Objective To investigate whether paraptosis and autophagy have an effect on acute retinal ischemia-reperfusion injury (RIRI) in an experimental rat model that recapitulates features of acute hypertensive glaucoma and to explore the possible underlying mechanisms.Methods A total of 30 adult male Sprague-Dawley rats were randomly divided into RIRI group and control group.The acute RIRI model was induced with normal saline in the right eye of rats from the RIRI group by anterior chamber perfusion,while the rats in the control group left untreated.On day 1,day 3,day 7,day 28 after RIRI model establishment,the changes in morphology of retinal ganglion cells (RGCs) were observed by transmission electron microscopy (TEM),and the expression of microtubule-associated protein 1 light chain 3 (LC3) was measured by immumofluorescence methods.Results When compared with the control group,the number of cytoplasmic vacuoles predominantly derived from the progressive swelling of mitochondria and/or endoplasmic reticulum (ER) in RGCs were increased in the RIRI group from day 1 to day 28 by TEM.And ultra-structural analyses showed the double-or multiple-membrane autophagosomes were markedly accumulated in the cytoplasm of RGCs following acute RIRI.The average number of autophagic vacuoles in the cytoplasm of RGCs was 0.79 per 50 μm2 in the control group,and the average number of autophagosomes reached to a maximum on day 7 after acute RIRI at 2.29 per 50 μm2,which was statistically significant compared with the control group (P ＜ 0.05).Compared to the control group,LC3 expression in the cytoplasm of RGCs was up-regulated on day 1 after acute RIRI,which sustained throughout the experimental period.The percentage of LC3 positive cells in the retinal ganglion cell layer was 15.90％ in the control group,and the data was 46.95％ and 52.30％ on day 1 and day 28 after RIRI,respectively,both which were statistically significant compared with the normal control group (both P ＜ 0.05).Conclusion Both paraptosis and autophagy participate in death of RGCs after acute RIRI.Programmed cell death in different cells,either coexistence of multiple-cell death form or a single-cell death form,participates in the pathogenesis of acute RIRI.

Objective To evaluate the clinical efficacy and safety of Kanglaite injection combined with emcitabine injection and tegafur-gimeracil-oteracil potassium capsule in the treatment of advanced pancreatic cancer(PC).Methods A total of 45 patients with advanced pancreatic cancer were randomly divided into treatment group (n =23) and control group (n =22).The control group was given gemcitabine (1000 mg · m2,iv gtt,at day 1 and day 8) and tegafur-gimeracil-oteracil potassium capsule (1.25 m2 ≤ body surface area ＜ 1.5 m2,40 mg,bid;body surface area≥ 1.5 m2,50 mg,bid,day 1-day 14).The treatment group was treated with Kanglaite (20 g,qd,day 1-day 14) on the basis of control group.Both groups were treated for more than 4 cycles.The clinical benefit rate (CBR),overall survival (OS) and the adverse drug reactions (ADRs) were evaluated between the two groups.Results The CBR of treatment group and control group were 78.26％ (18 cases/23 cases) and 50.00％ (11 cases/22 cases) respectively,with significant difference (P ＜ 0.05).The median OS of treatment group and control group were 6.67 months and 5.60 months,respectively,with significant difference (P ＜ 0.05).The ADRs in the treatment group and control group were bone marrow depression,fatigue,gastrointestinal reaction,abnormal liver and kidney function and skin reaction,and there was no significant difference in the incidence of ADRs reactions between the two groups (P ＞ 0.05).Conclusion Kanglaite combined gemcitabine and tegafur-gimeracil-oteracil potassium is effective and safe in the treatment of advanced pancreatic cancer,with a longer OS,a higher incidence of clinical benefit and less ADRs.

OBJECTIVETo study the anti-inflammatory and analgesic actions of Aike Mixture (AKM).

METHODSA total of 100 male mice were randomly assigned into 5 groups: a normal control group, a drug control group (a hydrocortisone subgroup and an atropine subgroup), a high-dose AKM group, a mid-dose AKM group and a low-dose AKM group. Xylene was spread on the left ear of the experimental mice to induce inflammation, and 1% acetic acid solution injected into the abdominal cavity to produce pain so as to cause the body bend. Different doses of AKM were given and their actions observed.

RESULTSAKM had obvious anti-inflammatory effect on the xylene-induced ear tumefaction and inhibited the pain-caused body bend in the AKM groups, with significant difference from the normal control (P < 0.01).

CONCLUSIONAKM has good anti-inflammatory and analgesic effects, which is of clinical significance in the treatment of chronic prostatitis.

Animals ; Chronic Disease ; Disease Models, Animal ; Drug Combinations ; Male ; Mice ; Mice, Inbred ICR ; Oleanolic Acid ; analogs & derivatives ; pharmacology ; therapeutic use ; Phytotherapy ; Prostatitis ; drug therapy ; Saponins ; pharmacology ; therapeutic use

Objective To establish a dynamic prediction model of fatal massive hemorrhage in trauma based on the vital signs time series data and machine learning algorithms.Methods Retrospectively analyze the vital signs time series data of 7522 patients with trauma in the Medical Information Mart for Intensive Care-Ⅳ(MIMIC-Ⅳ)database from 2008 to 2019.According to the occurrence of posttraumatic fatal massive hemorrhage,the patients were divided into two groups:fatal massive hemorrhage group(n=283)and non-fatal massive hemorrhage group(n=7239).Six machine learning algorithms,including logistic regression(LR),support vector machine(SVM),random forests(RF),adaptive boosting(AdaBoost),gated recurrent unit(GRU),and GRU-D were used to develop a dynamic prediction models of fatal massive hemorrhage in trauma.The probability of fatal massive hemorrhage in the following 1,2,and 3 h was dynamically predicted.The performance of the models was evaluated by accuracy,sensitivity,specificity,positive predictive value,negative predictive value,Youden index,and area under receiver operating characteristic curve(AUC).The models were externally validated based on the trauma database of the Chinese PLA General Hospital.Results In the MIMIC-Ⅳ database,the set of dynamic prediction models based on the GRU-D algorithm was the best.The AUC for predicting fatal major bleeding in the next 1,2,and 3 h were 0.946±0.029,0.940±0.032,and 0.943±0.034,respectively,and there was no significant difference(P=0.905).In the trauma dataset,GRU-D model achieved the best external validation effect.The AUC for predicting fatal major bleeding in the next 1,2,and 3 h were 0.779±0.013,0.780±0.008,and 0.778±0.009,respectively,and there was no significant difference(P=0.181).This set of models was deployed in a public web calculator and hospital emergency department information system,which is convenient for the public and medical staff to use and validate the model.Conclusion A set of dynamic prediction models has been successfully developed and validated,which is greatly significant for the early diagnosis and dynamic prediction of fatal massive hemorrhage in trauma.

OBJECTIVE: To detect and analyze the mutation status of FANCJ gene in adult AML patients, so as to provide the basis for studying the mechanism of FANCJ driven AML and guiding the preventim and treatment of deseese. METHODS: The cDNAs were extracted and transeripted from bone marrow cells and normal skin cells in 222 newly diagnosed AML patients. The primers were designed for FANCJ gene coding region, the mutations of FANCJ gene coding region in AML patients as well as the mutations of FANCJ gene in mucous membrane epethelia in patients were detected by PCR and sanger seguencing; the evolutionary conservation of FANCJ mutation in different organisms was analyzed by NCBI Blast online bioinformaties software. RESULTS: The sequencing analysis showed that the mutations of FANCJ gene happened in 11 sites of FANCJ gene coding region, which were as followed: exon5:c.G430A:p.A144T, exon6:c.A587G:pN196S, exon9:c.C1255T:p.R419W, exon10:c.G1442A:p.G481D, exon11:c.C1609G:p.L537V, exon16:c.C2360T:p.P787L, exon17:c.C2440T:p.R814C, exon19:c.C2608T:pH870Y, exon19:c.A2686G:p.I896V, exon19:c.C2830G:p.Q944E, exon20:c.G3412A:p.D1138N. Among them, the repeatability existed in mutations of A144T, N196S, R814C, I896V and Q944E. Beside, the mutation sites of A144, R419, G381, L537, P787, H870, Q944 and D1138 were highly conserved in different organisms. CONCLUSION Among 222 adult AML patients, the mutations of FANCJ gene have been found in 26 patients, moreover, the mutation sites are relatively conserved in different organisms, and possess important fanction. The results of this study provide the basis for exploring the mexhanism of FANCJ gene driven AML and for guiding the prevantion and treatment of AML.
Adult ; DNA Primers ; Humans ; Leukemia, Myeloid, Acute ; Mutation ; Polymerase Chain Reaction ; Prognosis

To efficiently remove all recurrent lymph nodes (rLNs) and minimize complications, we developed a combination approach that consisted of ⁶⁸Gallium prostate-specific membrane antigen (PSMA) ligand positron emission tomography (PET)/computed tomography (CT) and integrated indocyanine green (ICG)-guided salvage lymph node dissection (sLND) for rLNs after radical prostatectomy (RP). Nineteen patients were enrolled to receive such treatment. ⁶⁸Ga-PSMA ligand PET/CT was used to identify rLNs, and 5 mg of ICG was injected into the space between the rectum and bladder before surgery. Fluorescent laparoscopy was used to perform sLND. While extensive LN dissection was performed at level I, another 5 mg of ICG was injected via the intravenous route to intensify the fluorescent signal, and laparoscopy was introduced to intensively target stained LNs along levels I and II, specifically around suspicious LNs, with ⁶⁸Ga-PSMA ligand PET/CT. Next, both lateral peritonea were exposed longitudinally to facilitate the removal of fluorescently stained LNs at levels III and IV. In total, pathological analysis confirmed that 42 nodes were rLNs. Among 145 positive LNs stained with ICG, 24 suspicious LNs identified with ⁶⁸Ga-PSMA ligand PET/CT were included. The sensitivity and specificity of ⁶⁸Ga-PSMA ligand PET/CT for detecting rLNs were 42.9% and 96.6%, respectively. For ICG, the sensitivity was 92.8% and the specificity was 39.1%. At a median follow-up of 15 (interquartile range [IQR]: 6-31) months, 15 patients experienced complete biochemical remission (BR, prostate-specific antigen [PSA] <0.2 ng ml^-1), and 4 patients had a decline in the PSA level, but it remained >0.2 ng ml^-1. Therefore, ⁶⁸Ga-PSMA ligand PET/CT integrating ICG-guided sLND provides efficient sLND with few complications for patients with rLNs after RP.
Gallium Isotopes ; Gallium Radioisotopes ; Humans ; Indocyanine Green ; Ligands ; Lymph Node Excision ; Lymphatic Metastasis/diagnostic imaging* ; Male ; Neoplasm Recurrence, Local/surgery* ; Positron Emission Tomography Computed Tomography ; Prostate ; Prostatectomy ; Prostatic Neoplasms/surgery* ; Salvage Therapy

Objective: To investigate the prognostic value of clonal gene mutations detected by second-generation sequencing in patients with positive RUNX1-RUNX1T1 acute myeloid leukemia (AML) who received high-dose chemotherapy or autologous transplantation (intensive consolidation therapy) in the first complete remission (CR(1)) state. Methods: 79 AML patients with positive RUNX1-RUNX1T1 who received intensive consolidation therapy in CR(1) state from July 2011 to August 2017 were analyzed retrospectively. Kaplan-Meier curve and Cox regression model were used to figure out the effect of leukocyte counts at onset and gene mutations for prognosis. Results: C-KIT, FLT3, CEBPA and DNMT3A gene mutations were found in 25 (31.6%) , 6 (7.6%) , 7 (8.9%) and 1 (1.3%) patient among the population. Mutations in C-KIT exon17 and C-KIT exon8 were detected in 19 (24.1%) and 5 (6.3%) cases, respectively, and mutations of FLT3-ITD were confirmed in 5 (6.3%) cases. The higher leukocyte counts presented at onset of leukemia, the shorter overall survival (OS) was seen in these patients (P=0.03) . Patients with C-KIT exon17 mutation had significantly shorter OS (P=0.01) and disease free survival (DFS) (P=0.006) compared with those without gene mutations, and patients with FLT3-ITD gene mutation got the inferior OS (P=0.048) and DFS (P=0.071) . Conclusion: In AML patients with positive RUNX1-RUNX1T1 receiving intensive consolidation therapy, the white blood cell counts at onset of leukemia, C-KIT mutations in exon 17, and FLT3-ITD gene mutations suggest poor prognosis, which would contribute to elaborate risk stratification, personalized treatment and predict prognosis for these patients.
Consolidation Chemotherapy ; Core Binding Factor Alpha 2 Subunit/genetics* ; Humans ; Leukemia, Myeloid, Acute/genetics* ; Mutation ; Prognosis ; RUNX1 Translocation Partner 1 Protein/genetics* ; Retrospective Studies ; fms-Like Tyrosine Kinase 3

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.