Objective To investigate the relationship between platelet distribution width(PDW)and coronary artery calcification(CAC)in overweight and obese populations.Methods Clinical and chest CT data of 10 838 subjects with overweight or obesity(body mass index[BMI]≥24 kg/m2)were retrospectively analyzed.The subjects were divided into CAC group(n=4 237)and non-CAC group(n=6 601)based on CAC scores obtained from chest CT.The relationship between PDW and CAC in overweight and obese populations was analyzed after controlling confounding variables.A threshold effect analysis was conducted using a two-stage logistic model to find the non-linear inflection point.Subgroup analyses and interaction tests were conducted to validate the stability of the relationship between PDW and CAC.Results Non-linear relationship was observed between PDW and CAC risk in overweight and obese populations.The risk of CAC decreased with the increase of PDW which ≤17.80％(OR=0.82),but increased with the increase of PDW(OR=1.04)which＞17.80％.Subgroup analysis showed that the relationship between PDW and CAC remained stable in subgroups of different genders,BMI(＜28 kg/m2,≥28 kg/m2)and hypertension(all P＞0.05).Compared with aged＜40 years or ≥60 years subgroups,under the same PDW,aged≥40 and＜60 years subgroups had higher risk of CAC(interaction P=0.015).Conclusion Nonlinear relationship existed between PDW and CAC in overweight and obese populations.Both excessively high and low PDW were risk factors of CAC.

Objective:To investigate the effect and preliminary mechanism of hypervirulent Klebsiella pneumoniae (hvKP) on the immune response to sepsis induced by liver abscess in mice. Methods:C57BL/6 mice were intraperitoneally injected with hvKP strain NTUH-K2044 or classical Klebsiella pneumoniae (cKP) strain HS11286 suspension to prepare the model of sepsis. The survivals rates of mice within 24 h were recorded. HE staining was used to observed the inflammatory cell infiltration in mouse liver tissues. The levels of neutrophil marker lymphocyte antigen 6G (Ly6G) in mouse liver tissues were detected by immunohistochemistry. The activity of reactive oxygen species (ROS) in mouse liver macrophages and peripheral blood monocytes was measured by ROS assay kit. The activation of p105/p50 and p65 in NF-κB signaling pathway in mouse liver macrophages and peripheral blood monocytes was detected by Western blot. The expression of IL-1β, IL-6 and TNF-α at mRNA and protein levels in mouse liver macrophages and peripheral blood monocytes were detected by qRT-PCR and ELISA, respectively. One-way analysis of variance and t test were used for statistical analysis. Results:Compared with cKP, hvKP infection could induce C57BL/6 mice to develop obvious liver abscess with massive inflammatory cell infiltration. Moreover, the level of Ly6G in liver tissues was significantly higher in hvKP-infected mice than in cKP-infected mice ( P<0.000 1), but the survival rate of hvKP-infected mice was significantly lower than that of cKP-infected mice ( P<0.000 1). hvKP significantly promoted the ROS activity ( P<0.000 1) and enhanced the phosphorylation of p105/p50 and p65 in NF-κB signaling pathway in mouse liver macrophages and peripheral blood monocytes as compared with cKP ( P<0.001). The expression of IL-1β, IL-6 and TNF-α at mRNA and protein levels in mouse liver macrophages and peripheral blood monocytes were significantly higher in hvKP-infected mice than in cKP-infected mice ( P<0.001). Conclusion:hvKP can promote the development of liver abscess and induce sepsis in mice.

Objective:To investigate the role of TcpC, a virulence factor of uropathogenic Escherichia coli (UPEC), in inhibiting the formation of neutrophil extracellular traps (NETs) in mouse bone marrow neutrophils, and to analyze its pathogenic mechanism. Methods:C57BL/6 mice were injected with either wild-type (CFT073 wt) or tcpc gene-knockout UPEC CFT073(CFT073 Δ tcpc) to establish a mouse model of cystitis. Mice were sacrificed 3 d post-infection, and their bladders were collected to observe gross pathological changes. Hematoxylin-eosin (HE) staining was used to assess histopathological changes in bladder tissues, and immunohistochemistry was performed to localize TcpC in bladder tissues. Bacterial loads in urine samples were quantified using the ten-fold dilution method, and the presence of tcpc gene in genomic DNA from bladder or urine samples was confirmed by PCR. The expression of TcpC at mRNA and protein levels in mouse bone marrow nuetrophils infected with CFT073 wt was detected by qRT-PCR and Western blot. The effects of UPEC infection on expression of NETs-related proteins and the production of pro-inflammatory factors in mouse bone marrow neutrophils were analyzed by Western blot and ELISA, respectively. Reactive oxygen species(ROS) level and bacterial viability in mouse bone marrow nuetrophils were measured using ROS and bacterial viability detection kits. Results:Compared to the CFT073 Δ tcpc group, the bladder of CFT073 wt group mice exhibited significant enlargement, extensive inflammatory cell infiltration, and the presence of TcpC in bladder tissue. The bacterial load in the urine of CFT073 wt -infected mice was significantly higher than that in the CFT073 Δ tcpc group ( P<0.01). PCR confirmed the presence of the tcpc gene in bladder and urine samples from CFT073 wt-infected mice. Increased expression of TcpC at both mRNA and protein levels was observed in CFT073 wt-infected mouse bone marrow neutrophils. CFT073 wt infection inhibited the mRNA and protein expression of NETs-related proteins and reduced the production of pro-inflammatory factors in mouse bone marrow neutrophils. TcpC suppressed ROS level and promoted the survival of CFT073 wt in mouse bone marrow neutrophils. Conclusions:TcpC enhances the pathogenicity of UPEC CFT073 by inhibiting the formation and activation of NETs in mouse bone marrow neutrophils. This study provides new insights into the pathogenic mechanisms of UPEC and the immune evasion strategies of other pathogenic bacteria, as well as potential targets for clinical prevention and treatment of UPEC-induced urinary tract infections.

Blood-bi-syndrome is primarily characterized by localized numbness and mild pain in the limbs.Records about the diagnosis and treatment of blood-bi-syndrome are scattered throughout classical medical literature.According to the theory of Yindan and Yangdan formulas in the classical prescription system,when the body's ascending function of qi movement is insufficiency,Yangdan formulas which contain Astragali Radix can be used for warming and uplifting yang qi.Conversely,when the descending function of qi movement is insufficiency,Yindan formulas which contain containing Bupleuri Radix can be used for astringing,descending,clearing and purging.This article,based on the principles of Yindan and Yangdan formulas,analyzed the fundamental pathogenesis of blood-bi-syndrome developing from the transmission of superficial syndromes,as well as its clinical manifestations during the transmission and change between taiyin disease and yangming disease.And the therapeutic strategies for blood-bi-syndrome were also summarized.It is proposed that taiyin blood-bi-syndrome arises in individuals with constitutionally deficient cold after the attack of pathogenic factors,resulting from fluid depletion,blood insufficiency,and stomach deficiency,which should be treated by Yangdan Formulas with pungent-sweet-warm properties for warming and uplifting yang qi.For the treatment of patients with taiyin blood-bi-syndrome characterized by exterior syndrome,Astragali Radix-containing classical prescriptions like Astragali Radix and Cinnamomi Ramulus Five-Component Decoction(Huangqi Guizhi Wuwu Decoction)can be chosen;for the treatment of patients with taiyin blood-bi-syndrome characterized by interior syndrome,Zingiberis Rhizoma Recens-containing classical prescriptions like Citri Reticulatae Pericarpium and Bambusae Caulis in Taenia Decoction(Jupi Zhuru Decoction)is adopted.Conversely,yangming blood-bi-syndrome occurs in individuals with constitutionally excessive heat after the attack of pathogenic factors,resulting from the internal accumulation of blood stasis and heat and the impairment of the fluid and blood,which should be treated by Yindan Formulas with pungent-sweet-cold or sour-cold properties for astringing,descending,clearing and purging.For the treatment of patients with yangming blood-bi-syndrome characterized by exterior syndrome,Puerariae Lobatae Radix-containing classical prescriptions like Phyllostachydis Henonis Folium and Puerariae Lobatae Radix Decoction(Zhuye Gegen Decoction)can be used;for the treatment of patients with yangming blood-bi-syndrome characterized by interior syndrome,Paeoniae Radix Alba-containing classical prescriptions like Rhei Radix et Rhizoma and Eupolyphaga seu Steleophaga Decoction(Dahuang Zhechong Wan)is recommended.

Objective:To investigate the clinical efficacy of hair follicle-bearing microskin transplantation as a novel therapeutic approach for subacute wounds.Methods:A prospective randomized controlled trial was conducted from June to October 2024, involving patients with subacute wounds treated in the Department of Plastic and Reconstructive Surgery, Hand Microsurgery at Ningbo No.6 Hospital, and the Medical Aesthetics Center at Hangzhou First People’s Hospital. Participants were randomly assigned via a random number table into two groups: the observation group received hair follicle-bearing microskin transplantation, while the control group received conventional treatment including debridement, dressing changes, antimicrobial therapy, and local pressure relief. The observation endpoint was set at 6 weeks post-treatment. Outcome measures included time to complete wound healing, wound healing score (comprising five items: wound area, appearance, exudate, signs of infection, and condition of surrounding skin; total score 0-15, with a higher score indicating poorer healing), donor site recovery, adverse reactions, and patient satisfaction [rated on a 4-level scale: very satisfied, satisfied, basically satisfied, dissatisfied; satisfaction rate was calculated as (very satisfied + satisfied) cases/total cases×100%]. Data were analyzed using SPSS 25.0 software, with continuous variables expressed as Mean±SD and compared via t-test; enumeration data were expressed as cases (relative numbers) and analyzed using Fisher’s exact test. P<0.05 was considered statistically significant. Results:Sixteen patients were enrolled (8 per group), including 12 males and 4 females, with a mean age of 46 years (range: 41-71). No significant differences in baseline characteristics (gender, age, wound duration, and wound area) were observed between the two groups (all P>0.05). All procedures in the observation group were completed successfully without intraoperative or short-term postoperative complications. The donor site area was (28.2±11.8) cm 2 (9.0-50.0 cm 2). All wounds in the observation group healed completely within 2-5 weeks post-treatment, with a mean healing time of (26.2±5.0) d. The donor sites healed within two weeks, leaving only pinpoint scars. In contrast, only 4 cases in the control group achieved complete healing within the observation period (6 weeks post-treatment), with a mean healing time of (33.2±5.7) d. The other 4 patients showed no tendency to heal at 6 weeks and progressed to chronic wounds. Before treatment, no significant difference in wound healing scores was found between the two groups (9.6±2.6 vs. 9.1±2.0, t=0.43, P=0.676). At 6 weeks post-treatment, the observation group showed significantly lower wound healing scores than the control group (1.2±1.5 vs. 7.9±3.9, t=-4.48, P=0.001). At 6 weeks post-treatment, patient satisfaction in the observation group was significantly higher than that in the control group (8/8 vs. 4/8, P=0.006). Conclusion:Hair follicle-bearing microskin transplantation demonstrates significant clinical advantages in treating subacute wounds, including accelerated healing, improved aesthetic outcomes, minimal donor site morbidity, and rapid recovery.

Traditional development of small protein scaffolds has relied on display technologies and mutation-based engineering, which limit sequence and functional diversity, thereby constraining their therapeutic and application potential. Protein design tools have significantly advanced the creation of novel protein sequences, structures, and functions. However, further improvements in design strategies are still needed to more efficiently optimize the functional performance of protein-based drugs and enhance their druggability. Here, we extended an evolution-based design protocol to create a novel minibinder, BindHer, against the human epidermal growth factor receptor 2 (HER2). It not only exhibits super stability and binding selectivity but also demonstrates remarkable properties in tissue specificity. Radiolabeling experiments with ^99mTc, ⁶⁸Ga, and ¹⁸F revealed that BindHer efficiently targets tumors in HER2-positive breast cancer mouse models, with minimal nonspecific liver absorption, outperforming scaffolds designed through traditional engineering. These findings highlight a new rational approach to automated protein design, offering significant potential for large-scale applications in therapeutic mini-protein development.

Objective:To explore the potential mechanism underlying IL-6 production through the TLR7 signaling pathway,which regulates Th17 cell differentiation in the context of Coxsackievirus B3(CVB3)-induced acute viral myocarditis(AVMC).Meth-ods:A total of 110 patients diagnosed with AVMC were admitted to Quanzhou First Hospital,Fujian between January 2020 and Janu-ary 2023,alongside 93 healthy volunteers.CD4+T cells were isolated from the subjects'blood,and the levels of CVB3 and the number of Th17 cells were assessed.Subsequently,CD4+T cells were infected with CVB3,and the levels of Th17 cells,IL-17,IL-21,and TNF-α were measured.After knockdown of TLR7 or treatment with TLR7 inhibitors,the differentiation of CVB3-infected CD4+T cells into Th17 cells was observed.Results:In comparison to healthy controls,AVMC patients exhibited elevated plasma levels of hsCRP,IL-17,IL-21,and TNF-α(P<0.05).The levels of CVB3 mRNA in CD4+T cells were also notably higher in AVMC patients compared to healthy controls(P<0.05).The mean viral titer in AVMC patients measured 230 PFU/ml,while no detectable virus was found in healthy volunteers(P<0.05).In CD4+T cells,the count of Th17 cells was significantly increased in AVMC patients compared to healthy volunteers(P<0.05).Moreover,the number of Th17 cells in peripheral blood CD4+T cells of AVMC patients showed a positive correlation with CVB3 virus titer(P<0.05).Following CVB3 infection,the number of Th17 cells increased compared with the control group(P<0.05),accompanied by elevated levels of IL-17,IL-21,and TNF-α in the supernatant(P<0.05).Knockdown of TLR7 and CVB3 infection in CD4+T cells significantly reduced the levels of Th17 cells(P<0.05),while the expression level of phosphorylated-activated TLR7 increased significantly after CVB3 infection of CD4+T cells compared to the control group(P<0.05).Treatment with the TLR7 inhibitor M5049 and CVB3 infection led to a significant decrease in Th17 cell levels(P<0.05).The secretion of IL-6 in CD4+T cells increased after CVB3 infection(P<0.05),and this increase was mitigated by TLR7 knockdown and CVB3 infection(P<0.05)as well as TLR7 inhibitor M5049 treatment and CVB3 infection(P<0.05).Conclusion:CVB3 activates TLR7 via phosphoryla-tion,prompting CD4+T cells to release IL-6 and undergo differentiation into Th17 cells.Consequently,TLR7 emerges as a promising therapeutic target for AVMC.

OBJECTIVE To explore the expressions of eosinophilic chemotactic factor 11(CCL11),leukotriene B4(LTB4),percentage of neutrophils(NEUT％)and C-reactive protein(CRP)in peripheral blood of the children with Mycoplasma pneumoniae(MP)infection complicated with plastic bronchitis and analyze the clinical signifi-cance.METHODS A total of 80 children with MP pneumonia complicated with plastic bronchitis who were trea-ted in the Second Hospital of Longyan City,Fujian Province from Jan.2020 to Dec.2023 were assigned as the study group,and 115 patients with MP pneumonia were chosen as the control group.The clinical data,manifesta-tions and Pediatric Risk of Mortality Ⅲ(PRISM Ⅲ)score were statistically analyzed.The levels of peripheral blood CCL11,LTB4,NEUT％and CRP were observed and compared between the two groups.Pearson analysis was performed for the associations of the levels of CCL11,LTB4,NEUT％and CRP with the PRISM Ⅲscore.The value of the joint detection of CCL11,LTB4,NEUT％and CRP in diagnosis of the MP pneumoni-a-induced plastic bronchitis was analyzed.RESULTS There were significant differences in reduction of bronchial breathing sound,pleural effusion and PRISM Ⅲ score between the two groups(P＜0.05).There were significant differences in the levels of peripheral blood CCL11,LTB4,NEUT％and CRP between the study group and the control group(P＜0.05);the CRP level of the study group was(29.42±8.14)mg/L,higher than that of the control group(t=10.138,P＜0.001).The levels of CCL11,LTB4,NEUT％and CRP were positively correlated with the PRISM Ⅲ score(r=0.723,0.710,0.771,0.754,respectively,all P＜0.001).The area under the curve(AUC)of the single detection of CCL11,LTB4,NEUT％and CRP was remarkably higher in diagnosis of MP pneumonia-induced plastic bronchitis than that of the joint detection of the four markers(P＜0.05).CONCLUSIONS The children with MP pneumonia complicated with plastic bronchitis show increased expressions of CCL11,LTB4,NEUT％and CRP.The four markers are positively correlated with the PRISM Ⅲ score.The four markers have high values in diagnosis of the MP pneumonia complicated with plastic bronchitis.

Objective: To develop a facial image generation method based on a facial color-preserving generative adversarial network (FCP-GAN) that effectively decouples identity features from diagnostic facial complexion characteristics in traditional Chinese medicine (TCM) inspection, thereby addressing the critical challenge of privacy preservation in medical image analysis. Methods: A facial image dataset was constructed from participants at Nanjing University of Chinese Medicine between April 23 and June 10, 2023, using a TCM full-body inspection data acquisition equipment under controlled illumination. The proposed FCP-GAN model was designed to achieve the dual objectives of removing identity features and preserving colors through three key components: (i) a multi-space combination module that comprehensively extracts color attributes from red, green, blue (RGB), hue, saturation, value (HSV), and Lab spaces; (ii) a generator incorporating efficient channel attention (ECA) mechanism to enhance the representation of diagnostically critical color channels; and (iii) a dual-loss function that combines adversarial loss for de-identification with a dedicated color preservation loss. The model was trained and evaluated using a stratified 5-fold cross-validation strategy and evaluated against four baseline generative models: conditional GAN (CGAN), deep convolutional GAN (DCGAN), dual discriminator CGAN (DDCGAN), and medical GAN (MedGAN). Performance was assessed in terms of image quality [peak signal-to-noise ratio (PSNR) and structural similarity (SSIM)], distribution similarity [Fréchet inception distance (FID)], privacy protection (face recognition accuracy), and diagnostic consistency [mean squared error (MSE) and Pearson correlation coefficient (PCC)]. Results: The final analysis included facial images from 216 participants. Compared with baseline models, FCP-GAN achieved superior performance, with PSNR = 31.02 dB and SSIM = 0.908, representing an improvement of 1.21 dB and 0.034 in SSIM over the strongest baseline (MedGAN). The FID value (23.45) was also the lowest among all models, indicating superior distributional similarity to real images. The multi-space feature fusion and the ECA mechanism contributed significantly to these performance gains, as evidenced by ablation studies. The stratified 5-fold cross-validation confirmed the model’s robustness, with results reported as mean ± standard deviation (SD) across all folds. The model effectively protected privacy by reducing face recognition accuracy from 95.2% (original images) to 60.1% (generated images). Critically, it maintained high diagnostic fidelity, as evidenced by a low MSE (< 0.051) and a high PCC (> 0.98) for key TCM facial features between original and generated images. Conclusion The FCP-GAN model provides an effective technical solution for ensuring privacy in TCM diagnostic imaging, successfully having removed identity features while preserving clinically vital facial color features. This study offers significant value for developing intelligent and secure TCM telemedicine systems.

OBJECTIVE: To evaluate the functional and aesthetic evaluation of external fixator lengthening through plantar approach for fourth brachymetatarsia. METHODS: A retrospective analysis was conducted on 20 patients (23 feet) with fourth brachymetatarsia who met the selection criteria between January 2016 and January 2024, including 3 males and 17 females, with 8 left, 9 right, and 3 bilateral cases. The mean age was 24.7 years (range, 14-51 years). The preoperative metatarsal shortening length was (13.8±3.2) mm. The preoperative American Orthopaedic Foot and Ankle Society (AOFAS) forefoot score was 79.5±3.9, the visual analogue scale (VAS) score of appearance satisfaction was 1.7±0.8, and the appearance index (AI) score was 13.6±0.9. All patients underwent external fixator lengthening through plantar approach. The lengthening length of metatarsal bone, lengthening ratio, healing time, and healing index were recorded. Functional outcomes were assessed using the AOFAS forefoot score, VAS score of appearance satisfaction, and quality-of-life impact with AI questionnaire. RESULTS: All 20 patients were followed up 14-55 months with an average of 36.3 months. During the follow-up, complications occurred in 4 cases (17.4%), including 2 cases of metatarsophalangeal joint stiffness, which had no significant effect on the function and appearance. Delayed union of osteotomy occurred in 1 case (healed at 12 weeks after operation). Pin loosening occurred in 1 case and recovered after outpatient reinforcement. No complications related to plantar scar occurred. At last follow-up, the lengthening length of metatarsal bone was (13.9±3.1) mm, and the lengthening ratio was 25.8%±5.6%. All cases achieved bony union, with a mean healing time of (64.3±12.5) days and a healing index of (46.9±4.8) d/cm. At last follow-up, AOFAS score was 98.9±2.1, the VAS score of appearance satisfaction was 9.3±0.7, and the AI score was 0.6±0.8, which significantly improved when compared with those before operation ( t=27.398, P<0.001; t=32.994, P<0.001; t=56.135, P<0.001). CONCLUSION External fixator lengthening through plantar approach is a safe and effective technique for fourth brachymetatarsia, achieving satisfactory functional and aesthetic outcomes.
Humans ; Male ; Female ; Adult ; External Fixators ; Retrospective Studies ; Bone Lengthening/instrumentation* ; Middle Aged ; Metatarsal Bones/abnormalities* ; Adolescent ; Young Adult ; Treatment Outcome ; Patient Satisfaction ; Esthetics ; Osteotomy/methods* ; Foot Deformities, Congenital/surgery*