Objective:To explore the influencing factors for skin pruritus and to construct a nomogram prediction model in peritoneal dialysis (PD) patients.Methods:It was a retrospective cross-sectional investigation study. The PD patients who were regularly followed up between July, 2023 and April, 2024 in PD center of the First Affiliated Hospital of Sun Yat-sen University were enrolled in this study. The pruritus status was evaluated by the 14-Item UP-Dial Scale. The general demographic data and clinical data were collected. The patients were divided into pruritus group and non-pruritus group according to the presence or absence of skin itching. The differences of clinical data and laboratory results were compared between the two groups. Logistic regression was used to analyze the associated factors for pruritus in PD patients. The nomogram model was constructed by R software. The receiver operating characteristic (ROC) curve analysis and the Hosmer-Lemeshow goodness-of-fit test were used to evaluate the performance of the model, and its clinical effectiveness was evaluated using the calibration curve.Results:A total of 315 PD patients were enrolled in this study, with age of (48.0±12.9) years, including 134 females (42.5%). Among them, 161 patients (51.1%) experienced skin pruritus. Of whom, 111 patients (68.9%) had mild pruritus, 34 patients (21.1%) had moderate pruritus, 16 patients (9.9%) had severe pruritus. The age ( t=-2.266, P=0.024), proportion of diabetes mellitus ( χ2=3.910, P=0.048), Charson comorbidity index ( Z=-2.458, P=0.014), blood eosinophil percentage ( Z=-2.385, P=0.017), C-reactive protein ( Z=-2.590, P=0.010), serum phosphorus ( Z=-3.233, P=0.001) and β2 microglobulin ( Z=-2.756, P=0.006) level in the pruritus group were higher than those in the non-pruritus group, and the measured glomerular filtration rate (mGFR) level ( Z=-3.708, P<0.001) of patients in the pruritus group was lower than that in the non-pruritus group. There were 262 patients in the training set and 53 patients in the validation set. The multivariate logistic regression analysis in the training set revealed that advanced age ( OR=1.032, 95% CI 1.010-1.054, P=0.004), lower mGFR ( OR=0.758, 95% CI 0.648-0.886, P<0.001), higher serum phosphorus ( OR=2.761, 95% CI 1.282-6.024, P=0.010), and elevated blood eosinophil percentage ( OR=1.098, 95% CI 1.012-1.191, P=0.025) were independent factors associated with pruritus in PD patients. The nomogram model constructed based on these indicators demonstrated good discrimination and calibration. In the training set, the area under the ROC curve ( AUC) was 0.757 (95% CI 0.699-0.816), with Hosmer-Lemeshow test χ2=4.979, P=0.760. In the validation set, the AUC was 0.779 (95% CI 0.651-0.907), and Hosmer-Lemeshow test χ2=12.938, P=0.114. Conclusions:The prevalence of skin pruritus is 51.1% in PD patient. Advanced age, lower mGFR, higher serum phosphorus and higher blood eosinophil percentage are the independent influencing factors for pruritus in PD patients. The nomogram model constructed based on these indicators shows excellent predictive performance for skin pruritus in PD patients.

OBJECTIVE: To investigate the inhibitory effect of Tanreqing Injection (TRQ) on the activation of nucleotide-binding oligomerization domain-like receptor pyrin domain containing 3 (NLRP3) inflammasome in macrophages infected with influenza A virus and the underlying mechanism based on mitophagy pathway. METHODS: The inflammatory model of murine macrophage J774A.1 induced by influenza A virus [strain A/Puerto Rico/8/1934 (H1N1), PR8] was constructed and treated by TRQ, while the mitochondria-targeted antioxidant Mito-TEMPO and autophagy specific inhibitor 3-methyladenine (3-MA) were used as controls to intensively study the anti-inflammatory mechanism of TRQ based on mitophagy-mitochondrial reactive oxygen species (mtROS)-NLRP3 inflammasome pathway. The levels of NLRP3, Caspase-1 p20, microtubule-associated protein 1 light chain 3 II (LC3II) and P62 proteins were measured by Western blot. The release of interleukin-1β (IL-1β) was tested by enzyme linked immunosorbent assay, the mtROS level was detected by flow cytometry, and the immunofluorescence and co-localization of LC3 and mitochondria were observed under confocal laser scanning microscopy. RESULTS: Similar to the effect of Mito-TEMPO and contrary to the results of 3-MA treatment, TRQ could significantly reduce the expressions of NLRP3, Caspase-1 p20, and autophagy adaptor P62, promote the expression of autophagy marker LC3II, enhance the mitochondrial fluorescence intensity, and inhibit the release of mtROS and IL-1β (all P<0.01). Moreover, LC3 was co-localized with mitochondria, confirming the type of mitophagy. CONCLUSION TRQ could reduce the level of mtROS by promoting mitophagy in macrophages infected with influenza A virus, thus inhibiting the activation of NLRP3 inflammasome and the release of IL-1β, and attenuating the inflammatory response.
Mitophagy/drug effects* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Animals ; Macrophages/virology* ; Inflammasomes/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Mice ; Mitochondria/metabolism* ; Reactive Oxygen Species/metabolism* ; Influenza A virus/physiology* ; Interleukin-1beta/metabolism* ; Cell Line ; Injections

OBJECTIVE: To investigate the regulatory effects of two traditional mineral medicines (TMMs), Gypsum Fibrosum (Shigao, GF) and Terra Flava Usta (Zaoxintu, TFU), on gut-beneficial bacteria in mice, and preliminarily explore their mechanisms of action. METHODS: Mice were randomly divided into 3 groups (n=10 per group): the control group (standard diet), the GF group (diet supplemented with 2% GF), and the TFU group (diet supplemented with 2% TFU). After 4-week intervention, 16S rRNA gene sequencing was used to analyze the changes in the gut microbiota (GM). Scanning electron microscopy, in combination with coumarin A tetramethyl rhodamine conjugate and Hoechst stainings, was used to observe the bacteria and biofilm formation. RESULTS: Principal coordinate analysis revealed that GF and TFU significantly altered the GM composition in mice. Further analysis revealed that GF and TFU affected different types of gut bacteria, suggesting that different TMMs may selectively modulate specific bacterial populations. For certain bacteria, such as Faecalibaculum and Ileibacterium, both GF and TFU exhibited growth-promoting effects, implying that they may be sensitive to TMMs and that different TMMs can increase their abundance through their respective mechanisms. Notably, Lactobacillus reuteri, a widely recognized and used probiotic, was significantly enriched in the GF group. Random forest analysis identified Ileibacterium valens as a potential indicator bacterium for TMMs' impact on GM. Further mechanistic studies showed that gut bacteria formed biofilm structures on the TFU surface. CONCLUSIONS This study provides new insights into the interaction between TMMs and GM. As safe and effective natural clays, GF and TFU hold promise as potential candidates for prebiotic development.
Animals ; Gastrointestinal Microbiome/drug effects* ; Bacteria/growth & development* ; Mice ; Biofilms/drug effects* ; Male ; RNA, Ribosomal, 16S/genetics*

The angiogenic response is essential for the repair of ischemic brain tissue. Integrin α6 (Itga6) expression has been shown to increase under hypoxic conditions and is expressed exclusively in vascular structures; however, its role in post-ischemic angiogenesis remains poorly understood. In this study, we demonstrate that mice with endothelial cell-specific knockout of Itga6 exhibit reduced neovascularization, reduced pericyte coverage on microvessels, and accelerated breakdown of microvascular integrity in the peri-infarct area. In vitro, endothelial cells with ITGA6 knockdown display reduced proliferation, migration, and tube-formation. Mechanistically, we demonstrated that ITGA6 regulates post-stroke angiogenesis through the PI3K/Akt-eNOS-VEGFA axis. Importantly, the specific overexpression of Itga6 in endothelial cells significantly enhanced neovascularization and enhanced the integrity of microvessels, leading to improved functional recovery. Our results suggest that endothelial cell Itga6 plays a crucial role in key steps of post-stroke angiogenesis, and may represent a promising therapeutic target for promoting recovery after stroke.
Animals ; Nitric Oxide Synthase Type III/metabolism* ; Mice ; Proto-Oncogene Proteins c-akt/metabolism* ; Integrin alpha6/genetics* ; Endothelial Cells/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Stroke/pathology* ; Vascular Remodeling/physiology* ; Vascular Endothelial Growth Factor A/metabolism* ; Mice, Knockout ; Signal Transduction/physiology* ; Mice, Inbred C57BL ; Male ; Neovascularization, Physiologic/physiology*

Objective:To investigate the role and underlying mechanism of protein arginine methyltransferase 1 (PRMT1) and its inhibitor in alkali burn-induced corneal neovascularization (CNV).Methods:Seventy-two SPF-grade C57BL/6 mice were randomly divided into a normal group and 1 day post-modeling, 4 days post-modeling, and 7 days post-modeling groups to establish an alkali burn-induced CNV model and determine the optimal time point for analysis.Another 90 mice were randomly assigned to five groups: alkali burn group, dimethyl sulfoxide (DMSO) group, PRMT1 inhibitor group, fibroblast growth factor 2 (FGF2) inhibitor group, and PRMT1 inhibitor combined with FGF2 group to evaluate the role of PRMT1 in CNV.Human umbilical vein endothelial cells (HUVECs) and murine macrophage-like RAW264.7 cells were used to establish a hypoxia/reoxygenation (H/R)-induced in vitro model to mimic the ischemic microenvironment.Cells were assigned to the following groups: control group, H/R group, H/R+ DMSO group, H/R+ si-NC group, H/R+ si-PRMT1 group, H/R+ si-FGF2 group, H/R+ PRMT1 inhibitor group, and H/R+ PRMT1 inhibitor+ FGF2 group.Corneal opacity and CNV areas were assessed by slit-lamp microscopy.Corneal structural changes and inflammatory cell count were determined by hematoxylin and eosin staining.PRMT1-positive cell count was determined by immunohistochemistry and the expression of PRMT1, CD31, vascular endothelial growth factor (VEGF), F4/80, CD206, and inducible nitric oxide synthase (iNOS) was assessed by immunofluorescence staining.The expression levels of macrophage markers, including F4/80, iNOS, CD206, interleukin-10 (IL-10), and arginase-1 (Arg-1), were quantified by real-time quantitative PCR and Western blot.Cell proliferation, migration, and angiogenic capacity were evaluated by functional assays including the CCK-8 assay, wound healing assay, Transwell migration assay, and tube formation assay.The research process followed the relevant regulations of the Visual and Ophthalmology Association, and the research plan was approved by the Laboratory Animal Committee of Wuhan University (No.20220504A). Results:Compared with the normal group, the 7 days post-modeling group showed significantly increased corneal opacity scores and CNV area, upregulated VEGF expression, and increased inflammatory cells (all P<0.05).The number of PRMT1-positive cells in the alkali burn group was (39.67±3.51) cells/visual field, which was significantly higher than (3.33±0.58) cells/visual field in the normal group ( t=17.68, P<0.01).Both mRNA and protein expression levels of PRMT1 and FGF2 were significantly elevated in the alkali burn group compared with the normal group (all P<0.01).Compared with the alkali burn group, the PRMT1 inhibitor group showed reduced corneal opacity scores, decreased CNV area, fewer inflammatory cells, and lower expression levels of PRMT1, FGF2, VEGF, Arg-1, IL-10 proteins, as well as CD206 mRNA (all P<0.05).Cell viability, migration distance, migration number, and tubes formed were significantly increased in the H/R group compared with the control group, significantly reduced in the H/R+ si-PRMT1 and H/R+ PRMT1 inhibitor groups compared with the H/R group and significantly increased in H/R+ PRMT1 inhibitor+ FGF2 group than in H/R+ PRMT1 inhibitor group (all P<0.05).Compared with the H/R group, the H/R+ PRMT1 inhibitor group exhibited reduced expression of FGF2, VEGFA, p-PI3K, and p-Akt, while those were upregulated in the H/R+ PRMT1 inhibitor+ FGF2 group compared with the H/R+ PRMT1 inhibitor group (all P<0.05).The proportions of CD206-positive cells in the H/R, H/R+ DMSO, H/R+ PRMT1 inhibitor, and H/R+ PRMT1 inhibitor+ FGF2 groups were all significantly higher than those in the control group, and significantly higher in the H/R, H/R+ DMSO, and H/R+ PRMT1 inhibitor+ FGF2 groups compared with the H/R+ PRMT1 inhibitor group (all P<0.05).Compared with the alkali burn group, the FGF2 inhibitor group, PRMT1 inhibitor group, and PRMT1 inhibitor+ FGF2 group all showed reduced corneal opacity scores, CNV area, and decreased number of VEGFA-, CD206-, and F4/80-positive cells, with the above indicators being lower in the PRMT1 inhibitor group compared with the FGF2 inhibitor and PRMT1 inhibitor+ FGF2 groups and higher in PRMT1 inhibitor+ FGF2 group than in the FGF2 inhibitor group (all P<0.05).Compared with the alkali burn group, the PRMT1 inhibitor group had decreased protein expression levels of FGF2, p-PI3K, p-Akt, CD31, VEGFA and Arg-1, with higher protein expression levels in the PRMT1 inhibitor+ FGF2 group than in the PRMT1 inhibitor group (all P<0.05). Conclusions:PRMT1 may regulate macrophage activation and anti-inflammatory polarization via the FGF2/PI3K/Akt signaling pathway, thereby promoting the occurrence and development of CNV.Targeted inhibition of PRMT1 may serve as an effective therapeutic strategy for CNV.

Objective Exploring the effect of Bian-stone-based herbal heat therapy on herbal heat ironing in gastrointestinal reactions during the preconditioning period of hematopoietic stem cell transplantation patients.Methods Convenience sampling method was used to select 68 cases of hematopoietic stem cell transplantation patients who attended the hematology department of a tertiary-level Chinese medicine hospital in Hangzhou from October 2023 to April 2024 as the study subjects,and the SPSS 26.0 statistical software was used to generate a random number for grouping into an experimental and a control group,with 34 cases in each group.On the basis of intravenous antiemetic medication and routine,the experimental group implemented the Bian-stone-based herbal heat therapy on the basis of intravenous antiemetic medication and conventional nursing care.In the control group,intravenous antiemetic drugs and routine care were used,and the intervention duration of both groups was 14 d,of which 7 d was a course of treatment,with a total of 2 courses of treatment.The incidence of gastroin-testinal reactions,Gastrointestinal Symptom Rating Scale(GSRS)score,Pepsin Ⅰ(PG Ⅰ),Pepsin Ⅱ(PG Ⅱ),and the ratio of PG Ⅰ to PG Ⅱ(PGR)before and after the intervention were compared between the 2 groups.Results The final sample of 66 cases was collected in this study,and 1 patient was dislodged from each of the control group and the experimental group.The comparison of the incidence of gastrointestinal reactions between the 2 groups within 14 days showed that the incidences of nausea,vomiting,abdominal distension,and diarrhea were lower in the experimental group than those in the control group(P＜0.05).GSRS scores on days 1,8,and 14 of intervention were compared,and there were effects between groups in both groups(F=5.338,P=0.017).The levels of PG Ⅰ,PG Ⅱ in the experimental group on day 8 of the intervention were lower than those in the control group.The levels of PGR was higher than that in the control group(all P＜0.05).The safety of the 2 groups after treatment was evaluated,and the results showed that no serious adverse events occurred in the 2 groups.Conclusion Bian-stone-based herbal heat therapy can improve gastrointestinal reactions and reduce the incidence of gastrointestinal reactions during the preconditioning period of hematopoietic stem cell transplantation patients,which provides clinical guidance for the application of Bian-stone-based herbal heat therapy by nursing staff in the future.

Objective To investigate the efficacy of leaflet augmentation technique to repair the recurrent mitral valve (MV) regurgitation after mitral repair in children. Methods A retrospective analysis was conducted on the clinical data of children who underwent redo MV repair for recurrent regurgitation after initial MV repair, using a leaflet augmentation technique combined with a standardized repair strategy at Fuwai Hospital, Chinese Academy of Medical Sciences, from 2018 to 2022. The pathological features of the MV, key intraoperative procedures, and short- to mid-term follow-up outcomes were analyzed. Results A total of 24 patients (12 male, 12 female) were included, with a median age of 37.6 (range, 16.5–120.0) months. The mean interval from the initial surgery was (24.9±17.0) months. All children had severe mitral regurgitation preoperatively. The cardiopulmonary bypass time was (150.1±49.5) min, and the aortic cross-clamp time was (94.0±24.2) min. There were no early postoperative deaths. During a mean follow-up of (20.3±9.1) months, 3 (12.5%) patients developed moderate or severe mitral regurgitation (2 severe, 1 moderate). One (4.2%) patient died during follow-up, and one (4.2%) patient underwent a second MV reoperation. The left ventricular end-diastolic diameter was significantly reduced postoperatively compared to preoperatively [ (43.5±8.6) mm vs. (35.8±7.8)mm, P<0.001]. Conclusion The leaflet augmentation technique combined with a standardized repair strategy can achieve satisfactory short- to mid-term outcomes for the redo mitral repair after previous MV repair. It can be considered a safe and feasible technical option for cases with complex valvular lesions and severe pathological changes.

A single-center, randomized, double-blind, dose-controlled trial of modified Sini Powder in treating mild to moderate generalized anxiety disorder(GAD) in the patients with syndrome of liver depression transforming into fire was conducted at Xiyuan Hospital, China Academy of Chinese Medical Sciences. A total of 80 patients with mild to moderate GAD and the syndrome of liver depression transforming into fire were included. Patients were assigned by the central randomization system at a ratio of 3∶1 into an observation group(n=60, receiving a conventional-dose of granules of modified Sini Powder) and a control group(n=20, receiving low-dose granules with the active ingredients being 50% of that in observation group). Assessments were conducted before treatment(baseline), after 2 weeks of introduction, after 2/4/8 weeks of treatment, and after 4 weeks of follow-up. The results were summarized as follows. In terms of primary outcome indicators, the observation group(62.2%) showed higher total response rate than the control group(26.6%)(P<0.05), and greater Hamilton anxiety scale(HAMA) score reduction after 8 weeks of treatment(P<0.05). In terms of secondary outcome indicators, the HAMA score(somatic anxiety score), traditional Chinese medicine(TCM) syndrome scores, Pittsburgh sleep quality index(PSQI) scale, and clinical global impression(CGI) scale score in the observation group showed a significant compared to the control group at each visit points(P<0.05). Adverse events occurred in 10 cases, including 9(16.9%) cases in the observation group and 1(6.6%) case in the control group. No adverse reaction was observed. In conclusion, conventional-dose modified Sini Powder demonstrated superior efficacy and favorable safety for mild and moderate GAD in the patients with the syndrome of liver depression transforming into fire over low-dose treatment.
Humans ; Male ; Female ; Adult ; Middle Aged ; Double-Blind Method ; Drugs, Chinese Herbal/administration & dosage* ; Anxiety Disorders/drug therapy* ; Treatment Outcome ; Young Adult ; Powders ; Aged ; Liver/drug effects* ; Generalized Anxiety Disorder

OpenSim is an open source, free motion simulation and gait analysis software, which can be used to dynamically simulate and analyze the complex motion of the human body, and is widely used in human biomechanical research. Since OpenSim can analyze multi-dimensional motion data such as muscle strength, joint torque, and muscle synergistic activation during human movement, it can be used to study the biomechanical mechanism of musculoskeletal imbalance diseases and various treatment methods in TCM orthopedics, and has a broad application prospect in the field of TCM orthopedics. By the analysis of the basic characteristics, elements, analysis process, and application prospects of OpenSim, it is concluded that OpenSim musculoskeletal model has a large application space in the field of traditional Chinese medicine orthopedic, which is helpful to explain the pathogenesis and mechanism of diseases, and promote the precision diagnosis and treatment of orthopedics diseases;the application of OpenSim musculoskeletal model can solve the problem that the previous research paid attention to the bone malalignment and not enough attention to the tendon, and provide a new method for the research of orthopedic diseases. At present, there are still problems in the promotion and application of OpenSim, such as large equipment requirements and high operation threshold. Therefore, multidisciplinary cooperation, clinical research, and data sharing are the basic research strategies in this field.
Humans ; Biomechanical Phenomena ; Orthopedics ; Traumatology ; Software ; Medicine, Chinese Traditional ; Musculoskeletal System ; Models, Biological

Medical therapy and surgical intervention are the two primary approaches for treating myocardial bridge.However,there remains controversy regarding the use of coronary artery bypass grafting(CABG)and myocardial bridge unroofing.Here,we report a case of myocardial infarction following CABG in a patient with a myocardial bridge.The patient was admitted to Lanzhou First Peopie's Hospital with persistent chest pain,chest tightness,and shortness of breath lasting 2 hours.Physical examination revealed no significant abnormalities.Electrocardiography(ECG)indicated extensive anterior wall myocardial infarction.Laboratory findings showed myoglobin levels of 140.1 ng/ml and troponin Ⅰ levels of 2.59 ng/ml,with no other significant abnormalities.The initial diagnosis was acute extensive anterior wall myocardial infarction.Emergency coronary angiography revealed a myocardial bridge in the mid-segment of the left anterior descending artery(LAD).Emergency CABG using the left internal mammary artery to the LAD was performed,leading to symptomatic improvement,and the patient was discharged in stable condition.However,the patient experienced a recurrent myocardial infarction seven years post-surgery and received secondary preventive medical therapy.The patient is currently under ongoing follow-up care.CABG is an effective treatment for myocardial bridge.However,based on the case reported in this study,we recommend careful evaluation of whether a patient may benefit from CABG.