ObjectiveTo explore the clinical efficacy and mechanism of Bupi Qingfei prescription （BPQF） in treating stable bronchiectasis in the patients with syndromes of lung-spleen Qi deficiency and phlegm-heat accumulation in the lungs. MethodsA randomized， double-blind， placebo-controlled trial was conducted. Patients were randomized into BPQF and placebo control （PC） groups. On the basis of conventional Western medicine treatment， the BPQF granules and placebo were respectively administered at 10 g each time， twice a day， for a course of 24 weeks. The TCM symptom scores， Quality of Life Questionnaire for Bronchiectasis （QOL-B） scores， lung function indicators， T lymphocyte subsets， level of inflammatory factors in the sputum， level of neutrophil elastase （NE） in the sputum， and occurrence of adverse reactions were observed before and after treatment in the two groups. ResultsA total of 64 patients completed the study， encompassing 32 in the BPQF group and 32 in the PC group. After treatment， the BPQF group showed decreased TCM symptom scores （P<0.01）， increased QOL-B scores （P<0.01）， and declined levels of tumor necrosis factor （TNF）-α and NE （P<0.05， P<0.01）. The PC group showed decreased TCM symptom （except spleen deficiency） scores （P<0.01）， increased the QOL-B health cognition and respiratory symptom domain scores （P<0.05， P<0.01）， and a declined TNF-α level （P<0.01）. Moreover， the BPQF group had lower TCM symptom （except chest tightness） scores （P<0.05， P<0.01）， higher QOL-B （except treatment burden） scores （P<0.05， P<0.01）， and lower levels of interleukin-6 and TNF-α （P<0.05） than the PC group. Neither group showed serious adverse reactions during the treatment process. ConclusionBPQF can ameliorate the clinical symptoms of stable bronchiectasis patients who have lung-spleen Qi deficiency or phlegm-heat accumulation in the lungs by regulating the immune balance and inhibiting airway inflammatory responses.

OBJECTIVE:Repetitive transcranial magnetic stimulation and transcranial direct current stimulation have shown positive effects in improving gross motor function in children with cerebral palsy.A network meta-analysis was performed to analyze the clinical efficacy of repetitive transcranial magnetic stimulation and transcranial direct current stimulation on the improvement of lower limb motor function and gait in children with cerebral palsy.METHODS:Randomized controlled trials(RCT)about repetitive transcranial magnetic stimulation and transcranial direct current stimulation on lower limb motor function and gait in children with cerebral palsy were collected from CNKI,WanFang,VIP,SinoMed,PubMed,Web of Science,Medline.The search time limit was from the inception to October 5,2024.After screening literature,extracting data and evaluating the risk of bias of included studies,Stata 15.0 software was used for network meta-analysis,AND GRADE profiler was used for quality evaluation.RESULTS:A total of 19 studies were included,involving 4 treatment measures:conventional therapy,high-frequency repetitive transcranial magnetic stimulation,low-frequency repetitive transcranial magnetic stimulation and anodic transcranial direct current stimulation.The results of network meta-analysis showed that in terms of improving gross motor function,low-frequency repetitive transcranial magnetic stimulation[mean difference(MD)=9.48,95％confidence interval(CI)(6.61,12.34),P＜0.05]was the most effective.In terms of alleviating spasticity,high-frequency repetitive transcranial magnetic stimulation[MD=-0.63,95％CI(-1.72,0.45),P＜0.05]had the best efficacy.In terms of improving ankle joint range of motion and step speed,transcranial direct current stimulation[MD=2.27,95％CI(1.37,3.17),P＜0.05;MD=0.11,95％CI(0.05,0.17),P＜0.05]was the most effective.CONCLUSION:Existing clinical evidence suggests that low-frequency repetitive transcranial magnetic stimulation has the best therapeutic effect compared with other intervention measures in terms of improving lower limb gross motor function.In terms of reducing spasticity,high-frequency repetitive transcranial magnetic stimulation has a more significant effect.In terms of improving gait,transcranial direct current stimulation has more advantages.

OBJECTIVE:Repetitive transcranial magnetic stimulation and transcranial direct current stimulation have shown positive effects in improving gross motor function in children with cerebral palsy.A network meta-analysis was performed to analyze the clinical efficacy of repetitive transcranial magnetic stimulation and transcranial direct current stimulation on the improvement of lower limb motor function and gait in children with cerebral palsy.METHODS:Randomized controlled trials(RCT)about repetitive transcranial magnetic stimulation and transcranial direct current stimulation on lower limb motor function and gait in children with cerebral palsy were collected from CNKI,WanFang,VIP,SinoMed,PubMed,Web of Science,Medline.The search time limit was from the inception to October 5,2024.After screening literature,extracting data and evaluating the risk of bias of included studies,Stata 15.0 software was used for network meta-analysis,AND GRADE profiler was used for quality evaluation.RESULTS:A total of 19 studies were included,involving 4 treatment measures:conventional therapy,high-frequency repetitive transcranial magnetic stimulation,low-frequency repetitive transcranial magnetic stimulation and anodic transcranial direct current stimulation.The results of network meta-analysis showed that in terms of improving gross motor function,low-frequency repetitive transcranial magnetic stimulation[mean difference(MD)=9.48,95％confidence interval(CI)(6.61,12.34),P＜0.05]was the most effective.In terms of alleviating spasticity,high-frequency repetitive transcranial magnetic stimulation[MD=-0.63,95％CI(-1.72,0.45),P＜0.05]had the best efficacy.In terms of improving ankle joint range of motion and step speed,transcranial direct current stimulation[MD=2.27,95％CI(1.37,3.17),P＜0.05;MD=0.11,95％CI(0.05,0.17),P＜0.05]was the most effective.CONCLUSION:Existing clinical evidence suggests that low-frequency repetitive transcranial magnetic stimulation has the best therapeutic effect compared with other intervention measures in terms of improving lower limb gross motor function.In terms of reducing spasticity,high-frequency repetitive transcranial magnetic stimulation has a more significant effect.In terms of improving gait,transcranial direct current stimulation has more advantages.

Oral submucous fibrosis (OSF), characterized by excessive deposition of extracellular matrix (ECM) that causes oral mucosal tissue sclerosis, and even cancer transformation, is a chronic, progressive fibrosis disease. However, despite some advancements in recent years, no targeted antifibrotic strategies for OSF have been approved; likely because the complicated mechanisms that initiate and drive fibrosis remain to be determined. In this review, we briefly introduce the epidemiology and etiology of OSF. Then, we highlight how cell-intrinsic changes in significant structural cells can drive fibrotic response by regulating biological behaviors, secretion function, and activation of ECM-producing myofibroblasts. In addition, we also discuss the role of innate and adaptive immune cells and how they contribute to the pathogenesis of OSF. Finally, we summarize strategies to interrupt key mechanisms that cause OSF, including modulation of the ECM, inhibition of inflammation, improvement of vascular disturbance. This review will provide potential routes for developing novel anti-OSF therapeutics.
Humans ; Oral Submucous Fibrosis/immunology* ; Extracellular Matrix/metabolism* ; Myofibroblasts

Periodontal bone defects, primarily caused by periodontitis, are highly prevalent in clinical settings and manifest as bone fenestration, dehiscence, or attachment loss, presenting a significant challenge to oral health. In regenerative medicine, harnessing developmental principles for tissue repair offers promising therapeutic potential. Of particular interest is the condensation of progenitor cells, an essential event in organogenesis that has inspired clinically effective cell aggregation approaches in dental regeneration. However, the precise cellular coordination mechanisms during condensation and regeneration remain elusive. Here, taking the tooth as a model organ, we employed single-cell RNA sequencing to dissect the cellular composition and heterogeneity of human dental follicle and dental papilla, revealing a distinct Platelet-derived growth factor receptor alpha (PDGFRA) mesenchymal stem/stromal cell (MSC) population with remarkable odontogenic potential. Interestingly, a reciprocal paracrine interaction between PDGFRA⁺ dental follicle stem cells (DFSCs) and CD31⁺ Endomucin⁺ endothelial cells (ECs) was mediated by Vascular endothelial growth factor A (VEGFA) and Platelet-derived growth factor subunit BB (PDGFBB). This crosstalk not only maintains the functionality of PDGFRA⁺ DFSCs but also drives specialized angiogenesis. In vivo periodontal bone regeneration experiments further reveal that communication between PDGFRA⁺ DFSC aggregates and recipient ECs is essential for effective angiogenic-osteogenic coupling and rapid tissue repair. Collectively, our results unravel the importance of MSC-EC crosstalk mediated by the VEGFA and PDGFBB-PDGFRA reciprocal signaling in orchestrating angiogenesis and osteogenesis. These findings not only establish a framework for deciphering and promoting periodontal bone regeneration in potential clinical applications but also offer insights for future therapeutic strategies in dental or broader regenerative medicine.
Receptor, Platelet-Derived Growth Factor alpha/metabolism* ; Humans ; Neovascularization, Physiologic/physiology* ; Dental Sac/cytology* ; Single-Cell Analysis ; Transcriptome ; Mesenchymal Stem Cells/metabolism* ; Bone Regeneration ; Animals ; Dental Papilla/cytology* ; Periodontium/physiology* ; Stem Cells/metabolism* ; Regeneration ; Angiogenesis

ObjectiveThis study aims to observe the clinical effect of Danggui Liuhuang Tang （DGLHT） on patients with type 2 diabetes mellitus （T2DM） complicated by atherosclerotic cardiovascular disease （ASCVD） at high risk， focus on evaluating the influence of DGLHT on cardiovascular risk indicators such as flow-mediated dilation （FMD）， atherogenic index of plasma （AIP）， and triglyceride-glucose index （TyG）， and explore the regulatory effect of DGLHT on the myeloid differentiation factor 88/nuclear factor-kappa B （MyD88/NF-κB） signaling pathway. MethodsThe clinical study was a single-center， double-blind， and randomized controlled trial. A total of 68 patients with T2DM-ASCVD at high risk for cardiovascular events with Yin deficiency and fire excess syndrome were enrolled and randomly assigned to a treatment group and a control group. The treatment group was given atorvastatin calcium tablets and DGLHT， while the control group was given atorvastatin calcium tablets and placebos. The treatment course was 12 weeks， with a final study completion of 30 patients in the treatment group and 29 in the control group. Changes in cardiovascular risk indicators such as FMD， AIP， TyG， and small dense low-density lipoprotein cholesterol （sdLDL-C） index were compared. Human umbilical vein endothelial cells （HUVECs） were used to establish a vascular endothelial injury and inflammation model. The protective effect of DGLHT on endothelial injury was verified by reverse transcription polymerase chain reaction （Real-time PCR） and Western blot . ResultsAfter 12 weeks of treatment， the AIP in the treatment group significantly decreased compared with that before the treatment （P<0.05）. Compared with the control group， the treatment group showed significant improvements in FMD and TyG （P<0.05）. Additionally， the treatment group demonstrated significant reductions in two-hour postprandial glucose （2 hPG）， glycated albumin （GA）， triglycerides （TG）， apolipoprotein E （Apo E）， and sdLDL-C （P<0.05）. Analysis of traditional Chinese medicine （TCM） syndrome efficacy indicated that in the treatment group， Yin deficiency and fire excess syndromes， including dry throat and mouth （P<0.05）， excessive thirst （P<0.01）， tidal fever and night sweats （P<0.05）， and dry stools （P<0.05）， improved. Compared with the control group， the treatment group showed significant improvements in symptoms of dry throat and mouth （P<0.05） and excessive thirst （P<0.01）. TCM syndrome scores significantly decreased （P<0.01）， and the overall efficacy rate was 56.67%， significantly higher than the 10.34% observed in the control group （P<0.01）. At the cellular level， increasing concentrations of DGLHT led to decreased messenger ribonucleic acid （mRNA） levels of pro-inflammatory cytokines interleukin-6 （IL-6）， tumor necrosis factor-alpha （TNF-α）， and interleukin-1-beta （IL-1β） in lipopolysaccharide （LPS）-stimulated HUVECs （P<0.01）， with significant reductions in the high-concentration group （P<0.01）. DGLHT may inhibit the expressions of MyD88 and phosphorylated （p）-NF-κB p65 proteins in a concentration-dependent manner. ConclusionDGLHT shows significant effects in reducing cardiovascular risks and may exert an anti-inflammatory effect by inhibiting the MyD88/NF-κB signaling pathway. This finding provides a new perspective for the prevention and treatment of cardiovascular diseases in high-risk individuals with T2DM-ASCVD.

Objective:To develop a clinical predictive model for dampness constitution based on laboratory testing indicators.Methods:A retrospective cohort study was conducted on 1 355 healthy individuals who underwent physical examinations at the Health Examination Center of Guangdong Provincial Hospital of Traditional Chinese Medicine from October 1 st, 2022 to October 31 st, 2023. Basic information and blood routine, blood glucose, liver function, lipid metabolism, and kidney function test results of 1 355 apparently healthy individuals were collected. According to the diagnostic criteria for dampness constitution in traditional Chinese medicine, they were divided into a dampness constitution group (683 cases, including 394 with phlegm-dampness constitution and 289 with damp-heat constitution) and a non-dampness constitution group (672 cases). Among them, there were 547 males and 136 females in the dampness constitution group, with an age of 38.0 (32.0, 45.0) years; and there were 355 males and 317 females in the non-dampness constitution group, with an age of 33.0 (27.0, 41.0) years. A total of 1 355 apparently healthy individuals were randomly divided into a training set ( n=948) and a validation set ( n=407) using computer-generated random numbers in a 7∶3 ratio. Logistic regression analysis was employed to identify risk factors associated with dampness constitution. Utilizing these identified risk factors, a predictive model was constructed and subsequently visualized. The model′s predictive accuracy, consistency, and clinical utility were assessed using the receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA), respectively. Results:Among 1 355 subjects, there were statistically significant differences ( P<0.05) in gender, age, body mass index (BMI), blood glucose, some indicators of renal function, some indicators of blood routine, liver function, and four indicators of lipid metabolism between the dampness constitution group and the non-dampness constitution group. Gender ( OR=0.434,95 %CI 0.253-0.738), Cr ( OR=0.981,95 %CI 0.967-0.996), BMI ( OR=1.366,95 %CI 1.290-1.450), and LDL-C ( OR=1.388,95 %CI 1.014-1.897) were independent risk factors for dampness constitution ( P<0.05). A nomogram was subsequently developed based on these identified risk factors. The areas under the ROC curves (AUC) of the training set and validation set were 0.810 (95 %CI 0.783-0.837) and 0.804 (95 %CI 0.762-0.846), respectively. Conclusion:Gender,BMI,Cr and LDL-C were risk factors for the development of dampness constitution, and the clinical predictive model has clinical application value in predicting the risk of dampness constitution.

Objective To explore the clinical efficacy and safety of single-port laparoscopic ovarian cyst removal surgery.Methods A total of 145 patients who underwent laparoscopic surgery for ovarian cyst in Wenzhou People's Hospital from January 2023 to June 2024.Among them,single-port laparoscopic ovarian cystectomy+oophoroplasty was performed in 67 cases as single-port group,and traditional multi-port laparoscopic ovarian cystectomy+oophoroplasty was performed in 78 cases as multi-port group.Clinical indicators during and after surgery in two groups were recorded and compared.Results There were significant difference the operation time and pain scores at 1 day after surgery between two groups(P＜0.05).There was no significant difference in intraoperative bleeding,postoperative exhaust time and postoperative hospitalization time between two groups(P＞0.05).Neither of two groups had intraoperative vascular or nerve damage in the abdominal wall,and there were no postoperative complications such as incision infection,intestinal obstruction,or lower limb venous thrombosis,and the incision healed well.Continuing the follow-up for 3 months after discharge,both surgical procedures had no significant effect on menstruation,and there was no short-term recurrence of ovarian cyst in either case.Conclusion The single-port laparoscopic technique for the treatment of ovarian cyst incision is concealed and beautiful,the postoperative pain is lighter.No obvious effect on menstruation,and the curative effect is definite and safe.

Objective:To evaluate the diagnostic value of multimodal Nomogram model combining 18F-FDG PET/CT and ultrasound for triple negative breast cancer (TNBC) . Methods:A total of 61 breast cancer patients admitted at Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School from November 2016 to May 2024 were selected as the study subjects, including 12 cases of TNBC and 49 cases of non-TNBC. 18F-FDG PET/CT metabolic parameters maximum standardized uptake value (SUV max), mean standardized uptake value (SUV mean), minimum standardized uptake value (SUV min), tumor metabolic volume (MTV), and total lesion glycolysis (TLG), as well as the ultrasound parameters long diameter, short diameter, echogenicity, morphology, boundaries, posterior echogenicity, aspect ratio, microcalcifications, blood flow grading and Breast Imaging Reporting and Data System (BI-RADS) grading were compared between patients with and without TNBC. Least absolute shrinkage and selection operator (LASSO) regression was used for feature screening, and binary multivariate logistic regression analysis was conducted on the screened variables to obtain the independent influencing factors for diagnosing TNBC. The independent factors influencing the diagnosis of TNBC were established as Nomogram model and visualized. Receiver operator characteristic (ROC) curve, calibration curve and decision curve analysis (DCA) were used to evaluate the diagnostic efficacy, accuracy and clinical practicability of the model, respectively. Results:There were statistically significant differences in SUV max ( Z=-2.43, P=0.015), SUV mean ( Z=-2.54, P=0.011), morphology ( P=0.004), boundaries ( χ2=4.86, P=0.028), posterior echogenicity ( P=0.027), and blood flow grading ( χ2=4.52, P=0.034) between TNBC and non-TNBC patients. LASSO regression screened out three variables: SUV max, morphology and blood flow grading. Multivariate analysis showed that, SUV max ( OR=1.20, 95% CI: 1.04-1.38, P=0.012), morphology ( OR=0.02, 95% CI: 0.01-0.49, P=0.016), and blood flow grading ( OR=0.06, 95% CI: 0.01-0.74, P=0.028) were the independent influencing factors for diagnosing TNBC. A Nomogram model was established based on the above independent influencing factors. ROC curve showed that, area under the curve (AUC) of SUV max, morphology, blood flow grading, and the Nomogram model were 0.73 (95% CI: 0.60-0.83), 0.66 (95% CI: 0.52-0.77), 0.67 (95% CI: 0.54-0.79), 0.90 (95% CI: 0.79-0.96), respectively, and the diagnostic value of the Nomogram model was higher than that of SUV max ( Z=2.71, P=0.007), morphology ( Z=3.61, P<0.001), and blood flow grading ( Z=2.51, P=0.012) alone. Calibration curve and DCA showed better accuracy and clinical practicability of the Nomogram model. Conclusions:Nomogram model constructed by combining the SUV max of 18F-FDG PET/CT with the morphology and blood flow grading of ultrasound has a promising potential for diagnosing TNBC.

Background and aims:Hepatocellular carcinoma(HCC)is a leading cause of cancer-related mortality worldwide,and its etiology involves a complex interplay of genetic and environmental factors.Despite ad-vancements in our understanding of HCC biology and the development of novel therapeutic strategies,the molecular mechanisms underlying its onset,progression,and resistance to therapy remain largely vague.This study aimed to investigate the role of mechanosensitive ion channel-related genes(MICRGs)in HCC,focusing on their potential as prognostic biomarkers and their involvement in immune modulation and drug resistance.Methods:A comprehensive analysis was conducted using The Cancer Genome Atlas database to identify MICRGs that are upregulated in HCC.Gene expression profiling,bioinformatics tools,and functional experiments were employed to elucidate the role of these channels.In addition,protein-protein interaction(PPI)network analyses and enrichment analyses were performed to explore the biological significance of these genes.An immune cell infiltration analysis was also conducted to understand MICRG-related immune landscape.Single-cell RNA sequencing(scRNA-seq)data were utilized to identify MICRGs in different cell types within the HCC tissue.Deep-learning neural network analysis across patient cohorts was conducted to identify genes associated with sorafenib resistance.Knockdown ex-periments,cell viability assays,and apoptosis assays on HCC cell lines were performed to examine the role of Piezo-type mechanosensitive ion channel component 1(PIEZO1)in sorafenib resistance.Results:The analysis identified a subset of MICRGs,including PIEZO1,that were significantly upregulated in HCC and associated with poor prognosis.The PPI network analysis revealed complex interactions among these genes.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses proposed the involvement of these genes in calcium signaling pathways.Immune cell infiltration analysis demonstrated distinct associations between MICRGs and various immune subpopulations,highlighting their potential roles in immune modulation.scRNA-seq data indicated the upregulation of MICRGs in various cell types in HCC tissues,particularly in endothelial cells and tumor-associated macrophages.Deep-learning neural network analysis across different patient cohorts identified PIEZO1 as a crucial regulator of sorafenib resistance in HCC,which was further validated by functional assays on HCC cell lines.Conclusions:This study provides evidence that MICRGs,particularly PIEZO1,take on crucial roles in HCC progression and drug resistance.The upregulation of PIEZO1 in HCC cells is associated with poor prog-nosis and resistance to sorafenib.These findings indicate that PIEZO1 could serve as a potential thera-peutic target for overcoming drug resistance and a prognostic biomarker in HCC.Future studies should focus on validating these findings in larger patient cohorts and exploring the functional implications of targeting PIEZO1 in preclinical models.