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 frequencies and subset distribution of peripheral helper(Tph)T cells in patients with immune thrombocytopenia(ITP),and explore the pathogenesis of ITP.Methods:A total of 25 newly diagnosed ITP patients treated in The Second Affiliated Hospital of Dalian Medical University from January to December 2022 were selected,and 25 healthy volunteers(age-and sex-matched)were recruited as the control group.Flow cytometry was used to detect the subsets of CD4+T cells and Tph cells.Results:The frequency of effector memory(CCR7-CD45RO+CD4+)T cells in ITP patients was significantly higher than that in healthy controls(P＜0.05).The frequency of Tph cells in ITP patients was also significantly higher than that in healthy controls(P＜0.001),and most of the Tph cells in ITP patients were effector memory T cells.Furthermore,the expressions of T-cell costimulatory molecules in Tph cells,including ICOS and CD84,were similar to those in follicular helper T(Tfh)cells.CXCR3-CCR6-Tph(Tph2)subgroup was dominant in Tph cells,but the frequency of CXCR3+CCR6-Tph(Tph1)cells in ITP patients was much higher than that in healthy controls(P＜0.05).Conclusion:Tph cells,especially Tph1 cells,were abnormally expanded in ITP patients,which may be a potential etiology of ITP.

Objective:To explore the strategy of prostate biopsy in patients with prostate specific antigen(PSA)gray zone based on prostate imaging reporting and data system (PI-RADS).Methods:The clinical data of 427 patients who underwent transperineal prostate biopsy in the First Affiliated Hospital of Nanjing Medical University from January 2020 to December 2022 were retrospectively analyzed. The median age was 66 (61, 72) years old. The median PSA was 6.62 (5.46, 8.19) ng/ml. The median PSA density (PSAD) was 0.15 (0.11, 0.21) ng/ml 2. The median prostate volume (PV) was 43.68 (31.12, 56.82) ml. PSA velocity (PSAV) data were available in 65 patients with negative MRI examination(PI-RADS <3), and the median PSAV was 1.40 (0.69, 2.89) ng/(ml· year). Among the patients with positive MRI(PI-RADS≥3), there were 174 patients with only 1 lesion and 83 patients with ≥2 lesions. A total of 170 patients with negative MRI underwent systematic biopsy, and 257 patients with positive MRI underwent systematic combined targeted biopsy. The PI-RADS score, regions of interest(ROI), PSAD, f/tPSA and PSAV were analyzed to explore the biopsy strategy for patients with PSA gray area based on bpMRI imaging. Results:Of the 427 patients included in the study, 194 were positive and 233 were negative. Among the patients with positive biopsy pathology, 140 cases were clinically significant prostate cancer (CsPCa). Among the MRI-negative patients, there were 33 cases with PSAV ≥1.4 ng/(ml·year), and 10 cases of prostate cancer and 6 cases of CsPCa were detected by systematic biopsy.In 32 cases with PSAV <1.4 ng/(ml·year), 3 cases of prostate cancer and 0 case of CsPCa were detected by systematic biopsy. The sensitivity of systematic biopsy for the diagnosis of prostate cancer and CsPCa in patients with PSAV≥1.4 ng/(ml·year) were 76.9% (10/13) and 100.0% (6/6) respectively, the specificity were 55.8% (29/52) and 54.2% (32/59) respectively, the negative predictive value were 90.6% (29/32) and 100.0% (32/32) respectively, and the positive predictive value were 30.3% (10/33) and 18.2% (6/33) respectively. In MRI-positive patients with PI-RADS 3, the prostate cancer detection rates of targeted biopsy combined with systematic biopsy, systematic biopsy and targeted biopsy were 41.7% (45/108), 32.4% (35/108) and 35.2% (38/108), respectively ( P=0.349). The detection rates of CsPCa were 27.8% (30/108), 21.3% (23/108) and 25.0% (27/108), respectively ( P=0.541). In patients with PI-RADS 4-5 and PSAD > 0.15 ng/ml 2, the detection rates of CsPCa in targeted biopsy combined with systematic biopsy, systematic biopsy and targeted biopsy were 67.8% (61/90), 58.9% (53/90) and 67.8% (61/90), respectively ( P=0.354). Conclusions:For MRI-negative patients, all CsPCa could be detected by perineal systematic biopsy when PSAV ≥1.4 ng/(ml·year), and active observation could be performed when PSAV <1.4 ng/(ml·year). For MRI-positive patients, targeted combined systemic biopsy was required when PI-RADS score was 3, and targeted biopsy only could be performed when PI-RADS score ≥4 and PSAD >0.15 ng/ml 2, otherwise targeted combined systemic biopsy was required.

Objective:To evaluate the effect of activation of splenic plasmacytoid dendritic cells (pDCs) on myocardial ischemia-reperfusion (I/R) injury in mice.Methods:The experiment was performed in two parts. Animal experiment Thirty-six SPF healthy male C57BL/6J mice, aged 10 weeks, weighing 22-27 g, were assigned to 3 groups ( n=12 each) using a random number table method: sham operation group (Sham group), myocardial ischemia group (MI group) and myocardial I/R group (MI/R group). The myocardial ischemia was induced by occluding the left anterior descending coronary artery for 40 min in MI group, while the model of myocardial I/R was established by occlusion of the left anterior descending coronary artery for 40 min followed by 1-h reperfusion in MI/R group. Following successful preparation of the model, 3 animals from each group were randomly selected, and their hearts were removed for determination of myocardial infarct size through a combination of TTC and methylene blue double staining. Another 3 animals from each group were randomly selected, and their hearts were removed for examination of pathological changes of myocardial tissues using HE staining. Blood samples were collected from the abdominal aorta of 6 mice left in each group for determination of plasma interferon alpha (IFN-α) concentrations by enzyme-linked immunosorbent assay. Then the animals were sacrificed and hearts were harvested for collection of cardiac perfusate (CP). Cell experiment Twelve SPF healthy male C57BL/6J mice, aged 10 weeks, weighing 22-27 g, were selected and the splenic pDCs were isolated using anti-mPDCA-1 MicroBeads according to the manufacturer′s instructions (with a positivity rate of >85% for the isolated cells). The cells were divided into 4 groups: group pDCs stimulated by CP in Sham group (pDCs+ CP-Sham group), group pDCs stimulated by CP in MI group (pDCs+ CP-MI group), group pDCs stimulated by CP in MI/R group (pDCs+ CP-MI/R group) and pDCs stimulated by PBS group (pDCs+ PBS group). The CP in Sham, MI and MI/R groups and PBS were used to induce and culture pDCs for 8 h. Flow cytometry was employed to detect the expression of CD45 and co-stimulatory molecules CD80, CD86 and Major Histocompatibility Complex Ⅱ (MHC Ⅱ) on the surface of pDCs. The levels of IFN-α in the cell culture supernatant were determined using enzyme-linked immunosorbent assay. Results:Animal experiments Compared with Sham group and MI group, the percentage of myocardial infarct size was significantly increased, the concentrations of plasma IFN-α were increased ( P<0.05), and cardiomyocytes displayed evident vacuolar degeneration, severe myocardial fiber rupture, and infiltration of a substantial number of inflammatory cells in MI/R group. There was no significant difference in each parameter between Sham group and MI group ( P>0.05). Cell experiment Compared with pDCs+ CP-Sham group, the expression of CD80, CD86 and MHCⅡ was significantly up-regulated in pDCs+ CP-MI group ( P<0.05), and no significant change was found in the aforementioned parameters in pDCs+ CP-MI/R group ( P>0.05). The expression of aforementioned parameters was significantly up-regulated in pDCs+ CP-MI group as compared with pDCs+ CP-MI/R group ( P<0.05). Compared with pDCs+ CP-Sham group and pDCs+ CP-MI/R group, the concentrations of IFN-α in the cell culture supernatant were significantly increased in pDCs+ CP-MI group ( P<0.05). There was no statistically significant difference in the concentrations of IFN-α between pDCs+ CP-MI/R group and pDCs+ CP-Sham group ( P>0.05). Conclusions:The mechanism underlying myocardial I/R injury may be related to activation of splenic pDCs leading to the production of IFN-α following myocardial ischemia in mice.

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with unclear etiology and limited treatment options. The median survival time for IPF patients is approximately 2-3 years and there is no effective intervention to treat IPF other than lung transplantation. As important components of lung tissue, endothelial cells (ECs) are associated with pulmonary diseases. However, the role of endothelial dysfunction in pulmonary fibrosis (PF) is incompletely understood. Sphingosine-1-phosphate receptor 1 (S1PR1) is a G protein-coupled receptor highly expressed in lung ECs. Its expression is markedly reduced in patients with IPF. Herein, we generated an endothelial-conditional S1pr1 knockout mouse model which exhibited inflammation and fibrosis with or without bleomycin (BLM) challenge. Selective activation of S1PR1 with an S1PR1 agonist, IMMH002, exerted a potent therapeutic effect in mice with bleomycin-induced fibrosis by protecting the integrity of the endothelial barrier. These results suggest that S1PR1 might be a promising drug target for IPF therapy.

As one of the main diseases leading to end-stage renal disease, steroid-resistant nephrotic syndrome(SRNS) can cause serious complications such as infection. Without effective control, this disease can further lead to the malignant development of the renal function, bringing serious social and economic burdens. As previously reported, the formation of SRNS is mostly related to the podocyte injury in the body, i.e., the injury of glomerular visceral epithelial cells. Phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt) signaling pathway, nuclear transcription factor-κB(NF-κB) signaling pathway, mammalian target of rapamycin(mTOR)/adenosine monophosphate(AMP)-activated protein kinase(AMPK), transforming growth factor(TGF)-β1/Smads, and other signaling pathways are classical signaling pathways related to podocyte injury. By regulating the expression of signaling pathways, podocyte injury can be intervened to improve the adhesion between podocyte foot processes and glomerular basement membrane and promote the function of podocytes, thereby alleviating the clinical symptoms of SRNS. Through the literature review, traditional Chinese medicine(TCM) has unique advantages and an important role in intervening in podocyte injury. In the intervention in podocyte injury, TCM, by virtue of multi-target and multi-pathway role, can regulate and intervene in podocyte injury in many ways, alleviate the clinical symptoms of SRNS, and interfere with the progress of SRNS, reflecting the unique advantages of TCM. On the other hand, TCM can directly or indirectly inhibit podocyte injury by regulating the above signaling pathways, which can not only promote the effect of hormones and immunosuppressants and shorten the course of treatment, but also reduce the toxic and side effects caused by various hormones and immunosuppressants to exert the advantages of small side effects and low price of TCM. This article reviewed TCM in the treatment of SRNS by interfering with podocyte injury-related signaling pathways and is expected to provide a reference for the in-depth study of TCM in the treatment of SRNS, as well as a theoretical basis and a new direction for the clinical application of TCM to shorten the course of treatment of SRNS and delay the progression to end-stage renal disease.
Humans ; Podocytes ; Nephrotic Syndrome/genetics* ; Medicine, Chinese Traditional ; Phosphatidylinositol 3-Kinases/genetics* ; Signal Transduction ; NF-kappa B ; AMP-Activated Protein Kinases ; Hormones

Background::Accurate prediction of ischemic stroke is required for deciding anticoagulation use in patients with atrial fibrillation (AF). Even though only 6% to 8% of AF patients die from stroke, about 90% are indicated for anticoagulants according to the current AF management guidelines. Therefore, we aimed to develop an accurate and easy-to-use new risk model for 1-year thromboembolic events (TEs) in Chinese AF patients.Methods::From the prospective China Atrial Fibrillation Registry cohort study, we identified 6601 AF patients who were not treated with anticoagulation or ablation at baseline. We selected the most important variables by the extreme gradient boosting (XGBoost) algorithm and developed a simplified risk model for predicting 1-year TEs. The novel risk score was internally validated using bootstrapping with 1000 replicates and compared with the CHA 2DS 2-VA score (excluding female sex from the CHA 2DS 2-VASc score). Results::Up to the follow-up of 1 year, 163 TEs (ischemic stroke or systemic embolism) occurred. Using the XGBoost algorithm, we selected the three most important variables (congestive heart failure or left ventricular dysfunction, age, and prior stroke, abbreviated as CAS model) to predict 1-year TE risk. We trained a multivariate Cox regression model and assigned point scores proportional to model coefficients. The CAS scheme classified 30.8% (2033/6601) of the patients as low risk for TE (CAS score = 0), with a corresponding 1-year TE risk of 0.81% (95% confidence interval [CI]: 0.41%-1.19%). In our cohort, the C-statistic of CAS model was 0.69 (95% CI: 0.65-0.73), higher than that of CHA 2DS 2-VA score (0.66, 95% CI: 0.62-0.70, Z = 2.01, P = 0.045). The overall net reclassification improvement from CHA 2DS 2-VA categories (low = 0/high ≥1) to CAS categories (low = 0/high ≥1) was 12.2% (95% CI: 8.7%-15.7%). Conclusion::In Chinese AF patients, a novel and simple CAS risk model better predicted 1-year TEs than the widely-used CHA 2DS 2- VA risk score and identified a large proportion of patients with low risk of TEs, which could potentially improve anticoagulation decision-making. Trial Registration::www.chictr.org.cn (Unique identifier No. ChiCTR-OCH-13003729).

OBJECTIVE: To investigate the effects of exosomes from human umbilical cord mesenchymal stem cells on the development of Treg and TH17 cells. METHODS: Exosomes from the serum-free-culture supernatants of hUC-MSC were harvested by ultracentrifugation. The electron microscopy, nanoparticle tracking analysis and western blot were used to identify the hUC-MSC-exosomes, such as the morphology, the paticle chameter, and the protein content. The PBMC stimulated with anti-CD3/CD28 were incubated with the exosomes for five days, and then the percentage changes of Treg and TH17 cells were analyzed by using flow cytometry. RESULTS: The hUC MSC-derived exosomes were saucer-like in morphology the averge diameter was approximately 142 nm. They were identified as positive for CD9 and CD63. Flow cytometry showed that the proportion of CD4CD25Foxp3 Treg cells in the PBMC were significantly higher, but the proportion of CD4IL17A T cells in the hUC-MSC-exosome group was obviously lower than that in the group without the hUC-MSC-exosom (control group) (P<0.05). CONCLUSION The hUC-MSC-exosomes have an immunomodulatory effect on T cells in vitro by increasing the ratio of Treg and reducing the ratio of TH17 cells, expecting the hUC-MSC-exosom as a novel cell-free target for immunotherapy.
Exosomes ; Humans ; Leukocytes, Mononuclear ; Mesenchymal Stem Cells ; T-Lymphocytes, Regulatory ; Th17 Cells ; Umbilical Cord

Objective: To investigate the effects of artesunate treatment on chronic graft-versus-host disease (cGVHD). Methods: Recipient BALB/c mice received 8 × 10(6) bone marrow cells with 8×10(6) spleen cells from B10D2 mice. Artesunate solubilized in acetone was injected intraperitoneally every day at the dose of 1 mg/kg at Day 28 after BMT. The clinical scores, survival and histopathological damage were analyzed. The frequency of Th17 and Tregs in PB and spleens from the mice were evaluated by flow cytometry. In addition, CD4(+) T cells from the spleens of mice were cultured in vitro, then stimulated with artesunate, the frequency of Th17 and Tregs in these splenocytes were evaluated by flow cytometry. Results: Artesunate administration diminished clinical and histopathological damage, and improved the survival of cGVHD mice[(46.57±7.83)% vs (55.71±6.99)%, χ(2)=5.457, P=0.020]; Artesunate contributed to Tregs development [(4.45±0.04)% vs (8.40±0.23)%, t=15.679, P<0.001; (6.62±0.24)% vs (10.48±0.48)%, t=6.587, P=0.003] while decreased Th17 cells [(1.51±0.18)% vs (0.58±0.19)%, t=7.233, P<0.001; (1.48±0.38)% vs (0.71±0.18)%, t=3.653, P=0.011] expressions in both PB and spleens, and decreased the Th17/Treg ratio (0.34±0.05 vs 0.09±0.03, t=7.621, P=0.002; 0.19±0.03 vs 0.06±0.02, t=6.993, P=0.002). Moreover, artesunate suppressed the Th17 cells expressions [(0.82±0.37) % vs (3.39±1.22) %, t=4.044, P=0.007] and contributed to Tregs development [(34.63±1.29) % vs (14.28±1.69) %, t=19.119, P<0.001], and also decreased the Th17/Treg ratio (0.24±0.09 vs 0.02±0.01, t=4.780, P=0.003) in vitro. Conclusions: Artesunate suppressed the Th17 cells expressions and contributed to Tregs development, which provided new sights into the development of a novel drug for cGVHD, e.g., artemisinin.
Animals ; Artesunate ; Graft vs Host Disease ; Mice ; Mice, Inbred BALB C ; T-Lymphocytes, Regulatory ; Th17 Cells

Objective To assess the dietary risk of organophosphates pesticides residues in some vegetables in Shaanxi Province. Methods The monitoring data of organophosphorus pesticides in vegetables from 2012 to 2016 were derived from Shaanxi Province Food Contamination Monitoring Network. The exposure of organophosphorus to vegetables by using exposure risk index (ERI) , dietary exposure risk index (RI) and dietary exposure risk assessment. Results Exposed risk index (ERI) of organophosphorus in some vegetables in Shaanxi Province ranged from 1.25E-06 to 1.87E-01, and among them, the highest ERI of clozaptid in garlic was 1.87E-01, followed by onion. In some vegetables, the highest exposure to organophosphorus was isocarbophos of fresh beans with an exposure of 4.27E-02 μg / (kg body weight · day) and the lowest dietary exposure was bulbs, and stems and fresh beans were 2.00E-04μg / (kg body weight·day) . The exposure of organophosphorus to all kinds of vegetables was less than their respective daily allowable intake (ADI) . The risk of dietary exposure to organic- phosphorus in vegetables was 187％ and greater than 100％ for the risk index (RI) of lettuce, and RI for all other vegetables was <100％. Conclusion The dietary exposure and risk index of organophosphates pesticides in some vegetables in Shaanxi Province was safe, and more attention should be paid to dimethoate and isazofos.