ObjectiveTo explore the pharmacological mechanism of Tanreqing gel （TRQG） in the treatment of acne by regulating the Toll-like receptor 2 （TLR2）/myeloid differentiation 88 （MyD88）/nuclear factor-κB （NF-κB） signaling pathway. MethodsThe minimum inhibitory concentration （MIC） of Tanreqing injection （TRQ） against Cutibacterium acnes was determined through the microdilution broth method， and drug resistance induction experiments were conducted. A mouse model of acne was established through inoculation of C. acnes on the back. The effects of TRQG on skin structure， pustule formation， collagen repair， and inflammatory response were evaluated by dermoscopy， histopathology， two-photon excitation fluorescence microscopy （TPEF）， and optical coherence tomography （OCT）. Differentially expressed genes （DEGs） were identified through transcriptome sequencing and then subjected to KEGG pathway enrichment analysis. In the RAW264.7 cell model， the optimal dosage of TRQG was determined through cell viability assays. Subsequently， the expression of key proteins in the TLR2/MyD88/NF-κB pathway and downstream inflammatory factors ［tumor necrosis factor-α （TNF-α）， interleukin （IL）-1β， and IL-6］ was determined by Western blot and real-time PCR. ResultsThe MIC of TRQ against C. acnes was 4 125 mg·L^-1. Although TRQ had weaker antibacterial activity than erythromycin （ERY） and fusidic acid （FA）， it was less likely to induce bacterial resistance. In vivo experiments showed that TRQG improved the skin structure， promoted collagen repair （P<0.01）， inhibited pustule formation （P<0.01）， alleviated follicular keratinization and sebaceous gland hyperplasia， and reduced inflammatory responses in the mouse model of acne compared with erythromycin gel （ERYG）. Transcriptome analysis suggested that the TLR/MyD88/NF-κB signaling pathway was a key enriched pathway. Further experimental validation indicated that TRQG inhibited the expression of TLR2， MyD88， TNF receptor-associated factor 6 （TRAF6）， phosphorylated （p）-transforming growth factor-β-activated kinase 1 （TAK1）， p-inhibitor of NF-κB subunit α （IκBα）， and p-NF-κB in this pathway （P<0.01）. Meanwhile， Real-time PCR results confirmed that TRQG reduced the mRNA levels of TNF-α， IL-1β， and IL-6 （P<0.01）. ConclusionTRQG exerts its therapeutic effect on acne by inhibiting the activation of the TLR2/MyD88/NF-κB signaling pathway and reducing the release of downstream inflammatory factors. Furthermore， it is less likely to induce bacterial resistance， indicating a promising application prospect.

ObjectiveTo explore the pharmacological mechanism of Tanreqing gel （TRQG） in the treatment of acne by regulating the Toll-like receptor 2 （TLR2）/myeloid differentiation 88 （MyD88）/nuclear factor-κB （NF-κB） signaling pathway. MethodsThe minimum inhibitory concentration （MIC） of Tanreqing injection （TRQ） against Cutibacterium acnes was determined through the microdilution broth method， and drug resistance induction experiments were conducted. A mouse model of acne was established through inoculation of C. acnes on the back. The effects of TRQG on skin structure， pustule formation， collagen repair， and inflammatory response were evaluated by dermoscopy， histopathology， two-photon excitation fluorescence microscopy （TPEF）， and optical coherence tomography （OCT）. Differentially expressed genes （DEGs） were identified through transcriptome sequencing and then subjected to KEGG pathway enrichment analysis. In the RAW264.7 cell model， the optimal dosage of TRQG was determined through cell viability assays. Subsequently， the expression of key proteins in the TLR2/MyD88/NF-κB pathway and downstream inflammatory factors ［tumor necrosis factor-α （TNF-α）， interleukin （IL）-1β， and IL-6］ was determined by Western blot and real-time PCR. ResultsThe MIC of TRQ against C. acnes was 4 125 mg·L^-1. Although TRQ had weaker antibacterial activity than erythromycin （ERY） and fusidic acid （FA）， it was less likely to induce bacterial resistance. In vivo experiments showed that TRQG improved the skin structure， promoted collagen repair （P<0.01）， inhibited pustule formation （P<0.01）， alleviated follicular keratinization and sebaceous gland hyperplasia， and reduced inflammatory responses in the mouse model of acne compared with erythromycin gel （ERYG）. Transcriptome analysis suggested that the TLR/MyD88/NF-κB signaling pathway was a key enriched pathway. Further experimental validation indicated that TRQG inhibited the expression of TLR2， MyD88， TNF receptor-associated factor 6 （TRAF6）， phosphorylated （p）-transforming growth factor-β-activated kinase 1 （TAK1）， p-inhibitor of NF-κB subunit α （IκBα）， and p-NF-κB in this pathway （P<0.01）. Meanwhile， Real-time PCR results confirmed that TRQG reduced the mRNA levels of TNF-α， IL-1β， and IL-6 （P<0.01）. ConclusionTRQG exerts its therapeutic effect on acne by inhibiting the activation of the TLR2/MyD88/NF-κB signaling pathway and reducing the release of downstream inflammatory factors. Furthermore， it is less likely to induce bacterial resistance， indicating a promising application prospect.

Objective:To investigate the impact of postoperative complications on adverse outcomes following curative-intent resection for gallbladder cancer (GBC).Methods:The multi-center real-world study was conducted. The clinicopathological data of 629 patients with GBC, who were admitted to 14 medical centers including The First Affiliated Hospital of Army Medical University from the national multicenter database of Biliary Surgery Group of Elite Group of Chinese Journal of Digestive Surgery, from April 2020 to April 2024 were collected. There were 225 males and 404 females, aged (64±10)years. Patients underwent open curative-intent resection for GBC. Observation indicators: (1)surgery, postoperative complica-tions and adverse outcomes; (2) analysis of risk factors affecting postoperative adverse outcomes in patients and population attributable fraction (PAF). Missing data in predictor variables were addressed using multiple imputation with chained equations, while cases with missing outcome variables were addressed using the "multiple imputation then deletion (MID)" strategy. The severity of multicollinearity among independent variables was assessed using the variance inflation factor (VIF) test. Multivariable possion regression models with log link and robust error variance were construc-ted incorporating restricted cubic splines (3 knots) to address nonlinear relationships in continuous variables, calculating adjusted relative risk ( RR) with corresponding 95% confidence interval ( CI). Adjusted PAF was calculated for each imputed dataset using the AF package of R software, with subsequent pooling performed according to Rubin's rules. Results:(1) Surgery, postoperative complications and adverse outcomes. All 629 patients underwent curative-intent resection for GBC, of which 143 cases had postoperative complications, including 68 cases of intra-abdominal ascites, 39 cases of pulmonary infection, 21 cases of bile leakage, 12 cases of intra-abdominal hemorrhage, 11 cases of liver failure, 10 cases of pan-creatic fistula, 10 cases of wound infection, 10 cases of gastroparesis, 7 cases of cholangitis, 7 cases of sepsis. The same patient could have more than one kind of complication. Of 629 patients, there were 19 cases of postoperative 90-day death and 11 cases of missing data, 42 cases with post-operative 90-day reoperation and 7 cases with missing data, 44 cases with postoperative 90-day readmission and 3 cases with missing data, 155 cases with prolonged postoperative hospital stay and 3 cases with missing data. (2) Analysis of risk factors affecting the postoperative adverse outcomes in patients and PAF. Results of multivariate analysis showed that pulmonary infection and liver failure were independent risk factors for postoperative 90-day mortality ( RR=3.74, 12.15, 95% CI as 1.18-11.83, 1.98-74.48, P<0.05). Pulmonary infection demons-trated the highest PAF as 4.61% (95% CI as 3.94%-5.28%, P<0.05). Intra-abdominal ascites, pulmonary infection, bile leakage, and intra-abdominal hemorrhage were independent risk factors for post-operative 90-day reoperation ( RR=4.80, 3.62, 3.46, 4.99, 95% CI as 2.49-9.26, 1.42-9.21, 1.34-8.92, 1.55-16.06, P<0.05). Intra-abdominal ascites demonstrated the highest PAF as 8.65% (95% CI as 8.22%-9.08%, P<0.05). Intra-abdominal ascites, bile leakage, and liver failure were independent risk factors for postoperative 90-day readmission ( RR=6.20, 3.33, 14.33, 95% CI as 3.21-11.95, 1.33-8.35, 3.72-55.28, P<0.05). Intra-abdominal ascites demonstrated the highest PAF as 9.11% (95% CI as 8.85%-9.37%, P<0.05). Intra-abdominal ascites, pulmonary infection, bile leakage, liver failure, and wound infection were independent risk factors for prolonged postoperative hospital stay ( RR=2.29, 2.21, 2.26, 2.14, 3.35, 95% CI as 1.63-3.23, 1.41-3.46, 1.32-3.86, 1.11-4.13, 1.70-6.60, P<0.05). Intra-abdominal ascites demonstrated the highest PAF as 6.03% (95% CI as 5.71%-6.35%, P<0.05). Conclusion:Pulmonary infection is the most significant risk factor for postoperative 90-day mortality after curative-intent resection for GBC, while intra-abdominal ascites is the most significant risk factor for postoperative 90-day reoperation, postoperative 90-day readmission, and prolonged postoperative hospital stay.

Klebsiella pneumoniae is a widespread Gram-negative bacterium in Asia,and the emergence of antibiotic-resistant strains has sig-nificantly complicated treatment strategies.Traditional Chinese medicine,which has made remarkable contributions to public health in Asia for thousands of years,may offer promising antibacterial strategies.Chinese herbal medicine(CHM),the primary therapeutic modality of traditional Chinese medicine,exhibits antimicrobial activity,modulates the immune system,and has the potential to reverse antibiotic resistance through various mechanisms.However,no review has comprehensively summarized the efficacy and underlying mechanisms of CHM in treating antibiotic-resistant K.pneumoniae infections.In this study,we conducted a comprehen-sive review of relevant literatures published up to 2025,using the keywords"Klebsiella pneumoniae,""traditional Chinese medicine,"and"Chinese herbal medicine"across databases including PubMed,Web of Science,ScienceDirect,and China National Knowledge Infrastructure.This review first introduces the taxonomy,virulence factors,and antibiotic resistance profile of K.pneumoniae.We then summarize CHM formulas,extracts,and active ingredients with reported antibacterial effects against K.pneumoniae,including their minimum inhibitory concentrations and mechanisms.Additionally,we highlight CHM interventions that enhance host immune responses and alleviate symptoms associated with K.pneumoniae infections.Furthermore,combining CHM with antibiotics rep-resents a novel strategy to enhance antibiotic efficacy and combat resistance.We therefore summarize the synergistic effects and mechanisms of CHM-antibiotic combinations.Overall,this review underscores the multifaceted therapeutic potential of CHM and its active ingredients,including direct antibacterial action,immune modulation,and synergy with conventional antibiotics,providing an integrative approach to address the global challenge of antimicrobial resistance.

OBJECTIVE Exploring the specific changes in brain signal variability during healthy aging using functional near-infrared spectroscopy technology.METHODS Twenty-eight young adults and 30 elderly adults were included,and functional near-infrared spectroscopy was used to record the changes in brain blood oxygen and calculate the brain signal variability during the execution of visual-audio dual tasks.RESULTS The brain signal variability of the elderly group was significantly reduced when performing visual-audio dual tasks,especially in the bilateral dorsolateral prefrontal cortex,right Broca,bilateral primary somatosensory cortex,bilateral Wernicke area,bilateral frontopolar area,bilateral primary motor cortex,bilateral somatosensory association cortex,bilateral orbitofrontal area,bilateral pre-motor and supplementary motor cortex.The brain signal variability in the left primary somatosensory cortex(r=-0.385,P=0.043)and right primary somatosensory cortex(r=-0.386,P=0.042)of young adults was negatively correlated with visual reaction time;The brain signal variability in the right somatosensory association cortex(r=-0.371,P=0.044),left pre-motor and supplementary motor cortex(r=-0.393,P=0.032)of elderly adults was negatively correlated with visual reaction time.CONCLUSION Elderly individuals exhibit a significant reduction in neural signal variability within the prefrontal cortex and sensory related cortex,resulting in diminished neural dynamic adaptability that compromises behavioral performance during visual-audio dual tasks.

Objective:To compare the diagnostic efficacy of 68Ga-prostate-specific membrane antigen (PSMA)-617 PET/CT and multiparametric magnetic resonance imaging (mpMRI) in detecting extraprostatic extension (EPE) and seminal vesicle invasion (SVI) in prostate cancer. Methods:A retrospective analysis was conducted on the clinical data of 113 patients with localized prostate cancer who underwent both 68Ga-PSMA-617 PET/CT and mpMRI at Xiangya Hospital, Central South University, from May 2018 to May 2024 prior to radical prostatectomy (RP). The median age of the patients was 66.0 (61.3, 71.0) years old, with a median body mass index of 28.86 (19.01, 24.77) kg/m 2, and a median prostate-specific antigen (PSA) level of 13.50(9.26, 21.99) ng/ml. The pathological results after RP were used as the gold standard to compare the sensitivity, specificity, positive predictive value, and negative predictive value of the two imaging modalities in diagnosing EPE and SVI. Additionally, the diagnostic value of combining both imaging modalities was explored, employing a parallel strategy where a positive result from either modality was deemed positive, and only when both tests were negative was the result considered negative. Results:Pathological results after RP indicated EPE in 46 cases (40.71%) and SVI in 11 cases (9.70%). In diagnosing EPE, the sensitivity, specificity, positive predictive value, and negative predictive value of 68Ga-PSMA-617 PET/CT were 17.39% (8/46), 97.01% (65/67), 80.00% (8/10), and 63.11% (65/103), respectively, while for mpMRI they were 34.78% (16/46), 83.58% (56/67), 59.26% (16/27), and 65.12% (56/86), respectively. The sensitivity of mpMRI was significantly higher than that of 68Ga-PSMA-617 PET/CT ( P=0.048), while the specificity was the opposite ( P=0.008). When combining both imaging modalities, the sensitivity, specificity, positive predictive value, and negative predictive value were 45.65% (21/46), 80.60% (54/67), 61.76% (21/34), and 68.35% (54/79), respectively. In diagnosing SVI, the sensitivity, specificity, positive predictive value, and negative predictive value of 68Ga-PSMA-617 PET/CT were 27.27% (3/11), 96.08% (98/102), 42.86% (3/7), and 92.45% (98/106), respectively, while for mpMRI they were 36.36% (4/11), 88.24% (90/102), 25.00% (4/16), and 92.78% (90/97), respectively. The specificity of 68Ga-PSMA-617 PET/CT was significantly higher than that of mpMRI ( P=0.033). When combining both imaging modalities, the sensitivity, specificity, positive predictive value, and negative predictive value were 45.45% (5/11), 85.29% (87/102), 25.00% (5/20), and 93.55% (87/93), respectively. Conclusions:mpMRI has higher sensitivity in diagnosing EPE and SVI in prostate cancer, while 68Ga-PSMA-617 PET/CT shows higher specificity. The combined use of both imaging modalities can increase diagnostic sensitivity but may reduce specificity. PSMA PET/MRI may be a more accurate diagnostic tool for discerning EPE and SVI.

Klebsiella pneumoniae is a widespread Gram-negative bacterium in Asia,and the emergence of antibiotic-resistant strains has sig-nificantly complicated treatment strategies.Traditional Chinese medicine,which has made remarkable contributions to public health in Asia for thousands of years,may offer promising antibacterial strategies.Chinese herbal medicine(CHM),the primary therapeutic modality of traditional Chinese medicine,exhibits antimicrobial activity,modulates the immune system,and has the potential to reverse antibiotic resistance through various mechanisms.However,no review has comprehensively summarized the efficacy and underlying mechanisms of CHM in treating antibiotic-resistant K.pneumoniae infections.In this study,we conducted a comprehen-sive review of relevant literatures published up to 2025,using the keywords"Klebsiella pneumoniae,""traditional Chinese medicine,"and"Chinese herbal medicine"across databases including PubMed,Web of Science,ScienceDirect,and China National Knowledge Infrastructure.This review first introduces the taxonomy,virulence factors,and antibiotic resistance profile of K.pneumoniae.We then summarize CHM formulas,extracts,and active ingredients with reported antibacterial effects against K.pneumoniae,including their minimum inhibitory concentrations and mechanisms.Additionally,we highlight CHM interventions that enhance host immune responses and alleviate symptoms associated with K.pneumoniae infections.Furthermore,combining CHM with antibiotics rep-resents a novel strategy to enhance antibiotic efficacy and combat resistance.We therefore summarize the synergistic effects and mechanisms of CHM-antibiotic combinations.Overall,this review underscores the multifaceted therapeutic potential of CHM and its active ingredients,including direct antibacterial action,immune modulation,and synergy with conventional antibiotics,providing an integrative approach to address the global challenge of antimicrobial resistance.

Approximately 30%-40% of epilepsy patients do not respond well to adequate anti-seizure medications (ASMs), a condition known as pharmacoresistant epilepsy. The management of pharmacoresistant epilepsy remains an intractable issue in the clinic. Its early prediction is important for prevention and diagnosis. However, it still lacks effective predictors and approaches. Here, a classical model of pharmacoresistant temporal lobe epilepsy (TLE) was established to screen pharmacoresistant and pharmaco-responsive individuals by applying phenytoin to amygdaloid-kindled rats. Ictal electroencephalograms (EEGs) recorded before phenytoin treatment were analyzed. Based on ictal EEGs from pharmacoresistant and pharmaco-responsive rats, a convolutional neural network predictive model was constructed to predict pharmacoresistance, and achieved 78% prediction accuracy. We further found the ictal EEGs from pharmacoresistant rats have a lower gamma-band power, which was verified in seizure EEGs from pharmacoresistant TLE patients. Prospectively, therapies targeting the subiculum in those predicted as "pharmacoresistant" individual rats significantly reduced the subsequent occurrence of pharmacoresistance. These results demonstrate a new methodology to predict whether TLE individuals become resistant to ASMs in a classic pharmacoresistant TLE model. This may be of translational importance for the precise management of pharmacoresistant TLE.
Epilepsy, Temporal Lobe/diagnosis* ; Animals ; Drug Resistant Epilepsy/drug therapy* ; Electroencephalography/methods* ; Rats ; Anticonvulsants/pharmacology* ; Neural Networks, Computer ; Male ; Humans ; Phenytoin/pharmacology* ; Adult ; Disease Models, Animal ; Female ; Rats, Sprague-Dawley ; Young Adult ; Convolutional Neural Networks

This study aims to explore the scientific connotation of sinking Rehmanniae Radix has the best quality and compare the quality between floating and sinking fresh Rehmanniae Radix samples. Ultra-performance liquid chromatography tandem quadrupole electrostatic field Orbitrap high-resolution mass spectrometry(UHPLC-Q-Orbitrap HRMS) was employed to detect the chemical components in floating and sinking fresh Rehmanniae Radix samples. The fingerprint of fresh Rehmanniae Radix was established by high performance liquid chromatography(HPLC), and four index components were determined simultaneously. The cluster analysis, principal component analysis(PCA), and orthogonal partial least squares-discriminant analysis(OPLS-DA) were conducted to compare the quality of floating and sinking fresh Rehmanniae Radix samples. An evaporative light-scattering detector was used to compare the content of five sugars. The extract yield and drying rate were determined, and the quality connotation of sinking Rehmanniae Radix has the best quality was explained by multiple indicators. A total of 41 components were preliminarily identified from fresh Rehmanniae Radix by UHPLC-Q-Orbitrap HRMS, including 7 iridoid glycosides, 9 phenylethanol glycosides, 6 amino acids, 4 sugars, 3 phenolic acids, 5 nucleosides, 3 organic acids, 1 ionone, 1 furan, 1 coumarin, and 1 phenylpropanoid. The results showed that the main chemical components were consistent between floating and sinking fresh Rehmanniae Radix. Nine common peaks were identified in the fingerprints of 15 batches of floating and sinking fresh Rehmanniae Radix samples, and the similarity of fingerprints was greater than 0.9. The cluster analysis, PCA, and OPLS-DA classified floating and sinking fresh Rehmanniae Radix sasmples into two categories, indicating differences in the quality between them. The total content of catalpol, rehmannioside D, ajugol, and verbascoside in sinking fresh Rehmanniae Radix samples was higher than that in floating samples of the same batch and specification, and the main differential component was catalpol. The total content of fructose, glucose, sucrose, raffinose, and stachyose in sinking fresh Rehmanniae Radix samples was higher than that in floating samples of the same batch and specification, and the main differential component was stachyose. The extract yield and drying rate of the sinking samples were higher than those of floating samples. This study preliminarily showed that floating and sinking fresh Rehmanniae Radix samples had the same components but great differences in the content of medicinal substance basis. The total content of four glycosides and five sugars, extract yield, and drying rate of sinking fresh Rehmanniae Radix samples is higher than that of floating samples of the same batch and specification. These findings, to a certain extent, explains the scientificity of sinking Rehmanniae Radix has the best quality recorded in ancient books and provide a reference for the quality control and clinical application of fresh Rehmanniae Radix.
Chromatography, High Pressure Liquid/methods* ; Drugs, Chinese Herbal/chemistry* ; Rehmannia/chemistry* ; Chemometrics ; Mass Spectrometry/methods* ; Quality Control ; Principal Component Analysis ; Plant Extracts

Objective To investigate the association between D-dimer levels within 2 hours of admission and in-hospital major adverse events (MAEs) in patients with acute type A aortic dissection (ATAAD) who underwent total arch replacement combined with frozen elephant trunk (FET) implantation. Methods This retrospective study included patients with ATAAD who underwent total arch replacement with FET implantation at Fuwai Yunnan Cardiovascular Hospital from September 2017 to December 2022. Patients were divided into two groups based on the occurrence of in-hospital MAEs: a MAEs group and a non-MAEs group (control). Perioperative data were compared between the two groups. Univariate and multivariate logistic regression analyses were performed to identify risk factors for in-hospital MAEs, which included in-hospital death, gastrointestinal bleeding, paraplegia, acute kidney injury, low cardiac output syndrome, stroke, respiratory failure, multiple organ dysfunction syndrome, and severe infection. The predictive value of D-dimer was evaluated using the area under the receiver operating characteristic curve (AUC). Results A total of 218 patients were included (157 males, 61 females), with a mean age of (51.54±9.79) years. There were 152 patients in the non-MAEs group and 66 in the MAEs group. The overall incidence of in-hospital MAEs was 30.3%, and the in-hospital mortality rate was 2.8% (6/218). Compared to the non-MAEs group, the MAEs group had significantly higher levels of D-dimer and lactate, as well as longer cardiopulmonary bypass time, aortic cross-clamp time, and ICU length of stay (all P<0.05). Multivariate logistic regression analysis identified D-dimer as an independent risk factor for in-hospital MAEs [OR=1.077, 95%CI (1.020, 1.137), P=0.013]. The AUC for the D-dimer level within 2 hours of admission to predict in-hospital MAEs was 0.83 [95%CI (0.736, 0.870), P<0.001]. The optimal cutoff value was 2.2 μg/mL, with a sensitivity of 84.8% and a specificity of 73.0%. Conclusion The serum D-dimer level is an independent risk factor for in-hospital MAEs in patients with ATAAD following total arch replacement with FET implantation. D-dimer levels on admission can help clinicians optimize risk stratification and perioperative management, potentially reducing the incidence of early adverse events.