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 value of metanephrine, normetanephrine, and some steroid hormones in the assessment of adrenal venous sampling (AVS).Methods:This retrospective study enrolled 101 patients with primary aldosteronism who underwent AVS at Peking Union Medical College Hospital between June 1, 2021, and October 1, 2024. Multiple hormones, including aldosterone, cortisol, metanephrine, normetanephrine and steroid hormone profiles, were measured in samples from the inferior vena cava and bilateral adrenal veins during AVS. Selectivity index and lateralization index were calculated based on the levels of different hormones to determine successful AVS cannulation (selectivity index≥2) and aldosterone hypersecretion lateralization (lateralization index≥2). Patients who underwent unilateral adrenalectomy were followed for at least 6 months. Clinical and biochemical outcomes were assessed according to the Primary Aldosteronism Surgical Outcome (PASO) criteria, with biochemical remission defined as achieving complete or partial biochemical remission postoperatively. The efficacy of different hormones relative to cortisol for calculating selectivity index and lateralization index was evaluated for subtype classification.Results:The age at diagnosis of the enrolled patients was (50.5±9.6) years, including 77 males. Regarding the selectivity index, five hormones including metanephrine, normetanephrine, androstenedione, 17α-hydroxypregnenolone, and dehydroepiandrosterone demonstrated significantly higher selectivity index compared to cortisol (all P<0.05). Based on the cortisol-derived selectivity index, AVS cannulation was unsuccessful in 8 patients; using the five indices, unsuccessful cannulation occurred in 2, 2, 3, 4, and 5 patients, respectively. Based on postoperative follow-up, 55 patients were identified as having unilateral surgically relievable primary aldosteronism. In identifying these patients, the performance of metanephrine, normetanephrine, androstenedione, 17α-hydroxypregnenolone, and dehydroepiandrosterone was non-inferior to cortisol, correctly identifying 95% (52/55), 93% (51/55), 91% (50/55), 87% (48/55), and 89% (49/55) of cases, respectively. However, among these patients, there were no statistically significant differences in the success rate of intubation in AVS and the ability to identify patients with unilateral primary aldosteronism between the five indicators and cortisol (all P>0.05). Using cortisol-based lateralization as the reference standard, androstenedione and dehydroepiandrosterone both achieved an accuracy of 90% (84/93) for determining the lateralized side, while 17α-hydroxypregnenolone, normetanephrine, and metanephrine achieved accuracies of 89% (83/93), 81% (74/93), and 80% (73/93), respectively. Conclusion:Metanephrine, normetanephrine, androstenedione, 17α-hydroxypregnenolone and dehydroepiandrosterone could increase the success rate of intubation in AVS, with a high ability to identify patients with unilateral primary aldosteronism, and are expected to replace cortisol as new indicators of AVS.

Objective To establish a rat model of venous thrombosis in a plateau hypobaric hypoxic environment and to investigate the effect of this environment on venous thrombosis.Methods A total of 144 healthy male SD rats were assigned randomly to four groups(n=36 rats per group):a plains sham operation(A)group,plains operation(B)group,plateau altitude 6000 m+sham operation(C)group,and plateau altitude 6000 m+surgery(D)group.Rats in A and B groups were maintained in a plains normoxic environment,while rats in C and D groups C and D were subjected to a plateau environment.Rats in the surgical groups underwent quantitative constriction to incompletely obstruct the inferior vena cava blood flow.Each group was further divided into subgroups based on time:1,3,5,7,14,and 21 d(n=6 rats per group).Regular vascular ultrasound monitoring was conducted,and blood samples were taken for whole blood viscosity testing and the assessment of inflammatory indicators,including endothelin-1(ET-1),interleukin-6(IL-6)and tissue factor(TF).Coagulation function was evaluated through the activated partial thromboplastin time(APTT),prothrombin time(PT),thrombin time(TT),fibrinogen(FIB)and D-dimer.After the observation period,the experimental animals were sacrificed and the limbs were removed.Thrombus samples were stained with hematoxylin/eosin(HE),and the thrombus wet mass was measured.Results The thrombosis incidence was significantly higher in the plateau D group than in B group,accompanied by a marked increase in blood viscosity and hematocrit(P＜0.01).Additionally,levels of ET-1,IL-6,and TF were significantly elevated(P＜0.05),indicating a coagulation disorder.Conclusions A plateau hypoxic environment model can be successfully simulated by quantitative coarctation of the inferior vena cava,combined with a specialized environmental chamber.The findings of this study suggest that a plateau hypoxic environment promotes venous thrombosis.

Objective:To explore the influencing factors of decision to delivery interval (DDI) for emergency cesarean section with the aim of further optimizing the emergency cesarean section treatment process, improving the quality of emergency cesarean section treatment and the prognosis of mothers and infants.Methods:This study was a qualitative study. From January to June 2024, 20 healthcare professionals from the International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University School of Medicine were selected by purposive sampling to conduct semi-structured interviews. The data was analyzed using the Colaizzi 7-step analysis.Results:A total of five influencing factors for DDI of emergency cesarean section were refined, including healthcare decision-making power as the primary factor, teamwork as an important factor, process optimization as a key factor, simulation exercise as a core factor, and operational skills as a basic factor.Conclusions:Hospital administrators should focus on improving the decision-making ability of medical and nursing staff, developing standardized processes, establishing rapid response teams, and conducting periodic simulation exercises at the same time, in order to continually improve the team's cooperation and emergency response ability, shorten the DDI of emergency cesarean section, and ensure the safety of the parturient woman and the neonate.

Objective To establish a rat model of venous thrombosis in a plateau hypobaric hypoxic environment and to investigate the effect of this environment on venous thrombosis.Methods A total of 144 healthy male SD rats were assigned randomly to four groups(n=36 rats per group):a plains sham operation(A)group,plains operation(B)group,plateau altitude 6000 m+sham operation(C)group,and plateau altitude 6000 m+surgery(D)group.Rats in A and B groups were maintained in a plains normoxic environment,while rats in C and D groups C and D were subjected to a plateau environment.Rats in the surgical groups underwent quantitative constriction to incompletely obstruct the inferior vena cava blood flow.Each group was further divided into subgroups based on time:1,3,5,7,14,and 21 d(n=6 rats per group).Regular vascular ultrasound monitoring was conducted,and blood samples were taken for whole blood viscosity testing and the assessment of inflammatory indicators,including endothelin-1(ET-1),interleukin-6(IL-6)and tissue factor(TF).Coagulation function was evaluated through the activated partial thromboplastin time(APTT),prothrombin time(PT),thrombin time(TT),fibrinogen(FIB)and D-dimer.After the observation period,the experimental animals were sacrificed and the limbs were removed.Thrombus samples were stained with hematoxylin/eosin(HE),and the thrombus wet mass was measured.Results The thrombosis incidence was significantly higher in the plateau D group than in B group,accompanied by a marked increase in blood viscosity and hematocrit(P＜0.01).Additionally,levels of ET-1,IL-6,and TF were significantly elevated(P＜0.05),indicating a coagulation disorder.Conclusions A plateau hypoxic environment model can be successfully simulated by quantitative coarctation of the inferior vena cava,combined with a specialized environmental chamber.The findings of this study suggest that a plateau hypoxic environment promotes venous thrombosis.

Objective:To explore the influencing factors of decision to delivery interval (DDI) for emergency cesarean section with the aim of further optimizing the emergency cesarean section treatment process, improving the quality of emergency cesarean section treatment and the prognosis of mothers and infants.Methods:This study was a qualitative study. From January to June 2024, 20 healthcare professionals from the International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University School of Medicine were selected by purposive sampling to conduct semi-structured interviews. The data was analyzed using the Colaizzi 7-step analysis.Results:A total of five influencing factors for DDI of emergency cesarean section were refined, including healthcare decision-making power as the primary factor, teamwork as an important factor, process optimization as a key factor, simulation exercise as a core factor, and operational skills as a basic factor.Conclusions:Hospital administrators should focus on improving the decision-making ability of medical and nursing staff, developing standardized processes, establishing rapid response teams, and conducting periodic simulation exercises at the same time, in order to continually improve the team's cooperation and emergency response ability, shorten the DDI of emergency cesarean section, and ensure the safety of the parturient woman and the neonate.

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 value of metanephrine, normetanephrine, and some steroid hormones in the assessment of adrenal venous sampling (AVS).Methods:This retrospective study enrolled 101 patients with primary aldosteronism who underwent AVS at Peking Union Medical College Hospital between June 1, 2021, and October 1, 2024. Multiple hormones, including aldosterone, cortisol, metanephrine, normetanephrine and steroid hormone profiles, were measured in samples from the inferior vena cava and bilateral adrenal veins during AVS. Selectivity index and lateralization index were calculated based on the levels of different hormones to determine successful AVS cannulation (selectivity index≥2) and aldosterone hypersecretion lateralization (lateralization index≥2). Patients who underwent unilateral adrenalectomy were followed for at least 6 months. Clinical and biochemical outcomes were assessed according to the Primary Aldosteronism Surgical Outcome (PASO) criteria, with biochemical remission defined as achieving complete or partial biochemical remission postoperatively. The efficacy of different hormones relative to cortisol for calculating selectivity index and lateralization index was evaluated for subtype classification.Results:The age at diagnosis of the enrolled patients was (50.5±9.6) years, including 77 males. Regarding the selectivity index, five hormones including metanephrine, normetanephrine, androstenedione, 17α-hydroxypregnenolone, and dehydroepiandrosterone demonstrated significantly higher selectivity index compared to cortisol (all P<0.05). Based on the cortisol-derived selectivity index, AVS cannulation was unsuccessful in 8 patients; using the five indices, unsuccessful cannulation occurred in 2, 2, 3, 4, and 5 patients, respectively. Based on postoperative follow-up, 55 patients were identified as having unilateral surgically relievable primary aldosteronism. In identifying these patients, the performance of metanephrine, normetanephrine, androstenedione, 17α-hydroxypregnenolone, and dehydroepiandrosterone was non-inferior to cortisol, correctly identifying 95% (52/55), 93% (51/55), 91% (50/55), 87% (48/55), and 89% (49/55) of cases, respectively. However, among these patients, there were no statistically significant differences in the success rate of intubation in AVS and the ability to identify patients with unilateral primary aldosteronism between the five indicators and cortisol (all P>0.05). Using cortisol-based lateralization as the reference standard, androstenedione and dehydroepiandrosterone both achieved an accuracy of 90% (84/93) for determining the lateralized side, while 17α-hydroxypregnenolone, normetanephrine, and metanephrine achieved accuracies of 89% (83/93), 81% (74/93), and 80% (73/93), respectively. Conclusion:Metanephrine, normetanephrine, androstenedione, 17α-hydroxypregnenolone and dehydroepiandrosterone could increase the success rate of intubation in AVS, with a high ability to identify patients with unilateral primary aldosteronism, and are expected to replace cortisol as new indicators of AVS.

Objective:To investigate the effect of high-dose vitamin B6 on stress-induced liver cell death in rats with severe trauma and its possible mechanism.Methods:Thirty-two male SD rats were selected and divided into sham surgery group, sham surgery+B6 group, trauma group, and trauma+B6 group by using a random number table, with 8 rats in each group. Rat models of severe trauma were established by inducing abdominal wall injury, bilateral femoral fractures, unilateral cranial injury, and withdrawal of 4 ml blood from the femoral artery. The sham surgery+B6 group and trauma+B6 group were treated with saline solution plus high-dose vitamin B6, while the sham surgery group and trauma group with infusion of saline solution only. At 36 hours after injury, rat liver tissues were collected for the following experiments: (1) the genes differentially expressed in the liver tissues of the rats of the trauma group and the trauma+B6 group were screened with next-generation sequencing, followed by an analysis of the possible involvement of cell death pathways; (2) validation was conducted to ascertain whether high-dose vitamin B6 could influence various cell death pathways in the liver cells in the sham surgery group, sham surgery+B6 group, trauma group, and trauma+B6 group: apoptosis was confirmed through terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) staining; necroptosis was verified by mixed lineage kinase domain-like protein (MLKL) immunohistochemical staining; autophagy was examined via transmission electron microscopy; ferroptosis was confirmed by detecting oxidative malondialdehyde (MDA) levels, oxidized glutathione levels, Prussian blue staining with diaminobenzidine (DAB) enhancement, transmission electron microscopy, and immunohistochemical staining for acyl-CoA synthetase long-chain family member 4 (ACSL4); (3) Biological information analyses [Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Enrichment analysis (GSEA)] were performed for biological processes and signaling pathways represented by liver tissue sequencing results of rats between the trauma group and the trauma+B6 group.Results:(1) In the liver tissues of rats, there were 344 significantly differentially expressed genes between the trauma group and trauma+B6 group, comprising 137 upregulated genes and 207 downregulated genes, of which 18 genes were associated with apoptosis, autophagy, necroptosis, ferroptosis, and pyroptosis. (2) No significant differences were found in TUNEL staining among the sham surgery group, sham surgery+B6 group, trauma group or trauma+B6 group; MLKL protein expression levels in the liver tissues after trauma were improved, of which the trauma+B6 group was lower than that of the trauma group; Electron microscopy showed that autophagic activity in the liver cells were significantly increased after trauma, which was significantly lower of the trauma+B6 group than that of the trauma group; MDA levels in the rat liver tissues were (0.20±0.05)nmol/mg, (0.17±0.07)nmol/mg, (0.69±0.11)nmol/mg and (0.52±0.07)nmol/mg in the sham surgery group, sham surgery+B6 group, trauma group, and trauma+B6 group respectively ( P<0.01), with the trauma group having the highest MDA levels and trauma+B6 group having lower MDA levels than the trauma group; Oxidized glutathione levels in the liver tissues of the four groups were (11.75±2.09)μmol/g, (11.69±1.66)μmol/g, (19.75±3.40)μmol/g, and (14.51±1.46)μmol/g respectively ( P<0.01), with the trauma group having the highest levels and trauma+B6 group having lower levels than the trauma group; Significantly increased iron deposition was observed in the liver tissues after trauma, with lower iron deposition in trauma+B6 group than the trauma group; Electron microscopy revealed significantly lower mitochondrial membrane density in the trauma+B6 group compared to the trauma group. ACSL4 protein expression level was lower in the trauma+B6 group compared to the trauma group; (3) GO, KEGG and GSEA enrichment analyses suggested that high-dose vitamin B6 may enhance cholesterol synthesis metabolism in the liver cells and alleviate oxidative stress to reduce liver cell damage and restore normal liver cell function after trauma. Conclusions:High-dose vitamin B6 attenuates stress-induced liver injury in rats with severe trauma by inhibiting the progression of necroptosis, autophagy and ferroptosis. Its molecular mechanism may be associated with enhanced hepatic cholesterol synthesis metabolism and alleviation of oxidative stress in the liver cells.

Objective To develop an effective method for delivering VEGF and CD47 double-modified exosomes to treat renal damage induced by heat stroke so as to reduce and repair renal damage.Methods A plasmid fusion-expressing VEGF and CD47 targeting renal injury was constructed,transfected into rat bone marrow derived mesenchymal stem cells (BMMSCs),and then fusion-exosomes were isolated and extracted.Transmission electron microscopy,nanoparticle tracking analysis,and Western blotting were used to identify the obtained exosomes.Rats were intravenously injected with 200 μg of DiD-labeled unmodified exosomes,VEGF-modified exosomes and VEGF-CD47 double-modified exosomes,respectively,through the tail vein,and the effects of exosomes on the kidneys were detected and analyzed using a small animal in vivo imaging instrument.A total of 60 SD rats were randomly divided into 6 groups,with 10 rats in each group,that is,blank control group (group A),heat stroke-induced renal injury model receiving PBS in 12,24 and 36 h after modelling (group B),empty plasmid group (group C),Exos group (group D),ExosVEGF group (group E) and ExosVEGF-CD47.Kidney tissue and blood samples were collected in 72 h after 3 times of treatment.Pathological changes in kidney tissue were observed at the tissue level and the damage were scored.Changes in serum blood urea nitrogen (BUN)and serum creatinine (Scr)levels were detected to evaluate the therapeutic effect.Western blotting and qRT-PCR were used to analyze the expression of the pro-inflammatory factors TNF-α and NF-κB,the proliferation regulatory signaling molecules Ki67,FGF2,pAMPK and pERK,and the fibrosis regulatory molecule FGF23,in order to comprehensively analyze the effects on proliferation and inhibition of fibrosis.Results BMMSCs and ExosVEGF-CD47 were successfully isolated and characterized,and a rat model of acute kidney injury was effectively constructed.Higher fluorescence intensity was found in the kidney tissue of the Exos VEGF-CD47group than the Exos-Ctrl group and Exos VEGF group (P<0.05).In 72 h after treatment,the ExosVEGF-CD47 group had significantly lower serum BUN and Scr levels (P<0.0001),and notably lower Tubular casts score (P<0.0001),decreased levels of pro-inflammatory factors TNF-α and NF-κB (P<0.0001),up-regulated Ki67 and FGF2 expression (P<0.05),and down-regulated FGF23 expression (P<0.0001)when compared with the AKI+Exos group and AKI+ExosVEGF group.Conclusion VEGF and CD47 show promise in targeting acute kidney injury induced by heat stroke,effectively mitigate damage and facilitate repair,which may be due to exosome-mediated inhibition of renal tissue inflammation,promotion of proliferation,and inhibition of fibrosis.