Objective:To explore the feasibility of chemical exchange saturation transfer (CEST) imaging at 3.0 T MRI in quantifying renal redox metabolism in vitro models and experimental animals.Methods:Redox metabolites in vitro models with physiological concentrations were prepared, including reduced metabolites (glutamate, alanine, glutathione) and oxidized metabolites (2-ketoglutarate, pyruvate, glutathione disulfide, ammonium hydroxide). CEST examinations were performed at 3.0 T MRI. The imaging parameters were as follows: CEST images with different saturation pulse intensity (B 1) (1, 2, 3, 4 μT) and a fixed radio frequency (RF) duration of 2 000 ms; CEST images with different RF durations (1 500 and 2 000 ms) were acquired with a fixed B 1 value of 2 μT to obtain the optimal scanning parameters. CEST examinations with optimized parameters were performed on the left kidneys of seven healthy rabbits, and the differences in magnetic resonance ratio asymmetry (MTR asym) between rabbit renal cortex and outer medulla were measured. A paired t-test was used to compare the differences. Results:The optimal B 1 for CEST examination of redox metabolites was 2 μT, and the optimal RF duration was 2 000 ms. The MTR asym peaks of glutathione disulfide, glutathione, glutamic acid, and alanine were at 3.75, 3.5, 3, and 1.5 ppm, respectively. The MTR asym peaks of pyruvate, 2-ketoglutarate, and ammonium hydroxide were at 1 ppm. The MTR asym peak values of reduced metabolites were higher than those of oxidized metabolites. When the B 1 value was 2 μT and the RF duration was 2 000 ms, the MTR asym signal of the renal cortex was (2.60±1.10) %, (2.86±1.32) %, (3.04±1.06) %, and (2.98±0.91) % at 1, 3, 3.5, and 3.75 ppm, respectively. The MTR asym signal of the outer medulla was (1.00±0.56) %, (2.43±0.94) %, (2.29±0.88) % and (1.98±0.58) %, respectively. The MTR asym signal of the renal cortex was higher than that of the outer medulla, and the differences were statistically significant ( t=3.04, P=0.023; t=2.56, P=0.043; t=3.50, P=0.013; t=3.45, P=0.014). Conclusion:CEST imaging at 3.0 T MRI can be used to quantitatively evaluate redox metabolism of healthy rabbit kidneys in vitro model and normal experimental rabbits.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective:To investigate the feasibility of 3.0 T glutamate chemical exchange saturation transfer (GluCEST) imaging in evaluating renal redox metabolism in renal ischemia-reperfusion injury (IRI).Methods:Rabbits in the IRI group ( n=56) underwent surgery by clamping the left renal artery for 45 min and then releasing to establish IRI. Rabbits in the sham group ( n=8) underwent the same operation without clamping the left renal artery. GluCEST MRI was performed before and at 1 h, 12 h, 1 day, 3 days, 7 days, and 14 days after the operations, with eight rabbits in the IRI group sacrificed immediately after each scanning and eight in the sham group sacrificed at 14 days after scanning. The left kidneys were removed for histopathological examination and reactive oxygen species (ROS) fluorescence staining. Differences in the magnetic resonance ratio asymmetry (MTR asym) of the renal cortex and outer medulla among different groups were compared. Correlations between the MTR asym and ROS were analyzed. Results:The MTR asym of the renal cortex in the sham and IRI subgroups were higher than that of the outer medulla ( t=8.16, P<0.001; t=4.78, P=0.002; t=4.94, P=0.002; t=5.76, P=0.001, t=6.68, P<0.001; t=6.40, P<0.001; t=5.16, P=0.001; t=3.30, P=0.013). The MTR asym of the renal cortex and outer medulla in the IRI-1h, IRI-12h, IRI-1d, IRI-3d, IRI-7d, and IRI-14d groups were lower than in the sham and IRI-pre groups (all P<0.05). The MTR asym of the renal cortex and outer medulla in the IRI-1h group were lower than in the IRI-12h, IRI-1d, IRI-3d, IRI-7d, and IRI-14d groups (all P<0.05). The MTR asym of the renal cortex in the IRI-12h group was lower than in the IRI-7d and IRI-14d groups (1.84%±0.09% vs.2.42%±0.19%, 2.41%±0.31%, all P<0.05). The MTR asym of the renal cortex in the IRI-1d group was lower than in the IRI-7d group (1.99%±0.17% vs. 2.42%±0.19%, P=0.008). The MTR asym of the outer medulla in the IRI-12h group was lower than in the IRI-3d, IRI-7d, and IRI-14d groups (1.32%±0.27% vs. 1.79%±0.31%, 1.98%±0.18%, 1.66%±0.40%, respectively, all P<0.05]. The MTR asym of the outer medulla in the IRI-7d group was higher than in the IRI-1d and IRI-14d groups (1.98%±0.18% vs. 1.52%±0.31%, 1.66%±0.40%, all P<0.05). The MTR asym of the renal cortex and outer medulla had a strong negative correlation with the mean fluorescence intensity of ROS ( ρ=-0.889, P<0.001; ρ=-0.784, P<0.001). Conclusion:3.0 T GluCEST imaging can indirectly reflect the changes of renal redox metabolism in renal IRI.

AIM To investigate the effects of tectorigenin on preadipocyte differentiation and the possible mechanism.METHODS CCK8 method was used to detect the effects of tectorigenin on 3T3-L1 cell viability.After 2 days contact inhibition(Day 0 of differentiation),the cells were exposed to inducer and tectorigenin of different concentrations(0,10,20,40,60 μmol/L),in contrast to those of the control group with no inducer use.On the 9th day of differentiation,the cells had their lipid droplets observed by oil red O staining;their levels of TG and NEFA detected by biochemical kit;their protein expressions of PPARγ,C/EBPα,perilipin-1,ADFP,AMPKα and p-AMPKα detected by Western blot;and their mRNA expressions of Adiponectin,FABP4,FAS and Acly detected by RT-qPCR.RESULTS Tectorigenin concentration of 60 μmol/L or lower levels left no impact upon the cell viability(P＞0.05).Compared with the model group with induced differentiation,the groups intervened with tectorigenin administration displayed decreased formation of lipid droplets;lower levels of TG and NEFA(P＜0.01);decreased protein expressions of C/EBPα,PPAR γ,perilipin-1 and ADFP(P＜0.01);increased protein expressions of AMPKα and p-AMPKα(P＜0.01);and decreased mRNA expressions of Adiponectin,FABP4,FAS and Acly(P＜0.01).CONCLUSION Tectorigenin inhibits preadipocyte differentiation into mature adipocytes,which may be related to its efficacy in the regulation of C/EBPα,PPARγ,AMPKα and p-AMPKα.

The present study was aimed to investigate the role and mechanism of glutaminolysis of cardiac fibroblasts (CFs) in hypertension-induced myocardial fibrosis. C57BL/6J mice were administered with a chronic infusion of angiotensin II (Ang II, 1.6 mg/kg per d) with a micro-osmotic pump to induce myocardial fibrosis. Masson staining was used to evaluate myocardial fibrosis. The mice were intraperitoneally injected with BPTES (12.5 mg/kg), a glutaminase 1 (GLS1)-specific inhibitor, to inhibit glutaminolysis simultaneously. Immunohistochemistry and Western blot were used to detect protein expression levels of GLS1, Collagen I and Collagen III in cardiac tissue. Neonatal Sprague-Dawley (SD) rat CFs were treated with 4 mmol/L glutamine (Gln) or BPTES (5 μmol/L) with or without Ang II (0.4 μmol/L) stimulation. The CFs were also treated with 2 mmol/L α-ketoglutarate (α-KG) under the stimulation of Ang II and BPTES. Wound healing test and CCK-8 were used to detect CFs migration and proliferation respectively. RT-qPCR and Western blot were used to detect mRNA and protein expression levels of GLS1, Collagen I and Collagen III. The results showed that blood pressure, heart weight and myocardial fibrosis were increased in Ang II-treated mice, and GLS1 expression in cardiac tissue was also significantly up-regulated. Gln significantly promoted the proliferation, migration, mRNA and protein expression of GLS1, Collagen I and Collagen III in the CFs with or without Ang II stimulation, whereas BPTES significantly decreased the above indices in the CFs. α-KG supplementation reversed the inhibitory effect of BPTES on the CFs under Ang II stimulation. Furthermore, in vivo intraperitoneal injection of BPTES alleviated cardiac fibrosis of Ang II-treated mice. In conclusion, glutaminolysis plays an important role in the process of cardiac fibrosis induced by Ang II. Targeted inhibition of glutaminolysis may be a new strategy for the treatment of myocardial fibrosis.
Rats ; Mice ; Animals ; Rats, Sprague-Dawley ; Angiotensin II/pharmacology* ; Fibroblasts ; Mice, Inbred C57BL ; Fibrosis ; Collagen/pharmacology* ; Collagen Type I/metabolism* ; RNA, Messenger/metabolism* ; Myocardium/pathology*

Objective: To explore the long-term clinical efficacy of transcatheter repair of mitral paravalvular leak (PVL) post surgical mitral valve replacement. Methods: This study is a retrospective study. Patients who completed transcatheter repair of paravalvular leak after surgical mitral valve replacement at Shanghai Chest Hospital, Shanghai Jiaotong University School of Medicine from March 2010 to December 2018 were included. Technical success was defined as the occluder being stably implanted in the paravalvular leak site without affecting the function of the mitral valve and surrounding tissues; and there were no intervention-related complications, such as new hemolysis or aggravated hemolysis, and echocardiography confirmed mitral paravalvular regurgitation reduced by more than 1 grade. Patients were followed up at 30 days, 1, and 3 years after the intervention. The main endpoints were all-cause death and re-surgery due to interventional failure or serious complications. The occurrence of occluder-mediated hemolysis and chronic renal insufficiency was recorded, and patients were monitored with echocardiography during follow up. Results: A total of 75 patients were included, aged (54.3±22.9) years old, and 38 patients were males. All patients had decreased cardiac function and/or hemolysis before intervention. Procedural success was achieved in 54 patients (72.0%). Incidence of device-mediated hemolysis was 18.7% (14/75). During the follow-up period, all-cause death occurred in 7 patients (9.3%), and 3 were cardiac deaths.The 3-year event-free survival rate was 81.3% (61/75). The need for cardiac surgery was 9.3% (7/75): 3 cases due to severe device-mediated hemolysis, 2 cases due to prosthetic valve failure and 2 cases due to moderate to severe residual regurgitation. The echocardiography follow-up results showed that the position of the occluder was stable, there was no impact on the artificial valve function and surrounding structures, and the residual regurgitation was stable without progressive increase in event-free patients. Compared with pre-intervention, the left ventricular end systolic diameter ((33.9±7.4)mm vs. (38.3±8.9) mm, P=0.036), end diastolic diameter ((53.7±8.3) mm vs. (58.4±9.1) mm, P=0.045) and left atrial diameter (59.3 (44.5, 90.7) mm vs. 64.3 (44.8, 96.6) mm, P=0.049) were significantly reduced, pulmonary artery systolic pressure was also significantly decreased ((36.5±15.8) mmHg vs. (46.3±14.9) mmHg, P=0.022, 1 mmHg=0.133 kPa). There was no significant difference between 3 years and 1 year after transcatheter repair of mitral paravalvular leak post surgical mitral valve replacement (all P>0.05). Conclusion: Transcatheter repair of mitral paravalvular leak post surgical mitral valve replacement is an effective treatment option in selective patients.
Male ; Humans ; Adult ; Middle Aged ; Aged ; Female ; Mitral Valve/surgery* ; Heart Valve Prosthesis Implantation ; Heart Valve Prosthesis ; Retrospective Studies ; Hemolysis ; China ; Mitral Valve Insufficiency/surgery* ; Treatment Outcome ; Cardiac Catheterization ; Prosthesis Failure

Management and treatment of terminal metastatic castration-resistant prostate cancer (mCRPC) remains heavily debated. We sought to investigate the efficacy of programmed cell death 1 (PD-1) inhibitor plus anlotinib as a potential solution for terminal mCRPC and further evaluate the association of genomic characteristics with efficacy outcomes. We conducted a retrospective real-world study of 25 mCRPC patients who received PD-1 inhibitor plus anlotinib after the progression to standard treatments. The clinical information was extracted from the electronic medical records and 22 patients had targeted circulating tumor DNA (ctDNA) next-generation sequencing. Statistical analysis showed that 6 (24.0%) patients experienced prostate-specific antigen (PSA) response and 11 (44.0%) patients experienced PSA reduction. The relationship between ctDNA findings and outcomes was also analyzed. DNA-damage repair (DDR) pathways and homologous recombination repair (HRR) pathway defects indicated a comparatively longer PSA-progression-free survival (PSA-PFS; 2.5 months vs 1.2 months, P = 0.027; 3.3 months vs 1.2 months, P = 0.017; respectively). This study introduces the PD-1 inhibitor plus anlotinib as a late-line therapeutic strategy for terminal mCRPC. PD-1 inhibitor plus anlotinib may be a new treatment choice for terminal mCRPC patients with DDR or HRR pathway defects and requires further investigation.
Male ; Humans ; Prostate-Specific Antigen ; Treatment Outcome ; Prostatic Neoplasms, Castration-Resistant/drug therapy* ; Immune Checkpoint Inhibitors/therapeutic use* ; Retrospective Studies

We conducted a prospective study to assess the non-inferiority of adjuvant chemotherapy alone versus adjuvant concurrent chemoradiotherapy (CCRT) as an alternative strategy for patients with early-stage (FIGO 2009 stage IB-IIA) cervical cancer having risk factors after surgery. The condition was assessed in terms of prognosis, adverse effects, and quality of life. This randomized trial involved nine centers across China. Eligible patients were randomized to receive adjuvant chemotherapy or CCRT after surgery. The primary end-point was progression-free survival (PFS). From December 2012 to December 2014, 337 patients were subjected to randomization. Final analysis included 329 patients, including 165 in the adjuvant chemotherapy group and 164 in the adjuvant CCRT group. The median follow-up was 72.1 months. The three-year PFS rates were both 91.9%, and the five-year OS was 90.6% versus 90.0% in adjuvant chemotherapy and CCRT groups, respectively. No significant differences were observed in the PFS or OS between groups. The adjusted HR for PFS was 0.854 (95% confidence interval 0.415-1.757; P = 0.667) favoring adjuvant chemotherapy, excluding the predefined non-inferiority boundary of 1.9. The chemotherapy group showed a tendency toward good quality of life. In comparison with post-operative adjuvant CCRT, adjuvant chemotherapy treatment showed non-inferior efficacy in patients with early-stage cervical cancer having pathological risk factors. Adjuvant chemotherapy alone is a favorable alternative post-operative treatment.
Female ; Humans ; Uterine Cervical Neoplasms/drug therapy* ; Prospective Studies ; Quality of Life ; Neoplasm Staging ; Chemoradiotherapy ; Chemotherapy, Adjuvant/adverse effects* ; Adjuvants, Immunologic ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Retrospective Studies

From 2015 to 2019, the annual average incidence rate of scarlet fever was 7.80/100 000 in Yantai City, which showed an increasing trend since 2017 (χ²_trend=233.59, P<0.001). The peak period of this disease was from April to July and November to January of the next year. The ratio of male to female was 1.49∶1, with a higher prevalence among cases aged 3 to 9 years (2 357/2 552, 92.36%). Children in kindergartens, primary and middle school students, and scattered children were the high risk population, with the incidence rate of 159.86/100 000, 25.57/100 000 and 26.77/100 000, respectively. The global spatial auto-correlation analysis showed that the global Moran's I index of the reported incidence rate of scarlet fever in Yantai from 2015 to 2019 was 0.28, 0.29, 0.44, 0.48, and 0.22, respectively (all P values<0.05), suggesting that the incidence rate of scarlet fever in Yantai from 2015 to 2019 was spatial clustering. The local spatial auto-correlation analysis showed that the "high-high" clustering areas were mainly located in Laizhou City, Zhifu District, Haiyang City, Fushan District and Kaifa District, while the "low-high" clustering areas were mainly located in Haiyang City and Fushan District.
Child ; Humans ; Male ; Female ; Scarlet Fever/epidemiology* ; Spatial Analysis ; Cities/epidemiology* ; Seasons ; Risk Factors ; Incidence ; Cluster Analysis ; China/epidemiology*

The purpose of this study was to investigate the epidemiological characteristics and risk factors of influenza in Hainan province,to provide evidence to support influenza prevention and control efforts.Pathogen monitoring data of influenza-like illness(ILI)in six national sentinel hospitals in Hainan province from 2013 to 2021 were analyzed in SPSS 20.0 software.A total of 50 415 ILI cases were detected during the 2013-2021 season,of which 5 581 were positive for influenza viruses,with a positivity rate of 11.07％.The dominant strains were type B,type A(H1N1)pdm09 and type A(H3N2).The positivi-ty rate of influenza virus was highest in people 5-14 years of age(17.56％)and lowest in people 0-4 years of age(7.32％).Influenza activity showed both a summer peak and a winter-spring peak in the 2014-2016,2017-2018 and 2019-2020 sea-sons,and was concentrated in April to September,with a maximum peak of 53.64％,and in November to March of the next year,with a peak of 47.30％.The 2013-2014,2016-2017 and 2018-2019 seasons showed only a winter-spring peak concen-trated between October and March of the next year,with a maximum peak of 54.17％,but no obvious summer peak.The pre-dominant influenza viruses during the eight surveillance seasons varied among H1N1,H3N2 and type B.The positive detection rate of influenza virus steeply declined during the 2020-2021 season:the positive detection rate was only 0.25％,and no obvi-ous epidemic period was observed.The intensity of influenza epidemic varied among monitoring years,and the dominant strains changed rapidly in Hainan Province.People 5-14 years of age were the key population affected.Summer,winter and spring were the key periods for influenza prevention and control.Etiological surveillance of influenza should continue to be strength-ened,the roles of health education and publicity should be emphasized,and the dual measures of influenza vaccination and non-drug intervention should be actively promoted to decrease the occurrence of influenza.