Objective:To observe and verify the changes of transcriptome in hyperoxia-induced acute lung injury (HALI), and to further clarify the changes of pathways in HALI.Methods:Twelve healthy male C57BL/6J mice were randomly divided into normoxia group and HALI group according to the random number table, with 6 mice in each group. The mice in the normoxia group were fed normally in the room, and the mice in the HALI group was exposed to 95% oxygen to reproduce the HALI animal model. After 72 hours of hyperoxia exposure, the lung tissues were taken for transcriptome sequencing, and then Kyoto Encyclopedia of Genes and Genomes database (KEGG) pathway enrichment analysis was performed. The pathological changes of lung tissue were observed under light microscope after hematoxylin-eosin (HE) staining. Real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting were used to verify the key molecules in the signal pathways closely related to HALI identified by transcriptomics analysis.Results:Transcriptomic analysis showed that hyperoxia induced 537 differentially expressed genes in lung tissue of mice as compared with the normoxia group including 239 up-regulated genes and 298 down-regulated genes. Further KEGG pathway enrichment analysis identified 20 most significantly enriched pathway entries, and the top three pathways were ferroptosis signaling pathway, p53 signaling pathway and glutathione (GSH) metabolism signaling pathway. The related genes in the ferroptosis signaling pathway included the up-regulated gene heme oxygenase-1 (HO-1) and the down-regulated gene solute carrier family 7 member 11 (SLC7A11). The related genes in the p53 signaling pathway included the up-regulated gene tumor suppressor gene p53 and the down-regulated gene murine double minute 2 (MDM2). The related gene in the GSH metabolic signaling pathway was up-regulated gene glutaredoxin 1 (Grx1). The light microscope showed that the pulmonary alveolar structure of the normoxia group was normal. In the HALI group, the pulmonary alveolar septum widened and thickened, and the alveolar cavity shrank or disappeared. RT-RCR and Western blotting confirmed that compared with the normoxia group, the mRNA and protein expressions of HO-1 and p53 in lung tissue of the HALI group were significantly increased [HO-1 mRNA (2 -ΔΔCt): 2.16±0.17 vs. 1.00±0.00, HO-1 protein (HO-1/β-actin): 1.05±0.01 vs. 0.79±0.01, p53 mRNA (2 -ΔΔCt): 2.52±0.13 vs. 1.00±0.00, p53 protein (p53/β-actin): 1.12±0.02 vs. 0.58±0.03, all P < 0.05], and the mRNA and protein expressions of Grx1, MDM2, SLC7A11 were significantly decreased [Grx1 mRNA (2 -ΔΔCt): 0.53±0.05 vs. 1.00±0.00, Grx1 protein (Grx1/β-actin): 0.54±0.03 vs. 0.93±0.01, MDM2 mRNA (2 -ΔΔCt): 0.48±0.03 vs. 1.00±0.00, MDM2 protein (MDM2/β-actin): 0.57±0.02 vs. 1.05±0.01, SLC7A11 mRNA (2 -ΔΔCt): 0.50±0.06 vs. 1.00±0.00, SLC7A11 protein (SLC7A11/β-actin): 0.72±0.03 vs. 0.98±0.01, all P < 0.05]. Conclusions:HALI is closely related to ferroptosis, p53 and GSH metabolism signaling pathways. Targeting the key targets in ferroptosis, p53 and GSH metabolism signaling pathways may be an important strategy for the prevention and treatment of HALI.

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.

Purpose::Vibrio vulnificus ( V. Vulnificus) infection is characterized by rapid onset, aggressive progression, and challenging treatment. Bacterial resistance poses a significant challenge for clinical anti-infection treatment and is thus the subject of research. Enhancing host infection tolerance represents a novel infection prevention strategy to improve patient survival. Our team initially identified cytochrome P4501A1 (CYP1A1) as an important target owing to its negative modulation of the body's infection tolerance. This study explored the superior effects of the CYP1A1 inhibitor bergamottin compared to antibiotic combination therapy on the survival of mice infected with multidrug-resistant V. Vulnificus and the protection of their vital organs. Methods::An increasing concentration gradient method was used to induce multidrug-resistant V. Vulnificus development. We established a lethal infection model in C57BL/6J male mice and evaluated the effect of bergamottin on mouse survival. A mild infection model was established in C57BL/6J male mice, and the serum levels of creatinine, urea nitrogen, aspartate aminotransferase, and alanine aminotransferase were determined using enzyme-linked immunosorbent assay to evaluate the effect of bergamottin on liver and kidney function. The morphological changes induced in the presence of bergamottin in mouse organs were evaluated by hematoxylin and eosin staining of liver and kidney tissues. The bacterial growth curve and organ load determination were used to evaluate whether bergamottin has a direct antibacterial effect on multidrug-resistant V. Vulnificus. Quantification of inflammatory factors in serum by enzyme-linked immunosorbent assay and the expression levels of inflammatory factors in liver and kidney tissues by real-time quantitative polymerase chain reaction were performed to evaluate the effect of bergamottin on inflammatory factor levels. Western blot analysis of IκBα, phosphorylated IκBα, p65, and phosphorylated p65 protein expression in liver and kidney tissues and in human hepatocellular carcinomas-2 and human kidney-2 cell lines was used to evaluate the effect of bergamottin on the nuclear factor kappa-B signaling pathway. One-way ANOVA and Kaplan-Meier analysis were used for statistical analysis. Results::In mice infected with multidrug-resistant V. Vulnificus, bergamottin prolonged survival ( p = 0.014), reduced the serum creatinine ( p = 0.002), urea nitrogen ( p = 0.030), aspartate aminotransferase ( p = 0.029), and alanine aminotransferase ( p = 0.003) levels, and protected the cellular morphology of liver and kidney tissues. Bergamottin inhibited interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α expression in serum (IL-1β: p = 0.010, IL-6: p = 0.029, TNF-α: p = 0.025) and inhibited the protein expression of the inflammatory factors IL-1β, IL-6, TNF-α in liver (IL-1β: p = 0.010, IL-6: p = 0.011, TNF-α: p = 0.037) and kidney (IL-1β: p = 0.016, IL-6: p = 0.011, TNF-α: p = 0.008) tissues. Bergamottin did not affect the proliferation of multidrug-resistant V. Vulnificus or the bacterial load in the mouse peritoneal lavage fluid ( p = 0.225), liver ( p = 0.186), or kidney ( p = 0.637). Conclusion::Bergamottin enhances the tolerance of mice to multidrug-resistant V. Vulnificus infection. This study can serve as a reference and guide the development of novel clinical treatment strategies for V. Vulnificus.

Here,5 important pathogens carried by ticks in Maanshan City,Anhui Province,China were identified.In to-tal,642 ticks were collected from 13 villages around Maanshan City and identified by morphological and mitochondrial COI genes.The 16S rRNA gene of Francisella tularensis,ssrA gene of Bartonella,16S rRNA,ompA and ompB genes of Rickett-sia,16S rRNA and gltA genes of Anaplasma,and groEL and rpoB genes of Coxiella were sequenced.Reference sequences were retrieved from a public database.Phylogenetic trees were constructed with MEG A1 1.0 software.In total,36 Rickettsiae isolates were detected in 640 Haemaphysalis longicornis ticks,which included 20 isolates of Rickettsia heilongjian-gensis,16 of Candidatus Rickettsia jingxinensis,2 of Ana-plasma bovis,and 186 of Coxiella-like endosymbiont.R.hei-longjiangensis HY2 detected in this study and Anhui B8 strain,Ca.R.jingxinensis QL3 and those from Shanxi Prov-ince and Jiangsu Province,A.bovis JX4 and those from Shanxi Province were clustered on the same branch.Overall,17 ticks had combined infections and none of the 5 bacteria were detected in two Amblyomma testudinarium ticks.This is the first report of Ca.R.jingxinensis detected in H.longicornis ticks from Anhui Province.It is recommended that the two types of Rickettsia that cause spotted fever and A.bovis should be reported to local health authorities to initiate appropriate prevention and control measures.

Objective:To explore the clinical efficacy and safety of flumatinib mesylate produced in China in patients with newly diagnosed chronic myeloid leukemia in chronic phase(CML-CP).Methods:32 newly diagnosed CML-CP patients admitted to the Hematology Department of the Affiliated Hospital of Southwest Medical University from March 1,2020 to March 31,2022,who had never received any tyrosine kinase inhibitor(TKI)were included in the study.The patients were treated by flumatinib mesylate 600mg once daily.The hematologic,cytogenetic and molecular responses were assessed at 3-,6-and 12-month,and adverse effects of the drug were evaluated.Results:31 patients were treated with flumatinib for≥3 months,of which 24 patients were treated for ≥ 6 months and 14 patients were treated for ≥ 12 months.At 3rd month of treatment,30 out of 31 patients achieved complete hematologic response(CHR);24 patients underwent cytogenetic testing and 22 cases achieved major cytogenetic response(MCyR),of which 21 cases achieved complete cytogenetic response(CCyR);Among 25 patients who underwent molecular testing,22 patients had BCR-ABLIS ≤ 10％,including 10 patients with BCR-ABLIS ≤ 0.1％,and 6 patients with BCR-ABLIS≤0.01％.At 6th month of treatment,23 out of 24 patients achieved CHR;17 patients underwent cytogenetic testing and all achieved CCyR;Among 23 patients who underwent molecular testing,20 patients had BCR-ABLIS ≤1％,including 16 patients with BCR-ABL1S≤0.1％and 12 patients with BCR-ABLIS ≤ 0.01％.At 12nd month of treatment,all 14 patients achieved CHR and CCyR;Among them,10 patients had BCR-ABLIS ≤ 0.1％,including 9 patients with BCR-ABLIS ≤ 0.01％.The grade Ⅲ/Ⅳ leukopenia,thrombocytopenia and anemia rates in the patients were 13.3％,20.0％and 3.3％,respectively.One patient stopped flumatinib therapy due to severe and persistent hematologic toxicity.The major non-hematologic adverse events were abnormal liver function(20％),diarrhea(10％),bone/joint pain(10％),muscle spasm(10％),rash(6.7％),acute kidney injury(6.7％)and nausea(3.3％),most of which were grade Ⅰ-Ⅱ.No patient experienced grade Ⅳnon-hematologic adverse events.No drug toxicity-related death occurred.Conclusion:Flumatinib mesglate,as the first-line treatment for newly diagnosed CML-CP,can enable the patients to achieve early and deep molecular and cytogenetic responses,and shows good safety.

AIM To establish an LC-MS/MS method for the simultaneous content determination of forsythin,forsythoside A,chlorogenic acid,neochlorogenic acid,amygdalin,emodin,rhein and salidroside in Lianhua Qingwen Capsules.METHODS The analysis was performed on a 35℃thermostatic ACQUITY UPlC-HSS T3 column(100 mm×2.1 mm,1.8 μm),with the mobile phase comprising of 0.1%formic acid-acetonitrile flowing at 0.3 mL/min in a gradient elution manner,and electron spray ionization source was adopted in negative ion scanning with multiple reaction monitoring mode.RESULTS Eight constituents showed good linear relationships within their own ranges(r≥0.999 5),whose average recoveries were 99.20%-100.96%with the RSDs of 0.62%-1.23%.CONCLUSION This simple,sensitive and reliable method can be used for the quality control of Lianhua Qingwen capsules.

OBJECTIVE: To investigate the difference in sensitivity between X-ray and three-dimensional reconstruction of computed tomography (3D-CT) for the diagnosis of distal fibular avulsion fracture, and the radiographic presentation of the ossicle. METHODS: From January to October 2018, 92 patients with distal fibular avulsion fracture were visited for surgical treatment in Department of Sports Medicine, Peking University Third Hospital, and 60 cases were finally enrolled according to the inclusion and exclusion criteria. Intraoperative detection was regarded as the gold standard, and the diagnostic sensitivity of preoperative ankle X-ray and 3D-CT for the distal fibular avulsion fractures was statistically determined. The ossicle maximum diameter as well as the degree of its displacement were also measured. On 3D-CT, the distance from the ossicle center point to the anterior fibular tuberosity (a), the distance to the fibular tip (b), and the a/b value was used to present the ossicle displacement. RESULTS: Among the 60 patients, 36 and the 52 patients were correctly detected by X-ray and 3D-CT, respectively, and the sensitivities was 60.0% and 86.7%, respectively (P=0.004). The mean diameter of the ossicle on X-ray and 3D-CT was (9.2±3.9) mm and (10.5±3.2) mm, respectively. The mean distance from the ossicle center to the anterior fibular tuberosity (a) was (17.5±3.6) mm and the mean distance to the fibular tip (b) was (17.4±4.8) mm, with mean a/b values of 1.1±0.7. The intraclass correlation coefficients (ICC) for each measurement ranged from 0.891-0.998 with a high degree of consistency. CONCLUSION Compared with X-ray, 3D-CT has higher sensitivity in diagnosing distal fibular avulsion fractures, can help clinicians evaluate ossicle's location and choose surgical methods, and is recommended to be performed in patients with suspected distal fibula avulsion fractures in clinical practice.
Humans ; Fibula/surgery* ; Fractures, Avulsion ; Ankle ; X-Rays ; Imaging, Three-Dimensional ; Ankle Fractures ; Ankle Joint ; Tomography, X-Ray Computed

OBJECTIVE: To investigate the clinical efficacy of posterior cervical pedicle screw short-segment internal fixation for the treatment of atlantoaxial fracture and dislocation. METHODS: The clinical data of 60 patients with atlantoaxial vertebral fracture and dislocation underwent surgery between January 2015 and January 2018 were retrospectively analyzed. The patients were divided into study group and control group according to different surgical methods. There were 30 patients in study group, including 13 males and 17 females, with an average age of (39.32±2.85) years old, were underwent short-segment internal fixation with posterior cervical pedicle screws. There were 30 patients in control group, including 12 males and 18 females, with an average age of (39.57±2.90) years old, were underwent posterior lamina clip internal fixation of the atlas. The operation time, intraoperative blood loss, postoperative ambulation time, hospitalization time and complications between two groups were recorded and compared. The pain visual analogue scale(VAS), Japanese Orthopedic Association(JOA) score of neurological function, and fusion status were evaluated between two groups. RESULTS: All patients were followed up for at least 12 months. The study group was better than control group in operation time, intraoperative blood loss, postoperative off-bed activity time, and hospital stay (P=0.000). One case of respiratory tract injury occurred in study group. In control group, 2 cases occurred incision infection, 3 cases occurred respiratory tract injury, and 3 cases occurred adjacent segmental joint degeneration. The incidence of complications in study group was lower than that in control group (χ²=4.705, P=0.030). At 1, 3, 7 days after operation, VAS of study group was lower than that of control group(P=0.000). At 1, 3 months after operation, JOA score of study group was higher than that of control group(P=0.000). At 12 months after operation, all the patients in the study group achieved bony fusion. In control group, there were 3 cases of poor bony fusion and 3 cases of internal fixation fracture, the incidence rate was 20.00%(6/30). The difference between two groups was statistically significant (χ²=4.629, P=0.031). CONCLUSION Posterior cervical short-segment pedicle screw fixation for atlantoaxial fracture and dislocation has the advantages of less trauma, shorter operation time, fewer complications, and less pain, and can promote the recovery of nerve function as soon as possible.
Male ; Female ; Humans ; Adult ; Pedicle Screws ; Retrospective Studies ; Fractures, Bone ; Fracture Fixation, Internal/methods* ; Joint Dislocations/surgery* ; Spinal Fractures/surgery* ; Treatment Outcome ; Postoperative Hemorrhage

OBJECTIVE: This study was aimed at investigating the carrier rate of, and molecular variation in, α- and β-globin gene mutations in Hunan Province. METHODS: We recruited 25,946 individuals attending premarital screening from 42 districts and counties in all 14 cities of Hunan Province. Hematological screening was performed, and molecular parameters were assessed. RESULTS: The overall carrier rate of thalassemia was 7.1%, including 4.83% for α-thalassemia, 2.15% for β-thalassemia, and 0.12% for both α- and β-thalassemia. The highest carrier rate of thalassemia was in Yongzhou (14.57%). The most abundant genotype of α-thalassemia and β-thalassemia was -α ^3.7/αα (50.23%) and β ^IVS-II-654/β ^N (28.23%), respectively. Four α-globin mutations [CD108 (ACC>AAC), CAP +29 (G>C), Hb Agrinio and Hb Cervantes] and six β-globin mutations [CAP +8 (C>T), IVS-II-848 (C>T), -56 (G>C), beta nt-77 (G>C), codon 20/21 (-TGGA) and Hb Knossos] had not previously been identified in China. Furthermore, this study provides the first report of the carrier rates of abnormal hemoglobin variants and α-globin triplication in Hunan Province, which were 0.49% and 1.99%, respectively. CONCLUSION Our study demonstrates the high complexity and diversity of thalassemia gene mutations in the Hunan population. The results should facilitate genetic counselling and the prevention of severe thalassemia in this region.
Humans ; beta-Thalassemia/genetics* ; alpha-Thalassemia/genetics* ; Hemoglobinopathies/genetics* ; China/epidemiology* ; High-Throughput Nucleotide Sequencing

A randomized, double-blind, placebo-controlled, multi-center phase Ⅱ clinical trial design was used in this study to recruit subjects who were in line with the syndrome of excess heat and fire toxin, and were diagnosed as recurrent oral ulcers, gingivitis, and acute pharyngitis. A total of 240 cases were included and randomly divided into a placebo group and a Huanglian Jiedu Pills group. The clinical efficacy of Huanglian Jiedu Pills in treating the syndrome of excess heat and fire toxin was evaluated by using the traditional Chinese medicine(TCM) syndrome scale. Enzyme-linked immunosorbent assay(ELISA) was used to determine and evaluate the levels of adenosine triphosphate(ATP), 4-hydroxynonenal(4-HNE), and adrenocorticotropic hormone(ACTH) in plasma of the two groups before and after administration and to predict their application value as clinical biomarkers. The results showed that the disappearance rate of main symptoms in the Huanglian Jiedu Pills group was 69.17%, and that in the placebo group was 50.83%. The comparison between the Huanglian Jiedu Pills group and the placebo group showed that 4-HNE before and after administration was statistically significant(P<0.05). The content of 4-HNE in the Huanglian Jiedu Pills group decreased significantly after administration(P<0.05), but that in the placebo group had no statistical significance and showed an upward trend. After administration, the content of ATP in both Huanglian Jiedu Pills group and placebo group decreased significantly(P<0.05), indicating that the energy metabolism disorder was significantly improved after administration of Huanglian Jiedu Pills and the body's self-healing ability also alleviated the increase in ATP level caused by the syndrome of excess heat and fire toxin to a certain extent. ACTH in both Huanglian Jiedu Pills group and placebo group decreased significantly after administration(P<0.05). It is concluded that Huanglian Jiedu Pills has a significant clinical effect, and can significantly improve the abnormal levels of ATP and 4-HNE in plasma caused by the syndrome of excess heat and fire toxin, which are speculated to be the effective clinical biomarkers for Huanglian Jiedu Pills to treat the syndrome of excess heat and fire toxin.
Humans ; Adrenocorticotropic Hormone ; Hot Temperature ; Medicine, Chinese Traditional ; Adenosine Triphosphate