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.

Background/Aims: Chronic hepatitis C (CHC) patients who failed antiviral therapy are at increased risk for hepatocellular carcinoma (HCC). This study assessed the potential role of metformin and statins, medications for diabetes mellitus (DM) and hyperlipidemia (HLP), in reducing HCC risk among these patients. Methods: We included CHC patients from the T-COACH study who failed antiviral therapy. We tracked the onset of HCC 1.5 years post-therapy by linking to Taiwan’s cancer registry data from 2003 to 2019. We accounted for death and liver transplantation as competing risks and employed Gray’s cumulative incidence and Cox subdistribution hazards models to analyze HCC development. Results: Out of 2,779 patients, 480 (17.3%) developed HCC post-therapy. DM patients not using metformin had a 51% increased risk of HCC compared to non-DM patients, while HLP patients on statins had a 50% reduced risk compared to those without HLP. The 5-year HCC incidence was significantly higher for metformin non-users (16.5%) versus non-DM patients (11.3%; adjusted sub-distribution hazard ratio [aSHR]=1.51; P=0.007) and metformin users (3.1%; aSHR=1.59; P=0.022). Statin use in HLP patients correlated with a lower HCC risk (3.8%) compared to non-HLP patients (12.5%; aSHR=0.50; P<0.001). Notably, the increased HCC risk associated with non-use of metformin was primarily seen in non-cirrhotic patients, whereas statins decreased HCC risk in both cirrhotic and non-cirrhotic patients. Conclusions Metformin and statins may have a chemopreventive effect against HCC in CHC patients who failed antiviral therapy. These results support the need for personalized preventive strategies in managing HCC risk.

Metabolic reprogramming is a hallmark of cancer, including lung cancer. However, the exact underlying mechanism and therapeutic potential are largely unknown. Here we report that protein arginine methyltransferase 6 (PRMT6) is highly expressed in lung cancer and is required for cell metabolism, tumorigenicity, and cisplatin response of lung cancer. PRMT6 regulated the oxidative pentose phosphate pathway (PPP) flux and glycolysis pathway in human lung cancer by increasing the activity of 6-phospho-gluconate dehydrogenase (6PGD) and α-enolase (ENO1). Furthermore, PRMT6 methylated R324 of 6PGD to enhancing its activity; while methylation at R9 and R372 of ENO1 promotes formation of active ENO1 dimers and 2-phosphoglycerate (2-PG) binding to ENO1, respectively. Lastly, targeting PRMT6 blocked the oxidative PPP flux, glycolysis pathway, and tumor growth, as well as enhanced the anti-tumor effects of cisplatin in lung cancer. Together, this study demonstrates that PRMT6 acts as a post-translational modification (PTM) regulator of glucose metabolism, which leads to the pathogenesis of lung cancer. It was proven that the PRMT6-6PGD/ENO1 regulatory axis is an important determinant of carcinogenesis and may become a promising cancer therapeutic strategy.

The bacterial ATP-competitive GyrB/ParE subunits of type II topoisomerase are important anti-bacterial targets to treat super drug-resistant bacterial infections. Herein we discovered novel pyrrolamide-type GyrB/ParE inhibitors based on the structural modifications of the candidate AZD5099 that was withdrawn from the clinical trials due to safety liabilities such as mitochondrial toxicity. The hydroxyisopropyl pyridazine compound 28 had a significant inhibitory effect on Gyrase (GyrB, IC₅₀ = 49 nmol/L) and a modest inhibitory effect on Topo IV (ParE, IC₅₀ = 1.513 μmol/L) of Staphylococcus aureus. It also had significant antibacterial activities on susceptible and resistant Gram-positive bacteria with a minimum inhibitory concentration (MIC) of less than 0.03 μg/mL, which showed a time-dependent bactericidal effect and low frequencies of spontaneous resistance against S. aureus. Compound 28 had better protective effects than the positive control drugs such as DS-2969 ( 5) and AZD5099 ( 6) in mouse models of sepsis induced by methicillin-resistant Staphylococcus aureus (MRSA) infection. It also showed better bactericidal activities than clinically used vancomycin in the mouse thigh MRSA infection models. Moreover, compound 28 has much lower mitochondrial toxicity than AZD5099 ( 6) as well as excellent therapeutic indexes and pharmacokinetic properties. At present, compound 28 has been evaluated as a pre-clinical drug candidate for the treatment of drug-resistant Gram-positive bacterial infection. On the other hand, compound 28 also has good inhibitory activities against stubborn Gram-negative bacteria such as Escherichia coli (MIC = 1 μg/mL), which is comparable with the most potent pyrrolamide-type GyrB/ParE inhibitors reported recently. In addition, the structure-activity relationships of the compounds were also studied.

Objective: To evaluate the clinical value of dynamic volumetric CT perfusion combined with energy spectrum imaging in bronchial arterial chemoembolization (BACE) in patients with lung cancer. Methods: The data of 31 patients with lung cancer confirmed by pathology and treated with BACE in Lishui Central Hospital from January 2018 to February 2022 were retrospectively collected, including 23 men and 8 women, aged 31-84 (67) years. All patients received perfusion scans of lesion sites within 1 week before surgery and 1 month after surgery. We collected and compared the changes in preoperative and postoperative perfusion parameters such as blood flow (BF), blood volume (BV), mean through time (MTT), permeability surface (PS) and energy spectrum parameters including arterial phase CT value (CTA), venous phase CT value (CTV), arterial phase iodine concentration (ICA), venous phase of iodine concentration (ICV), arterial standardization iodine concentration (NICA), and intravenous standardized iodine concentration (NICV) to confirm the significance of these parameters in evaluating the short-term efficacy of BACE in the treatment of advanced lung cancer. Data normality was tested using the Kolmogorov-Smirnov test and normally distributed measurement data are expressed here as mean ± standard deviation; the independent-samples t-test was used for comparisons between two groups. The measurement data that were not normally distributed are expressed as median (interquartile interval) [M (Q₁, Q₃)], and the comparison between the two groups used the Kruskal-Wallis test. Count data are expressed as cases (%), and comparisons between groups used the χ² test. Results: The objective response rate (ORR) and disease control rate (DCR) at 1 month after BACE were 54.8% (17/31) and 96.8% (30/31), respectively. CT perfusion parameters and energy spectrum parameters of patients before and after BACE treatment were compared. The results showed that BF, BV, MTT, ICA, ICV and NICV were significantly decreased after BACE treatment compared with before treatment, and the differences were statistically significant[58.06 (40.47,87.22) vs.23.57(10.92, 36.24) ml·min^-1·100g^-1,3.33(2.86,6.09) vs.2.12(1.96,3.61)ml/100g,2.70(2.19,3.88) vs.1.53 (1.12,2.25)s, 3.51 (3.11,4.14)vs.1.74 (1.26,2.50)mg/ml,2.00 (1.30,2.45) vs.1.32(0.92,1.76)mg/ml,0.51(0.42,0.57) vs.0.33(0.23,0.39)](all P<0.05). At the same time, compared with the non-remission group, the study results showed that the difference of parameters in remission group before and after BACE was more obvious, including ΔBF, ΔBV, ΔMTT, ΔPS, ΔCTA, ΔCTV, ΔICA, ΔICV, ΔNICA, ΔNICV were significantly increased, and the difference was statistically significant [36.82(32.38, 45.34) vs.9.50(-1.43, 12.34) ml·min^-1·100g^-1,4.46(2.52, 5.79) vs.0.22(-0.76, 4.09) ml/100g,4.22(2.25, 6.77) vs.0.43(-2.53, 1.88) s,10.07 (2.89, 13.13) vs.-2.01(-6.77, 4.28) ml·min^-1·100g^-1,14.22(11.88, 20.57) vs.4.18(-5.25, 6.37) HU, 34.6(14.88, 43.15) vs.11.60(0.26, 25.05) HU,0.95(0.54, 1.47) vs.0.11(0.20, 0.59) mg/ml,1.57(1.10, 2.38) vs. 0.26(-0.21, 0.63) mg/ml,0.05(0.03, 0.08) vs.-0.02(-0.04, 0.01),0.18(0.13, 0.21)vs. 0.11(-0.06, 0.16)](all P<0.05). Conclusions: CT perfusion combined with spectral imaging could effectively evaluate the changes in tumor vascular perfusion in patients with advanced lung cancer before and after BACE treatment, which has important value in judging the short-term efficacy after treatment.
Male ; Humans ; Female ; Retrospective Studies ; Tomography, X-Ray Computed/methods* ; Lung Neoplasms ; Iodine ; Perfusion

To investigate the inflammatory mechanism of nasal instillation of fine particulate matter (PM)on hippocampal tissue injury in mice. Thirty C57BL/6J mice were randomly divided into 3 groups(n=10):control group, low-dose group, high-dose group. The nasal instillation doses of PM in the low-dose group and the high-dose group were 1.5 mg/kg BW and 7.5 mg/kg BW, respectively, and the control group was given saline with an equal volume. Saline was sprayed once every other time for 12 times. The serum levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) were determined by ELISA method. HE staining and electron microscopy were used to observe the pathological changes and ultrastructure of lung tissue and hippocampus. The inflammatory cytokine levels in hippocampus were detected by antibody chip technique. There was no significant effect of PM nasal instillation on serum TNF-α, IL-1β and IL-6 levels (P＞0.05), and there was no obvious pathological changes in lung tissue structure. In hippocampus, low-dose and high-dose PM exposure could lead to disordered neuronal arrangement in the hippocampal CA3 region, and there were neurological changes around the neuron cells and ultrastructural changes such as edema around small blood vessels. Compared with the control group, the levels of inflammatory cytokines such as CX3CL1, CSF2 and TECK in the low-dose group were increased significantly (P ＜0.05), while sTNFR1 was decreased significantly (P＜0.05); the inflammatory factors CX3CL1, CSF2, and TCA-3 were significantly increased in the high-dose group (P＜0.05), while leptin, MIG, and FASLG were significantly decreased (P＜0.05). Nasal instillation of PM can induce tissue damage in the hippocampus of mice, and its mechanism of action may be the olfactory brain pathway. The increasing of TNF-α and IL-6 and the decreasing of sTNFR1 and FASLG may be involved in inflammatory mechanisms.

Background: Allogeneic stem-cell transplantation (SCT) is a well-established immunotherapeutic strategy for multiple myeloma (MM) with a potent and often sustained graft-vs.-myeloma effect. This multicenter investigation aimed to analyze the complications and survival of haploidentical SCT in patients with MM, and compare the main outcomes with matched-related donors (MRDs). Methods: Haploidentical and MRD SCT was identified from a cohort of 97 patients with MM who received a myeloablative transplantation in 13 hospitals from May 2001 to December 2017. A matched-pair analysis was designed. For each haplo recipient, the recipients were randomly selected from the MRD group and were matched according to the following criteria: year of the hematopoietic SCT (±2 years), disease status at transplantation, and the length of follow-up. Results: Seventy cases received MRD and 27 received haploidentical transplantation. The two groups showed no significant differences regarding age, gender, cytogenetic risk, and diagnostic stage. The cumulative incidences of non-relapse mortality (NRM) at 1 and 3 years based on donor type were 20.5% (95% confidence interval [CI], 10.90–30.10%) and 24.2% (95% CI, 13.81–34.59%) for the MRD group and 16.80% (95% CI, 1.71–31.89%) and 28.70% (95% CI, 8.71–48.69%) for the haplo group, respectively. Cumulative incidence of NRM did not differ significantly between the two groups (χ² = 0.031, P = 0.861). The cumulative incidences of progression-free survival (PFS) and 1 year and 3 years by type of donors were 59.8% (95% CI, 48.24–71.36%) and 45.4% (95% CI, 33.44–57.36%), and 65.6% (95% CI, 47.18–84.02%) and 26.8% (95% CI, 7.59–46. 01%) for MRD and haploidentical donor, respectively. Cumulative incidence of PFS did not differ significantly between the two groups (χ² = 0.182, P = 0.670). In multivariate analyses, no statistically significant differences were observed between haploidentical and MRD for relapse, NRM, PFS, and overall survival. There were no statistically differences on main outcomes after haploidentical and MRD. Conclusion Haploidentical SCT could be performed safely and feasibly for patients with MM in need.

Isoflavones are widely consumed by people around the world in the form of soy products, dietary supplements and drugs. Many isoflavones or related crude extracts have been reported to exert pain-relief activities, but the mechanism remains unclear. Voltage-gated sodium channels (VGSCs) play important roles in excitability of pain sensing neurons and many of them are important nociceptors. Here, we report that several isoflavones including 3'-methoxydaidzein (3MOD), genistein (GEN) and daidzein (DAI) show abilities to block VGSCs and thus to attenuate chemicals and heat induced acute pain or chronic constriction injury (CCI) induced pain hypersensitivity in mice. Especially, 3MOD shows strong analgesic potential without inducing addiction through inhibiting subtypes Na1.7, Na1.8 and Na1.3 with the IC of 181 ± 14, 397 ± 26, and 505 ± 46 nmol·L, respectively, providing a promising compound or parent structure for the treatment of pain pathologies. This study reveals a pain-alleviating mechanism of dietary isoflavones and may provide a convenient avenue to alleviate pain.
Analgesics ; administration & dosage ; chemistry ; Animals ; Humans ; Isoflavones ; administration & dosage ; chemistry ; Male ; Mice ; Mice, Inbred C57BL ; Pain ; drug therapy ; genetics ; metabolism ; Voltage-Gated Sodium Channel Blockers ; administration & dosage ; Voltage-Gated Sodium Channels ; genetics ; metabolism

Objective To compare split-cuff nipple and direct ureteroileal anastomosis during ureteroileal anastomosis.Methods Between December,2014 and March,2017,a prospective randomized study was conducted on 70 patients who underwent radical cystectomy and urinary diversion.In every patient,both ureters were randomized to be implanted using an antireflux,split-cuff nipple technique (group A) or a reflux,direct technique (group B).After pelvic lymph node dissection and radical cystectomy,a Mshape orthotopic ileal neobladder was constructed and two ureters were implanted with single-J tubes placed for 10-12 days.For split-cuff nipple technique,a 0.5 cm longitudinal incision in the ureter was made,and the ureteral wall was turned back on itself,construction a nipple.The cuff was stabilized at the corners with sutures.The ureter was then placed into the bowel with 0.5 cm nipple.The ureter was sutured to the full thickness of the bowel wall with interrupted 4-0 PDS.For direct technique,a 0.5 cm incision in the ureter was made,the full thickness of the ureter was sewn to the mucosa of the bowel.Results 70 patients were enrolled in the study,63 males and 7 females,(62.5 ± 10.4) years old.Over a median follow-up of 13.2 months,one patients had bilateral anastomosis stricture 3 months after operation,1 patient in group A had stricture 6 months after operation,2 patients in group B had stricture 6 and 12 months after operation,respectively.Six patients (8.6％) in group A found reflux compared with 21 patients (30.0％) in group B (P =0.004).The reflux pressure was (23.5 ± 9.0) cmH2O and (15.5 ± 4.9) cmH2O in group A and group B (P =0.042),respectively.The GFR of group A was (38.1 ± 7.6) ml/min compared with (38.6 ± 12.9) ml/min in group B at 12 months after operation.One patient in group A and four patients in group B had acute nephropyelitis.Four patients in group A had renal stones formation compared with 1 patients in group B.The time of anastomosis was (8.8 ± 3.5) minutes and (6.7 ± 1.5) minutes (P =0.037) for group A and group B,respectively.The patients in both groups had no urine leakage.Conclusion Compared with direct technique,split-cuff nipple technique had lower reflux rate,higher antireflux pressure and longer anastomosis time than direct technique.