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 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.

Abstract: Objective　To explore the effect of Yiaikang on the expression of sterile alpha motif and histidine-aspartic acid domain-containing protein 1(SAMHD1), a host restriction factor, and interferon levels in peripheral blood of HIV-infected patients with lung-spleen Qi deficiency syndrome. This aims to provide insights into the mechanism of YiaiKang in the treatment of AIDS. Methods According to the diagnostic criteria of Western medicine for AIDS and traditional Chinese medicine for lung-spleen Qi deficiency syndrome, 22 cases of HIV patients with lung and spleen Qi deficiency syndrome were enrolled in the study from the First Affiliated Hospital of Henan University of TCM between September 2020 and May 2021, and 20 healthy people in the area were taken as control. The patients with lung and spleen Qi deficiency syndrome were treated with Yiaikang for 6 months. T lymphocyte subpopulation changes and expression level of SAMHD1 protein in T cells were detected by flow cytometry. SAMHD1 mRNA expression in peripheral blood mononuclear cells (PBMCs) was detected by fluorescence quantitative PCR. The levels of IFN-α, IFN-β, IFN-γ, and IL-2 in plasma were detected by enzyme-linked immunosorbent assay (ELISA). The changes of SAMHD1 and interferon in peripheral blood of HIV patients with lung and spleen Qi deficiency syndrome were analyzed to explore the intervention effect of Yiaikang. Results Compared with healthy people, HIV patients with lung and spleen Qi deficiency syndrome exhibited a reduction in the CD4 + T lymphocyte count and CD4/CD8 ratio (Z=-3.526, P<0.001; Z=-0.881, P<0.001). There was an increase in the expression of SAMHD1 protein in T lymphocytes (SAMHD1 MFI/CD4: Z=-3.425, P=0.001; SAMHD1 MFI/CD8: Z=-2.153, P=0.031) and an increase in the expression of SAMHD1 gene in PBMCs (Z=-3.828, P<0.001). Yiaikang treatment significantly increased the CD4 + T cell count and CD4/CD8 ratio (Z=-2.711, P=0.007; Z=-2.062, P=0.039), decreased the expression of SAMHD1 mRNA (Z=-2.581, P=0.010), and decreased the levels of IFN-α and IFN-γ (Z=-1.985, P=0.047; Z=-2.744, P=0.006). Conclusions Patients with lung-spleen Qi deficiency syndrome have reduced numbers of CD4 + T cells and CD4/CD8 ration, with increased expression of SAMHD1 and interferon factors. Yiaikang treatment can increase the number of CD4 + T cells and CD4/CD8 ratio and reduce the expression of SAMHD1 and interferon factor, thereby improving the immune imbalance caused by HIV infection.

Acquired immune deficiency syndrome is an infectious disease with high mortality caused by human immunodefi-ciency virus(HIV).Even after antiretroviral therapy,the virus reservoir formed by the provirus integrated in the host genome can evade host immune surveillance and clearance.The existing methods of HIV reservoir detection mainly include cell culture induced virus growth assay in vitro and direct detection of the provirus genome based on PCR technology.Understanding and measuring accurately of HIV reservoir can provide reliable technical basis for HIV treatment research.This article summarizes and analyzes various detection methods of HIV reservoirs in recent years and their advantages and disadvantages,in order to select the suitable method for different detection objects of HIV reservior,and give appropriate suggestions,to provide technical support and theoretical guidance for further research on acquired immune deficiency syndrome.

【Objective】 To explore the effect of childhood maltreatment on clinical symptoms and early efficacy of antipsychotics in patients with schizophrenia. 【Methods】 Totally 73 schizophrenic patients were divided into mild maltreatment group(n=42) and severe maltreatment group(n=31) according to the Child Trauma Questionnaire(CTQ). The Positive and Negative Symptom Scale(PANSS) and Clinical Global Impression(CGI) were measured and compared between the two groups at baseline and 3 weeks after antipsychotic treatment to analyze the correlation between child maltreatment experience and mental symptoms and the response to early treatment of antipsychotics. 【Results】 PANSS positive factor score(P=0.026) and cognitive deficit factor score (P=0.042) were significantly higher in severe abuse group than in mild abuse group. The positive factor was significantly positively correlated with emotional abuse factor in CTQ score(r=0.257, P=0.028), and the cognitive deficit factor was significantly positively correlated with emotional neglect factor(r=0.283, P=0.015). After antipsychotic treatment, the reduction rate of PANSS negative factor in severe abuse group was significantly lower than that in mild abuse group(P=0.035), and had the highest correlation with CTQ physical abuse factor(r=-0.302, P=0.011). 【Conclusion】 The severity of childhood maltreatment experienced by schizophrenic patients is more related to positive symptoms and cognitive deficits, and more childhood maltreatment experience will affect the improvement of negative symptoms by antipsychotics, suggesting a poor prognosis.

With the continuous development of precision targeting medicine, antiangiogenic drugs have achieved good therapeutic effects in the treatment of advanced cancer, but renal injury and other adverse reactions often occur during the use, which reduce the quality of life of patients. This article reviews the mechanism of renal injury induced by antiangiogenic drugs and the potential relation between renal injury and prognosis.

【Objective】 To study the correlation of clinical symptoms and cognitive functions with serum inflammatory factors in schizophrenia. 【Methods】 A total of 42 SCz patients (case group) and 47 healthy controls (control group) were enrolled in this study. We used enzyme-linked immunosorbent assay (ELSA) to determine six inflammatory factors in serum. PANSS was used to assess clinical symptoms and MCCB was used to assess the patients’ cognitive functions. 【Results】 ① Inflammatory factors: The serum levels of IL-1β, IL-4, IL-6 and IL-8 were significantly higher in case group than in control group (P<0.01). ② Cognitive functions: The scores of Trail Making Test, Hopkins Verbal Learning Test, Symbol Coding, Spatial Span, Brief Visuospatial Memory Test, Assessment Battery-Mazes, Category Fluency and Test-Managing Emotions of case group were significantly lower than those of control group (P<0.05). ③ Correlation between serum inflammatory factors and clinical symptoms: There was no correlation between serum inflammatory factors and psychiatric symptoms in schizophrenia. ④ Correlation between serum inflammatory factors and cognitive functions: The levels of IL-6 (rs=-0.33, P<0.05) and IL-8 (rs=-0.50, P<0.01) in case group were significantly negatively correlated with the scores of Space Scan test. 【Conclusion】 Patients with schizophrenia are presented with immune dysfunction, and the latter is correlated with cognitive impairments.

Objective:To investigate the effects of hyperbaric oxygen (HBO) combined with selegiline on motor function, serum microRNA-124 (miR-124), insulin-like growth factor-1 (IGF-1) in patients with Parkinson′s disease (PD).Methods:A total of 120 PD patients, admitted in the Department of Neurology of Jining No.1 People′s Hospital from the March of 2017 to the March of 2019, were selected and divided into control group and HBO group according to the random number table method with each group consisting of 60 patients. The patients in the control group received levodopa and selegiline treatment, while the patients of HBO group were treated with HBO combined with the same medication of the control group. After three courses of treatment, clinical symptoms of the two groups were observed; motor function was assessed by the unified Parkinson′s disease rating scale (UPDRS); non-motor function was assessed by the PD non-motor symptom questionnaire (NMSQuest) and the Parkinson′s disease sleep scale (PDSS); the levels of serum oxidative stress index, inflammatory factor, IGF-1 and miR-124 before and after treatment were compared.Results:After 30 d treatment, the incidences of mental disorders, sensory disturbances, autonomic nervous dysfunction and sleep disorders of the two groups were significantly lower than those before treatment, and those of HBO group after treatment were significantly lower than those of the control group ( P<0.01). The UPDRS II and UPDRS III scores of both groups after treatment were significantly lower than those before treatment ( P<0.05). The UPDRS II and UPDRS III scores of the HBO group after treatment were significantly lower than those of the control group ( P<0.05 or P<0.01). Compared with those before treatment, the NMSQuest score of both two groups decreased and the PDSS score of both two groups increased. After treatment, the NMSQuest score of the HBO group was significantly lower than that of the control group; while the PDSS score of the HBO group was significantly higher than that of the control group ( P<0.05 or P<0.01). Compared with those before treatment, the levels of hs-CRP, IL-6, and MDA of the HBO group were significantly lower than those of the control group, while the SOD was significantly higher than that of the control group ( P<0.05). After treatment, the relative quantitative expressions of miR-124 and the levels of IGF-1 of both two groups were significantly higher than those before treatment, and the relative quantitative expressions of miR-124 and the levels of IGF-1 of the HBO group was significantly higher than those of the control group ( P<0.05 or P<0.01). Conclusion:HBO combined with selegiline can significantly improve the oxidative stress disorder in PD patients, promote the expressions of miR-124 and IGF-1, strengthen neuroprotective effects, and significantly improve motor function and non-motor disorders, so as to improve the therapeutic effect.

Objective:To investigate the effects of hyperbaric oxygen (HBO) combined with selegiline on motor function, serum microRNA-124 (miR-124), insulin-like growth factor-1 (IGF-1) in patients with Parkinson′s disease (PD).Methods:A total of 120 PD patients, admitted in the Department of Neurology of Jining No.1 People′s Hospital from the March of 2017 to the March of 2019, were selected and divided into control group and HBO group according to the random number table method with each group consisting of 60 patients. The patients in the control group received levodopa and selegiline treatment, while the patients of HBO group were treated with HBO combined with the same medication of the control group. After three courses of treatment, clinical symptoms of the two groups were observed; motor function was assessed by the unified Parkinson′s disease rating scale (UPDRS); non-motor function was assessed by the PD non-motor symptom questionnaire (NMSQuest) and the Parkinson′s disease sleep scale (PDSS); the levels of serum oxidative stress index, inflammatory factor, IGF-1 and miR-124 before and after treatment were compared.Results:After 30 d treatment, the incidences of mental disorders, sensory disturbances, autonomic nervous dysfunction and sleep disorders of the two groups were significantly lower than those before treatment, and those of HBO group after treatment were significantly lower than those of the control group ( P<0.01). The UPDRS II and UPDRS III scores of both groups after treatment were significantly lower than those before treatment ( P<0.05). The UPDRS II and UPDRS III scores of the HBO group after treatment were significantly lower than those of the control group ( P<0.05 or P<0.01). Compared with those before treatment, the NMSQuest score of both two groups decreased and the PDSS score of both two groups increased. After treatment, the NMSQuest score of the HBO group was significantly lower than that of the control group; while the PDSS score of the HBO group was significantly higher than that of the control group ( P<0.05 or P<0.01). Compared with those before treatment, the levels of hs-CRP, IL-6, and MDA of the HBO group were significantly lower than those of the control group, while the SOD was significantly higher than that of the control group ( P<0.05). After treatment, the relative quantitative expressions of miR-124 and the levels of IGF-1 of both two groups were significantly higher than those before treatment, and the relative quantitative expressions of miR-124 and the levels of IGF-1 of the HBO group was significantly higher than those of the control group ( P<0.05 or P<0.01). Conclusion:HBO combined with selegiline can significantly improve the oxidative stress disorder in PD patients, promote the expressions of miR-124 and IGF-1, strengthen neuroprotective effects, and significantly improve motor function and non-motor disorders, so as to improve the therapeutic effect.

Objective To investigate the effect of 1α, 25-dihydroxyvitamin D3 [1α,25-(OH)2 D3] on tumor necrosis factor-α ( TNF-α) induced activation of human umbilical vein endothelial cells ( HUVECs ) . The mechanism involved in this process was also studied. Methods HUVECs were cultured and treated with TNF-α( 40 ng/ml), 1α,25-(OH)2D3(10-8 mol/L), and SN50 as indicated. Vascular cell adhesion molecule (VCAM) and E-selectin were used as markers of endothelial activation, which were detected by Western blotting and realtime PCR (RT-PCR). NF-κB signaling pathway was investigated to study the mechanism. Western blotting, RT-PCR, immunofluorescence assay, and chromatin immunoprecipitation ( ChIP ) method were used to evaluate the effects of 1α,25-( OH) 2 D3 on its early activation, nuclear transport, and binding to VCAM and E-selectin promoters. Results (1) Western blotting and RT-PCR showed that TNF-α could significantly up-regulate the expression of VCAM and E-selectin in HUVECs, which can be inhibited by specific NF-κB blocker SN50. 1α,25-( OH) 2 D3 down-regulated the expression of VCAM and E-selectin induced by TNF-α. ( 2 ) Western blotting showed that TNF-α induces I-κBαphosphorylation, thereby activating NF-κB p65 subunit. Immunofluorescence showed that 1α, 25-( OH ) 2 D3 significantly inhibited the nuclear translocation of NF-κB p65 subunit. ChIP analysis revealed that 1α,25-( OH) 2 D3 inhibited the binding of NF-κB p65 to VCAM and E-selectin promoters and thus affected gene expression. Conclusions TNF-αenhanced the expression of E-selectin and VCAM in HUVECs via NF-κB signaling pathway. 1α,25-( OH) 2 D3 may inhibit NF-κB early activation, nuclear transport and the binding of NF-κB p65 to VCAM and E-selectin promoters, thereby inhibiting TNF-α-induced endothelial cell activation.