Effective axon regeneration is essential for the successful restoration of nerve functions in patients suffering from axon injury-associated neurological diseases. Certain self-regeneration occurs in injured peripheral axonal branches of dorsal root ganglion (DRG) neurons but does not occur in their central axonal branches. By performing rat sciatic nerve or dorsal root axotomy, we determined the expression of the dysbindin domain containing 2 (DBNDD2) in the DRGs after the regenerative peripheral axon injury or the non-regenerative central axon injury, respectively, and found that DBNDD2 is down-regulated in the DRGs after peripheral axon injury but up-regulated after central axon injury. Furthermore, we found that DBNDD2 expression differs in neonatal and adult rat DRGs and is gradually increased during development. Functional analysis through DBNDD2 knockdown revealed that silencing DBNDD2 promotes the outgrowth of neurites in both neonatal and adult rat DRG neurons and stimulates robust axon regeneration in adult rats after sciatic nerve crush injury. Bioinformatic analysis data showed that transcription factor estrogen receptor 1 (ESR1) interacts with DBNDD2, exhibits a similar expression trend as DBNDD2 after axon injury, and may targets DBDNN2. These studies indicate that reduced level of DBNDD2 after peripheral axon injury and low abundance of DBNDD2 in neonates contribute to axon regeneration and thus suggest the manipulation of DBNDD2 expression as a promising therapeutic approach for improving recovery after axon damage.
Animals ; Ganglia, Spinal/metabolism* ; Nerve Regeneration/genetics* ; Rats ; Axons/metabolism* ; Sciatic Nerve/injuries* ; Rats, Sprague-Dawley ; Male

The occurrence and development of colitis associated cancer(CAC)is closely related to the intestinal microenvironment.Traditional Chinese medicine(TCM)posits that"spleen deficiency"is the basic pathogenesis of colon cancer occurrence and development,and plays a key role in the process of"inflammation-cancer transformation".However,at present,the pathogenesis of spleen in the course of its pathogenesis is mostly focused on the body's own system,and few are discussed in combination with the theoretical basis of TCM's holistic view of"correspondence between man and nature".The spleen,as a taiyin organ with a damp-earth nature,relies on yang energy for movement,inherently averses dampness,and governs ascending qi.Late summer is mainly wet,which can easily obstruct the spleen qi,curb the upward trend and stop the spread opportunity when the wettability sticks and has a downward trend.This suggests that the influence of external environmental factors on the body should be comprehensively considered in the study of the classical process of"intestinal flora disturbance-inflammatory microenvironment formation-tumor formation"experienced in the pathogenesis of CAC.Based on the complementarity,mutual penetration and mutual promotion of the theories of traditional Chinese and western medicine,this paper discusses the role of external environmental factors in the occurrence of CAC focused on the mechanism of macrophage polarization imbalance during the formation of tumor inflammatory microenvironment,and provides a basis for the theoretical integration and development of TCM"time-dependent treatment"prevention and treatment strategies.

Objective:To explore the efficacy of non-invasive prenatal testing (NIPT) of fetal free DNA in maternal peripheral blood in fetuses with increased nuchal translucency (NT).Methods:A retrospective analysis was conducted on 1 184 singleton pregnant women that underwent chromosomal microarray analysis (CMA) at Nanjing Drum Tower Hospital, Nanjing University Medical School from June 2014 to December 2022 due to fetal increased NT (≥3.0 mm). These subjects were categorized based on whether the increased NT was accompanied by other high-risk factors into isolated increased NT without advanced maternal age (further subdivided into 3.0 mm≤NT<3.5 mm, 3.5 mm≤NT<4.0 mm, and NT≥4.0 mm subgroups), isolated increased NT with advanced maternal age, increased NT with nasal bone abnormalities, increased NT with other soft markers, and increased NT with structural abnormalities groups. Assuming the sensitivity and specificity of NIPT and expanded NIPT at this center were both 100%, genomic abnormalities outside the detection range of NIPT or expanded NIPT were termed as residual risk of NIPT or expanded NIPT. Chi-square test and Bonferroni correction were used to compare the residual risks of NIPT and expanded NIPT among the three subgroups of isolated increased NT without advanced maternal age group. Results:(1) In the group of isolated increased NT without advanced maternal age: For the 3.0 mm≤NT<3.5 mm subgroup (329 cases), 19 abnormalities were detected by CMA [12 cases of chromosome aneuploidy, seven cases of pathogenic copy number variation (pCNV)], with residual risks of NIPT and expanded NIPT both at 2.1% (7/329). For the 3.5 mm≤NT<4.0 mm subgroup (173 cases), 29 abnormalities were detected by CMA (17 cases of chromosome aneuploidy, nine cases of pCNV, three cases of chromosome unbalanced translocation), with residual risks of NIPT at 8.1% (14/173) and expanded NIPT at 7.5% (13/173). For the NT≥4.0 mm subgroup (270 cases), CMA detected abnormalities in 70 cases (50 cases of chromosome aneuploidy, 16 cases of pCNV, three cases of unbalanced translocations, and one case of sex chromosome abnormality combined with pCNV). The residual risk of NIPT was 12.2% (33/270), and the residual risk of expanded NIPT was 7.0% (19/270). The residual risks of NIPT and expanded NIPT in the 3.0 mm≤NT<3.5 mm subgroup were lower than those in the 3.5 mm≤NT<4.0 mm and NT≥4.0 mm subgroups (Bonferroni correction, all P<0.017). (2) In the group of 92 cases with isolated increased NT and advanced maternal age, CMA detected abnormalities in 36 cases (29 cases of chromosome aneuploidy, five cases of pCNV, one case of trisomy 21 combined with sex chromosome abnormality, and one case of trisomy 18 combined with sex chromosome abnormality). The residual risk of NIPT was 7.6% (7/92), and that of expanded NIPT was 5.4% (5/92). (3) In the group of 49 cases with increased NT combined with nasal bone abnormalities, CMA detected abnormalities in 24 cases (23 cases of chromosome aneuploidy and one case of pCNV). The residual risks of NIPT and expanded NIPT were both 2.0% (1/49). (4) In the group of 26 cases with increased NT combined with other soft markers, CMA detected abnormalities in nine cases (six cases of chromosome aneuploidy, one case of pCNV, and two cases of chromosome unbalanced translocations). The residual risks of NIPT and expanded NIPT were both 11.5% (3/26). (5) In the group of 245 cases with increased NT combined with structural abnormalities, CMA detected abnormalities in 121 cases (107 cases of chromosome aneuploidy, seven cases of pCNV, four cases of chromosome unbalanced translocations, one case of trisomy 21 combined with trisomy 20, and two cases of trisomy 18 combined with sex chromosome abnormalities). The residual risk of NIPT was 16.7% (41/245), and that of expanded NIPT was 4.1% (10/245). Conclusions:For isolated NT≥3.5 mm or NT≥3.0 mm combined with other high-risk factors, chorionic villus sampling in early pregnancy can be recommended, advancing the timing of prenatal diagnosis from the second trimester to the first trimester. For fetuses with isolated 3.0 mm≤NT<3.5 mm, the 2.1% residual risk of chromosomal abnormalities should be fully informed during counseling, even if the risk of NIPT is low.

Objective To investigate the effect and mechanism of miR-155-5p targeting suppressor of cytokine signaling 1(SOCS1)in regulating the Janus kinase 2(JAK2)/signal transducer and activator of transcrip-tion 3(STAT3)signaling pathway in renal injury associated with lupus nephritis(LN).Methods Thirty female MRL-faslpr lupus model mice were randomly divided into five groups(n=6 per group):the model group,the antagomir NC group,the miR-155-5p antagomir group,the miR-155-5p antagomir+shRNA control group,and the miR-155-5p antagomir+SOCS1 shRNA group.The mice were treated with adeno-associated virus vectors carrying miR-155-5p antagomir,antagomir NC,SOCS1 shRNA,or shRNA control.Additionally,six age-matched C57BL/6 mice served as a control group and received an equivalent volume of saline.Serum blood urea nitrogen(BUN)and creatinine(Scr)levels,renal histopathological changes,and the expression levels of miR-155-5p,SOCS1,phosphorylated JAK2(p-JAK2),and phosphorylated STAT3(p-STAT3)in renal tissues were evaluated.Results Compared with the normal group,the model group exhibited significantly elevated levels of BUN,Scr,miR-155-5p,p-JAK2,and p-STAT3 proteins in the kidneys(P<0.01),while the expression level of SOCS1 was markedly reduced(P<0.01).Compared with both the model group and the antagomir NC group,the miR-155-5p antagomir group showed decreased levels of BUN,Scr,miR-155-5p,p-JAK2,and p-STAT3 proteins(P<0.01),along with a significant increase in SOCS1 expression(P<0.01).Similarly,compared with the miR-155-5p antagomir group and the miR-155-5p antagomir+shRNA control group,the miR-155-5p antagomir+SOCS1 shRNA group demon-strated significantly higher levels of BUN,Scr,miR-155-5p,p-JAK2,and p-STAT3 proteins(P<0.01),while SOCS1 expression was notably decreased(P<0.01).Renal pathology analysis revealed that,compared to the normal group,the model group exhibited glomerular atrophy,extensive infiltration of inflammatory cells in the renal tubulointerstitial region,and partial renal tubular necrosis.In contrast,the miR-155-5p antagomir group showed marked improvements in glomerular atrophy,tubular necrosis,and inflammatory cell infiltration compared with the model group and antagomir NC group.Furthermore,compared with the miR-155-5p antagomir group and the miR-155-5p antagomir+shRNA control group,the miR-155-5p antagomir+SOCS1 shRNA group exhibited more severe glomerular atrophy,tubular necrosis,and inflammatory cell infiltration.Conclusion MiR-155-5p exacerbates renal damage in MRL-faslpr lupus model mice by targeting SOCS1,potentially through the activation of the JAK2/STAT3 signaling pathway.

Objective To investigate the effect and mechanism of miR-155-5p targeting suppressor of cytokine signaling 1(SOCS1)in regulating the Janus kinase 2(JAK2)/signal transducer and activator of transcrip-tion 3(STAT3)signaling pathway in renal injury associated with lupus nephritis(LN).Methods Thirty female MRL-faslpr lupus model mice were randomly divided into five groups(n=6 per group):the model group,the antagomir NC group,the miR-155-5p antagomir group,the miR-155-5p antagomir+shRNA control group,and the miR-155-5p antagomir+SOCS1 shRNA group.The mice were treated with adeno-associated virus vectors carrying miR-155-5p antagomir,antagomir NC,SOCS1 shRNA,or shRNA control.Additionally,six age-matched C57BL/6 mice served as a control group and received an equivalent volume of saline.Serum blood urea nitrogen(BUN)and creatinine(Scr)levels,renal histopathological changes,and the expression levels of miR-155-5p,SOCS1,phosphorylated JAK2(p-JAK2),and phosphorylated STAT3(p-STAT3)in renal tissues were evaluated.Results Compared with the normal group,the model group exhibited significantly elevated levels of BUN,Scr,miR-155-5p,p-JAK2,and p-STAT3 proteins in the kidneys(P<0.01),while the expression level of SOCS1 was markedly reduced(P<0.01).Compared with both the model group and the antagomir NC group,the miR-155-5p antagomir group showed decreased levels of BUN,Scr,miR-155-5p,p-JAK2,and p-STAT3 proteins(P<0.01),along with a significant increase in SOCS1 expression(P<0.01).Similarly,compared with the miR-155-5p antagomir group and the miR-155-5p antagomir+shRNA control group,the miR-155-5p antagomir+SOCS1 shRNA group demon-strated significantly higher levels of BUN,Scr,miR-155-5p,p-JAK2,and p-STAT3 proteins(P<0.01),while SOCS1 expression was notably decreased(P<0.01).Renal pathology analysis revealed that,compared to the normal group,the model group exhibited glomerular atrophy,extensive infiltration of inflammatory cells in the renal tubulointerstitial region,and partial renal tubular necrosis.In contrast,the miR-155-5p antagomir group showed marked improvements in glomerular atrophy,tubular necrosis,and inflammatory cell infiltration compared with the model group and antagomir NC group.Furthermore,compared with the miR-155-5p antagomir group and the miR-155-5p antagomir+shRNA control group,the miR-155-5p antagomir+SOCS1 shRNA group exhibited more severe glomerular atrophy,tubular necrosis,and inflammatory cell infiltration.Conclusion MiR-155-5p exacerbates renal damage in MRL-faslpr lupus model mice by targeting SOCS1,potentially through the activation of the JAK2/STAT3 signaling pathway.

Objective:To explore the efficacy of non-invasive prenatal testing (NIPT) of fetal free DNA in maternal peripheral blood in fetuses with increased nuchal translucency (NT).Methods:A retrospective analysis was conducted on 1 184 singleton pregnant women that underwent chromosomal microarray analysis (CMA) at Nanjing Drum Tower Hospital, Nanjing University Medical School from June 2014 to December 2022 due to fetal increased NT (≥3.0 mm). These subjects were categorized based on whether the increased NT was accompanied by other high-risk factors into isolated increased NT without advanced maternal age (further subdivided into 3.0 mm≤NT<3.5 mm, 3.5 mm≤NT<4.0 mm, and NT≥4.0 mm subgroups), isolated increased NT with advanced maternal age, increased NT with nasal bone abnormalities, increased NT with other soft markers, and increased NT with structural abnormalities groups. Assuming the sensitivity and specificity of NIPT and expanded NIPT at this center were both 100%, genomic abnormalities outside the detection range of NIPT or expanded NIPT were termed as residual risk of NIPT or expanded NIPT. Chi-square test and Bonferroni correction were used to compare the residual risks of NIPT and expanded NIPT among the three subgroups of isolated increased NT without advanced maternal age group. Results:(1) In the group of isolated increased NT without advanced maternal age: For the 3.0 mm≤NT<3.5 mm subgroup (329 cases), 19 abnormalities were detected by CMA [12 cases of chromosome aneuploidy, seven cases of pathogenic copy number variation (pCNV)], with residual risks of NIPT and expanded NIPT both at 2.1% (7/329). For the 3.5 mm≤NT<4.0 mm subgroup (173 cases), 29 abnormalities were detected by CMA (17 cases of chromosome aneuploidy, nine cases of pCNV, three cases of chromosome unbalanced translocation), with residual risks of NIPT at 8.1% (14/173) and expanded NIPT at 7.5% (13/173). For the NT≥4.0 mm subgroup (270 cases), CMA detected abnormalities in 70 cases (50 cases of chromosome aneuploidy, 16 cases of pCNV, three cases of unbalanced translocations, and one case of sex chromosome abnormality combined with pCNV). The residual risk of NIPT was 12.2% (33/270), and the residual risk of expanded NIPT was 7.0% (19/270). The residual risks of NIPT and expanded NIPT in the 3.0 mm≤NT<3.5 mm subgroup were lower than those in the 3.5 mm≤NT<4.0 mm and NT≥4.0 mm subgroups (Bonferroni correction, all P<0.017). (2) In the group of 92 cases with isolated increased NT and advanced maternal age, CMA detected abnormalities in 36 cases (29 cases of chromosome aneuploidy, five cases of pCNV, one case of trisomy 21 combined with sex chromosome abnormality, and one case of trisomy 18 combined with sex chromosome abnormality). The residual risk of NIPT was 7.6% (7/92), and that of expanded NIPT was 5.4% (5/92). (3) In the group of 49 cases with increased NT combined with nasal bone abnormalities, CMA detected abnormalities in 24 cases (23 cases of chromosome aneuploidy and one case of pCNV). The residual risks of NIPT and expanded NIPT were both 2.0% (1/49). (4) In the group of 26 cases with increased NT combined with other soft markers, CMA detected abnormalities in nine cases (six cases of chromosome aneuploidy, one case of pCNV, and two cases of chromosome unbalanced translocations). The residual risks of NIPT and expanded NIPT were both 11.5% (3/26). (5) In the group of 245 cases with increased NT combined with structural abnormalities, CMA detected abnormalities in 121 cases (107 cases of chromosome aneuploidy, seven cases of pCNV, four cases of chromosome unbalanced translocations, one case of trisomy 21 combined with trisomy 20, and two cases of trisomy 18 combined with sex chromosome abnormalities). The residual risk of NIPT was 16.7% (41/245), and that of expanded NIPT was 4.1% (10/245). Conclusions:For isolated NT≥3.5 mm or NT≥3.0 mm combined with other high-risk factors, chorionic villus sampling in early pregnancy can be recommended, advancing the timing of prenatal diagnosis from the second trimester to the first trimester. For fetuses with isolated 3.0 mm≤NT<3.5 mm, the 2.1% residual risk of chromosomal abnormalities should be fully informed during counseling, even if the risk of NIPT is low.

The occurrence and development of colitis associated cancer(CAC)is closely related to the intestinal microenvironment.Traditional Chinese medicine(TCM)posits that"spleen deficiency"is the basic pathogenesis of colon cancer occurrence and development,and plays a key role in the process of"inflammation-cancer transformation".However,at present,the pathogenesis of spleen in the course of its pathogenesis is mostly focused on the body's own system,and few are discussed in combination with the theoretical basis of TCM's holistic view of"correspondence between man and nature".The spleen,as a taiyin organ with a damp-earth nature,relies on yang energy for movement,inherently averses dampness,and governs ascending qi.Late summer is mainly wet,which can easily obstruct the spleen qi,curb the upward trend and stop the spread opportunity when the wettability sticks and has a downward trend.This suggests that the influence of external environmental factors on the body should be comprehensively considered in the study of the classical process of"intestinal flora disturbance-inflammatory microenvironment formation-tumor formation"experienced in the pathogenesis of CAC.Based on the complementarity,mutual penetration and mutual promotion of the theories of traditional Chinese and western medicine,this paper discusses the role of external environmental factors in the occurrence of CAC focused on the mechanism of macrophage polarization imbalance during the formation of tumor inflammatory microenvironment,and provides a basis for the theoretical integration and development of TCM"time-dependent treatment"prevention and treatment strategies.

BACKGROUND: One of the most important treatment modalities for non-small cell lung cancer (NSCLC) is immune checkpoint inhibitor. Nevertheless, a small percentage of patients do not respond well to these therapies, highlighting the significance of identifying important CD8+ T cell subsets for immunotherapy and creating trustworthy biomarkers. The purpose of this study is to assess the potential utility of TIM3+CD8+ T cells as new biomarkers by examining their expressions in various areas of the NSCLC tumor microenvironment. METHODS: Based on biopsy techniques, tumor tissue samples were obtained from patients with NSCLC and categorized into tumor central and non-central regions. Using flow cytometry, the infiltration of TIM3+CD8+ T cells and the surface expression of programmed cell death 1 (PD-1) on these cells were examined, and their correlations with the effectiveness of immunotherapy were assessed. RESULTS: The non-central region of tumor tissues had considerably larger infiltration of TIM3+CD8+ T lymphocytes compared to the non-central region (P<0.0001). This pattern was found in both subgroups with tumor diameters ≥3 cm or <3 cm (P<0.01). In comparison to TIM3-CD8+ T cells, TIM3+CD8+ T cells showed higher levels of PD-1 (P<0.001), with more PD-1+TIM3+CD8+ T cells invading the non-central region (P<0.01). Clinical responders to immunotherapy had considerably lower infiltration levels of TIM3+CD8+ T cells in the tumor non-central region compared to non-responders, with lower levels correlated with better clinical outcomes (P<0.01), while no correlation was identified in the tumor central region (P>0.05). According to reciever operating characteristic (ROC) curve analysis, TIM3+CD8+ T cells in the tumor non-central region had an area under the curve (AUC) of 0.9375 for predicting the effectiveness of immunotherapy, which was considerably higher than that of TIM3+CD8+ T cells in the tumor central region and programmed cell death ligand 1 (PD-L1) [tumor proportion score (TPS)]. CONCLUSIONS In the tumor microenvironment of NSCLC, TIM3+CD8+ T cells show regional distribution patterns. The expression of this cell population in the non-central region of the tumor microenvironment may be a biomarker for predicting the effectiveness of immunotherapy.
Humans ; Carcinoma, Non-Small-Cell Lung/metabolism* ; Lung Neoplasms/metabolism* ; Hepatitis A Virus Cellular Receptor 2/immunology* ; Tumor Microenvironment/immunology* ; CD8-Positive T-Lymphocytes/metabolism* ; Male ; Female ; Middle Aged ; Aged ; Adult ; Programmed Cell Death 1 Receptor/metabolism* ; Immunotherapy ; Clinical Relevance

China prospective multicenter birth cohort (Prospective Omics Health Atlas birth cohort, POHA birth cohort) study was officially launched in 2022. This study, in collaboration with 12 participating units, aims to establish a high-quality, multidimensional cohort comprising 20 000 naturally conceived families and assisted reproductive families. The study involves long-term follow-up of parents and offspring, with corresponding biological samples collected at key time points. Through multi-omics testing and analysis, the study aims to conduct multi-omics big data research across the entire maternal and infant life cycle. The goal is to identify new biomarkers for maternal and infant diseases and provide scientific evidence for risk prediction related to maternal diseases and neonatal health.

Objective To investigate the potential of immune-inflammatory markers and the characteristics of magnetically controlled capsule endoscopy in distinguishing gastric adenocarcinoma from precancerous lesions,as well as to develop and validate a risk prediction model.Methods Retrospective analysis was conducted on medical records of 578 patients who underwent magnetic controlled capsule endoscopy at our hospital between January 2021 and December 2023.Following the principle of Pareto's law(80/20 rule),they were randomly divided into a training set(462 cases)and a validation set(116 cases).Magnetic controlled capsule endoscopy and blood cell tests were performed,with pathological diagnosis results serving as the"gold standard",to classify patients into groups of gastric adenocarcinoma and precancerous lesions.The magnetic controlled capsule endoscopic features,neutrophil-lymphocyte ratio(NLR),platelet-lymphocyte ratio(PLR)in patients with gastric adenocarcinoma and precancerous lesions were compared to develop and validate a risk diagnostic model for gastric adenocarcinoma.Results Among the 462 patients who underwent magnetic controlled capsule endoscopy,gastric adenocarcinoma was diagnosed in 76 cases through pathological examination,accounting for 16.45%(76/462),while precancerous lesions were observed in 386 cases,accounting for 83.55%(386/462).In the validation set of 116 patients who underwent gastric endoscopy,there were 22 cases of gastric adenocarcinoma,representing an incidence rate of 18.97%(22/116),and a total of 94 cases with precancerous lesions,accounting for an incidence rate of 81.03%(94/116).No statistically significant differences(P＞0.05)were found between the two groups regarding lesion size,border appearance,mucus presence or lesion morphology.However,compared to the precancerous lesion group,the proportion of whitish coloration as well as irregular surface microstructure and grid-like microvessels was significantly higher in the gastric adenocarcinoma group(P＜0.05).Moreover,both NLR and PLR values were significantly higher in the gastric adenocarcinoma group compared to those in the precancerous lesion group(P＜0.05).Irregular surface microstructure(OR=2.213,95%CI:1.288～3.801),irregular grid-like microvessels(OR=2.489,95%CI:1.458～4.249),NLR(OR=2.369,95%CI:1.389～4.046),and PLR(OR=3.016,95%CI:1.767～5.148)were identified as risk factors for gastric adenocarcinoma(P＜0.05).The sensitivity of the risk model for diagnosing gastric adenocarci-noma in the training set was 0.800(95%CI:0.716～0.891),with a specificity of 0.783(95%CI:0.694～0.851)and an area under the curve of 0.858(95%CI:0.787～0.931).In the validation set,the sensitivity for diagnosing gastric adenocarcinoma was 0.861(95%CI:0.771～0.945),with a specificity of 0.769(95%CI:0.683～0.841)and an area under the curve of 0.844(95%CI:0.765～0.923).Conclusion The surface microstructure,microvas-cular morphology,NLR,and PLR of gastric lesions are correlated with the occurrence of gastric adenocarcinoma.Developing a risk diagnostic model facilitates early identification and diagnosis of gastric adenocarcinoma.