Carcinoma, Hepatocellular ; metabolism ; pathology ; Female ; Humans ; Liver Neoplasms ; metabolism ; pathology ; Male ; Neoplasm Invasiveness ; Neoplasm Metastasis ; PTEN Phosphohydrolase ; biosynthesis ; genetics ; Vascular Endothelial Growth Factor A ; biosynthesis ; genetics

OBJECTIVETo study the effect of oral fluid resuscitation with pyruvate sodium-glucose-electrolyte solution (PGES) on hemodynamics, organ functions and mortalities during shock stage in dogs with burn.

METHODSIn comparison of oral pyruvate sodium-glucose-electrolyte solution (PGES) with NaHCO₃-glucose-electrolyte solution (HGES), beagle dogs with intubation of the carotid artery, jugular vein and jejunum for 24 hours were subjected to a 50% total body surface area (TBSA) burn, and were divided into three groups: pure burn without fluid resuscitation (NR, n = 8), and two oral fluid resuscitation (each n = 10), in which dogs were given with Pry-GES (OP) or NaHCO₃-GES (OH) according to Parkland formula. The hemodynamic and organ functions were measured serially before burn and 2, 6, 8, 12 and 24 hours after burn at no anaesthesia state A. Twenty-four hours mortality rate following burn was also recorded.

RESULTSTwo hours after burn, the mean arterial pressure of NR, OH and OP group was (45 ± 8), (57 ± 8) and (80 ± 9) mmHg (1 mmHg = 0.133 kPa) respectively, which were significantly reduced (t = 16.967, 14.595 and 10.100, all P < 0.05) compared with those before injury ((42 ± 6), (144 ± 6) and (142 ± 6) mmHg respectively), the change of cardiac output, dp/dtmax of left ventricular contractility and intestinal mucosal blood flow had the same trend as the mean arterial pressure. The systemic vascular resistance and organ parameters (Cr, CK-MB, ALT and DAO) in all groups increased obviously (t = -46.894--2.465, all P < 0.05). All measurements of NR group kept worsening, and all died within 24 hours after burn; while those of two oral resuscitation groups had improved gradually (F = 0.001-1.600, all P < 0.05), OP group was significantly superior to OH group (F = 0.013-0.466, P < 0.05). At 24 hours after burn, 6 (6/10) survived in OP group, 4 (4/10) in OH group and 0 (0/8) in NR group.

CONCLUSIONThe Pyr-GES may be superior to the standard NaHCO₃-GES in the improvement of hemodynamics and organ functions during oral resuscitation in dogs with 50%TBSA full thickness burn.

Animals ; Body Surface Area ; Burns ; complications ; physiopathology ; therapy ; Disease Models, Animal ; Dogs ; Fluid Therapy ; Hemodynamics ; drug effects ; Male ; Pyruvates ; therapeutic use ; Rehydration Solutions ; Shock ; etiology ; physiopathology ; therapy

Objective:To evaluate the clinical effect of high-intensity focused ultrasound(HIFU)and drug con-servative treatment on the treatment of type Ⅰ and type Ⅱ cesarean scar pregnancy(CSP).Methods:A retrospec-tive analysis was performed on 191 patients diagnosed with type Ⅰ and type Ⅱ CSP by ultrasonography and trea-ted in Mianyang Central Hospital from January 2018 to December 2021,and they were divided into drug group(n=67)and HIFU group(n=124)according to different treatment methods before curettage surgery.After receiv-ing conservative drug treatment or HIFU treatment,preformnegative pressure suction curettage under ultrasound monitoring to evaluate the effectiveness and safety of the two pretreatment methods.Results:There were no sig-nificant differences in age,number of cesarean sections,gestational age,the maximum diameter of the gestational sac,number of incision pregnancies,the β-hCG level before pretreatment,the heart tube pulse in the gestational sac,size of fetal bud,and fertility requirements between the medication group and HIFU group(P＞0.05).The proportion of type Ⅱ incision in HIFU group was higher than that in drug group(P＜Q.05).There were no signifi-cant differences between the two groups in intraoperative bleeding,treatment outcome effective rate after pretreat-ment,postoperative vaginal bleeding duration,postoperative uterine cavity residual,rate of reoperation and rate of repregnancy(P＞0.05).There were statistical differences between the two groups in the operation time of curet-tage surgery,whether the operation method was changed after pre-treatment,total hospital stay,β-hCG recovery time and hospitalization cost(P＜0.05).Following up to November 2022,there were 12 cases re-pregnancies in the drug group and 16 cases re-pregnancies in the HIFU group.Conclusions:For type Ⅰ and type Ⅱ CSP,HIFU pretreatment before negative pressure suction curettage under ultrasound monitoring is a safe and effective treat-ment,which improves the treatment effect and reduces the hospitalization time of patients.It may be an effective clinical therapy for type Ⅰ and type Ⅱ CSP treatment.

Objective:To explore the predictive value of 18F-fluorodeoxyglucose (FDG) PET/CT radiomics for the programmed death ligand-1 (PD-L1) expression level in lung adenocarcinoma patients. Methods:A total of 101 patients (43 males, 58 females; median age 60 years) with histologically confirmed lung adenocarcinoma who received pre-treatment 18F-FDG PET/CT from January 2017 to January 2019 in Peking University Cancer Hospital were included retrospectively. There were 44 patients with positive PD-L1 by immunohistochemical assays, and 57 with PD-L1 negative. Patients were assigned to a training set ( n=71) and a validation set ( n=30). Clinical data, PET/CT radiomics parameters, conventional metabolic parameters, and observed CT characteristics of these patients were included in the models. The filter method and embedded method were used in feature selection. Models based on logistic regression, random forest, XGBoost and Light Gradient Boosting Machine (LightGBM) were trained and evaluated, and the optimal parameters to predict the PD-L1 expression as well as the area under curve (AUC) were attained. Results:All models had predictive ability in the prediction of PD-L1 expression, while LightGBM was more powerful than the others, with the precision for positive and negative predictions of 0.85 and 0.76, respectively. Incorporating clinical data and data derived from thin-section CT images (clinical data+ CT) into the LightGBM, the precision, recall and F1-score for positive and negative patients were 0.71, 0.67, 0.69 and 0.69, 0.73, 0.72, respectively, with the accuracy of 0.70 and the AUC of 0.79. As for clinical data+ PET, the precision, recall and F1-score for positive and negative patients were 0.79, 0.73, 0.76 and 0.75, 0.80, 0.77, respectively, with the accuracy of 0.77 and the AUC of 0.80. As for clinical data+ CT+ PET, the precision, recall and F1-score for positive and negative patients were 0.85, 0.73, 0.79 and 0.76, 0.87, 0.81, respectively, with the accuracy of 0.80 and the AUC of 0.83. Features with significant importance in the model (clinical data+ CT+ PET) were as follows: maximum standardized uptake value (SUV max), peak of standardized uptake value (SUV peak), CT_shape_Maximum2DDiameterSlice, PET_shape_Elongation, PET_gray level co-occurrence matrix (GLCM)_Correlation, etc. Conclusions:Incorporating clinical data, PET/CT radiomics features and conventional metabolic parameters, the PD-L1 expression can be effectively predicted, which help to assist the selection of patients who may benefit from the immunotherapy.

OBJECTIVE: To detect metabolic changes of bilateral frontal lobe in patients with multiple system atrophy (MSA) and cognitive dysfunction by 1H-proton magnetic resonance spectroscopy (1H-MRS).
 METHODS: N-acetylaspartate (NAA)/creatine(Cr), choline (Cho)/Cr, myoinositol (mI)/Cr in three sides of frontal lobe were detected by 1H-MRS in 48 healthy controls, 23 patients with MSA and cognitive dysfunction and 19 patients with MSA but without cognitive dysfunction.
 RESULTS: NAA/Cr of bilateral frontal lobes in patients with MSA and cognitive dysfunction was significantly decreased compared with MSA patients without cognitive dysfunction and healthy controls (P<0.05). mI/Cr of right frontal lobes was significantly increased in patients with MSA and cognitive dysfunction compared with healthy controls (P<0.05). There was a negative correlation between NAA/Cr of bilateral frontal lobes and duration while a positive correlation between NAA/Cr of bilateral frontal lobes and MoCA score in patients with MSA and cognitive dysfunction.
 CONCLUSION There is a decrease in NAA/Cr and an increase in mI/Cr in frontal lobes in patients with MSA and cognitive dysfunction, which may be associated with cognitive dysfunction in MSA patients.
Aspartic Acid ; analogs & derivatives ; metabolism ; Choline ; metabolism ; Cognition Disorders ; physiopathology ; Creatine ; metabolism ; Frontal Lobe ; metabolism ; Humans ; Inositol ; metabolism ; Multiple System Atrophy ; physiopathology ; Proton Magnetic Resonance Spectroscopy

Genome packaging is a fundamental process in a viral life cycle and a prime target of antiviral drugs. Herpesviruses use an ATP-driven packaging motor/terminase complex to translocate and cleave concatemeric dsDNA into procapsids but its molecular architecture and mechanism are unknown. We report atomic structures of a herpesvirus hexameric terminase complex in both the apo and ADP•BeF3-bound states. Each subunit of the hexameric ring comprises three components-the ATPase/terminase pUL15 and two regulator/fixer proteins, pUL28 and pUL33-unlike bacteriophage terminases. Distal to the nuclease domains, six ATPase domains form a central channel with conserved basic-patches conducive to DNA binding and trans-acting arginine fingers are essential to ATP hydrolysis and sequential DNA translocation. Rearrangement of the nuclease domains mediated by regulatory domains converts DNA translocation mode to cleavage mode. Our structures favor a sequential revolution model for DNA translocation and suggest mechanisms for concerted domain rearrangements leading to DNA cleavage.

OBJECTIVES: There is less clinical data on multiple myeloma (MM) in China, and the aim of this study was to collect and analyze the clinical data of newly diagnosed multiple myeloma (NDMM) patients in Hunan Province during 1 year, to understand the real clinical features and treatment outcome for Hunan Province patients with MM, and to strengthen the understanding of the standardized diagnosis process and treatment plan of MM. METHODS: The clinical data of 529 patients with NDMM in 12 large-scale general hospitals in Hunan Province from January 1 to December 31, 2019 were collected and analyzed, including baseline data, treatment regimens, duration of treatment, and adverse reactions. The clinical characteristics, treatment, and safety of patients were analyzed by SPSS 21.0. RESULTS: Among the 529 NDMM patients, the age was 33-90 (median 64) years and the male-female ratio was 1.38꞉1. The clinical features ranged from high to low were as follows: Bone pain (77.7%), anemia (66.8%), renal insufficiency (40.6%), hypercalcemia (15.1%). Typing: IgG 46.5%, IgA 24.6%, IgD 2.6%, IgM 0.8%, light chain 15.7%, double clone 3.0%, no secretion 0.6%, absence 6.2%. Staging: Durie-Salmon stage I, II, and III were 4.5%, 10.6%, 77.3%, respectively, and 40 cases (7.6%) missed this data. International Staging System (ISS) stage I, II, and III were 10.4%, 24.4%, and 47.6%, respectively, and 93 cases (17.6%) were missing. Revised International Staging System (R-ISS) stage I, II, and III were 5.5%, 27.0%, 23.1%, respectively, and 235 cases (44.4%) missed this data. Among the 98 NDMM patients in the Third Xiangya Hospital, Central South University, Durie-Salmon (DS) stage missing 2.0%, ISS stage missing 12.3%, and R-ISS stage missing 12.3%.Treatment: Among the 529 patients,475 received treatment, the rate of treatment was 89.8%; 67.4% of the patients were able to complete four courses of chemotherapy at induction phase, 90.3% of the patients received proteasome inhibitor based combination chemotherapy regimen more than once, 67.2% received immunomodulator based regimen more than once, and 59.8% of the patients received proteasome inhibitor and immunomodulator based combination chemotherapy regimen more than once. Curative: Overall response rate (ORR) and high quality response rate (HQR) of the 4-course group were better than those of the 2-course group (ORR: 85% vs 65%, P=0.006; HQR: 68.3% vs 24.0%, P<0.001). The HQR of the standard chemotherapy group was better than that of the non-standard chemotherapy group (65.1% vs 48.2%, P=0.035). Adverse reactions during treatment included hematologic toxicity (17.5%), peripheral neuropathy (24.8%), gastrointestinal adverse events (23.8%), pulmonary infection (25.9%), herpes zoster (4.6%), and venous thrombotic events (1.7%). CONCLUSIONS In 2019, the missed diagnosis rate of MM patients was high, the medium age of diagnosis was older, and the accuracy of patient diagnosis was not high. There is a great difference among medical centers, especially in the stage and risk stratified, nearly half of NDMM patients are not diagnosed with R-ISS stage; the lack of cytogenetic data needs to be supplemented by follow-up studies. A high proportion of patients with NDMM present with bone pain and anemia.Patients received treatment have higher use of chemotherapy regimens containing proteasome inhibitors and/or immunomodulators, but there is a significant gap among different medical centers, and standardized treatment needs to be strengthened. The safety during chemotherapy is controllable.
Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Female ; Humans ; Immunologic Factors/therapeutic use* ; Male ; Middle Aged ; Multiple Myeloma/therapy* ; Neoplasm Staging ; Pain ; Prognosis ; Proteasome Inhibitors/therapeutic use*

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