Objective: To investigate the microbial mechanisms of Banxia Xiexin Decoction (半夏泻心汤, BXXXD) in the treatment of esophageal precancerous lesions. Methods: A total of 30 specific pathogen-free (SPF) grade female C57BL/6J mice were randomly assigned to a control group (n = 6) and a 4-nitroquinoline 1-oxide (4-NQO)-exposed group (n = 24). Esophageal precancerous lesions were induced by providing the 4-NQO-exposed group with 4-NQO in drinking water (100 μg/mL) for 17 consecutive weeks, whereas control group received sterile drinking water. After model establishment, the mice in 4-NQO-exposed group were further randomized into model group and three BXXXD-treated groups: low-dose (BXXXD-L, 3.7 g/kg), medium-dose (BXXXD-M, 7.4 g/kg), and high-dose (BXXXD-H, 14.8 g/kg) groups (n = 6 per group). During the subsequent intervention period, mice in control and model groups were gavaged with sterile water, while mice in BXXXD groups were gavaged once daily with the corresponding dose of BXXXD aqueous extract for 4 weeks. Histopathological changes in esophageal tissues were observed by hematoxylin and eosin (HE) staining. The fecal and esophageal microbiota were profiled via 16S rDNA high-throughput sequencing to evaluate bacterial diversity, community structure, and co-occurrence networks. BXXXD chemical fingerprints were analyzed using ultra-high-performance liquid chromatography coupled with quadrupole QExactive Orbitrap mass spectrometry (UHPLC-QE-MS). Serum short-chain fatty acids (SCFA) level was quantified by targeted metabolomics using gas chromatography-mass spectrometry (GC-MS). Transcriptomic analysis of esophageal tissues was performed to assess gene expression profiles. Results: Compared with model group, BXXXD-M group exhibited reduced mucosal hyperplasia and more orderly epithelial cell arrangement, with superior therapeutic effects in comparison with both BXXXD-L and BXXXD-H groups (P < 0.01). Microbiota analysis revealed that BXXXD increased the abundance of beneficial Enterococcus and reduced pathogenic Escherichia-Shigella in the esophagus. In the gut, BXXXD elevated the relative abundance of beneficial taxa, including Lactobacillus, Dubosiella, Bacteroides, and Faecalibacterium. Targeted metabolomics showed that BXXXD significantly reduced total serum SCFA level (P < 0.01). Transcriptomic analysis indicated that BXXXD downregulated the expression of genes associated with the progression, migration, and invasion of esophageal cancer, which were identified as kallikrein-related peptidase 6 (Klk6), defensin beta 4 (Defb4), family with sequence similarity 3 member B (Fam3b), carboxypeptidase A4 (Cpa4), serum amyloid A1 (Saa1), and chitinase-like 1 (Chil1) (P < 0.05). Conclusion BXXXD may reduce the expression levels of esophageal cancer-related genes and improve esophageal precancerous lesions through modulation of the gut microbiota and metabolites.

ObjectiveThis paper aims to observe the syndrome improvement and negative antigen conversion rate of Qingxuan Daozhi formula in the treatment of influenza in children （heat accumulation in the lung and stomach syndrome）. MethodsThrough a multi-center randomized controlled methodology design，confirmed influenza cases were collected from October 2022 to April 2023 in the pediatrics department of eight hospitals，such as Dongfang Hospital of Beijing University of Chinese Medicine. A total of 180 children with influenza and heat accumulation in the lung and stomach syndrome conforming to the standard were recruited through the clinic. The sick children meeting the inclusion criteria were randomly divided into groups by a block-randomized method. The children in the experimental group were treated with Qingxuan Daozhi formula for five days，and those in the control group were treated with Oseltamivir Phosphate Granules for five days. The primary efficacy indicator was the negative conversion rate of influenza antigen detection. Secondary efficacy indicators were the Canadian acute respiratory illness and flu scale （CARIFS） and the incidence of complications，severe cases， and critical cases. Follow-up observation was conducted on the day of enrollment，48 hours after medication，72 hours after medication， and （6+1） d after medication. ResultsOne hundred and eighty participants were randomly assigned to the experimental group （90 cases） or the control group （90 cases）. All participants were followed up during the study. Comparison of influenza antigen detection results in the primary efficacy indicators showed that the average time of negative influenza antigen conversion in the experimental group was （5.29±1.25） d，and that in the control group was （5.40±1.68） d，without a statistically significant difference. After five days of intervention，52 cases in the experimental group and 51 cases in the control group converted to negative，without a statistically significant difference. CARIFS score results in the secondary efficacy indicators showed that during 72 hours after intervention，there were statistically significant differences between the experimental group and the control group in three dimensions， including headache，muscle soreness， and the need for extra care （P<0.05）. On the （6+1） days after the intervention，the differences in both the experimental group and the control group were statistically significant in 10 dimensions， including sore throat，bad sleep，uncomfortable feeling，poor spirit and fatigue，crying more than usual，the need for extra care，symptom，function，influence on parents，and total score （P<0.05）. The comparison results within the group in the dimensional scores of symptom， function， and influence on parents，as well as the CARIFS total score showed that with the delay of follow-up time，scores of both groups decreased significantly，with a statistically significant difference （P<0.01）. Inter-group comparison results showed that the mean score of the experimental group was higher than that of the control group at the time of enrollment. With the progress of intervention，the score of the experimental group was significantly decreased compared with that of the control group. At the end of follow-up，the mean score of the experimental group was lower than that of the control group，with no statistically significant difference. In terms of the incidence of complications，severe cases， and critical cases， there were no complications，severe cases， and critical cases in the two groups，without a statistically significant difference. ConclusionThe symptom improvement effect and negative antigen conversion rate of Qingxuan Daozhi formula in the treatment of influenza in children （heat accumulation in the lung and stomach syndrome） are not inferior to Oseltamivir Phosphate granules， and children's acceptance is better. It can be more widely used in clinical treatment of influenza in children （heat accumulation in the lung and stomach syndrome）.

[Objective] To evaluate the efficacy and safety of sacral neuromodulation (SNM) in the treatment of patients with benign prostatic hyperplasia (BPH) complicated with underactive bladder (UAB) who respond poorly to transurethral resection of the prostate (TURP). [Methods] A retrospective analysis was performed on 10 patients with BPH and UAB treated with TURP by the same surgeon in Zhongda Hospital Southeast University during Jan.2018 and Jan.2023.The residual urine volume was not significantly relieved after operation, and the maximum urine flow rate and urine volume per discharge were not significantly improved.All patients underwent phase I SNM, and urinary diaries were recorded before and after surgery to observe the average daily frequency of urination, volume per urination, maximum urine flow rate, and residual urine volume. [Results] The operation time was (97.6±11.2) min.During the postoperative test of 2-4 weeks, if the residual urine volume reduction by more than 50% was deemed as effective, SNM was effective in 6 patients (60.0%). Compared with preoperative results, the daily frequency of urination [(20.2±3.8) times vs. (13.2±3.2) times], volume per urination [(119.2±56.7) mL vs. (246.5±59.2) mL], maximum urine flow rate [(8.7±1.5) mL/s vs. (16.5±2.6) mL/s], and residual urine volume [(222.5±55.0) mL vs. (80.8±16.0) mL] were significantly improved, with statistical significance (P<0.05). There were no complications such as bleeding, infection, fever or pain.The 6 patients who had effective outcomes successfully completed phase II surgery, and the fistula was removed.During the follow-up of 1 year, the curative effect was stable, and there were no complications such as electrode displacement, incision infection, or pain in the irritation sites.The residual urine volume of the other 4 unsuccessful patients did not improve significantly, and the electrodes were removed and the vesicostomy tube was retained. [Conclusion] SNM is safe and effective in the treatment of BPH with UAB patients with poor curative effects after TURP.

ObjectiveTo investigate the anti-Alzheimer's disease （AD） effect of Dipsacus asper（DA） in the Caenorhabditis elegans model， and decipher the underlying mechanism via the peroxisome proliferator-activated receptor α （PPARα）/transcription factor EB （TFEB） pathway. MethodsFirst， transgenic AD C. elegans individuals were assigned into the blank control， model， positive control （WY14643， 20 µmol·L^-1）， and low-， medium-， and high-dose （100， 200， and 400 mg·L^-1， respectively） DA groups. The amyloid β-42 （Aβ₄₂） formation in the muscle cells， the paralysis time， and the deposition of amyloid β-protein （Aβ） in the head were detected. The lysosomal autophagy in the BV2 cell model was examined by Rluc-LC3wt/G120A. The expression levels of lysosomal autophagy-related proteins LC3Ⅱ， LC3I， LAMP2， and TFEB were detected by Western blot. Real-time quantitative polymerase chain reaction （Real-time PCR） was employed to determine the mRNA levels of autophagy-related genes beclin1 and Atg5 and lysosome-related genes LAMP2 and CLN2 downstream of PPARα/TFEB. A reporter gene assay was used to detect the transcriptional activities of PPARα and TFEB. Immunofluorescence was used to detect the fluorescence intensity of PPARα， and the active components of the ethanol extract of DA were identified by UPLC-MS. RCSB PDB， Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， and Autodock were used to analyze the binding between the active components and PPARα-ligand-binding domain （LBD）. ResultsCompared with the model group， the positive control group and 200 and 400 mg·L^-1 DA groups showed prolonged paralysis time （P<0.05）， and all the treatment groups showed decreased Aβ deposition in the head （P<0.01）. DA within the concentration range of 50-500 mg·L^-1 did not affect the viability of BV2 cells. In addition， DA enhanced the autophagy flux （P<0.05）， up-regulated the mRNA levels of beclin1， Atg5， LAMP2， and CLN2 （P<0.05， P<0.01）， promoted the nuclear translocation of TFEB （P<0.05）， increased LAMP2 expression and autophagy flux （P<0.05， P<0.01）， and enhanced the transcriptional activities of PPARα and TFEB （P<0.01）. The positive control group and 200 and 400 mg·L^-1 DA groups showed enhanced fluorescence intensity of PPARα in the BV2 nucleus （P<0.01）. UPLC-MS detected nine known compounds of DA， from which 8 active components of DA were screened out. The docking results suggested that a variety of components in DA could bind to PPARα-LBD and form stable hydrogen bonds. ConclusionDA may reduce the pathological changes in AD by regulating the PPARα-TFEB pathway.

BACKGROUND:The age distribution of patients with distal femur fracture is bimodal,being more common in young adults with high-energy injuries and older individuals with low-energy injuries.In cases of complex distal femoral fractures,a single less invasive stabilization system or retrograde femoral nail is insufficient to provide a stable environment for fracture healing and combined fixation is often necessary.OBJECTIVE:A novel combined fixation method(less invasive stabilization system combined with retrograde tibial nail)was developed for the treatment of type A3 distal femur fractures.Using finite element analysis,the bio-mechanical properties of this method were compared with two common combined fixation methods—dual plate(less invasive stabilization system combined with locking compression plate)and nail plate combination(less invasive stabilization system combined with retrograde femoral nail).This study aims to provide a theoretical basis for the selection of clinical internal fixation methods for distal femur fracture.METHODS:CT images of a 23-year-old healthy male volunteer were utilized to reconstruct the femur three-dimensional model using Mimics and Geomagic Studio software.This model was then compared with in vitro finite element analysis data from existing literature to validate the accuracy of the femoral three-dimensional model.The three-dimensional model of type A3 distal femur fractures and internal fixation were then created using Creo 5.0 software.Three kinds of different combined fixation methods(less invasive stabilization system+retrograde tibial nail,less invasive stabilization system+locking compression plate,less invasive stabilization system+retrograde femoral nail)were assembled and subjected to Boolean operation to establish three sets of finite element models.These models were then imported into Abaqus finite element analysis software to assign material properties,apply consistent boundary conditions,and submit calculations under three loads(normal standing,slow walking,and descending stairs).The resulting stress distribution within the internal fixation as well as overall and local deformation of the femur was analyzed.Furthermore,the failure risk and anti-deformation ability of the new combined fixation method(less invasive stabilization system combined with retrograde tibial nail)were evaluated.RESULTS AND CONCLUSION:(1)Although the anti-deformation ability of the less invasive stabilization system combined with retrograde tibial nail was approximately 10％lower than that of the less invasive stabilization system combined with locking compression plate,it was comparable to that of less invasive stabilization system combined with retrograde femoral nail and demonstrated good anti-deformation ability.(2)The stiffness of the femur with all three combined fixation methods remained consistent during gait,while femur displacement increased linearly with load,indicating high stability.(3)The failure risk associated with less invasive stabilization system combined with retrograde tibial nail was lower than that of the other two methods,with a 2.94％reduction in failure risk compared to less invasive stabilization system combined with locking compression plate.(4)This new combined fixation method offers distinct advantages in terms of anti-deformation ability,safety,and effectiveness,laying a theoretical foundation for further clinical application.

Objective:To revise the quality standards for pharmaceutical excipients such as medicinal brown sugar.Methods:This article combines the production and application of medicinal brown sugar,and refers to the requirements of GB/T35885-2018 brown sugar,the fourth general rules of the Chinese Pharmacopoeia 2020 edition,and other relevant requirements,and conducts research on its characteristics,identification,inspection,and assay.Results:A quality standard for medicinal brown sugar was established,and 10 batches of samples were tested according to the proposed quality standard.Conclusion:The establishment of this standard will provide quality assurance for the application of brown sugar in the pharmaceutical field.

Objective:To evaluate the diagnostic performance of the Vesical Imaging-Reporting and Data System（VI-RADS）based on multiparametric magnetic resonance imaging（mp-MRI）for muscle-invasive bladder cancer（MIBC）.Methods:A systematic search was conducted in PubMed，Web of Science，and Embase databases for studies published between September 2018 and December 2023 that investigated the use of VI-RADS for diagnosing MIBC. Inclusion criteria were studies utilizing mp-MRI-based VI-RADS scoring to determine MIBC. Exclusion criteria were studies with fewer than 10 patients，overlapping study populations，or those failing to assess the diagnostic performance of VI-RADS for MIBC. After quality assessment，RevMan 5.4 and Stata 15.1 were used to calculate pooled sensitivity and specificity，generate forest plots and summary receiver operating characteristic（SROC）curves，and determine the area under the curve（AUC）. Publication bias was assessed using Deeks funnel plot. Heterogeneity was evaluated using the I2 statistic，with meta-regression and subgroup analyses to explore its sources. Results:Twenty-nine studies involving 3 577 patients were included. At a VI-RADS cutoff of 3，the pooled sensitivity and specificity for MIBC diagnosis were 93%（95%CI 0.90-0.95）and 82%（95%CI 0.76-0.88），respectively. At a cutoff of 4，these values were 83%（95%CI 0.78-0.87）and 93%（95%CI 0.90-0.95）. The hierarchical SROC（HSROC）AUCs were 0.95 and 0.94 for cutoffs of 3 and 4，respectively. Subgroup and meta-regression analyses revealed that at a cutoff of 3，patient sample size，study design，MRI field strength，number of radiologists，surgical approach，and DWI/DCE imaging planes contributed to sensitivity heterogeneity（ P < 0.05）. All factors except study design and DWI plane were sources of specificity heterogeneity（ P < 0.05）. At a cutoff of 4，all factors significantly influenced heterogeneity in both sensitivity and specificity（ P < 0.05）. Meta-regression confirmed that both cutoffs（3 and 4）were significant sources of heterogeneity（ P < 0.05）. Conclusions:VI-RADS demonstrates excellent diagnostic performance for MIBC at both cutoffs（3 and 4），with VI-RADS ≥ 3 showing superior sensitivity and VI-RADS ≥ 4 offering higher specificity. The cutoff of 3 provides better overall diagnostic efficacy.

Objective:To explore the clinical characteristics and risk factors of acute kidney injury (AKI) in patients with diquat mixed with paraquat poisoning.Methods:We retrospectively analyzed the clinical data of 210 patients admitted to the department of emergency at our hospital with paraquat, diquat or mixed poisoning from January 20, 2016, to June 10, 2024. Based on the detection results of plasma toxicants, patients were categorized into three groups: the paraquat group (PQ group), and the diquat group (DQ group), the diquat-paraquat mixed group (mixed group). We compared clinical indices, occurrence, and severity of AKI among these groups. In the mixed group, patients were further divided into AKI and non-AKI subgroups based on the presence of AKI during hospitalization, and differences in clinical indices between these subgroups were analyzed. Univariate logistic regression and least absolute shrinkage and selection operator (Lasso) regressions were used to screen risk factors, and multivariate logistic regression was applied to establish the model. ROC curves were generated, and factors influencing AKI occurrence in the mixed group were identified.Results:A total of 88 patients were included in the PQ group, 28 in the DQ group, and 57 in the mixed group. Significant differences were observed among the three groups in terms of age, mortality rate, ingestion amount, body mass index(BMI), occurrence of AKI, the incidence of organ support therapy, SIRS score, PSS score, and APACHE Ⅱ score on admission ( P < 0.05). All three groups exhibited various degrees of AKI, with the mixed group showing a higher proportion and more severe conditions. In the mixed group, compared with the non-AKI group, the AKI group showed significantly higher values for age, number of deaths, ingestion amount, SIRS score, PSS score, APACHE Ⅱ score, plasma PQ concentration on admission, plasma DQ concentration on admission, white blood cell count (WBC), neutrophil count (NEUT), monocyte count (MONO), serum creatinine (SCr), procalcitonin (PCT), c-reactive protein (CRP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood lactic acid (Lac), and cystatin C (CysC) ( P < 0.05). Conversely, the estimated glomerular filtration rate (eGFR) and partial pressure of carbon dioxide (PCO2) were significantly lower in the AKI group ( P < 0.05). Additionally, in the mixed group, SCr levels at various times post-poisoning were significantly higher compared with the non-AKI group ( P < 0.05), showing an increasing trend and peaking at 212.19 ± 101.67 μmol/L on the fifth day after poisoning. Age, ingestion amount, SIRS score on admission, WBC, MONO, and PCO 2 were extracted by Lasso-Logistic regression. Multivariate logistic regression identified ingestion amount and SIRS score on admission as the independent risk factors for the occurrence of AKI in the mixed group. The area under the ROC curve for ingestion amount and SIRS score on admission was 0.991 (95% CI: 0.976-1.000), the sensitivity was 0.940 and the specificity was 1.000. Conclusions:The diquat mixed with paraquat poisoning is associated with a higher incidence and greater severity of AKI compared with poisoning with either PQ or DQ alone. Additionally, ingestion amount and SIRS score on admission have been identified as independent risk factors for the occurrence of AKI in patients with the mixed poisoning. The combined assessment of these two factors improves AKI prediction in patients with the mixed poisoning.

Food-derived bioactive peptides (FBPs), particularly those with ten or fewer amino acid residues and a molecular weight below 1300 Da, have gained increasing attention for their safe, diverse structures and specific biological activities. The development of FBP-based functional foods and potential medications depends on understanding their structure‒activity relationships (SARs), stability, and bioavailability properties. In this review, we provide an in-depth overview of the roles of FBPs in treating various diseases, including Alzheimer's disease, hypertension, type 2 diabetes mellitus, liver diseases, and inflammatory bowel diseases, based on the literature from July 2017 to Mar. 2023. Subsequently, attention is directed toward elucidating the associations between the bioactivities and structural characteristics (e.g., molecular weight and the presence of specific amino acids within sequences and compositions) of FBPs. We also discuss in silico approaches for FBP screening and their limitations. Finally, we summarize recent advancements in formulation techniques to improve the bioavailability of FBPs in the food industry, thereby contributing to healthcare applications.
Humans ; Peptides/therapeutic use* ; Structure-Activity Relationship ; Functional Food ; Diabetes Mellitus, Type 2/drug therapy* ; Biological Availability ; Alzheimer Disease/drug therapy* ; Inflammatory Bowel Diseases/drug therapy* ; Hypertension/drug therapy* ; Liver Diseases/drug therapy* ; Bioactive Peptides, Dietary