Objective:To compare the efficacy of 68Ga-Pentixafor PET/CT in guiding surgical treatment of primary aldosteronism (PA) with that of adrenal venous sampling (AVS), and to explore its value in the diagnosis and management of PA. Methods:A total of 83 patients (62 males, 21 females, age (48.5±10.4) years) who received unilateral adrenal PA based on 68Ga-Pentixafor PET/CT or AVS results at the Department of Urological Surgery of Peking Union Medical College Hospital from January 1, 2021 to May 31, 2023 were retrospectively enrolled. Clinical data of patients were collected and the postoperative benefit rates guided by the two examination methods were compared according to the international multi-center PA surgical outcome standard. Quantitative indexes in 68Ga-Pentixafor PET/CT (SUV max, ratio of lesion SUV max to normal-adrenal-tissue SUV mean (LAR), ratio of lesion SUV max to normal-liver SUV mean (LLR), and ratio of lesion SUV max to contralateral SUV max (LCR)) were obtained for comparative analysis in patients with different surgical outcomes. Mann-Whitney U test, χ2 test or Fisher′s exact test were used to analyze the data. Results:Among 83 patients, 35 underwent AVS-guided surgery and 48 underwent 68Ga-Pentixafor PET/CT-guided surgery, with no significant difference of surgical benefit rates (85.7%(30/35) vs 85.4%(41/48); χ2=0.01, P=0.970). There was no significant difference of surgical benefit rates between 2 methods in such subgroups: <35 years (2/3 vs 7/8), ≥35 years (87.5%(28/32) vs 85.0%(34/40)), males (85.2%(23/27) vs 88.6%(31/35), females (7/8 vs 10/13), patients with unilateral lesions indicated by CT results (13/15 vs 83.9%(26/31)), patients with bilateral lesions indicated by CT results (85.0%(17/20) vs 15/17) (all χ2<0.01, all P>0.05). In PET/CT group, the LCR of patients who benefited from surgery ( n=41) was higher than that of patients who did not benefit ( n=7; 3.19(2.24, 4.90) vs 1.89(1.59, 2.88); Z=-2.09, P=0.036), and other quantitative indicators also tended to be higher. Conclusions:The positive results of 68Ga-Pentixafor PET/CT and AVS have the same clinical value in guiding PA patients to receive unilateral adrenal surgery. 68Ga-Pentixafor PET/CT is expected to become a non-invasive examination method to guide the treatment decisions in PA patients.

BACKGROUND: Macrophage polarization anomalies and dysfunction play a crucial role in the pathogenesis of immune thrombocytopenia (ITP). Itaconate is a Krebs cycle-derived immunometabolite synthesized by myeloid cells to modulate cellular metabolism and inflammatory responses. This study aimed to evaluate the immunoregulatory effects of an itaconate derivative on macrophages in patients with ITP. METHODS: Peripheral blood-derived macrophages from patients with ITP and healthy controls were treated with 4-octyl itaconate (4-OI), a derivative of itaconate that can penetrate the cell membrane. Macrophage polarization, antigen-presenting functions, and phagocytic capability were measured via flow cytometry and enzyme-linked immunosorbent assay (ELISA). Macrophage glycolysis in patients with ITP and the metabolic regulatory effect of 4-OI were detected using a Seahorse XFe96 Analyzer. An active murine model of ITP was used to evaluate the therapeutic effects of 4-OI in vivo . RESULTS: 4-OI reduced the levels of CD80 and CD86 in M1 macrophages and suppressed the release of tumor necrosis factor-α (TNF-α) and interleukin (IL)-6 pro-inflammatory cytokines, suggesting that 4-OI could hinder the polarization of macrophages toward an M1 phenotype. We found that 4-OI pretreated M1 macrophages reduced the proliferation of CD4 + T cells and promoted the differentiation of regulatory T cells. In addition, after 4-OI treatment, the phagocytic capacity of M1 macrophages toward antibody-coated platelets decreased significantly in patients with ITP. In addition, the glycolytic function of M1 macrophages was elevated in individuals with ITP compared to those in healthy controls. 4-OI treatment downregulated glycolysis in M1 macrophages. The glycolysis inhibitor 2-deoxy-d-glucose (2-DG) also inhibited the polarization of M1 macrophages and restored their functions. In vivo , 4-OI treatment significantly increased platelet counts in the active ITP murine model. CONCLUSIONS Itaconate derivative 4-OI inhibited M1 macrophage polarization and restored impaired functions through metabolic reprogramming. This study provides a novel therapeutic option for ITP.
Macrophages/metabolism* ; Humans ; Animals ; Succinates/pharmacology* ; Mice ; Male ; Female ; Adult ; Middle Aged ; Flow Cytometry ; Tumor Necrosis Factor-alpha/metabolism* ; Enzyme-Linked Immunosorbent Assay ; Purpura, Thrombocytopenic, Idiopathic/metabolism* ; Glycolysis/drug effects* ; Metabolic Reprogramming

Objective To explore the interplay between MCT1-mediated lactate accumulation and ferroptosis in acute liver failure(ALF).Methods An ALF mouse model and a hepatocyte injury model were established using lipopolysaccharide(LPS)in combination with D-galactosamine(D-GalN).The mice were randomly assigned to three groups:a blank control group,an ALF model group,and an ALF+Liproxstatin-1(Lip-1)treatment group.In vitro experiments included four groups:A blank control,a hepatocyte injury model,a lactate intervention,and an MCT1 overexpression group.Commercial kits were used to measure lactate levels in both mouse liver tissues and cell supernatants,as well as the contents of malondialdehyde(MDA),ferrous ions(Fe2+),and reduced glutathi-one(GSH)in liver tissue.Liver histopathology was evaluated using hematoxylin and eosin(HE)staining.Trans-mission electron microscopy was employed to assess mitochondrial ultrastructure in hepatocytes.Western blot(WB)analysis was performed to determine the protein expression levels of MCT1,glutathione peroxidase 4(GPX4),and acyl-CoA synthetase long-chain family member 4(ACSL4)in both liver tissues and cultured cells.Real-time quantitative PCR and immunofluorescence assays were utilized to detect mRNA expression and fluorescence intensity of GPX4 and ACSL4,respectively.Results HE staining of liver tissue from the ALF mouse model revealed extensive hepatocyte necrosis and partial inflammatory cell infiltration.Both MCT1 and GPX4 protein expression were significantly downregulated(P<0.001),whereas ACSL4 protein expression was markedly upregulated(P<0.000 1),accompanied by a significant elevation in lactate levels(P<0.001).Trans-mission electron microscopy demonstrated reduced mitochondrial volume and disorganized cristae arrangement in hepatocytes.In contrast to the model group,histological analysis of liver tissue from ALF mice treated with an iron death inhibitor showed attenuated liver injury.GPX4 expression was restored(P<0.05),while ACSL4 expression was reduced(P<0.001).Levels of lactate,MDA,and Fe2+in liver tissue were significantly lower(P<0.001),whereas GSH levels were significantly higher(P<0.05).In vitro experiments indicated that lactate treatment suppressed GPX4 expression in hepatocytes in a concentration-dependent manner while promoting ACSL4 expres-sion(P<0.05).In the hepatocyte injury model group,MCT1 and GPX4 expression were downregulated,ACSL4 protein expression was upregulated(P<0.05),and lactate levels were significantly increased(P<0.05).However,MCT1 overexpression effectively reversed these alterations,resulting in increased GPX4 expression(P<0.05)and decreased ACSL4 expression(P<0.001).Furthermore,immunofluorescence results revealed enhanced GPX4 fluorescence intensity(P<0.001)and reduced ACSL4 signal intensity(P<0.01),along with a marked reduction in lactate levels in cell supernatants(P<0.000 1).Conclusions This study demonstrates that ferroptosis plays a critical role in cell death during ALF and is closely intertwined with lactate metabolism.MCT1 mitigates LPS/D-GalN-induced ferroptosis by facilitating lactate transport in hepatocytes,thereby reducing lactate accumulation.Conversely,inhibition of ferroptosis leads to decreased lactate levels,indicating a bidirectional'lactate-ferroptosis'regulatory loop.

This study analyzed soil-transmitted nematode infection surveillance data for children 3-9 years of age in Shaanxi Province from 2016 to 2023,to provide a scientific basis for control strategies for soil-transmitted nematode infections in children in the province.Since 2016,according to the requirements of the National Schistosomiasis and Soil-transmitted Nematode Surveillance Program(Trial),several counties and districts in Shaanxi Province were selected as surveillance sites every year.According to geo-graphical position,the surveillance sites were divided into five areas:east,west,south,north and middle,and one administrative vil-lage(community)was selected in each area for monitoring.The eggs of soil-transmitted nematodes(hookworm,Ascaris lumbricoides,Trichuris trichiura,and Enterobius vermicularis)were detected with the Kato-Katz technique in children 3-9 years of age at each sur-veillance site,and the eggs of Enterobius vermicularis were detected again with the cellophane tape anal swab method.The infection rate and intensity for E.vermicularis were calculated.Detection was performed in 12 462 children 3-9 years old at 75 surveillance sites in Shaanxi Province from 2016 to 2023;84 cases of soil-borne nematode infections were detected,and the overall infection rate was 0.67%.The infection rates for Ascaris lumbricoides and E.vermicularis were 0.18%(22/12 462)and 0.50%(62/12 462),respec-tively,and the infection rates for Trichuris trichiura and hookworm were not found.The infection rates of soil-transmitted nematodes in children were 1.28%(16/1 250),0.16%(2/1 252),1.25%(17/1 365),1.20%(18/1 494),0.17%(2/1 169),1.45%(20/1 382),0.00,and 0.36%(9/251),respectively.A linear trend was observed among years(χ2=11.973,P<0.001).The infection rates in the Weifen Basin ecological region,Loess Plateau ecological region,and Qinba Mountains ecological region were 0.51%,1.19%,and 0.72%,respectively,and the differences were statistically significant(χ2=9.726,P=0.008).Significant differences in infection rates were observed among scattered children(1.63%),preschool children(0.66%),and students(0.57%)(χ2=11.189,P=0.004).No significant differences in infection rates were observed by gender,age,and education level.Compared with the infection rates in the entire country and other provinces,the infection rate of soil-transmitted nematodes among children in Shaanxi Province was low,and the main infection species were Ascaris lumbricoides and E.vermicularis.The infection rates greatly varied within Shaanxi Prov-ince,possibly because of differences in economic development levels,children′s living habits,and personal hygiene status across re-gions.In the future,comprehensive control measures should be taken to strengthen the monitoring and control of key areas,popula-tions,and parasite species.

Objective:To compare the efficacy of 68Ga-Pentixafor PET/CT in guiding surgical treatment of primary aldosteronism (PA) with that of adrenal venous sampling (AVS), and to explore its value in the diagnosis and management of PA. Methods:A total of 83 patients (62 males, 21 females, age (48.5±10.4) years) who received unilateral adrenal PA based on 68Ga-Pentixafor PET/CT or AVS results at the Department of Urological Surgery of Peking Union Medical College Hospital from January 1, 2021 to May 31, 2023 were retrospectively enrolled. Clinical data of patients were collected and the postoperative benefit rates guided by the two examination methods were compared according to the international multi-center PA surgical outcome standard. Quantitative indexes in 68Ga-Pentixafor PET/CT (SUV max, ratio of lesion SUV max to normal-adrenal-tissue SUV mean (LAR), ratio of lesion SUV max to normal-liver SUV mean (LLR), and ratio of lesion SUV max to contralateral SUV max (LCR)) were obtained for comparative analysis in patients with different surgical outcomes. Mann-Whitney U test, χ2 test or Fisher′s exact test were used to analyze the data. Results:Among 83 patients, 35 underwent AVS-guided surgery and 48 underwent 68Ga-Pentixafor PET/CT-guided surgery, with no significant difference of surgical benefit rates (85.7%(30/35) vs 85.4%(41/48); χ2=0.01, P=0.970). There was no significant difference of surgical benefit rates between 2 methods in such subgroups: <35 years (2/3 vs 7/8), ≥35 years (87.5%(28/32) vs 85.0%(34/40)), males (85.2%(23/27) vs 88.6%(31/35), females (7/8 vs 10/13), patients with unilateral lesions indicated by CT results (13/15 vs 83.9%(26/31)), patients with bilateral lesions indicated by CT results (85.0%(17/20) vs 15/17) (all χ2<0.01, all P>0.05). In PET/CT group, the LCR of patients who benefited from surgery ( n=41) was higher than that of patients who did not benefit ( n=7; 3.19(2.24, 4.90) vs 1.89(1.59, 2.88); Z=-2.09, P=0.036), and other quantitative indicators also tended to be higher. Conclusions:The positive results of 68Ga-Pentixafor PET/CT and AVS have the same clinical value in guiding PA patients to receive unilateral adrenal surgery. 68Ga-Pentixafor PET/CT is expected to become a non-invasive examination method to guide the treatment decisions in PA patients.

Objective To explore the interplay between MCT1-mediated lactate accumulation and ferroptosis in acute liver failure(ALF).Methods An ALF mouse model and a hepatocyte injury model were established using lipopolysaccharide(LPS)in combination with D-galactosamine(D-GalN).The mice were randomly assigned to three groups:a blank control group,an ALF model group,and an ALF+Liproxstatin-1(Lip-1)treatment group.In vitro experiments included four groups:A blank control,a hepatocyte injury model,a lactate intervention,and an MCT1 overexpression group.Commercial kits were used to measure lactate levels in both mouse liver tissues and cell supernatants,as well as the contents of malondialdehyde(MDA),ferrous ions(Fe2+),and reduced glutathi-one(GSH)in liver tissue.Liver histopathology was evaluated using hematoxylin and eosin(HE)staining.Trans-mission electron microscopy was employed to assess mitochondrial ultrastructure in hepatocytes.Western blot(WB)analysis was performed to determine the protein expression levels of MCT1,glutathione peroxidase 4(GPX4),and acyl-CoA synthetase long-chain family member 4(ACSL4)in both liver tissues and cultured cells.Real-time quantitative PCR and immunofluorescence assays were utilized to detect mRNA expression and fluorescence intensity of GPX4 and ACSL4,respectively.Results HE staining of liver tissue from the ALF mouse model revealed extensive hepatocyte necrosis and partial inflammatory cell infiltration.Both MCT1 and GPX4 protein expression were significantly downregulated(P<0.001),whereas ACSL4 protein expression was markedly upregulated(P<0.000 1),accompanied by a significant elevation in lactate levels(P<0.001).Trans-mission electron microscopy demonstrated reduced mitochondrial volume and disorganized cristae arrangement in hepatocytes.In contrast to the model group,histological analysis of liver tissue from ALF mice treated with an iron death inhibitor showed attenuated liver injury.GPX4 expression was restored(P<0.05),while ACSL4 expression was reduced(P<0.001).Levels of lactate,MDA,and Fe2+in liver tissue were significantly lower(P<0.001),whereas GSH levels were significantly higher(P<0.05).In vitro experiments indicated that lactate treatment suppressed GPX4 expression in hepatocytes in a concentration-dependent manner while promoting ACSL4 expres-sion(P<0.05).In the hepatocyte injury model group,MCT1 and GPX4 expression were downregulated,ACSL4 protein expression was upregulated(P<0.05),and lactate levels were significantly increased(P<0.05).However,MCT1 overexpression effectively reversed these alterations,resulting in increased GPX4 expression(P<0.05)and decreased ACSL4 expression(P<0.001).Furthermore,immunofluorescence results revealed enhanced GPX4 fluorescence intensity(P<0.001)and reduced ACSL4 signal intensity(P<0.01),along with a marked reduction in lactate levels in cell supernatants(P<0.000 1).Conclusions This study demonstrates that ferroptosis plays a critical role in cell death during ALF and is closely intertwined with lactate metabolism.MCT1 mitigates LPS/D-GalN-induced ferroptosis by facilitating lactate transport in hepatocytes,thereby reducing lactate accumulation.Conversely,inhibition of ferroptosis leads to decreased lactate levels,indicating a bidirectional'lactate-ferroptosis'regulatory loop.

This study analyzed soil-transmitted nematode infection surveillance data for children 3-9 years of age in Shaanxi Province from 2016 to 2023,to provide a scientific basis for control strategies for soil-transmitted nematode infections in children in the province.Since 2016,according to the requirements of the National Schistosomiasis and Soil-transmitted Nematode Surveillance Program(Trial),several counties and districts in Shaanxi Province were selected as surveillance sites every year.According to geo-graphical position,the surveillance sites were divided into five areas:east,west,south,north and middle,and one administrative vil-lage(community)was selected in each area for monitoring.The eggs of soil-transmitted nematodes(hookworm,Ascaris lumbricoides,Trichuris trichiura,and Enterobius vermicularis)were detected with the Kato-Katz technique in children 3-9 years of age at each sur-veillance site,and the eggs of Enterobius vermicularis were detected again with the cellophane tape anal swab method.The infection rate and intensity for E.vermicularis were calculated.Detection was performed in 12 462 children 3-9 years old at 75 surveillance sites in Shaanxi Province from 2016 to 2023;84 cases of soil-borne nematode infections were detected,and the overall infection rate was 0.67%.The infection rates for Ascaris lumbricoides and E.vermicularis were 0.18%(22/12 462)and 0.50%(62/12 462),respec-tively,and the infection rates for Trichuris trichiura and hookworm were not found.The infection rates of soil-transmitted nematodes in children were 1.28%(16/1 250),0.16%(2/1 252),1.25%(17/1 365),1.20%(18/1 494),0.17%(2/1 169),1.45%(20/1 382),0.00,and 0.36%(9/251),respectively.A linear trend was observed among years(χ2=11.973,P<0.001).The infection rates in the Weifen Basin ecological region,Loess Plateau ecological region,and Qinba Mountains ecological region were 0.51%,1.19%,and 0.72%,respectively,and the differences were statistically significant(χ2=9.726,P=0.008).Significant differences in infection rates were observed among scattered children(1.63%),preschool children(0.66%),and students(0.57%)(χ2=11.189,P=0.004).No significant differences in infection rates were observed by gender,age,and education level.Compared with the infection rates in the entire country and other provinces,the infection rate of soil-transmitted nematodes among children in Shaanxi Province was low,and the main infection species were Ascaris lumbricoides and E.vermicularis.The infection rates greatly varied within Shaanxi Prov-ince,possibly because of differences in economic development levels,children′s living habits,and personal hygiene status across re-gions.In the future,comprehensive control measures should be taken to strengthen the monitoring and control of key areas,popula-tions,and parasite species.

Objective:To improve the understanding of the diagnosis and treatment of coagulation disorders after severe head trauma.Methods:One case of coagulation disorder after severe traumatic brain injury was reported and the literature was reviewed.Results:A 70-year-old female was admitted to the hospital with 10 hours of unconsciousness after head injury. The patient underwent emergency epidural hematoma removal, decompression, and epidural hematoma drainage, and then coagulation disorder occurred, followed by myocardial infarction with heart failure and venous thrombosis of the lower limbs. After multiple infusions of prothrombin complex, application of low molecular weight heparin and active anti-infective therapy, the patient eventually regained coagulation function.Conclusion:For trauma patients, especially those with head injuries, it is crucial to test coagulation as early as possible, take measures to maintain coagulation function, apply plasma or fibrinogen in the early stages, and be vigilant for later hypercoagulable states and thrombosis, with timely anticoagulation as needed.

Objective:To improve the understanding of the diagnosis and treatment of coagulation disorders after severe head trauma.Methods:One case of coagulation disorder after severe traumatic brain injury was reported and the literature was reviewed.Results:A 70-year-old female was admitted to the hospital with 10 hours of unconsciousness after head injury. The patient underwent emergency epidural hematoma removal, decompression, and epidural hematoma drainage, and then coagulation disorder occurred, followed by myocardial infarction with heart failure and venous thrombosis of the lower limbs. After multiple infusions of prothrombin complex, application of low molecular weight heparin and active anti-infective therapy, the patient eventually regained coagulation function.Conclusion:For trauma patients, especially those with head injuries, it is crucial to test coagulation as early as possible, take measures to maintain coagulation function, apply plasma or fibrinogen in the early stages, and be vigilant for later hypercoagulable states and thrombosis, with timely anticoagulation as needed.

Objective:To investigate the efficacy of atomization with budesonide, salbutamol, and acetylcysteine in the adjuvant treatment of bronchopneumonia in children.Methods:Seventy-two children with bronchopneumonia admitted to Huaiyuan Jingtu Hospital from July 2021 to June 2022 were retrospectively included in this study. These children were divided into BS and BSY groups according to different treatment methods. Based on conventional treatment, the BS group was given atomization treatment with budesonide and salbutamol, and the BSY group was given atomization treatment with budesonide, salbutamol, and acetylcysteine. After two courses of treatment, clinical efficacy, duration to improvements in symptoms and signs, adverse drug reactions, and changes in serum C-reactive protein and procalcitonin levels after treatment relative to those before treatment were compared between the two groups. The optimal medication plan was investigated.Results:The total response rate in the BSY group was 91.67% (33 cases/36 cases), which was significantly higher than 72.22% (26/36) in the BS group ( χ2 = 4.59, P = 0.032). The incidence of adverse drug reactions in the BSY group was 11.11% (4/36), which was significantly lower than 19.44% (7/36) in the BS group ( χ2 = 0.96, P = 0.326). After treatment, the levels of C-reactive protein and procalcitonin in the BSY group were (5.86 ± 5.66) mg/L and (2.59 ± 0.74) μg/L, respectively, which were lower than (15.64 ± 5.85) mg/L and (4.71 ± 0.93) μg/L in the BS group ( t = 7.20, 10.70, both P < 0.001). The durations to the disappearance of symptoms and signs including fever, cough, lung rales, and X-ray lung shadow in the BSY group were significantly shorter compared with the BS group ( t = 11.85, 4.19, 2.72, 2.39, all P < 0.05). Conclusion:Atomization with budesonide, salbutamol, and acetylcysteine in combination for the adjuvant treatment of bronchopneumonia in children can quickly relieve the clinical symptoms of children, improve the lung signs, reduce the degree of inflammation, and has a remarkable therapeutic effect on bronchopneumonia in children.