Glioblastoma(GBM)is a lethal cancer with limited therapeutic options.Dendritic cell(DC)-based cancer vaccines provide a promising approach for GBM treatment.Clinical studies suggest that other immu-notherapeutic agents may be combined with DC vaccines to further enhance antitumor activity.Here,we report a GBM case with combination immunotherapy consisting of DC vaccines,anti-programmed death-1(anti-PD-1)and poly I:C as well as the chemotherapeutic agent cyclophosphamide that was integrated with standard chemoradiation therapy,and the patient remained disease-free for 69 months.The patient received DC vaccines loaded with multiple forms of tumor antigens,including mRNA-tumor associated antigens(TAA),mRNA-neoantigens,and hypochlorous acid(HOCl)-oxidized tumor lysates.Furthermore,mRNA-TAAAs were modified with a novel TriVac technology that fuses TAAs with a destabilization domain and inserts TAAs into full-length lysosomal associated membrane protein-1 to enhance major histo-compatibility complex(MHC)class Ⅰ and Ⅱ antigen presentation.The treatment consisted of 42 DC cancer vaccine infusions,26 anti-PD-1 antibody nivolumab administrations and 126 poly I:C injections for DC infusions.The patient also received 28 doses of cyclophosphamide for depletion of regulatory T cells.No immunotherapy-related adverse events were observed during the treatment.Robust antitumor CD4+and CD8+T-cell responses were detected.The patient remains free of disease progression.This is the first case report on the combination of the above three agents to treat glioblastoma patients.Our results suggest that integrated combination immunotherapy is safe and feasible for long-term treatment in this patient.A large-scale trial to validate these findings is warranted.

ABSTRACT: Meningiomas are the most common primary intracranial neoplasm with diverse pathological types and complicated clinical manifestations. The fifth edition of the WHO Classification of Tumors of the Central Nervous System (WHO CNS5), published in 2021, introduces major changes that advance the role of molecular diagnostics in meningiomas. To follow the revision of WHO CNS5, this expert consensus statement was formed jointly by the Group of Neuro-Oncology, Society of Neurosurgery, Chinese Medical Association together with neuropathologists and evidence-based experts. The consensus provides reference points to integrate key biomarkers into stratification and clinical decision making for meningioma patients. REGISTRATION Practice guideline REgistration for transPAREncy (PREPARE), IPGRP-2022CN234.
Humans ; Meningioma/pathology* ; Consensus ; Neurosurgical Procedures ; Meningeal Neoplasms/pathology*

OBJECTIVETo investigate the effects of Th1/Th17 cell imbalance on the pathogenesis of acute graft-versus-host disease (GVHD) in mice.

METHODSIn a murine GVHD model of C57BL/6 (H-2(b)), a low dose of halofuginone (HF) was applied for treating the recipients in order to result in Th1/Th17 imbalance. Rechipient mice were divided into GVHD group (without HF intervention) and GVHD plus HF group (treated by HF). The recipients were monitored for survival rate, clinical scores of acute GVHD, contents of circulatory Th1 and Th17 cells, Th1/Th17 ratio and serum level of IFN-γ and IL-17A. Expression levels of IFN-γ and IL-17A in target organs were analyzed by using real-time PCR, and the target organs were delivered for histological examinations.

RESULTSRecipients treated with HF showed that all the mortality, circulatory Th1/Th17 ratio and clinical score were higher than those in the mice without HF intervention (P < 0.05). Circulatory Th1/Th17 ratio positively correlates with clinical score (P < 0.001). HF administration reduces the expression level of intestinal IL-17A and increases intrahepatic and intestinal IFN-γ level (P < 0.05), HF treatment aggravates GVHD in liver and small intestine with augmented hepatic and intestinal inflammation.

CONCLUSIONTh1/Th17 imbalance contributes to the pathogenesis of acute GVHD.

Animals ; Disease Models, Animal ; Graft vs Host Disease ; immunology ; Interferon-gamma ; blood ; Interleukin-17 ; blood ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Piperidines ; Quinazolinones ; Th1 Cells ; cytology ; Th17 Cells ; cytology

This study was aimed to investigate the effect of MEK inhibitor AZD8330 on proliferation and apoptosis of multiple myeloma IM9 and NCI-H929 cell lines and its possible mechanism. These two cell line cells were exposed to different concentrations of AZD8330 for 48 h. The CCK-8 assay was used to detect cell viability and the IC50 value at 48 h. These above-mentioned IM9 and NCI-H929 cells were treated with 5,10 and 100 nmol/L of AZD8330, then the change of cell cycle was analysed by flow cytometry with PI staining. The Wester blot was used to detect the expression levels of cyclin D and cyclin E, and multiple myeloma cells were treated with 10, 100, 1000 and 2000 nmol/L of AZD8330, the AnnexinV/7-AAD double staining was used to analyse cell apoptosis and the Western blot was used to detect the expression level of caspase-3. The results showed that AZD8330 could significantly inhibit the cell viability of IM9 and NCI-H929 cell lines in a time-and dose-dependent manner, the IC50 value (48 h) of IM9 and NCI-H929 were 19.88 ± 2.7 nmol/L and 29.3 ± 2.03 nmol/L respectively, these two cell lines were arrested on G1 phase of cell cycle, the apoptosis cells increased along with enhancement of AZD8330 concentration, and the expression level of cleaved caspase-3 protein was up-regulated. It is concluded that AZD8330 can efficiently inhibit the proliferation of NCI-H929 and IM9 cell lines, and induce apoptosis, suggesting that the AZD8330 may be a potential chemotherapeutic candidate for multiple myeloma therapy.
Apoptosis ; drug effects ; Caspase 3 ; Cell Cycle ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cyclin E ; Dihydropyridines ; pharmacology ; Humans ; Multiple Myeloma ; pathology ; Oncogene Proteins ; Protein Kinase Inhibitors ; pharmacology

OBJECTIVETo observe and evaluate the performances of intermittent positive pressure ventilation, beta-2 adrenergic receptor agonist, and pressure lavage in promoting residual fluid absorption and improving blood oxygen saturation during massive whole lung lavage (WLL).

METHODSA total of 155 patients were randomly divided into pressure ventilation (PV) group (n = 28), adrenaline (Ad) group (n = 31), PV plus Ad group (n = 29), pressure infusion bag (PIB) group (n = 30), and control group (n = 32). The patients underwent staged MWLL of bilateral lungs. The blood oxygen saturation (SpO2) of arterial blood of finger, chest X-ray findings, clinical symptoms, and lung functions were observed before and after MWLL.

RESULTSThere were no significant differences in change in clinical symptoms among the five groups after MWLL (P > 0.05). The Ad group showed 6.3% increase in forced vital capacity (FVC) and 10.9% increase in forced expiratory flow at 25% of vital capacity (FEF(25%)) after MWLL (P < 0.05). The control group showed 5.7% decrease in FVC, 10.9% increase in forced expiratory volume in one second (FEV(1.0)), and 12.0% increase in FEF(25%) after MWLL (P < 0.05). No significant difference was found in other groups (P > 0.05). During and after MWLL, the incidence rates of hypoxemia in PV group, PV plus Ad group, and control group were 0, 0, and 12.5% (8/64), respectively (P < 0.01). There were no significant differences in total amount of lavage fluid and amount of residual fluid in the lung among all groups (P > 0.05). The smallest difference between the optical densities of the two lung fields on chest x-ray at 3 h after WLL was 0.152 ± 0.053 in the PV plus Ad group, compared to 0.194 ± 0.074 in the PV group, 0.197 ± 0.054 in the PIB group, 0.214 ± 0.054 in the Ad group, and 0.241 ± 0.109 in the control group, with significant differences between the saline group and other groups except Ad group (P < 0.05).

CONCLUSIONPressure ventilation, adrenaline, and pressure lavage can promote the transportation and absorption of residual fluid in the lung and decrease the incidence of hypoxemia during WLL.

Adrenergic beta-2 Receptor Agonists ; therapeutic use ; Adult ; Blood Gas Analysis ; Bronchoalveolar Lavage ; methods ; Epinephrine ; therapeutic use ; Female ; Forced Expiratory Volume ; Humans ; Hypoxia ; prevention & control ; Male ; Middle Aged ; Oxygen Consumption ; Pneumoconiosis ; therapy ; Positive-Pressure Respiration ; methods

Mesenchymal stem cell (MSC)-based cell therapy has shifted into clinical trials to repair the damage of various tissues. In this setting, the survival of the transplanted cells contributes critically to the therapeutic effectiveness. To investigate the in vivo tracing of MSCs, a recombinant retroviral vector carrying firefly-luciferase reporter gene [pL (FLUC) SN] was constructed and several GPE+86 cell clones that stably expressed fluc were selected. The retroviral supernatants were collected and used to transfect MSC derived from C57 mice. The cells were then screened with G418 and the expression of the exogenous gene was identified by luciferase enzyme activity analysis. Labeled mouse MSCs (2x10(6)) were injected into skeletal muscles, and the in situ expression was noninvasively tracked by in vivo bioluminescence imaging for 1, 3 and 6 days after transplantation. The results showed that the survival rates of the grafted cells dropped sharply with time, they were 57.2+/-11.7%, 8.6+/-2.5% and 5.4+/-3.1% on day 1, 3 and 6 after transplantation, and no fluorescent signals above background were detected on day 10. It is concluded that the method described above could be used for in vivo tracing of grafted cells. Furthermore, MSCs could not survive even transplanted into the none-ischemic skeletal muscles.
Animals ; Bone Marrow Cells ; cytology ; Bone Marrow Transplantation ; methods ; Cell Survival ; Female ; Genetic Vectors ; Green Fluorescent Proteins ; Luminescent Measurements ; methods ; Mesenchymal Stem Cell Transplantation ; methods ; Mesenchymal Stromal Cells ; cytology ; Mice ; Mice, Inbred C57BL

OBJECTIVETo investigate the clinicopathological characteristics, diagnostic methods and prognosis of small pancreatic cancer.

METHODSFrom May 2000 to January 2007, 89 patients with pancreatic cancer underwent surgery in our hospital. Of those, 14 had a tumor < or = 2 cm in diameter (small tumor group), and the other 75 had a tumor >2 cm in diameter (controlled group). The clinicopathological data of all the cases were retrospectively reviewed and analyzed.

RESULTSIn the small pancreatic cancer group, CT and MRI detected 66.7% (8/12) and 77.8% (7/9) of the tumors, respectively. Serosal infiltration was found in 2 cases, lymph node involvement in 3 cases, and retroperitoneal infiltration in 3 cases. The follow-up duration of this group was 4-86 months. The overall 3- and 5-year survival rates were 42.8% and 31.7%, while in the control group, the overall 3- and 5-year survival rates were 29.7% and 22.5%, respectively. The multivariate analysis showed that the lymph node involvement, serosal infiltration and retroperitoneal infiltration were independent risk factors (P<0.05). However, the tumor size was not shown to be an independent risk factor (OR value = 1.45, P = 0.971).

CONCLUSIONCT and MRI are valuable in detecting small pancreatic cancer. Small pancreatic cancers are likely to have a better prognosis when compared with larger ones. Lymph node metastasis and local infiltration are independent predictors of prognosis but not tumor size.

Aged ; Female ; Follow-Up Studies ; Humans ; Lymphatic Metastasis ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Pancreatic Neoplasms ; diagnosis ; pathology ; surgery ; Proportional Hazards Models ; Retroperitoneal Space ; pathology ; Retrospective Studies ; Serous Membrane ; pathology ; Survival Rate ; Tomography, X-Ray Computed ; Tumor Burden

OBJECTIVETo investigate the therapeutic effects of Enalaprilat on the myocardial kinetics in rats at early stage of severe scald.

METHODSEighty-four SD rats were inflicted with 30% TBSA full-thickness scald, and randomly divided into scald (S, with intraperitoneal injection of isotonic saline according to Parkland formula, n=30), L (n=30), M (n=12) and H (n=12) groups. The rats in L,M,H groups were intraperitoneally injected with 1,2,4 mg/kg Enalaprilat. Other 6 healthy rats were enrolled into study as control (C group). The myocardial kinetic parameters including left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP), +/- dp/dt max and the levels of A II in myocardium were observed at 1,3,6,12 and 24 post scald hour (PBH) in L and S groups,and at 6,12 PBH in M and H groups. The above indices in C group were also examined.

RESULTSThe levels of LVSP, LVEDP, +/- dp/dt max in C group were higher than those in other groups during 3-24 PBH (P < 0.05 or P < 0.01), while those in L,M,H groups were obviously higher than those in S group (P < 0.05 or P < 0.01). The level of +/- dp/dt max in H group at 6,12 PBH were obviously lower than those in L and M groups. The level of A II in S group at 1 PBH was (53.0 +/- 2.6) pg/200 mg, which was significantly higher than thatin C group [(14.8 +/- 0.7) pg/200 mg, P < 0.05 or P < 0.01]; it peaked at6 PBH and lowered afterwards, and they were significantly higher than that in C group at 24 PBH (P < 0.01). The levels of A II in L group during 3-24 PBH were obviously higher than those in C group (P < 0.01), which were also lower than those in S group. The level of A II in S group was significantly higher than in L,M,H groups at 6 PBH [(145.2 +/- 14.5) pg/200 mg. vs. (65.1 +/- 0.9) pg/200 mg, (53.6 +/- 1.1) pg/200 mg, (34.2 +/- 0.9) pg/200 mg, respectively, P < 0.01].

CONCLUSIONMyocardium can be obviously damaged at early stage after severe scald,cardiac function is impaired. Enalaprilat injection (especially at low dose) can significantly ameliorate the myocardial kinetics indices, and it seems to exert a protective effect on cardiac function.

Animals ; Burns ; drug therapy ; physiopathology ; Dose-Response Relationship, Drug ; Enalaprilat ; pharmacology ; therapeutic use ; Myocardium ; pathology ; Rats ; Rats, Sprague-Dawley ; Ventricular Remodeling

An aberrant genotype of hepatitis B virus was discovered from a female child when we surveyed the status of the virus' infection in Guangxi of China. The full-length genome was amplified and sequenced. The length of genome is 3215 bp and the serotype of the virus is adr. In phylogenetic tree analysis with the standard genotype sequence of GenBank, the genome was clustered with genotype C, however, phylogenetic tree analysis of the individual segment supported recombination strain was formed. The segment between nt 1630 and 2880 was similar to genotype C, and the other part of genome close to genotype A. The result suggests it is a recombinant virus strain. The finding provides a reference to study the genotype and evolution of hepatitis B virus in China.
Cloning, Molecular ; Genome, Viral ; Hepatitis B virus ; classification ; genetics ; Phylogeny ; Recombination, Genetic

Objective In order to investigate the characterization of mutation and genotype distributing in the younger group which was under the universal vaccination. The sequence of HBV was analyzed to offer the information to control and prevention in the area. Methods young person's sera with positive HBsAg are collected, and the Large S sequence of HBV including preS and S gene are amplified and sequenced. The genotype and serotype were determined by clastwal with the standard genotype sequence. And one virus complete genome is amplified. Results The virus gene are successful amplified from the 33 sera. The sequence result indicate the 30of 33 (90.9%) HBV genotype is B and 3 of 33 (9.0%) is C. The HBV serotype including ayw (1), adr (3), adw (29), 5 of 33 mutated in the "a" dominant of HBV, and the percentage is 15.2%. The HBV full length gene of serum number of 5856 is amplified and sequenced. Its genotype is B, serotype is adw and length is 3215 base. Conclusion s The dominant genotype of HuNan is B, and t he dominant serotype is adw.