Objective To investigate the status of pain and influencing factors of patients with chronic wounds.Methods A convenience sampling was used to recruit 186 patients with chronic wounds from a tertiary hospital in Chongqing between January and August 2024.General information questionnaire,Numeric Rating Scale(NRS),and Chronic Wound Pain Status Questionnaire were used to collect data.Results The 186 patients had a median score for pain knowledge of 15(12,19),for pain attitude of 40(37,45),and for coping behaviors of 21(16,26).Generalized linear model analysis showed that age,education level,and per capita monthly household income were independent factors influencing pain knowledge(standardized regression coefficients:-1.625,2.071,1.209;95％CI:-2.479～-0.770,1.431～2.711,0.160～2.258,respectively;P＜0.05).Education level and baseline pain intensity were independent factors influencing pain attitude(standardized regression coefficients:3.036,-2.211;95％CI:2.146～3.926,-3.568～-0.854;P＜0.05).Education level and type of pain persistence were independent factors influencing coping behaviors to pain(standardized regression coefficients:1.001,-1.694;95％CI:0.194～1.809,-3.262～-0.126;P＜0.05).Conclusion Patients with chronic wounds have generally low levels of pain-related knowledge,attitudes,and coping behaviors.Age,per capita monthly household income,education level,and pain characteristics significantly influence their pain status.Education level plays a key role in influencing pain among patients with chronic wounds by shaping their access to pain-related knowledge,development of their attitudes toward pain,and execution of pain management behaviors.

Nicotinamide phosphoribosyl transferase (NAMPT) is considered as a promising target for cancer therapy given its critical engagement in cancer metabolism and inflammation. However, therapeutic benefit of NAMPT enzymatic inhibitors appears very limited, likely due to the failure to intervene non-enzymatic functions of NAMPT. Herein, we show that NAMPT dampens antitumor immunity by promoting the expansion of tumor infiltrating myeloid derived suppressive cells (MDSCs) via a mechanism independent of its enzymatic activity. Using proteolysis-targeting chimera (PROTAC) technology, PROTAC A7 is identified as a potent and selective degrader of NAMPT, which degrades intracellular NAMPT (iNAMPT) via the ubiquitin-proteasome system, and in turn decreases the secretion of extracellular NAMPT (eNAMPT), the major player of the non-enzymatic activity of NAMPT. In vivo, PROTAC A7 efficiently degrades NAMPT, inhibits tumor infiltrating MDSCs, and boosts antitumor efficacy. Of note, the anticancer activity of PROTAC A7 is superior to NAMPT enzymatic inhibitors that fail to achieve the same impact on MDSCs. Together, our findings uncover the new role of enzymatically-independent function of NAMPT in remodeling the immunosuppressive tumor microenvironment, and reports the first NAMPT PROTAC A7 that is able to block the pro-tumor function of both iNAMPT and eNAMPT, pointing out a new direction for the development of NAMPT-targeted therapies.

Objective To investigate the clinical pathologic features of a distinct variant of focal cortical dysplasia (FCD) characterized by neuronal loss of layer four.Methods Between 2005 and 2017,approximately 3 000 surgeries were performed for the treatment of intractable epilepsy at Xuanwu Hospital,Capital Medical University and Yuquan Hospital,Tsinghua University.Retrospective analysis of clinic-pathological data of patients with epilepsy surgery was made and histological manifestations of neuronal loss of cortical layer four were included in this study.Results In this cohort,25 patients (22 males and three females) were identified with early onset pharmaco-resistant epilepsy and regionally circumscribed neuronal loss of cortical layer four in surgical specimens from the occipital lobe.Histologically,except for neuronal loss in cortical layer four in all cases,glial scar lesions were found in some patients.Thus the histology of those cases can be subdivided into two groups:group A (13 cases):neuronal loss of cortical layer four without glial scar lesions;and group B (12 cases):neuronal loss of cortical layer four with glial scar lesions.Due to the prominent horizontal disorganization of cortical layering and lack of any other microscopically visible principle lesion,group A should be classified hitherto as FCD International League Against Epilepsy (ILAE) type Ⅰ b,however,group B with scar lesions and cortical dysplasia around the main leision,should be classified as FCD ILAE type Ⅲd.This retrospective analysis of clinical histories revealed a perinatal distress in 20 patients (80％),suggesting an acquired pathomechanism.Magnetic resonance imaging revealed abnormal signals in the occipital lobe in all patients,and signal changes suggestive of encephalomalacia were found in 18 patients.Surgical treatment achieved favorable seizure control (Engel class Ⅰ and Ⅱ) in 18 patients (75％ among 24 available follow up).Comparion of the two groups with age at epilepsy onset (group A:5.00±2.76,group B:5.01±3.78),the proportion of perinatal distress (group A:11/13,group B:9/12) and the follow-up results (favorable seizure control of the two groups was 9/13,9/11 respectively) showed that there was no statistically significant difference between the two groups.Conculsion Neuronal loss of cortical layer four in the occipital lobe should be classified as a distinct variant of FCD ILAE type Ⅲd.

Objective To explore the effect of robot-assisted gait training on pelvis kinematics and the walking function of hemiplegic stroke survivors.Methods Thirty stroke survivors with hemiplegia were randomly divided into a treatment group and a control group,each of 15.Both groups were given routine clinical medication and rehabilitation training,while the treatment group was additionally provided with 20 minutes of robot-assisted gait training a day,6 d/wk for 8 weeks.Before and after the treatment,all of the patients' pelvis kinematics were assessed using 10 m walking speed (MWS),the timed up and go test (TUGT) and functional ambulation categorization (FAC).Results Before the treatment there were no significant differences between the two group in any of the measurements.After the treatment,significant improvement was observed in both groups in the vertical displacement and rotation and tilt angles of the pelvis while walking,with significantly more improvement in the treatment group than in the control group.There was also significant improvement in the average walking speed,TUGT time and FAC score of both groups,with significantly more improvement in the treatment group.Conclusion Robot-assisted gait training can significantly improve the pelvis control and walking ability of hemiplegic stroke survivors.

Objective To analyze radiation induced alterations of vitronectin and collagen expressions in fibroblasts at different times post-irradiation,so as to evaluate the potential to apply vitronectin as a biomarker of radiation-induced lung fibrosis.Methods The human fibroblast cells WI-38 and IMR-90 were irradiated with 137Cs γ-rays at doses of 0 (control),4,6,8,10 and 12 Gy,respectively.The cells and its supernatant were collected at 6,12,24,36,48 and 60 h post-irradiation.The expressions of vitronectin and collagen Ⅰ and Ⅲ were analyzed by Western blot,PCR and ELISA.Results After irradiation,the expressions of vitronectin and collagen Ⅰ and Ⅲ were positively correlated (r=0.40-0.79,P＜0.05) and were all significantly higher than that in control group (t =3.04-25.45,P ＜0.05) and reached the highest expression levels at 48 h after 8-10 Gy of irradiation (t =2.92-18.86,P ＜ 0.05).Analyses of Real-time PCR and ELISA assay showed that expressions of vitronectin mRNA and its protein level in the cell lysis were significantly increased by radiation (F =27.09-42.62,P ＜ 0.05).Conclusions The expressions of vitronectin in cellular supernatant and its mRNA may be a potential biomarker of radiation-induced fibrosis,and 48 h after 8 Gy irradiation may be an optimum condition of measurement.

Objective To investigate ultrasonographic (US) features of mucinous breast carcinoma with pathological correlation and to improve the early diagnosis for the mucinous breast carcinoma.Methods Twenty-two patients with 23 focuses mucinous carcinoma of the breast confirmed by pathology were included in this study,retrospectively evaluate sonographic features according to the American College of Radiology(ACR) Breast Imaging Reporting and Data System(BI-RADS) Lexicon,all cases were classified by BI-RADS before operation.Histological type of mucinous breast carcinoma included mixed and pure two forms,the latter was classified into cellular variants and hypocellular variants.The correlation between the ultrasonographic findings of mucinous carcinoma and histologic features in different types were analysed.Results On US examination,all 22 cases presented as solid mass.In pure form,they showed well-defined margins with no pseudocapsule and isoechogenic or hypoechoic internal echo pattern relative to that of subcutaneous fat in 86.7％ (13/15) focuses which histological type were pure type.93.3％ (14/15) of pure type focuses had posterior enhancement.All pure type focuses demonstrated that the orientation of the mass is parallel to the skin line.75.0％ (6/8) of mixed type focuses and 13.3％ (2/15) of pure type focuses,however,demonstrated ill-defined and or spiculated margins with more hypoechogenic structure (P ＜0.01).Mixed type focuses have more aggressive malignant features.65.2％ (15/23) of cases being classified as BI-RADS 4 or 5 were suspected as malignancy,which included 6 mixed type focuses and 9 pure type respectively accounting for 75.0％ (6/8) and 60.0％ (6/15) of each type focuses.Conclusions Mucinous breast carcinoma especial pure type did not have the typical malignant breast masses sonographic features,which showed some benign masses sonographic features except no pseudocapsule benign feature.Mixed type mucinous carcinomas tumors have more aggressive margin imaging characteristics.It is suggested that mucinous breast carcinoma should be classified category 4 by BI-RADS to avoid diagnosis delay.

The human Gadd45 protein family plays critical roles in DNA repair, negative growth control, genomic stability, cell cycle checkpoints and apoptosis. Here we report the crystal structure of human Gadd45γ [corrected], revealing a unique dimer formed via a bundle of four parallel helices, involving the most conserved residues among the Gadd45 isoforms. Mutational analysis of human Gadd45γ [corrected] identified a conserved, highly acidic patch in the central region of the dimer for interaction with the proliferating cell nuclear antigen (PCNA), p21 and cdc2, suggesting that the parallel dimer is the active form for the interaction. Cellular assays indicate that: (1) dimerization of Gadd45γ [corrected] is necessary for apoptosis as well as growth inhibition, and that cell growth inhibition is caused by both cell cycle arrest and apoptosis; (2) a conserved and highly acidic patch on the dimer surface, including the important residues Glu87 and Asp89, is a putative interface for binding proteins related to the cell cycle, DNA repair and apoptosis. These results reveal the mechanism of self-association by Gadd45 proteins and the importance of this self-association for their biological function.
Amino Acid Motifs ; Animals ; Apoptosis ; radiation effects ; CDC2 Protein Kinase ; Cell Cycle ; Cell Survival ; Crystallography, X-Ray ; Cyclin B ; metabolism ; Cyclin-Dependent Kinase Inhibitor p21 ; metabolism ; Cyclin-Dependent Kinases ; HeLa Cells ; Humans ; Intracellular Signaling Peptides and Proteins ; chemistry ; genetics ; metabolism ; Mice ; Mutagenesis, Site-Directed ; Mutation, Missense ; Proliferating Cell Nuclear Antigen ; metabolism ; Protein Binding ; Protein Interaction Domains and Motifs ; Protein Multimerization ; Protein Structure, Quaternary ; Ultraviolet Rays

Objective To assess the value of prenatal ultrasonography on fetal forearm and crus malformations by studying the ultrasonographic characteristic in relation to methods of examination. Methods All fetus were evaluated by using a systematic continuous sequence approach (SCSA) with ultrasonography. A close attention was paid on shapes, structures and movement of fetal forearm and crus, and fetus specimens after induced labor were rescanned by ultrasonography under the condition of mimic intra-uterus. Results Thirty of 33 cases (90.9%) with fetal forearm and crus malformations (totally 48 of 54 limb anormalies, 88.9%) were correctly diagnosed by prenatal ultrasonography. Six limb malformations of 3 cases were missed. Conclusion Our study demonstrates that the malformations of forearm and crus detected with prenatal ultrasonography are highly accordant with the malformations revealed in fetus in vitro. It is important to abide by the SCSA in ultrasonographic diagnosis of fetal forearm and crus malformation.