Objective To explore the impact of number of positive regional lymph nodes (nPRLN) in N1 stage on the prognosis of non-small cell lung cancer (NSCLC) patients. Methods Patients with TxN1M0 stage NSCLC who underwent lobectomy and mediastinal lymph node dissection from 2010 to 2015 were screened from SEER database (17 Regs, 2022nov sub). The optimal cutoff value of nPRLN was determined using X-tile software, and patients were divided into 2 groups according to the cutoff value: a nPRLN≤optimal cutoff group and a nPRLN>optimal cutoff group. The influence of confounding factors was minimized by propensity score matching (PSM) at a ratio of 1 : 1. Kaplan-Meier curves and Cox proportional hazards models were used to evaluate overall survival (OS) and lung cancer-specific survival (LCSS) of patients. Results A total of 1316 patients with TxN1M0 stage NSCLC were included, including 662 males and 654 females, with a median age of 67 (60, 73) years. The optimal cutoff value of nPRLN was 3, with 1165 patients in the nPRLN≤3 group and 151 patients in the nPRLN>3 group. After PSM, there were 138 patients in each group. Regardless of before or after PSM, OS and LCSS of patients in the nPRLN≤3 group were superior to those in the nPRLN>3 group (P<0.001). N1 stage nPRLN>3 was an independent prognostic risk factor for OS [HR=1.52, 95%CI (1.22, 1.89), P<0.001] and LCSS [HR=1.72, 95%CI (1.36, 2.18), P<0.001]. Conclusion N1 stage nPRLN>3 is an independent prognostic risk factor for NSCLC patients in TxN1M0 stage, which may provide new evidence for future revision of TNM staging N1 stage subclassification.

OBJECTIVE: To investigate the effects of removing microglia from spinal cord on nerve repair and functional recovery after spinal cord injury (SCI) in mice. METHODS: Thirty-nine 6-week-old female C57BL/6 mice were randomly divided into control group ( n=12), SCI group ( n=12), and PLX3397+SCI group ( n=15). The PLX3397+SCI group received continuous feeding of PLX3397, a colony-stimulating factor 1 receptor inhibitor, while the other two groups were fed a standard diet. After 14 days, both the SCI group and the PLX3397+SCI group were tested for ionized calcium binding adapter molecule 1 (Iba1) to confirm that the PLX3397+SCI group had completely depleted the spinal cord microglia. The SCI model was then prepared by clamping the spinal cord in both the SCI group and the PLX3397+SCI group, while the control group underwent laminectomy. Preoperatively and at 1, 3, 7, 14, 21, and 28 days postoperatively, the Basso Mouse Scale (BMS) was used to assess the hind limb function of mice in each group. At 28 days, a footprint test was conducted to observe the gait of the mice. After SCI, spinal cord tissue from the injury site was taken, and Iba1 immunofluorescence staining was performed at 7 days to observe the aggregation and proliferation of microglia in the spinal cord. HE staining was used to observe the formation of glial scars at the injury site at 28 days; glial fibrillary acidic protein (GFAP) immunofluorescence staining was applied to astrocytes to assess the extent of the injured area; neuronal nuclei antigen (NeuN) immunofluorescence staining was used to evaluate neuronal survival. And 5-hydroxytryptamine (5-HT) immunofluorescence staining was performed to assess axonal survival at 60 days. RESULTS: All mice survived until the end of the experiment. Immunofluorescence staining revealed that the microglia in the spinal cord of the PLX3397+SCI group decreased by more than 95% compared to the control group after 14 days of continuous feeding with PLX3397 ( P<0.05). Compared to the control group, the BMS scores in the PLX3397+SCI group and the SCI group significantly decreased at different time points after SCI ( P<0.05). Moreover, the PLX3397+SCI group showed a further decrease in BMS scores compared to the SCI group, and exhibited a dragging gait. The differences between the two groups were significant at 14, 21, and 28 days ( P<0.05). HE staining at 28 days revealed that the SCI group had formed a well-defined and dense gliotic scar, while the PLX3397+SCI group also developed a gliotic scar, but with a more blurred and loose boundary. Immunofluorescence staining revealed that the number of microglia near the injury center at 7 days increased in the SCI group than in the control group, but the difference between groups was not significant ( P>0.05). In contrast, the PLX3397+SCI group showed a significant reduction in microglia compared to both the control and SCI groups ( P<0.05). At 28 days after SCI, the area of spinal cord injury in the PLX3397+SCI group was significantly larger than that in SCI group ( P<0.05); the surviving neurons significantly reduced compared with the control group and SCI group ( P<0.05). The axonal necrosis and retraction at 60 days after SCI were more obvious. CONCLUSION The removal of microglia in the spinal cord aggravate the tissue damage after SCI and affecte the recovery of motor function in mice, suggesting that microglia played a neuroprotective role in SCI.
Animals ; Spinal Cord Injuries/surgery* ; Microglia/pathology* ; Female ; Mice ; Mice, Inbred C57BL ; Nerve Regeneration/drug effects* ; Spinal Cord/pathology* ; Pyrroles/administration & dosage* ; Aminopyridines/administration & dosage* ; Recovery of Function ; Disease Models, Animal ; Calcium-Binding Proteins/metabolism* ; Receptors, Granulocyte-Macrophage Colony-Stimulating Factor/antagonists & inhibitors* ; Microfilament Proteins/metabolism* ; Glial Fibrillary Acidic Protein/metabolism*

Postoperative infection of internal fixation of closed fractures the lower limbs in adults represents a devastating complication, characterized by diagnostic challenges, prolonged treatment duration and high disability rates. Current management of these infections faces multiple challenges, such as difficulties in early accurate diagnosis, and various controversies about the treatment plan, leading to poor overall diagnosis and treatment results. To address these issues, based on evidence-based medicine and principles with emphasis on scientific rigor, clinical applicability and innovation, the Trauma Branch of the Chinese Medical Association, Orthopedic Branch of the Chinese Medical Doctor Association, Orthopedics Branch of the Chinese Medical Association, and Trauma Orthopedics and Polytrauma Group of the Resuscitation and Emergency Committee of the Chinese Medical Doctor Association have collaboratively organized a panel of relevant experts to develop the Guideline for diagnosis and treatment of infection after internal fixation of closed lower limb fractures in adults ( version 2025). The guideline proposed 10 recommendations, aiming to provide a foundation for standardized diagnosis and treatment of postoperative infection in adults with closed lower limb fractures.

Objective To evaluate the value of postoperative radiotherapy (PORT) in patients with stage ⅢA-N2 non-small cell lung cancer who received complete resection and chemotherapy. Methods Patients with stage ⅢA-N2 non-small cell lung cancer who received complete resection and chemotherapy were chosen from the SEER Research Plus Database [17 Registries, November 2012 Submission (2000-2019)]. The patients were divided into a PORT group and a non-PORT group according to whether the PORT was used. To balance baseline characteristics between non-PORT and PORT groups, R software was used to conduct a propensity score matching (PSM) with a ratio of 1 : 1 and a matching tolerance of 0.01. Both the Cox regression analysis and Kaplan-Meier survival analysis were conducted to evaluate the value of PORT in terms of overall survival (OS) and disease-specific survival (DSS). Results In total, 2468 patients with stage ⅢA-N2 non-small cell lung cancer were enrolled, including 1078 males and 1390 females with a median age of 65 (58-71) years. There were 1336 patients in the PORT group, and 1132 patients in the non-PORT group. Cox regression analysis showed that PORT was not significantly associated with OS (multivariate analysis: HR=1.051, 95%CI 0.949-1.164, P=0.338) and DSS (multivariate analysis: HR=1.094, 95%CI 0.976-1.225, P=0.123). No statistical difference was found in the OS or DSS between non-PORT group and PORT group after PSM analysis (P＞0.05). Conclusion PORT does not have a survival benefit for patients with stage ⅢA-N2 non-small cell lung cancer who received complete resection and chemotherapy.

Objective To investigate the effect of Tan Ⅰ on SA-AKI in rats by mediating Wnt/β-catenin signaling pathway.Methods Sprague-Dawley rats were randomly divided into the following groups(n=8 per group,including 2 reserve animals per group):Sham,SA-AKI,SA-AKI+5 mg/kg Tan I,SA-AKI+10 mg/kg Tan I,SA-AKI+15 mg/kg Tan I(SA-AKI+Tan I),SA-AKI+salinomycin sodium(SS,Wnt signal inhibitor,SA-AKI+SS),SA-AKI+SS+Tan I,SA-AKI+laduviglusib(LG,Wnt signal activator,SA-AKI+LG),and SA-AKI+LG+Tan I.Rat SA-AKI model was induced by cecal ligation and puncture(CLP),with Tan I,SS,and LG administered via intraperitoneal injection.Hematoxylin-eosin and TUNEL staining were used to observe renal tissue pathological damage.Enzyme-linked immunosorbent assay was used to detect serum concentrations of neutrophil gelatinase-associated lipocalin(NGAL),IL-1β,IL-8,IL-6,and TNF-α.Creatinine(Cre)and blood urea nitrogen(BUN)kit were used to detect serum Cre and BUN concentrations.Western blot and immunofluorescence staining were used to detect the expression and fluorescence intensity of Wnt1,GSK3β,and β-catenin.Results Administration of Tan I at doses of 10 mg/kg and 15 mg/kg significantly attenuated renal injury in rats with SA-AKI(P<0.05),suppressed the levels of SA-AKI biomarkers NGAL,Cre,and BUN and pro-inflammatory cytokines(P<0.05),reduced apoptosis,and downregulated Wnt1 and GSK3β while upregulating β-catenin expression(P<0.05).Although Tan I at 5 mg/kg exhibited a modest protective effect against SA-AKI in rats,no statistically significant difference was observed compared to the sham group(P>0.05).SS weakened CLP-induced kidney injury and the production of inflammatory cytokines in rats(P<0.05),and LG further aggravated CLP-induced kidney injury in rats(P<0.05).Tan Ⅰ reversed the promoting effect of LG on kidney injury in SA-AKI rats(P<0.05).Conclusion Tan Ⅰ provides a protective effect on CLP-induced SA-AKI rat by inhibiting Wnt/β-catenin signaling pathway.

Objective To explore the value of low contrast dose and low flow rate one-stop craniocervical CT angiography(CT A)-cerebral CT perfusion(CTP)for detecting carotid atherosclerosis(CAS).Methods Totally 117 CAS patients were prospectively enrolled and divided into group A(n=19),B(n=52),C(n=46),and low contrast dose and low flow rate one-stop craniocervical CTA-brain CTP scanning,low contrast dose and low flow rate craniocervical CT A scanning,as well as conventional craniocervical CT A scanning were performed,respectively.Virtual monoenergetic images(VMI)of 40,50 and 60 keV were reconstructed in group A and B.The subjective and objective evaluations of image quality were compared among 3 groups.Results Subjective scores of image quality and diagnostic confidence of 40 and 50 keV VMI,and the diagnostic confidence of 60 keV VMI in group A and B were not significant different compared with those in group C(all P＞0.05).Signal-to-noise ratio(SNR)and contrast-to-noise ratio(CNR)of each segment of craniocervical blood vessels at 40 and 50 keV VMI in group A and B were all higher than those in group C(all P＜0.05).CNR of cavernous sinus segment of internal carotid artery(C5 segment),horizontal segment of middle cerebral artery(MCA)(A1 segment),lateral sulcus segment of MCA(M2 segment)and basilar artery(BA)segment in group A at 60 keV VMI were all higher than those in group C(all P＜0.05).SNR of C5 segment,A1 segment and BA segment,as well as CNR of BA segment of 60 keV VMI in group B were all higher than those in group C(all P＜0.05).Conclusion Low contrast dose and low flow rate one-stop craniocervical was feasible for detecting CAS.

Postoperative infection of internal fixation of closed fractures the lower limbs in adults represents a devastating complication, characterized by diagnostic challenges, prolonged treatment duration and high disability rates. Current management of these infections faces multiple challenges, such as difficulties in early accurate diagnosis, and various controversies about the treatment plan, leading to poor overall diagnosis and treatment results. To address these issues, based on evidence-based medicine and principles with emphasis on scientific rigor, clinical applicability and innovation, the Trauma Branch of the Chinese Medical Association, Orthopedic Branch of the Chinese Medical Doctor Association, Orthopedics Branch of the Chinese Medical Association, and Trauma Orthopedics and Polytrauma Group of the Resuscitation and Emergency Committee of the Chinese Medical Doctor Association have collaboratively organized a panel of relevant experts to develop the Guideline for diagnosis and treatment of infection after internal fixation of closed lower limb fractures in adults ( version 2025). The guideline proposed 10 recommendations, aiming to provide a foundation for standardized diagnosis and treatment of postoperative infection in adults with closed lower limb fractures.

Objective To explore the value of low contrast dose and low flow rate one-stop craniocervical CT angiography(CT A)-cerebral CT perfusion(CTP)for detecting carotid atherosclerosis(CAS).Methods Totally 117 CAS patients were prospectively enrolled and divided into group A(n=19),B(n=52),C(n=46),and low contrast dose and low flow rate one-stop craniocervical CTA-brain CTP scanning,low contrast dose and low flow rate craniocervical CT A scanning,as well as conventional craniocervical CT A scanning were performed,respectively.Virtual monoenergetic images(VMI)of 40,50 and 60 keV were reconstructed in group A and B.The subjective and objective evaluations of image quality were compared among 3 groups.Results Subjective scores of image quality and diagnostic confidence of 40 and 50 keV VMI,and the diagnostic confidence of 60 keV VMI in group A and B were not significant different compared with those in group C(all P＞0.05).Signal-to-noise ratio(SNR)and contrast-to-noise ratio(CNR)of each segment of craniocervical blood vessels at 40 and 50 keV VMI in group A and B were all higher than those in group C(all P＜0.05).CNR of cavernous sinus segment of internal carotid artery(C5 segment),horizontal segment of middle cerebral artery(MCA)(A1 segment),lateral sulcus segment of MCA(M2 segment)and basilar artery(BA)segment in group A at 60 keV VMI were all higher than those in group C(all P＜0.05).SNR of C5 segment,A1 segment and BA segment,as well as CNR of BA segment of 60 keV VMI in group B were all higher than those in group C(all P＜0.05).Conclusion Low contrast dose and low flow rate one-stop craniocervical was feasible for detecting CAS.

Irritable bowel syndrome(IBS)is accompanied by impaired intestinal mucosal barrier,and there is currently no ideal drug therapy.Acupuncture has obvious advantages in protecting intestinal mucosal barrier of IBS,but the molecular biological mechanism needs to be further studied.Based on the overall intestinal homeostasis in the"flora-intestinal epithelial dialogue"study to repair damaged intestinal mucosal barrier has become a hot research in this field.Therefore,based on the frontier basis,this paper discusses the feasibility mechanism of acupuncture in repairing IBS intestinal mucosal barrier injury from the perspective of intestinal flora-short-chain fatty acid-intestinal PPAR γ pathway-mediated intestinal epithelial cell metabolic reprogramming,in order to interpret the scientific connotation of acupuncture in repairing intestinal mucosal barrier injury,and provide a scientific basis for acupuncture therapy to play a greater role in public health care and for the modernization of traditional Chinese medicine.

Breast cancer remains a leading cause of mortality in women worldwide.Triple-negative breast cancer(TNBC)is a particularly aggressive subtype characterized by rapid progression,poor prognosis,and lack of clear therapeutic targets.In the clinic,delineation of tumor heterogeneity and development of effective drugs continue to pose considerable challenges.Within the scope of our study,high hetero-geneity inherent to breast cancer was uncovered based on the landscape constructed from both tumor and healthy breast tissue samples.Notably,TNBC exhibited significant specificity regarding cell prolif-eration,differentiation,and disease progression.Significant associations between tumor grade,prog-nosis,and TNBC oncogenes were established via pseudotime trajectory analysis.Consequently,we further performed comprehensive characterization of the TNBC microenvironment.A crucial epithelial subcluster,E8,was identified as highly malignant and strongly associated with tumor cell proliferation in TNBC.Additionally,epithelial-mesenchymal transition(EMT)-associated fibroblast and M2 macrophage subclusters exerted an influence on E8 through cellular interactions,contributing to tumor growth.Characteristic genes in these three cluster cells could therefore serve as potential therapeutic targets for TNBC.The collective findings provided valuable insights that assisted in the screening of a series of therapeutic drugs,such as pelitinib.We further confirmed the anti-cancer effect of pelitinib in an orthotopic 4T1 tumor-bearing mouse model.Overall,our study sheds light on the unique characteristics of TNBC at single-cell resolution and the crucial cell types associated with tumor cell proliferation that may serve as potent tools in the development of effective anti-cancer drugs.