Glioma, the most prevalent primary tumor of the central nervous system (CNS), is also the most lethal primary malignant tumor. Currently, there are limited chemotherapeutics available for glioma treatment, necessitating further research to identify and develop new chemotherapeutic agents. A significant approach to discovering anti-glioma drugs involves isolating antitumor active ingredients from natural products (NPs) and optimizing their structures. Additionally, targeted drug delivery systems (TDDSs) are employed to enhance drug solubility and stability and overcome the blood-brain barrier (BBB). TDDSs can penetrate deep into the brain, increase drug concentration and retention time in the CNS, and improve the targeting efficiency of NPs, thereby reducing adverse effects and enhancing anti-glioma efficacy. This paper reviews the research progress of anti-glioma activities of NPs, including alkaloids, polyphenols, flavonoids, terpenoids, saponins, quinones, and their synthetic derivatives over the past decade. The review also summarizes anti-glioma mechanisms, such as suppression of related protein expression, regulation of reactive oxygen species (ROS) levels, control of apoptosis signaling pathways, reduction of matrix metalloproteinases (MMPs) expression, blocking of vascular endothelial growth factor (VEGF), and reversal of immunosuppression. Furthermore, the functions and advantages of NP-based TDDSs in anti-glioma therapy are examined. The key information presented in this review will be valuable for the research and development of NP-based anti-glioma drugs and related TDDSs.
Humans ; Glioma/metabolism* ; Biological Products/therapeutic use* ; Animals ; Brain Neoplasms/genetics* ; Drug Delivery Systems ; Antineoplastic Agents/therapeutic use* ; Blood-Brain Barrier/metabolism* ; Apoptosis/drug effects*

Objective:To detect pathogenic gene mutations in a patient with CARD14-associated papulosquamous eruption (CAPE) and his family, and to evaluate the short-term and long-term efficacy and safety of ustekinumab treatment.Methods:Clinical data were collected from a 6-year-old child presenting with erythroderma secondary to pityriasis rubra pilaris and from his family members. Peripheral blood samples were collected from the patient, his parents and younger brother, and DNA was extracted from these peripheral blood samples. A next-generation skin-targeted sequencing panel was used to detect gene mutations, and Sanger sequencing was performed for verification. Genomic DNA was also extracted from 100 unrelated healthy controls using the same method.Results:A heterozygous mutation c.349+1G>A in intron 6 of the CARD14 gene was identified in the proband and his mother, but was not identified in his father, younger brother or 100 healthy controls, leading to a diagnosis of CAPE in the proband. The patient received subcutaneous injections of ustekinumab at a dose of 45 mg at weeks 0 and 4, and every 12 weeks thereafter. After 1-week treatment, the skin lesions and symptoms improved markedly. No adverse events were reported during the 18-month treatment and follow-up.Conclusion:The heterozygous mutation c.349+1G>A in the CARD14 gene may be the cause of the disease in this family, and ustekinumab was effective and safe for the treatment of CAPE.

Objective:To investigate the effect of extracorporeal membrane oxygenation (ECMO) in assisting neonates with complex congenital heart diseases (CHD) and the survival rate of the patients.Methods:A retrospective case-control study was made on 22 newborns with complex CHD assisted by ECMO during the perioperative period in Fuwai Central China Cardiovascular Hospital from January 2018 to June 2024.There were 19 males and 3 females in the newborns included, with an average age of (10.4±8.7) days (range: 1-26 days) and an average weight of (3.1±0.3) kg.Complex CHD included total anomalous pulmonary venous connection in 9 cases (40.9%), interrupted aortic arch and coarctation in 8 cases (36.4%), transposition of great arteries in 3 cases (13.6%), double outlet right ventricle in 1 case (4.5%) and cardiac tumor in 1 case (4.5%).The patients were divided into the <5 d group, 5-12 d group, and >12 d group according to the duration of ECMO support.Data were compared using the t-test or χ2 test. Results:There were 8 cases (36.4%) successfully weaned from ECMO support and 6 cases (27.3%) survived.ECMO support was used routinely in 15 cases (68.2%), and for extracorporeal cardiopulmonary resuscitation in 7 cases (31.8%).The duration of ECMO support was (5.9±3.7) days.There were no statistically differences in age, weight, gender, disease composition, operation time, cardiopulmonary bypass time, cross-clamp time, assistant time, blood routine, liver and kidney function and other biochemical indicators, preoperative cardiac ejection fraction value, procalcitonin, C-reactive protein and other infection indicators between the death group and the survival group (all P>0.05).The highest lactate values 24 hours before [(8.1±5.4) mmol/L] and after ECMO support [(10.5±7.1) mmol/L] in the survival group were significantly lower than those in the death group [(18.7±9.2) mmol/L, (21.3±8.6) mmol/L] ( t=2.606, P=0.018; t=2.729, P=0.013).It was found that the survival rate was 0/9 (0) in the <5 d group, 6/12 (50.0%) in the 5-12 d group, and 0/1 (0) in the >12 d group.The survival rate of the 5-12 d group was the highest, which was significantly higher than that of the <5 d group ( χ2=6.300, P=0.012). Conclusions:ECMO support is an effective treatment for severe circulatory failure in neonates with complex CHD in the perioperative period.The highest lactate levels 24 hours before and after ECMO support affect the survival rate.Patients receiving 5-12 d ECMO support can achieve the highest survival rate.

Objective:To detect pathogenic gene mutations in a patient with CARD14-associated papulosquamous eruption (CAPE) and his family, and to evaluate the short-term and long-term efficacy and safety of ustekinumab treatment.Methods:Clinical data were collected from a 6-year-old child presenting with erythroderma secondary to pityriasis rubra pilaris and from his family members. Peripheral blood samples were collected from the patient, his parents and younger brother, and DNA was extracted from these peripheral blood samples. A next-generation skin-targeted sequencing panel was used to detect gene mutations, and Sanger sequencing was performed for verification. Genomic DNA was also extracted from 100 unrelated healthy controls using the same method.Results:A heterozygous mutation c.349+1G>A in intron 6 of the CARD14 gene was identified in the proband and his mother, but was not identified in his father, younger brother or 100 healthy controls, leading to a diagnosis of CAPE in the proband. The patient received subcutaneous injections of ustekinumab at a dose of 45 mg at weeks 0 and 4, and every 12 weeks thereafter. After 1-week treatment, the skin lesions and symptoms improved markedly. No adverse events were reported during the 18-month treatment and follow-up.Conclusion:The heterozygous mutation c.349+1G>A in the CARD14 gene may be the cause of the disease in this family, and ustekinumab was effective and safe for the treatment of CAPE.

Objective:To investigate the effect of extracorporeal membrane oxygenation (ECMO) in assisting neonates with complex congenital heart diseases (CHD) and the survival rate of the patients.Methods:A retrospective case-control study was made on 22 newborns with complex CHD assisted by ECMO during the perioperative period in Fuwai Central China Cardiovascular Hospital from January 2018 to June 2024.There were 19 males and 3 females in the newborns included, with an average age of (10.4±8.7) days (range: 1-26 days) and an average weight of (3.1±0.3) kg.Complex CHD included total anomalous pulmonary venous connection in 9 cases (40.9%), interrupted aortic arch and coarctation in 8 cases (36.4%), transposition of great arteries in 3 cases (13.6%), double outlet right ventricle in 1 case (4.5%) and cardiac tumor in 1 case (4.5%).The patients were divided into the <5 d group, 5-12 d group, and >12 d group according to the duration of ECMO support.Data were compared using the t-test or χ2 test. Results:There were 8 cases (36.4%) successfully weaned from ECMO support and 6 cases (27.3%) survived.ECMO support was used routinely in 15 cases (68.2%), and for extracorporeal cardiopulmonary resuscitation in 7 cases (31.8%).The duration of ECMO support was (5.9±3.7) days.There were no statistically differences in age, weight, gender, disease composition, operation time, cardiopulmonary bypass time, cross-clamp time, assistant time, blood routine, liver and kidney function and other biochemical indicators, preoperative cardiac ejection fraction value, procalcitonin, C-reactive protein and other infection indicators between the death group and the survival group (all P>0.05).The highest lactate values 24 hours before [(8.1±5.4) mmol/L] and after ECMO support [(10.5±7.1) mmol/L] in the survival group were significantly lower than those in the death group [(18.7±9.2) mmol/L, (21.3±8.6) mmol/L] ( t=2.606, P=0.018; t=2.729, P=0.013).It was found that the survival rate was 0/9 (0) in the <5 d group, 6/12 (50.0%) in the 5-12 d group, and 0/1 (0) in the >12 d group.The survival rate of the 5-12 d group was the highest, which was significantly higher than that of the <5 d group ( χ2=6.300, P=0.012). Conclusions:ECMO support is an effective treatment for severe circulatory failure in neonates with complex CHD in the perioperative period.The highest lactate levels 24 hours before and after ECMO support affect the survival rate.Patients receiving 5-12 d ECMO support can achieve the highest survival rate.

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.

Objective:To evaluate the role of nuclear factor E2-related factor 2 (Nrf2)/heme oxygenase (HO-1) signaling pathway in the attenuation of endotoxin-induced acute lung injury (ALI) by hydromorphone and the relationship with Golgi apparatus stress (GA stress) in mice.Methods:Eighteen SPF wild-type (WT) and 18 Nrf2 knockout (Nrf2 KO) male C57BL/6J mice, aged 6-8 weeks, weighing 18-20 g, were divided into 3 groups ( n=6 each) using a random number table method: control groups (WT+ Con group, Nrf2 KO+ Con group), ALI groups (WT+ ALI group, Nrf2 KO+ ALI group) and ALI+ hydromorphone groups (WT+ ALI+ HM group, Nrf2 KO+ ALI+ HM group). ALI was induced by injecting lipopolysaccharide (LPS) 15 mg/kg via the tail vein in anesthetized animals. Hydromorphone 120 μg was intraperitoneally injected at 15 min before LPS injection in WT+ ALI+ HM group and Nrf2 KO+ ALI+ HM group, and the equal volume of normal saline was given instead in control groups. The animals were sacrificed after anesthesia at 12 h after LPS injection, and lung tissues were obtained for examination of the pathological changes which were scored and Golgi ultrastructure (with a transmission electron microscope) and for determination of the content of malondialdehyde (MDA), activity of superoxide dismutase (SOD), and expression of Nrf2, HO-1 and Golgi stress-related markers (Golgi matrix protein 130 [GM130], Golgi autoantigen 97 kDa [Golgin-97], ATPase secretory pathway Ca 2+ Transporting 1 [ATP2C1], Golgi phosphoprotein 3 [GOLPH3]) (by Western blot). Results:Compared with WT+ Con group and Nrf2 KO+ Con group, the lung injury scores and content of MDA were significantly increased, the activity of SOD was decreased, the expression of GM130, Golgin-97 and ATP2C1 was down-regulated, the expression of GOLPH3 was up-regulated ( P<0.05), no significant changes were found in the expression of Nrf2 and HO-1 ( P>0.05), and the damage to the Golgi apparatus was aggravated in WT+ ALI group and Nrf2 KO+ ALI group. Compared with WT+ ALI group, the lung injury scores and content of MDA were significantly decreased, the activity of SOD was increased, the expression of Nrf2, HO-1, GM130, Golgin-97 and ATP2C1 was up-regulated, the expression of GOLPH3 was down-regulated ( P<0.05), and the damage to the Golgi apparatus was significantly attenuated in WT+ ALI+ HM group. Compared with Nrf2 KO+ ALI group, the lung injury scores were significantly decreased, and the activity of SOD was increased ( P<0.05), no significant changes were found in the content of MDA and expression of Nrf2, HO-1, GM130, Golgin-97, ATP2C1 and GOLPH3 ( P>0.05), and no significant reduction in the damage to the Golgi apparatus was found in Nrf2 KO+ ALI+ HM group. Compared with WT+ ALI+ HM group, the lung injury scores and content of MDA were significantly increased, the activity of SOD was decreased, the expression of Nrf2, HO-1, GM130, Golgin-97 and ATP2C1 was down-regulated, the expression of GOLPH3 was up-regulated ( P<0.05), and the damage to the Golgi apparatus was aggravated in Nrf2 KO+ ALI+ HM group. Conclusions:Nrf2/HO-1 signaling pathway is involved in the attenuation of endotoxin-induced ALI by hydromorphone, and it is associated with the inhibition of Golgi stress.

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.

Objective:To evaluate the role of nuclear factor E2-related factor 2 (Nrf2)/heme oxygenase (HO-1) signaling pathway in the attenuation of endotoxin-induced acute lung injury (ALI) by hydromorphone and the relationship with Golgi apparatus stress (GA stress) in mice.Methods:Eighteen SPF wild-type (WT) and 18 Nrf2 knockout (Nrf2 KO) male C57BL/6J mice, aged 6-8 weeks, weighing 18-20 g, were divided into 3 groups ( n=6 each) using a random number table method: control groups (WT+ Con group, Nrf2 KO+ Con group), ALI groups (WT+ ALI group, Nrf2 KO+ ALI group) and ALI+ hydromorphone groups (WT+ ALI+ HM group, Nrf2 KO+ ALI+ HM group). ALI was induced by injecting lipopolysaccharide (LPS) 15 mg/kg via the tail vein in anesthetized animals. Hydromorphone 120 μg was intraperitoneally injected at 15 min before LPS injection in WT+ ALI+ HM group and Nrf2 KO+ ALI+ HM group, and the equal volume of normal saline was given instead in control groups. The animals were sacrificed after anesthesia at 12 h after LPS injection, and lung tissues were obtained for examination of the pathological changes which were scored and Golgi ultrastructure (with a transmission electron microscope) and for determination of the content of malondialdehyde (MDA), activity of superoxide dismutase (SOD), and expression of Nrf2, HO-1 and Golgi stress-related markers (Golgi matrix protein 130 [GM130], Golgi autoantigen 97 kDa [Golgin-97], ATPase secretory pathway Ca 2+ Transporting 1 [ATP2C1], Golgi phosphoprotein 3 [GOLPH3]) (by Western blot). Results:Compared with WT+ Con group and Nrf2 KO+ Con group, the lung injury scores and content of MDA were significantly increased, the activity of SOD was decreased, the expression of GM130, Golgin-97 and ATP2C1 was down-regulated, the expression of GOLPH3 was up-regulated ( P<0.05), no significant changes were found in the expression of Nrf2 and HO-1 ( P>0.05), and the damage to the Golgi apparatus was aggravated in WT+ ALI group and Nrf2 KO+ ALI group. Compared with WT+ ALI group, the lung injury scores and content of MDA were significantly decreased, the activity of SOD was increased, the expression of Nrf2, HO-1, GM130, Golgin-97 and ATP2C1 was up-regulated, the expression of GOLPH3 was down-regulated ( P<0.05), and the damage to the Golgi apparatus was significantly attenuated in WT+ ALI+ HM group. Compared with Nrf2 KO+ ALI group, the lung injury scores were significantly decreased, and the activity of SOD was increased ( P<0.05), no significant changes were found in the content of MDA and expression of Nrf2, HO-1, GM130, Golgin-97, ATP2C1 and GOLPH3 ( P>0.05), and no significant reduction in the damage to the Golgi apparatus was found in Nrf2 KO+ ALI+ HM group. Compared with WT+ ALI+ HM group, the lung injury scores and content of MDA were significantly increased, the activity of SOD was decreased, the expression of Nrf2, HO-1, GM130, Golgin-97 and ATP2C1 was down-regulated, the expression of GOLPH3 was up-regulated ( P<0.05), and the damage to the Golgi apparatus was aggravated in Nrf2 KO+ ALI+ HM group. Conclusions:Nrf2/HO-1 signaling pathway is involved in the attenuation of endotoxin-induced ALI by hydromorphone, and it is associated with the inhibition of Golgi stress.

Objective To explore the relationship between peripheral blood T lymphocyte subsets and prognosis of patients with advanced non-small cell lung cancer (NSCLC) who received treatment with camrelizumab. Methods We retrospectively collected data from 88 patients with advanced NSCLC who underwent camrelizumab treatment. Peripheral blood lymphocyte subsets were collected from patients before and two months after treatment. Kaplan-Meier curves and Cox regression analysis were employed to investigate the relationship between peripheral blood T lymphocyte subsets and PFS and OS. Results Compared with non-responder group, the baseline peripheral blood CD4+/CD8+ ratio was higher (P=0.038), while the CD8+T lymphocyte percentage was lower (P=0.036) in the responder group. Kaplan-Meier curves showed that a high baseline CD4+/CD8+ ratio was associated with long PFS and OS (P=0.001, P=0.023). Multivariate Cox analysis revealed that the baseline CD4+/CD8+ ratio was a significant predictor for PFS and OS. Additionally, a high post-treatment CD4+/CD8+ ratio and high CD4+T lymphocyte percentage were associated with long PFS (P=0.005, P=0.015), whereas a low post-treatment CD8+T lymphocyte percentage was associated with long PFS and OS (P=0.001, P=0.016). Conclusion The peripheral blood CD4+/CD8+ ratio can serve as a predictive factor for survival of patients with NSCLC treated with camrelizumab.