products and standard decoction， and the content of CaCO₃ of the three samples were determined and the extract yield and transfer rate of CaCO₃ were calculated. The changes in elemental composition and their relative contents were investigated by X-ray fluorescence spectrometry（XRF）， X-ray diffraction（XRD） was used to study the changes in the phase compositions of the three samples and to establish their respective XRD specific chromatogram. Fourier transform infrared spectrometry（FTIR） was used to study the changes in the chemical composition and content changes of the three samples and to establish their respective FTIR specific chromatogram， while combining hierarchical cluster analysis（HCA）， principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA） to find the common and differential characteristics， in order to explore the quantity-quality transfer relationship in the preparation process of standard decoction of Haliotidis Concha（H. discus hannai）. ResultsThe CaCO₃ contents of the 20 batches of medicinal materials， decoction pieces and standard decoction of Haliotidis Concha（H. discus hannai） were 93.87%-98.95%， 96.02%-99.97% and 38.29%-51.96%， respectively， and the extract yield of standard decoction was 1.71%-2.37%， and the CaCO₃ transfer rate of decoction pieces-standard decoction was 0.68%-1.27%. XRF results showed that the elemental species and their relative contents contained in Haliotidis Concha and its calcined products had a high degree of similarity， and although there was no obvious difference in the elemental species contained in decoction pieces and standard decoction， the difference in the relative contents was obvious， which was mainly reflected in the decrease of the relative content of element Ca and the increase of the relative content of element Na. XRD results showed that Haliotidis Concha mainly contained CaCO₃ of aragonite and calcite， while calcined Haliotidis Concha only contained CaCO₃ of calcite， and standard decoction mainly contained CaCO₃ of calcite and Na₂CO₃ of natrite. FTIR results showed that there were internal vibrations of O-H， C-H， C=O， HCO₃^- and CO₃^2- groups in Haliotidis Concha， while O-H， HCO₃^- and CO₃^2- groups existed in the calcined products and standard decoction. ConclusionThe changes of Haliotidis Concha and calcined Haliotidis Concha are mainly the increase of CaCO₃ content， the transformation of CaCO₃ aragonite crystal form to calcite crystal form and the absence of organic components after calcination， and the changes of calcined products and standard decoction are mainly the decrease of CaCO₃ content and the increase of Na₂CO₃ relative content. The method established in the study is applicable to the quality control of the shellfish medicines-decoction pieces- standard decoction， which provides a new idea for the study of quality control of dispensing granules of shellfish medicines.

ObjectiveTo explore the quantity-quality transfer process of medicinal materials， decoction pieces and standard decoction of Haliotidis Concha（Haliotis discus hannai） by analyzing the physical phase and compositional changes， so as to provide references for the effective control of its quality. MethodsA total of 20 batches of Haliotidis Concha（H. discus hannai） from different habitats were collected and prepared into corresponding calcined products and standard decoction， and the content of CaCO₃ of the three samples were determined and the extract yield and transfer rate of CaCO₃ were calculated. The changes in elemental composition and their relative contents were investigated by X-ray fluorescence spectrometry（XRF）， X-ray diffraction（XRD） was used to study the changes in the phase compositions of the three samples and to establish their respective XRD specific chromatogram. Fourier transform infrared spectrometry（FTIR） was used to study the changes in the chemical composition and content changes of the three samples and to establish their respective FTIR specific chromatogram， while combining hierarchical cluster analysis（HCA）， principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA） to find the common and differential characteristics， in order to explore the quantity-quality transfer relationship in the preparation process of standard decoction of Haliotidis Concha（H. discus hannai）. ResultsThe CaCO₃ contents of the 20 batches of medicinal materials， decoction pieces and standard decoction of Haliotidis Concha（H. discus hannai） were 93.87%-98.95%， 96.02%-99.97% and 38.29%-51.96%， respectively， and the extract yield of standard decoction was 1.71%-2.37%， and the CaCO₃ transfer rate of decoction pieces-standard decoction was 0.68%-1.27%. XRF results showed that the elemental species and their relative contents contained in Haliotidis Concha and its calcined products had a high degree of similarity， and although there was no obvious difference in the elemental species contained in decoction pieces and standard decoction， the difference in the relative contents was obvious， which was mainly reflected in the decrease of the relative content of element Ca and the increase of the relative content of element Na. XRD results showed that Haliotidis Concha mainly contained CaCO₃ of aragonite and calcite， while calcined Haliotidis Concha only contained CaCO₃ of calcite， and standard decoction mainly contained CaCO₃ of calcite and Na₂CO₃ of natrite. FTIR results showed that there were internal vibrations of O-H， C-H， C=O， HCO₃^- and CO₃^2- groups in Haliotidis Concha， while O-H， HCO₃^- and CO₃^2- groups existed in the calcined products and standard decoction. ConclusionThe changes of Haliotidis Concha and calcined Haliotidis Concha are mainly the increase of CaCO₃ content， the transformation of CaCO₃ aragonite crystal form to calcite crystal form and the absence of organic components after calcination， and the changes of calcined products and standard decoction are mainly the decrease of CaCO₃ content and the increase of Na₂CO₃ relative content. The method established in the study is applicable to the quality control of the shellfish medicines-decoction pieces- standard decoction， which provides a new idea for the study of quality control of dispensing granules of shellfish medicines.

OBJECTIVE: To explore short-term clinical efficacy of minimally invasive diagnosis and treatment system for hallux valgus in guiding the treatment of hallux valgus. METHODS: From March 2021 to November 2023, 68 patients (136 feet) with hallux valgus were treated under guidance of minimally invasive diagnosis and treatment system, including 12 males and 56 females;aged from 25 to 68 years old with an average of (42.5±8.5) years old, the course of disease ranged from 3.2 to 15.6 years with an average of (10.3±2.6) years. The changes of hallux valgus angle (HVA) and intermetatarsal angle (IMA), visual analog scale (VAS) and American Orthopaedic Foot Ankle Society (AOFAS) forefoot score were recorded and compared before operation and 12 months after operation. RESULTS: Sixty-five patients (130 feet) were followed up for 12 to 15 months with an average of (13.8±0.5) months, 3 patients (6 feet) were not followed up as required. HVA and IMA improved from (35.5±3.5) ° and (12.5±2.0) ° before operation to (10.5±2.5) ° and (8.5±1.5) °12 months after operation, respectively, with statistically significant differences (P<0.05);VAS decreased from (5.5±1.2) before operation to (1.2±0.5) at 12 months after operation, and the difference was statistically significant (P<0.05);AOFAS forefoot score increased from (50.6±5.1) before operation to (93.8±5.6) at 12 months after operation, with a statistically significant difference (P<0.05). Among them, 102 feet were got excellent result, 24 feet good, and 4 feet fair. Two patients were developed calf intermuscular vein thrombosis, and were cured after 3 months of symptomatic treatment. CONCLUSION Under the guidance of minimally invasive diagnosis and treatment system for hallux valgus, the treatment of HV could obviously improve HVA and IMA, and significantly alleviate pain symptoms, and accelerate functional recovery.
Humans ; Hallux Valgus/diagnosis* ; Male ; Female ; Middle Aged ; Adult ; Aged ; Minimally Invasive Surgical Procedures/methods* ; Treatment Outcome

The v-Raf murine sarcoma viral oncogene homolog B (BRAF) gene is one of the most critical proto-oncogenes and functions as a key regulator in the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) signaling pathway. The incidence of BRAF mutations in non-small cell lung cancer (NSCLC) patients ranges from 1.5% to 5.5%, with BRAF V600 mutations accounting for approximately 30%-50% of all BRAF mutations, among which BRAF V600E represents the most prevalent mutation type. Currently, the combination of Dabrafenib and Trametinib has been recommended as first-line therapy for BRAF V600-mutant NSCLC by multiple domestic and international guidelines including National Comprehensive Cancer Network (NCCN), European Society of Medical Oncology (ESMO), and Chinese Society of Clinical Oncology (CSCO). However, there are no clear targeted treatment recommendations for BRAF non-V600 mutations. Although case reports suggest that Dabrafenib combined with Trametinib may be effective for patients with BRAF non-V600 mutations, the efficacy and safety require further validation due to limited sample size and lack of large-scale clinical trial data. This article reports a case of NSCLC with a rare BRAF insertion and deletion mutation that responded well to the treatment of Dabrafenib in combination with Trametinib, aiming to enhance clinicians' understanding of such NSCLC cases with extremely rare mutation and provide a reference for future treatment strategies.
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Humans ; Carcinoma, Non-Small-Cell Lung/pathology* ; Imidazoles/administration & dosage* ; Lung Neoplasms/pathology* ; Mutation ; Neoplasm Metastasis ; Oximes/administration & dosage* ; Proto-Oncogene Mas ; Proto-Oncogene Proteins B-raf/genetics* ; Pyridones/administration & dosage* ; Pyrimidinones/administration & dosage*

Aim To investigate the pharmacological mechanism of Ebselenin(Ebselen,EbSe)in the treat-ment of Escherichia coli(E.coli)infection,which had no significant inhibitory effect on Gram-negative bacte-ria,based on previous studies.Methods After EbSe intervention in E.coli infected Raw264.7 cells,the via-bility of Raw264.7 cells was determined by CCK-8 method,the morphology and structure of Raw264.7 cells were observed by electron microscope,and the in-tracellular bacterial load of Raw264.7 cells was calcu-lated by coated plate method.Polarization status of peritoneal macrophages,Raw264.7 intracellular NO and ROS content and intracellular HO-1 expression in Raw264.7 and E.coli acutely infected mice after E.co-li infection by flow cytometry.qPCR was used to detect the expression of related mRNAs in Raw264.7 cells.qPCR was used to detect the intracellular GSH content in Raw264.7 cells by spectrophotometric assay,and the state of cytoskeletal proteins was observed by immuno-fluorescence.Western blot assay was performed to de-tect the intracellular Txnrd1 expression level.Results Microtiter method,CCK-8,and electron microscopy observations showed that EbSe had no effect on the growth of E.coli and Raw264.7 cells in vitro.The re-sults of smear plate counting showed that EbSe reduced the intracellular bacterial load of Raw264.7 in the in-fected group.Flow cytometry results showed that EbSe upregulated the number of M2-type macrophages.The EbSe-treated infected group had reduced intracellular NO and ROS levels and increased GSH levels.The qPCR results showed that the expression of IL-6,IL-1β,and iNOS was decreased,and the expression of HO-1,Txnrd1,and Glut1 was increased in DHB4-in-fected Raw264.7 cells after EbSe treatment.Cytoskel-etal staining showed that the morphology of the EbSe-treated infected cells was similar to that of oxPAPC-in-duced cells.Western blot results showed the expres-sion of Txnrd1 protein in EbSe-treated infected cells in-creased.Conclusion EbSe exerts anti-E.coli acute infection effect by regulating macrophage polarization and inhibiting macrophage excessive inflammatory state.

This study aims to clarify the incidence and prevention status of dairy cow mastitis in 79 large-scale pastures in China in 2022,reduce the incidence of dairy cow mastitis,and provide scien-tific basis for formulating prevention and control strategies for dairy cow mastitis in large-scale pastures suitable for China's national conditions.The research team relied on the large-scale ranch of the Comprehensive Experimental Station of National Dairy Industry Technology System to car-ry out research.A total of 79 questionnaires were received.The information on the stock of large-scale farms,the proportion of cows in the herd,the level of cow yields,the incidence and cure rate of cow mastitis,the prevention and control of cow mastitis,diagnosis and treatment programs of cow mastitis,the cost of treating cow mastitis,and the culling rate of farms was collected.Chi-square test and correlation analysis were carried out on the incidence of mastitis in dairy cows and the prevention and control plan,treatment plan,yield level and elimination rate of mastitis in dairy cows by descriptive statistical cross table.The incidence of cow mastitis in some pastures was con-trolled between 5％and 10％,and the cure rate was mostly as high as 98％.According to the co-hort analysis,the importance of prevention and control measures for dairy cow mastitis was as fol-lows:DMT＞DHI＞milk yield＞milk traits＞breast apparent change＞electrical conductivity＞CMT.The importance of treatment measures for dairy cow mastitis is as follows:DMT＞DHI＞milk yield＞milk traits＞breast apparent changes＞electrical conductivity＞CMT.The importance of treatment measures for mastitis is as follows:traditional Chinese medicine＞pathogen detection and drug sensitivity test＞non-steroidal anti-inflammatory drugs＞regular maintenance of milking equipment＞normal milking without treatment＞broad-spectrum antibiotics.The incidence of mas-titis in dairy cows is moderately positively correlated with the yield per unit area,that is,the in-crease in the incidence of mastitis in dairy cows has a certain impact on the yield per unit area of dairy cows.Economic analysis shows that the treatment cost of mastitis is closely related to the in-cidence rate,and the treatment cost of pasture with higher incidence rate is higher.Pastures with higher yields usually have more efficient means of disease prevention and control,and the corre-sponding treatment costs are lower.In conclusion,China's large-scale pastures should strengthen the scientific feeding management level,improve the prevention and control methods to reduce the incidence of cow mastitis,improve the cure rate,and reduce the cost of pasture treatment.

This study was aimed at establishing a sensitive and specific sandwich ELISA detection method for Brucella.We screened monoclonal capture antibodies and detection antibodies for Brucella detection,and optimized and determined the opti-mal antibody coating time and concentration,as well as the optimal blocking solution,blocking time,and yin-yang critical val-ue.The specificity of this method was verified by examination of other bacteria prone to cross-reacting with Brucella.The sen-sitivity of the method was verified by detection of a gradient dilution of inactivated Brucella.Moreover,the sandwich ELISA detection results were compared with test tube agglutination and qPCR results.The selected capture antibody was 4A12,and the selected detection antibody was 6C12.Experimental analysis indicated that the optimal coating concentration for the 4A12 capture antibody was 5 μg/mL,and the optimal dilution ratio for the 6C12 detection antibody was 1∶2000.The optimal coating conditions were overnight at 4℃,and blocking with 5％skim milk powder for 2 hours.The established double antibody sand-wich ELISA method reacted with only Brucella but not other bacteria,thus demonstrating the method's good specificity.Inac-tivated Brucella solution was still detectable after dilution to 1 × 105 CFU/mL,thus demonstrating the method's good sensitiv-ity.The intra-and inter batch coefficients of variation were both below 10％,thus indicating the method's good repeatability.Thus,this study successfully established a dual antibody sandwich ELISA method for Brucella detection,which has good spe-cificity and sensitivity,and might provide an effective approach for the precise diagnosis and effective prevention and control of brucellosis.

Objective:To investigate the value of biparametric-MRI (bpMRI) based peritumoral radiomics for preoperative prediction of extraprostatic extension (EPE) in prostate cancer (PCa).Methods:In this cross-sectional study, consecutive bpMRI of patients undergoing prostatectomy for PCa were retrospectively collected from the First Medical Center (center 1) and the Third Medical Center (center 2) of Chinese PLA General Hospital. A total of 274 patients were finally enrolled. Patients at center 1 from January 2020 to December 2022 were randomly divided into a training set (149 cases) and an internal validation set (63 cases) by stratified random sampling. Patients at center 2 from January 2023 to March 2024 were assigned to the external test set (62 cases). Patients were categorized into EPE-positive group and EPE-negative group according to pathological assessment postoperatively. In the training set, there were 49 cases in EPE-positive group and 100 cases in EPE-negative group. In the internal validation set, there were 26 cases in EPE-positive group and 37 cases in EPE-negative group. In the external test set, there were 22 cases in EPE-positive group and 40 cases in EPE-negative group. Axial T 2WI and apparent diffusion coefficient (ADC) images were manually annotated to obtain index lesion regions of interest (ROIs), with the peritumoral ROIs subsequently delineated by semi-automatic segmentation technique. Radiomics features were extracted from intra-tumoral, peri-tumoral, and intra-tumoral plus peri-tumoral ROIs. The training set data was employed to select and optimize features to build the radiomics models. The logistic regression analysis was used to develop radiomics, clinical, and integrated models. The predictive performance was assessed by the area under the receiver operating characteristic curve (AUC) in the external test set, and compared by the DeLong test. The sensitivity and specificity were compared by the exact McNemar test. Results:In the external test set, the peri-tumoral radiomics model based on bpMRI showed the highest performance in evaluating EPE, with an AUC of 0.739 (95% CI 0.611-0.842), which was identified as the optimal radiomics model. EPE grade ( OR=6.151, 95% CI 3.371-11.226, P<0.001) was incorporated into the clinical model, with an AUC of 0.780 (95% CI 0.657-0.875) in the external test set. The integrated model had an AUC of 0.817 (95% CI 0.698-0.904) in the external test set. There was no statistically significant difference in comparisons of AUCs among the three models (all P>0.05). The sensitivity of the integrated model (68.2%) showed no significant difference from those of the clinical model and the optimal radiomics model (77.3% and 86.4%, respectively; P=0.500 and P=0.289). However, the specificity of the integrated model (85.0%) was significantly higher than those of the clinical model (67.5%, P=0.016) and the optimal radiomics model (50.0%, P<0.001). Conclusion:A bpMRI-based peritumoral radiomics integrating clinical model demonstrates high performance for preoperative prediction of EPE in PCa.