Objective To investigate the role of cytochrome P450 2E1 (CYP2E1) in trichloroethylene (TCE)-induced skin sensitization and liver damage in guinea pigs, using diallyl sulfide (DAS), a CYP2E1 inhibitor, as an intervention. Methods Specific pathogen-free female guinea pigs were randomly divided into blank control group, solvent control group, positive control (2,4-dinitrochlorobenzene) group, TCE-exposure group, and DAS-intervention group. Skin sensitization experiments were conducted using the guinea pig TCE maximal dose-skin sensitization test. Urinary trichloroacetic acid levels were determined following TCE induction and challenge. At 48 hours after the final challenge, serum liver function markers and inflammatory cytokines levels were detected. Histopathological examination on skin and liver tissues was performed, and hepatic CYP2E1 protein expression and oxidative stress indicators were assessed. Results The sensitization rates of guinea pigs were 100.0%, 75.0%, and 33.3% in the positive control, TCE-exposure, and DAS-intervention groups, respectively, while the blank control and solvent control groups were both 0.0%. Compared with the guinea pigs in TCE-exposure group, those in the DAS-intervention group had lower urinary trichloroacetic acid levels at intradermal induction, local induction, first challenge, and 24 hours after the final challenge time point (all P<0.05). Histopathology of guinea pigs showed dermal inflammatory infiltration and basal keratinocyte necrosis in the TCE-exposure group, whereas only mild dermal inflammation was observed in the DAS-intervention group. The guinea pigs in TCE-exposure group exhibited diffuse hepatocellular necrosis, while hepatic damage in the DAS-intervention group was alleviated, characterized by only mild hepatocellular steatosis and hepatocyte swelling around the central vein. The skin sensitization rate of guinea pigs in the TCE-exposure group increased (all P<0.01), the serum alanine aminotransferase (ALT )activity, the levels of interleukin (IL)-2, IL-17, and tumor necrosis factor-α (TNF- α) increased (all P<0.05), the relative expression of CYP2E1 protein, the activity of superoxide dismutase (SOD), and the level of malondialdehyde in liver tissue increased (all P<0.05), while the activity of catalase decreased (P<0.05), compared with the blank control and solvent control groups. The serum ALT activity and the levels of IL-2, IL-17, and TNF-α of guinea pigs in DAS-intervention group reduced (all P<0.05), as well as CYP2E1 protein expression, SOD activity, and malondialdehyde level in liver tissue reduced (all P<0.05), compared with the TCE-exposure group. Conclusion TCE can induce hepatic CYP2E1 expression, thereby promoting oxidative stress and inflammatory responses, which contributes to skin sensitization and liver damage. DAS alleviates TCE-induced toxic effects on skin and liver by inhibiting CYP2E1 expression.

Objective:To investigate the efficacy and safety of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for the treatment of BCR::ABL-negative chronic neutrophilic leukemia (CNL) and MDS/MPN with neutrophilia.Methods:This study retrospectively analyzed 12 cases of CNL and MDS/MPN with neutrophilia that underwent allo-HSCT from March 2017 to June 2024, comprising 7 males and 5 females with a median age of 48 ( IQR: 28, 59) years. The 2-year overall survival (OS), disease-free survival (DFS), cumulative incidence of relapse (CIR), and transplantation-related mortality (TRM) rates were analyzed. Complications were also assessed. Results:Of the 12 patients, 6 received matched sibling HSCT and 6 received haploidentical HSCT. All patients had successful engraftment, and the median times of neutrophil and platelet engraftment were 17 ( IQR: 11, 24) days and 15 ( IQR: 9, 28) days, respectively. Grade Ⅱ–Ⅳ acute graft versus host disease (GVHD) and chronic GVHD occurred in 2 and 4 cases, respectively. The 2-year OS, DFS, CIR, and TRM rates were (65.6 ± 16.4) %, (41.7 ± 16.6) %, (47.2 ±18.2) %, and (11.1 ± 11.4) %, respectively, after a median follow-up time of 637 ( IQR: 330, 943) days. One patient died from treatment-related complications due to respiratory failure caused by coronavirus disease 2019. Two patients died due to relapse. Conclusion:Allo-HSCT can be applied as a safe and effective approach to treat CNL and MDS/MPN with neutrophilia.

Objective To predict and analyze the"properties-efficacy"of foreign medicinal resource Moringa oleifera leaves by taking"Xiang"based on plant phylogenetic relationships and component structural characteristics.Methods The properties of Moringa oleifera were determined by screening plants with its genetic relationship.Network pharmacology was used to study the biological network characteristics of Moringa oleifera leaves and related Chinese materia medica,and the"properties-efficacy"of Moringa oleifera leaves was studied based on the"xiang"of medicinal plants.Using"the relationship chart between the efficacy of Chinese materia medica and 12 types of chemical components",the possible efficacy and distribution of medicinal properties of Moringa oleifera leaves were predicted,and a study on the"properties-efficacy"characteristics of Moringa oleifera leaves was conducted based on the structural features of the components.Results Moringaceae and Caricaceae had a genetic relationship in plant classification;Moringa oleifera leaves,Carica papaya and Carica papaya leaves had a relatively high number of common targets,common clinical phenotypes and signaling pathways.The large proportion of coincidence showed that Moringa oleifera leaves might have similar functional performance and mechanism to Carica papaya and Carica papaya leaves;Moringa oleifera leaves contain flavonoids,tannins,monophenols,which were related to the efficacy of Chinese materia medica on tonifying qi,dispersing wind heat,cooling blood and regulating qi.Clustering analysis method was used to get the corresponding"properties-efficacy"relationship,and the results indicated that Moringa oleifera leaves were cool in property and sweet in taste,which belonged to lung meridian and had the efficacy of dispersing wind heat.Conclusion It is feasible to predict and analyze the"properties-efficacy"of foreign medicinal resources by taking"xiang".

Objective:To investigate the correlation between transabdominal bowel ultrasongraphy (TBUS) parameters and disease activity of ulcerative colitis (UC).Methods:The results of TBUS, endoscopy and laboratory tests of 68 UC patients (108 examinations) who visited the Department of Gastroenterology of the Second Hospital (Eastern Campus) of Hebei Medical University From January 2022 to February 2024 were retrospectively analyzed. According to Mayo endoscopic score (MES), there were 10 cases of remission (MES=0) and 98 cases of active phase (MES>0); patients in active phase further classified into 16 cases of mild (MES=1), 19 cases of moderate (MES=2), and 63 cases of severe (MES=3). The TAUS parameters were compared between patients in remission and active phases. Spearman rank correlation analysis was used to analyze the correlation between the TBUS parameters including bowel wall thickness (BWT), Limberg score, wall layer stratification, fat wrapping and endoscopic activity score, laboratory inflammatory indicators. Receiver operating characteristic curve (ROC) analysis was applied to evaluate the predictive efficacy of the TBUS parameters and laboratory inflammatory indicators in identifying remission under endoscopy. Independent sample t-test and Fisher′s exact probability method were used to compare the two groups. Results:The BWT of patients in remission was significantly thinner than that of patients in active phase ((2.99±0.41) mm vs. (5.66±1.57) mm, t=-5.34, P<0.001). The proportions of patients in remisson with Limberg score ≤2, normal wall layer stratification, and absence of fat wrapping were significantly higher than those of patients in active phase (10/10 vs. 34/98, 10/10 vs. 48/98, 10/10 vs. 41/98, Fisher′s exact test, P<0.001, =0.002, =0.001). BWT, Limberg score, wall layer stratification, and fat wrapping were positively correlated with MES ( r=0.676, 0.677, 0.441, and 0.493, all P<0.001). BWT and Limberg score were moderate positively correlated with C-hypersensitive reactive protein, erythrocyte sedimentation rate and fecal calprotectin (BWT: r=0.561, 0.420 and 0.458, all P<0.001; Limberg score: r=0.576, 0.469 and 0.403, all P<0.001), and were negatively correlated with serum albumin and hemoglobin (BWT: r=-0.604 and -0.453, both P<0.001; Limberg score: r=-0.573 and -0.532, both P<0.001). The results of ROC analysis showed that BWT achieved the best predictive efficacy in identifying endoscopic remission, and the best cut-off value was 3.45 mm (area under the curve was 0.972, 95% confidence interval: 0.944 to 1.000, P<0.001), with a sensitivity of 93.9% and specificity of 100.0%. Conclusions:TBUS parameters can accurately reflect disease activity in UC. It is a powerful tool for UC monitoring. The BWT<3.45 mm is the best cut-off value in prediction of endoscopic remission.

Objective To predict and analyze the"properties-efficacy"of foreign medicinal resource Moringa oleifera leaves by taking"Xiang"based on plant phylogenetic relationships and component structural characteristics.Methods The properties of Moringa oleifera were determined by screening plants with its genetic relationship.Network pharmacology was used to study the biological network characteristics of Moringa oleifera leaves and related Chinese materia medica,and the"properties-efficacy"of Moringa oleifera leaves was studied based on the"xiang"of medicinal plants.Using"the relationship chart between the efficacy of Chinese materia medica and 12 types of chemical components",the possible efficacy and distribution of medicinal properties of Moringa oleifera leaves were predicted,and a study on the"properties-efficacy"characteristics of Moringa oleifera leaves was conducted based on the structural features of the components.Results Moringaceae and Caricaceae had a genetic relationship in plant classification;Moringa oleifera leaves,Carica papaya and Carica papaya leaves had a relatively high number of common targets,common clinical phenotypes and signaling pathways.The large proportion of coincidence showed that Moringa oleifera leaves might have similar functional performance and mechanism to Carica papaya and Carica papaya leaves;Moringa oleifera leaves contain flavonoids,tannins,monophenols,which were related to the efficacy of Chinese materia medica on tonifying qi,dispersing wind heat,cooling blood and regulating qi.Clustering analysis method was used to get the corresponding"properties-efficacy"relationship,and the results indicated that Moringa oleifera leaves were cool in property and sweet in taste,which belonged to lung meridian and had the efficacy of dispersing wind heat.Conclusion It is feasible to predict and analyze the"properties-efficacy"of foreign medicinal resources by taking"xiang".

Objective:To investigate the efficacy and safety of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for the treatment of BCR::ABL-negative chronic neutrophilic leukemia (CNL) and MDS/MPN with neutrophilia.Methods:This study retrospectively analyzed 12 cases of CNL and MDS/MPN with neutrophilia that underwent allo-HSCT from March 2017 to June 2024, comprising 7 males and 5 females with a median age of 48 ( IQR: 28, 59) years. The 2-year overall survival (OS), disease-free survival (DFS), cumulative incidence of relapse (CIR), and transplantation-related mortality (TRM) rates were analyzed. Complications were also assessed. Results:Of the 12 patients, 6 received matched sibling HSCT and 6 received haploidentical HSCT. All patients had successful engraftment, and the median times of neutrophil and platelet engraftment were 17 ( IQR: 11, 24) days and 15 ( IQR: 9, 28) days, respectively. Grade Ⅱ–Ⅳ acute graft versus host disease (GVHD) and chronic GVHD occurred in 2 and 4 cases, respectively. The 2-year OS, DFS, CIR, and TRM rates were (65.6 ± 16.4) %, (41.7 ± 16.6) %, (47.2 ±18.2) %, and (11.1 ± 11.4) %, respectively, after a median follow-up time of 637 ( IQR: 330, 943) days. One patient died from treatment-related complications due to respiratory failure caused by coronavirus disease 2019. Two patients died due to relapse. Conclusion:Allo-HSCT can be applied as a safe and effective approach to treat CNL and MDS/MPN with neutrophilia.

Objective:To investigate the correlation between transabdominal bowel ultrasongraphy (TBUS) parameters and disease activity of ulcerative colitis (UC).Methods:The results of TBUS, endoscopy and laboratory tests of 68 UC patients (108 examinations) who visited the Department of Gastroenterology of the Second Hospital (Eastern Campus) of Hebei Medical University From January 2022 to February 2024 were retrospectively analyzed. According to Mayo endoscopic score (MES), there were 10 cases of remission (MES=0) and 98 cases of active phase (MES>0); patients in active phase further classified into 16 cases of mild (MES=1), 19 cases of moderate (MES=2), and 63 cases of severe (MES=3). The TAUS parameters were compared between patients in remission and active phases. Spearman rank correlation analysis was used to analyze the correlation between the TBUS parameters including bowel wall thickness (BWT), Limberg score, wall layer stratification, fat wrapping and endoscopic activity score, laboratory inflammatory indicators. Receiver operating characteristic curve (ROC) analysis was applied to evaluate the predictive efficacy of the TBUS parameters and laboratory inflammatory indicators in identifying remission under endoscopy. Independent sample t-test and Fisher′s exact probability method were used to compare the two groups. Results:The BWT of patients in remission was significantly thinner than that of patients in active phase ((2.99±0.41) mm vs. (5.66±1.57) mm, t=-5.34, P<0.001). The proportions of patients in remisson with Limberg score ≤2, normal wall layer stratification, and absence of fat wrapping were significantly higher than those of patients in active phase (10/10 vs. 34/98, 10/10 vs. 48/98, 10/10 vs. 41/98, Fisher′s exact test, P<0.001, =0.002, =0.001). BWT, Limberg score, wall layer stratification, and fat wrapping were positively correlated with MES ( r=0.676, 0.677, 0.441, and 0.493, all P<0.001). BWT and Limberg score were moderate positively correlated with C-hypersensitive reactive protein, erythrocyte sedimentation rate and fecal calprotectin (BWT: r=0.561, 0.420 and 0.458, all P<0.001; Limberg score: r=0.576, 0.469 and 0.403, all P<0.001), and were negatively correlated with serum albumin and hemoglobin (BWT: r=-0.604 and -0.453, both P<0.001; Limberg score: r=-0.573 and -0.532, both P<0.001). The results of ROC analysis showed that BWT achieved the best predictive efficacy in identifying endoscopic remission, and the best cut-off value was 3.45 mm (area under the curve was 0.972, 95% confidence interval: 0.944 to 1.000, P<0.001), with a sensitivity of 93.9% and specificity of 100.0%. Conclusions:TBUS parameters can accurately reflect disease activity in UC. It is a powerful tool for UC monitoring. The BWT<3.45 mm is the best cut-off value in prediction of endoscopic remission.

ObjectiveBased on the integrated strategy of "empirical prescriptions in ancient books-medical cases by prestigious doctors-computational analysis"， this study aims to explore and analyze the prescriptions and medical cases for treating tremors in traditional Chinese medicine （TCM）， predict their efficacy， and obtain the core prescriptions for treating tremors in TCM， providing references for clinical application and new drug development. MethodThe Chinese Medicine Prescription Database and the China National Knowledge Infrastructure （CNKI） were searched for relevant prescriptions and medical cases for treating tremors in TCM to establish a database of prescriptions for tremors. The Traditional Chinese Medicine Inheritance Computer System （V3.0） was used to analyze and explore the medication rules including drug frequency， properties， flavor， meridian tropism， and pharmacological effects， as well as core drugs and formula associations. A multi-target drug efficacy prediction platform based on network robustness was used to evaluate the predicted efficacy of the core prescriptions obtained. Based on the integration of ancient prescriptions， prestigious doctors' medical cases， and network analysis results， the priority level of the developed prescriptions was determined through comprehensive evaluation. ResultA total of 81 ancient prescriptions were screened， involving 246 drugs， and 171 prescriptions were screened from prestigious doctors' medical cases， involving 278 drugs. The frequently used TCM drugs were mostly warm in nature and sweet in flavor， mainly acting on the liver， spleen， and kidney meridians. In terms of efficacy， they were mainly effective in tonifying deficiency， soothing liver and extinguishing wind， activating blood and resolving blood stasis， clearing heat， and resolving exterior. Through association rules and K-means clustering， the core prescriptions were composed of high-frequency drugs such as Glycyrrhizae Radix et Rhizoma， Ginseng Radix et Rhizoma， Astragali Radix， Atractylodis Macrocephalae Rhizoma， Angelicae Sinensis Radix， Poria， Gastrodiae Rhizoma， and Uncariae Ramulus Cum Uncis. Drug combinations mainly focused on tonifying Qi and nourishing blood， with the additional functions of calming wind and dredging collaterals. Clustering analysis of core prescriptions from ancient prescriptions and prestigious doctors' medical cases， as well as multi-target drug efficacy prediction， showed that Combination 1 had the highest disturbance score on the disease network. Furthermore， comparative analysis revealed consistent results with both the analysis of ancient prescriptions and prestigious doctors' medical cases， indicating its optimal development potential based on theoretical inheritance and empirical practice. In comparison， Combinations 3， 2， and 4 were less utilized in contemporary clinical practice， with lower rankings in network disturbance scores， suggesting that their development value still warranted further exploration. ConclusionTCM clinical treatment of tremors emphasizes the regulation of the liver， spleen， and kidney. In line of syndrome differentiation， drugs potent in soothing liver， extinguishing wind， activating blood， and resolving blood stasis are added based on deficiency-tonifying drugs. The core prescriptions based on Glycyrrhizae Radix et Rhizoma， Angelicae Sinensis Radix， Paeoniae Radix Alba， Astragali Radix， Poria， and Atractylodis Macrocephalae Rhizoma （combination 1） have the highest potential development value. The integrated strategy "empirical prescriptions in ancient books-medical cases by prestigious doctors-computational analysis" can be used for the screening of candidate prescriptions for new TCM drugs.

Humans ; Nephrotic Syndrome ; Hematopoietic Stem Cell Transplantation ; Tissue Donors ; Transplantation Conditioning ; Graft vs Host Disease

Objective:To analyze the clinical characteristics and outcomes of patients with invasive fungal sinusitis (invasive fungal rhinosinusitis, IFR) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and explored the risk factors for IFR after allo-HSCT.Methods:Nineteen patients with IFR after allo-HSCT at Peking University People’s Hospital from January 2012 to December 2021 were selected as the study group, and 95 patients without IFR after allo-HSCT during this period were randomly selected as the control group (1:5 ratio) .Results:Nineteen patients, including 10 males and 9 females, had IFR after allo-HSCT. The median age was 36 (10–59) years. The median IFR onset time was 68 (9–880) days after allo-HSCT. There were seven patients with acute myeloid leukemia, five with acute lymphoblastic leukemia, two with myelodysplastic syndrome, two with chronic myeloid leukemia, one with acute mixed-cell leukemia, one with multiple myeloma, and one with T-lymphoblastic lymph node tumor. There were 13 confirmed cases and 6 clinically diagnosed cases. The responsible fungus was Mucor in two cases, Rhizopus in four, Aspergillus in four, and Candida in three. Five patients received combined treatment comprising amphotericin B and posaconazole, one patient received combined treatment comprising voriconazole and posaconazole, nine patients received voriconazole, and four patients received amphotericin B. In addition to antifungal treatment, 10 patients underwent surgery. After antifungal treatment and surgery, 15 patients achieved a response, including 13 patients with a complete response and 2 patients with a partial response. Multivariate analysis revealed that neutropenia before transplantation ( P=0.021) , hemorrhagic cystitis after transplantation ( P=0.012) , delayed platelet engraftment ( P=0.008) , and lower transplant mononuclear cell count ( P=0.012) were independent risk factors for IFR after allo-HSCT. The 5-year overall survival rates in the IFR and control groups after transplantation were 29.00%±0.12% and 91.00%±0.03%, respectively ( P<0.01) . Conclusion:Although IFR is rare, it is associated with poor outcomes in patients undergoing allo-HSCT. The combination of antifungal treatment and surgery might be effective.