Iron metabolism is a critical factor in tumorigenesis and development. Although TP53 mutations are prevalent in glioblastoma (GBM), the mechanisms by which TP53 regulates iron metabolism remain elusive. We reveal an imbalance iron homeostasis in GBM via TCGA database analysis. TP53 mutations disrupted iron homeostasis in GBM, characterized by elevated total iron levels and reduced ferritin (FTH). The gain-of-function effect triggered by TP53 mutations upregulates itchy E3 ubiquitin-protein ligase (ITCH) protein expression in astrocytes, leading to FTH degradation and an increase in free iron levels. TP53-mut astrocytes were more tolerant to the high iron environment induced by exogenous ferric ammonium citrate (FAC), but the increase in intracellular free iron made them more sensitive to Erastin-induced ferroptosis. Interestingly, we found that Erastin combined with FAC treatment significantly increased ferroptosis. These findings provide new insights for drug development and therapeutic modalities for GBM patients with TP53 mutations from iron metabolism perspectives.
Ferroptosis/drug effects* ; Humans ; Iron/metabolism* ; Glioblastoma/metabolism* ; Tumor Suppressor Protein p53/metabolism* ; Homeostasis/physiology* ; Ferritins/metabolism* ; Brain Neoplasms/genetics* ; Mutation ; Astrocytes/drug effects* ; Cell Line, Tumor ; Piperazines/pharmacology* ; Quaternary Ammonium Compounds/pharmacology* ; Ferric Compounds

Objective:To investigate the effect of donor blood lipid levels and the degree of fat deposition on the pancreatic surface on the outcome of islet isolation.Method:A retrospective analysis was conducted on 171 cases of islet isolation data from organ donors between May 2015 and December 2024. According to the percentage of fat deposition area on the surface of the pancreatic capsule after trimming, the samples were divided into three groups: mild surface fat group (<30%, 60 cases) , moderate surface fat group (30%–70%, 55 cases) , and severe surface fat group (>70%, 56 cases). The modified Ricordi method was used to digest pancreatic tissue, and islets were purified by continuous density gradient centrifugation. The digestion efficiency, digestion time, islet yield (islet equivalent/quantity) , purity, score, and size were analyzed and compared among groups. One-way ANOVA was used for inter-group comparisons, and Pearson correlation analysis and multiple linear regression analysis were used to explore the relationship between blood lipid levels and islet isolation parameters.Result:The severe surface fat group had significantly higher pre-purification and post-purification islet equivalents, islet number, amount of digested pancreatic tissue, donor triglyceride levels, and low density lipoprotein (LDL) levels than the other groups (all P<0. 05) . Correlation analysis showed that LDL level was positively correlated with pre-purification islet equivalents (62 cases, r=0. 298, P=0. 019) and islet number (58 cases, r=0. 285, P=0. 030) . Donor high density lipoprotein (HDL) level was negatively correlated with post-purification islet equivalents (54 cases, r= – 0. 282, P=0. 039) ; donor triglyceride level was positively correlated with the amount of digested tissue (56 cases, r=0. 268, P=0. 046) and negatively correlated with purity (51 cases, r= - 0. 297, P=0. 035) ; donor very low density lipoprotein (VLDL) level was positively correlated with the amount of digested tissue (67 cases, r=0. 337, P=0. 005) and negatively correlated with purity (61 cases, r=- 0. 348 , P=0. 006) ; donor total cholesterol level was negatively correlated with pancreatic digestion efficiency (34 cases, r= - 0. 370, P=0. 032) , and the above differences were all statistically significant. Conclusion:Pancreata with heavier surface fat deposition can yield a higher number of islets. Meanwhile, donor blood lipid levels are correlated with islet isolation outcomes and can serve as important indicators for donor pancreas selection.

Objective:To evaluate the impact of roxadustat on thyroid function and to identify the associated factors in patients undergoing maintenance peritoneal dialysis (PD).Methods:This study was a single-center retrospective study. PD patients who received roxadustat or recombinant human erythropoietin (rHuEPO) treatment at Nanjing Drum Tower Hospital between January 2020 and June 2024 were included. The general and clinical information as well as laboratory indexes were collected. Serum free triiodothyronine (FT3), free thyroxine (FT4) and thyroid-stimulating hormone (TSH) were compared before and after treatment initiation. Hemoglobin (Hb) responses were also observed between the two groups. Logistic regression analysis was performed to explore the factors associated with thyroid function changes.Results:A total of 120 patients were enrolled, with an age of (55.17±16.42) years, including 66 males (55.0%). There were 81 patients received roxadustat (roxadustat group) and 39 patiens received rHuEPO (rHuEPO group). Compared to the rHuEPO group, the roxadustat group had a higher proportion of patients with diabetes ( χ 2= 4.172, P=0.041), a shorter PD vintage ( Z=-3.406, P=0.002), a lower serum level of total cholesterol ( Z=-2.082, P=0.037) and a lower level of fasting blood glucose ( Z=-2.589, P=0.010). Following treatment with roxadustat, the levels of FT4 ( Z=-5.349, P<0.01) and TSH ( Z=-3.720, P<0.01) decreased significantly. In contrast, no significant changes in FT4 or TSH levels were observed in the rHuEPO group (both P>0.05). For both roxadustat and rHuEPO groups, there were no significant changes in FT3 levels after treatment (both P>0.05). Multivariate analysis identified that higher baseline TSH (TSH≥2.27 μIU/ml, OR=1.581, 95% CI 1.196-2.089, P=0.001) and roxadustat exposure ( OR=3.432, 95% CI 1.410-8.355, P=0.007) as independent associated factors of subsequent TSH decline, and identified that higher baseline FT4 (FT4≥14.9 pmol/L, OR=1.390, 95% CI 1.162-1.662, P=0.001) and roxadustat exposure ( OR=5.798, 95% CI 2.225-15.113, P=0.001) as independent associated factors of subsequent FT4 decline. The degrees of hemoglobin changes after roxadustat or rHuEPO treatment did not differ significantly between roxadustat group and rHuEPO group ( t=-1.062, P=0.290). Of the 31 patients who underwent a second thyroid function test during roxadustat treatment, 24 continued with the original regimen, while 7 discontinued roxadustat. Among 24 patients who maintained roxadustat treatment, TSH ( Z=-0.400, P=0.689) and FT4 ( t=0.143, P=0.888) remained stable between the second and third tests. All 7 patients who discontinued roxadustat treatment showed TSH rebound and the changes of TSH levels were more significant than that in continuers ( Z=-2.505, P=0.012). FT4 recovery occurred in only 3 of them, with no significant difference in FT4 change between discontinuers and continuers ( Z=-0.685, P=0.493). Conclusions:Roxadustat commonly suppresses TSH and FT4, but not FT3, in PD patients. Baseline levels of TSH and FT4 are key associated factors of the inhibitory effect of roxadustat on thyroid function. This suppression does not intensify with prolonged exposure and is reversible after discontinuation, with TSH levels normalizing more quickly than FT4. Roxadustat-induced thyroid suppression does not compromise its efficacy in treating renal anemia.

The interplay between psychological pain and physical pain is one of the key issues in the research of non-suicidal self-injury (NSSI). Psychological pain, driven by negative self-perception and difficulties in emotional regulation, activates specific brain regions, such as the anterior cingulate gyrus and insula, areas that overlap with neural networks involved in physical pain. Physical pain can, in turn, activate distinct neural pathways that temporarily alleviate psychological pain. However, repeated self-injury may lead to increased pain tolerance over time, contributing to a vicious cycle. This paper reviews the potential neural network connections and interactions between psychological and physical pain in the context of NSSI behavior. It also summarizes current clinical interventions and their effectiveness in treating NSSI, aiming to offer new insights for future research and clinical practice in preventing and treating NSSI.

Objective To investigate the value of serum miR-196b-5p and miR-199a-3p levels in the diagnosis of non-small cell lung cancer(NSCLC).Methods A total of 202 patients with NSCLC admitted to Nantong First People's Hospital from January 2022 to March 2024 were retrospectively selected as the study objects,and 195 healthy subjects in the same period were selected as the controls.General baseline data and pathological features of NSCLC patients were collected.The expression levels of serum miR-196b-5p and miR-199a-3p were analyzed by quantitative reverse transcription polymerase chain reaction.The cor-relation between the expression levels of miR-196b-5p and miR-199a-3p and the concentration of cytokeratin 19 fragment anti-gen 21-1(Cyfra21-1)was analyzed by Pearson's correlation analysis.According to the mean expression levels of miR-196b-5p and miR-199a-3p,NSCLC patients were divided into high and low expression groups,and their clinical baseline and pathological characteristics were analyzed.Receiver operating characteristic(ROC)curves were drawn to analyze the diagnostic efficacy of se-rum Cyfra21-1,miR-196b-5p,miR-199a-3p and their combination in patients with NSCLC.Results Compared with the control group,the expression level of miR-196b-5p was increased and the expression level of miR-199a-3p was decreased in patients with NSCLC.Compared with stage Ⅰ/Ⅱ patients,the serum relative expression level of miR-196b-5p in stage Ⅲ/Ⅳ patients was significantly increased,and the relative expression level of miR-199a-3p was significantly decreased(all P＜0.01).Serum miR-196b-5p levels in NSCLC patients were positively correlated with Cyfra21-1,and serum miR-199a-3p levels were negatively correlated with Cyfra21-1(all P＜0.01).The expression differences of miR-196b-5p and miR-199a-3p were correlated with fam-ily history,pathological stage,tumor size,Cyfra21-1 level and lymph node metastasis of NSCLC patients(all P＜0.05).The are-a-under-the-curve(AUC)of serum miR-196b-5p level for the diagnosis of NSCLC was 0.882(sensitivity 75.25％,specificity 95.38％),and the AUC of serum miR-199a-3p level for the diagnosis of NSCLC was 0.857(sensitivity 68.32％,specificity 88.21％).The AUC of traditional biomarker Cyfra21-1 in the diagnosis of NSCLC patients was 0.818(sensitivity 63.86％,spe-cificity 87.18％).The diagnostic efficacy of the combined detection of miR-196b-5p and miR-199a-3p was significantly higher than that of serum Cyfra21-1(P＜0.01),miR-196b-5p(P＜0.01)and miR-199a-3p(P＜0.01)alone in patients with early stage(stage Ⅰ/Ⅱ)NSCLC.Conclusion The expression level of serum miR-196b-5p in NSCLC patients is significantly increased,and the expression level of miR-199a-3p is decreased,and the combined detection of miR-196b-5p and miR-199a-3p has a high effi-ciency in the diagnosis of NSCLC.

Objective To investigate the value of serum miR-196b-5p and miR-199a-3p levels in the diagnosis of non-small cell lung cancer(NSCLC).Methods A total of 202 patients with NSCLC admitted to Nantong First People's Hospital from January 2022 to March 2024 were retrospectively selected as the study objects,and 195 healthy subjects in the same period were selected as the controls.General baseline data and pathological features of NSCLC patients were collected.The expression levels of serum miR-196b-5p and miR-199a-3p were analyzed by quantitative reverse transcription polymerase chain reaction.The cor-relation between the expression levels of miR-196b-5p and miR-199a-3p and the concentration of cytokeratin 19 fragment anti-gen 21-1(Cyfra21-1)was analyzed by Pearson's correlation analysis.According to the mean expression levels of miR-196b-5p and miR-199a-3p,NSCLC patients were divided into high and low expression groups,and their clinical baseline and pathological characteristics were analyzed.Receiver operating characteristic(ROC)curves were drawn to analyze the diagnostic efficacy of se-rum Cyfra21-1,miR-196b-5p,miR-199a-3p and their combination in patients with NSCLC.Results Compared with the control group,the expression level of miR-196b-5p was increased and the expression level of miR-199a-3p was decreased in patients with NSCLC.Compared with stage Ⅰ/Ⅱ patients,the serum relative expression level of miR-196b-5p in stage Ⅲ/Ⅳ patients was significantly increased,and the relative expression level of miR-199a-3p was significantly decreased(all P＜0.01).Serum miR-196b-5p levels in NSCLC patients were positively correlated with Cyfra21-1,and serum miR-199a-3p levels were negatively correlated with Cyfra21-1(all P＜0.01).The expression differences of miR-196b-5p and miR-199a-3p were correlated with fam-ily history,pathological stage,tumor size,Cyfra21-1 level and lymph node metastasis of NSCLC patients(all P＜0.05).The are-a-under-the-curve(AUC)of serum miR-196b-5p level for the diagnosis of NSCLC was 0.882(sensitivity 75.25％,specificity 95.38％),and the AUC of serum miR-199a-3p level for the diagnosis of NSCLC was 0.857(sensitivity 68.32％,specificity 88.21％).The AUC of traditional biomarker Cyfra21-1 in the diagnosis of NSCLC patients was 0.818(sensitivity 63.86％,spe-cificity 87.18％).The diagnostic efficacy of the combined detection of miR-196b-5p and miR-199a-3p was significantly higher than that of serum Cyfra21-1(P＜0.01),miR-196b-5p(P＜0.01)and miR-199a-3p(P＜0.01)alone in patients with early stage(stage Ⅰ/Ⅱ)NSCLC.Conclusion The expression level of serum miR-196b-5p in NSCLC patients is significantly increased,and the expression level of miR-199a-3p is decreased,and the combined detection of miR-196b-5p and miR-199a-3p has a high effi-ciency in the diagnosis of NSCLC.

Objective:To evaluate the impact of roxadustat on thyroid function and to identify the associated factors in patients undergoing maintenance peritoneal dialysis (PD).Methods:This study was a single-center retrospective study. PD patients who received roxadustat or recombinant human erythropoietin (rHuEPO) treatment at Nanjing Drum Tower Hospital between January 2020 and June 2024 were included. The general and clinical information as well as laboratory indexes were collected. Serum free triiodothyronine (FT3), free thyroxine (FT4) and thyroid-stimulating hormone (TSH) were compared before and after treatment initiation. Hemoglobin (Hb) responses were also observed between the two groups. Logistic regression analysis was performed to explore the factors associated with thyroid function changes.Results:A total of 120 patients were enrolled, with an age of (55.17±16.42) years, including 66 males (55.0%). There were 81 patients received roxadustat (roxadustat group) and 39 patiens received rHuEPO (rHuEPO group). Compared to the rHuEPO group, the roxadustat group had a higher proportion of patients with diabetes ( χ 2= 4.172, P=0.041), a shorter PD vintage ( Z=-3.406, P=0.002), a lower serum level of total cholesterol ( Z=-2.082, P=0.037) and a lower level of fasting blood glucose ( Z=-2.589, P=0.010). Following treatment with roxadustat, the levels of FT4 ( Z=-5.349, P<0.01) and TSH ( Z=-3.720, P<0.01) decreased significantly. In contrast, no significant changes in FT4 or TSH levels were observed in the rHuEPO group (both P>0.05). For both roxadustat and rHuEPO groups, there were no significant changes in FT3 levels after treatment (both P>0.05). Multivariate analysis identified that higher baseline TSH (TSH≥2.27 μIU/ml, OR=1.581, 95% CI 1.196-2.089, P=0.001) and roxadustat exposure ( OR=3.432, 95% CI 1.410-8.355, P=0.007) as independent associated factors of subsequent TSH decline, and identified that higher baseline FT4 (FT4≥14.9 pmol/L, OR=1.390, 95% CI 1.162-1.662, P=0.001) and roxadustat exposure ( OR=5.798, 95% CI 2.225-15.113, P=0.001) as independent associated factors of subsequent FT4 decline. The degrees of hemoglobin changes after roxadustat or rHuEPO treatment did not differ significantly between roxadustat group and rHuEPO group ( t=-1.062, P=0.290). Of the 31 patients who underwent a second thyroid function test during roxadustat treatment, 24 continued with the original regimen, while 7 discontinued roxadustat. Among 24 patients who maintained roxadustat treatment, TSH ( Z=-0.400, P=0.689) and FT4 ( t=0.143, P=0.888) remained stable between the second and third tests. All 7 patients who discontinued roxadustat treatment showed TSH rebound and the changes of TSH levels were more significant than that in continuers ( Z=-2.505, P=0.012). FT4 recovery occurred in only 3 of them, with no significant difference in FT4 change between discontinuers and continuers ( Z=-0.685, P=0.493). Conclusions:Roxadustat commonly suppresses TSH and FT4, but not FT3, in PD patients. Baseline levels of TSH and FT4 are key associated factors of the inhibitory effect of roxadustat on thyroid function. This suppression does not intensify with prolonged exposure and is reversible after discontinuation, with TSH levels normalizing more quickly than FT4. Roxadustat-induced thyroid suppression does not compromise its efficacy in treating renal anemia.

The interplay between psychological pain and physical pain is one of the key issues in the research of non-suicidal self-injury (NSSI). Psychological pain, driven by negative self-perception and difficulties in emotional regulation, activates specific brain regions, such as the anterior cingulate gyrus and insula, areas that overlap with neural networks involved in physical pain. Physical pain can, in turn, activate distinct neural pathways that temporarily alleviate psychological pain. However, repeated self-injury may lead to increased pain tolerance over time, contributing to a vicious cycle. This paper reviews the potential neural network connections and interactions between psychological and physical pain in the context of NSSI behavior. It also summarizes current clinical interventions and their effectiveness in treating NSSI, aiming to offer new insights for future research and clinical practice in preventing and treating NSSI.

Objective:To investigate the effect of donor blood lipid levels and the degree of fat deposition on the pancreatic surface on the outcome of islet isolation.Method:A retrospective analysis was conducted on 171 cases of islet isolation data from organ donors between May 2015 and December 2024. According to the percentage of fat deposition area on the surface of the pancreatic capsule after trimming, the samples were divided into three groups: mild surface fat group (<30%, 60 cases) , moderate surface fat group (30%–70%, 55 cases) , and severe surface fat group (>70%, 56 cases). The modified Ricordi method was used to digest pancreatic tissue, and islets were purified by continuous density gradient centrifugation. The digestion efficiency, digestion time, islet yield (islet equivalent/quantity) , purity, score, and size were analyzed and compared among groups. One-way ANOVA was used for inter-group comparisons, and Pearson correlation analysis and multiple linear regression analysis were used to explore the relationship between blood lipid levels and islet isolation parameters.Result:The severe surface fat group had significantly higher pre-purification and post-purification islet equivalents, islet number, amount of digested pancreatic tissue, donor triglyceride levels, and low density lipoprotein (LDL) levels than the other groups (all P<0. 05) . Correlation analysis showed that LDL level was positively correlated with pre-purification islet equivalents (62 cases, r=0. 298, P=0. 019) and islet number (58 cases, r=0. 285, P=0. 030) . Donor high density lipoprotein (HDL) level was negatively correlated with post-purification islet equivalents (54 cases, r= – 0. 282, P=0. 039) ; donor triglyceride level was positively correlated with the amount of digested tissue (56 cases, r=0. 268, P=0. 046) and negatively correlated with purity (51 cases, r= - 0. 297, P=0. 035) ; donor very low density lipoprotein (VLDL) level was positively correlated with the amount of digested tissue (67 cases, r=0. 337, P=0. 005) and negatively correlated with purity (61 cases, r=- 0. 348 , P=0. 006) ; donor total cholesterol level was negatively correlated with pancreatic digestion efficiency (34 cases, r= - 0. 370, P=0. 032) , and the above differences were all statistically significant. Conclusion:Pancreata with heavier surface fat deposition can yield a higher number of islets. Meanwhile, donor blood lipid levels are correlated with islet isolation outcomes and can serve as important indicators for donor pancreas selection.

Objective To observe the effects of different frequencies of electroacupuncture on the degree of atrophy of quadriceps femoris in rabbits with anterior cruciate ligament(ACL)injury model;To explore the possible mechanisms of electroacupuncture in treating ACL injury.Methods Totally 24 New Zealand rabbits were randomly divided into blank group,model group,low-frequency electroacupuncture group and high-frequency electroacupuncture group,with 6 rabbits in each group.Except for the blank group,ACL injury models were established in the other groups.On the 7th day after modeling,the low-frequency electroacupuncture group and the high-frequency electroacupuncture group performed electroacupuncture treatment(continuous wave,frequency of 2 Hz and 100 Hz respectively,and left the needle in place for 20 min)at"Xuehai"and"Liangqiu"of the operation side,and the remaining groups were only grasped and immobilized,for 21 days.The mass ratio of the quadriceps femoris was calculated,the histopathological morphology of the quadriceps femoris tissue of the rabbits in each group was observed by HE staining,the expressions of NO,iNOS in quadriceps femoris tissue were detected by ELISA,the content of ROS in quadriceps femoris tissue was detected by fluorescent probe,the protein expressions of PERK,ATF6,IRE1,MuRF1,MAFbx in quadriceps femoris tissue were detected by Western blot.Results Compared with the blank group,the quadriceps femoris muscle mass ratio of the model group rabbits was significantly reduced(P<0.01),with irregular arrangement of muscle cells,accompanied by swelling and atrophy,significant interstitial edema,and extensive inflammatory infiltration,the contents of NO,iNOS and ROS in quadriceps femoris tissue significantly increased(P<0.01),while the expressions of PERK,ATF6,IRE1,MuRF1 and MAFbx proteins significantly increased(P<0.01).Compared with the model group,the quadriceps femoris muscle mass ratio in the low-frequency and high-frequency electroacupuncture groups significantly increased(P<0.01),with regular arrangement of muscle cells,improved swelling and atrophy of cells,and reduced interstitial edema and inflammation,the contents of NO,iNOS and ROS in quadriceps femoris tissue were significantly reduced(P<0.01),and the expressions of PERK,ATF6,IRE1,MuRF1 and MAFbx proteins significantly decreased(P<0.01).Moreover,the low-frequency electroacupuncture group had better effects than the high-frequency electroacupuncture group(P<0.05).Conclusion Different frequencies of electroacupuncture intervention in ACL injury rabbits can better delay the degree of quadriceps femoris atrophy,and its mechanism may be related to reducing the expressions of oxidative metabolites NO,iNOS,ROS,and reducing the expressions of endoplasmic reticulum stress-related proteins PERK,ATF6,IRE1 in quadriceps fermoris,which in turn inhibit the expressions of quadriceps atrophy factors MuRF1,MAFbx,and delaying the degradation of quadriceps muscle proteins.The effect of low-frequency electroacupuncture is superior to the high-frequency electroacupuncture.