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.

Objective:To develop a single-tube one-step multiplex nested real-time reverse transcription polymerase chain reaction (RT-PCR) assay for the simultaneous detection of 2019-nCoV, influenza A virus, influenza B virus and internal-control with human-derived gene.Methods:This study included 30 positive specimens for 2019-nCoV nucleic acid detection and 336 screening specimens collected from the arrivals at Guangzhou Baiyun Airport between February 2020 and February 2022. Sixty-four positive specimens of other respiratory pathogens were also collected from the arrivals at Guangzhou Baiyun Airport during the three-year period before the occurrence of COVID19 outbreak in 2020, and 7 positive viral strains of respiratory pathogens were provided by collaborative laboratories. In order to establish a set of multiplex nested real-time RT-PCR assay, a group of primers and probe combinations for a multiplex nested real-time RT-PCR was designed and screened according to a selection of nucleotide conserved regions of the ORF and N genes of 2019-nCoV and the M gene of influenza A and B viruses, while nested amplification primers and probe for the internal-control with human-derived gene were introduced. Then the prepared pseudovirus-positive quality control and sample discs were applied to evaluate the sensitivity and specificity. Clinical specimens were performed to validate the applicability of the method.Results:The results show that the established one-step multiplex nested real-time RT-PCR assay can specifically detect 2019-nCoV and influenza A and B viruses, with the limit-of-detection of about 125 copies/ml for 2019-nCoV and about 250 copies/ml for influenza A and B viruses. Totally 101 positive samples of various respiratory pathogens were detected, showing that the detection sensitivities of 2019-nCoV and influenza A and B viruses were 96.67%, 92.86% and 96.15%, respectively, with the specificity of 100%. No false-positive detection was found in the applied detection of more than 300 clinical samples.Conclusions:A one-step multiplex nested real-time RT-PCR assay for 2019-nCoV, influenza A and B viruses and human-derived gene internal-control was developed. The assay has good sensitivity and specificity and can be used for rapid screening of 2019-nCoV and influenza A and B viruses in high-volume samples.

OBJECTIVE: To explore the treatment methods and experience of open fracture of lower limb in high altitude area. METHODS: From January 2016 to January 2021, 62 patients with open fractures of lower limbs were treated by staged surgery with the concept of injury control orthopedics, emphasizing wound treatment and combining various fracture fixation methods. There were 51 males and 11 females, ranging in age from 14 to 59 years old, with a mean of (37.2±12.3) years old; and the course of disease ranged from 7 to 59 days, with a mean of (23.7±15.5) days. According to Gustilo Anderson classification, there were 14 cases of typeⅠ, 24 cases of typeⅡ, 14 cases of typeⅢA, 8 cases of typeⅢB and 2 cases of typeⅢC. The fracture repair and wound healing were observed, and the clinical efficacy was evaluated by Johner-Wruhs evaluation standard. RESULTS: Fifty-five patients were followed up, and the duration ranged from 4 to 36 months, with a mean of (14.7±8.5) months, and 7 cases were lost to follow-up. According to Johner-Wruhs evaluation criteria, 33 cases got an excellent result, 16 good, 4 poor and 2 bad. The wound healing was poor in 2 cases, partial necrosis of Achilles tendon in 1 case, nonunion of fracture in 1 case and delayed healing of fracture in 2 cases. CONCLUSION It is an effective method to treat the open fracture of lower extremity in high altitude area to pay attention to the management of soft tissue injury, the management of wound moisturizing, staged operation of fracture and full protection of blood supply at the fracture end. Paying attention to the treatment of soft tissue injury and the management of wound moisturizing, staged operation of fracture and full protection of blood supply at the fracture end are effective methods for the treatment of open fracture of lower limbs in high altitude areas.
Adolescent ; Adult ; Altitude ; Female ; Fracture Fixation ; Fracture Fixation, Internal ; Fracture Healing ; Fractures, Open ; Humans ; Lower Extremity/surgery* ; Male ; Middle Aged ; Tibial Fractures/surgery* ; Treatment Outcome ; Young Adult

INTRODUCTIONAcute myocardial infarction (AMI) due to unprotected left main coronary artery (ULMCA) disease is clinically catastrophic although it has a low incidence. Studies on the long-term prognosis of these patients are rare.

METHODSFrom January 1999 to September 2013, 55 patients whose infarct-related artery was the ULMCA were enrolled. Clinical, angiographic and interventional data was collected. Short-term and long-term clinical follow-up results as well as prognostic determinants during hospitalisation and follow-up were analysed.

RESULTSCardiogenic shock (CS) occurred in 30 (54.5%) patients. During hospitalisation, 22 (40.0%) patients died. Multivariate logistic regression analysis showed that CS (odds ratio [OR] 5.86; p = 0.03), collateral circulation of Grade 2 or 3 (OR 0.14; p = 0.02) and final flow of thrombolysis in myocardial infarction (TIMI) Grade 3 (OR 0.05; p = 0.03) correlated with death during hospitalisation. 33 patients survived to discharge; another seven patients died during the follow-up period of 44.6 ± 31.3 (median 60, range 0.67-117.00) months. The overall mortality rate was 52.7% (n = 29). Kaplan-Meier analysis showed that the total cumulative survival rate was 30.7%. Cox multivariate regression analysis showed that CS during hospitalisation was the only predictor of overall mortality (hazard ratio 4.07, 95% confidence interval 1.40-11.83; p = 0.01).

CONCLUSIONAMI caused by ULMCA lesions is complicated by high incidence of CS and mortality. CS, poor collateral blood flow and failure to restore final flow of TIMI Grade 3 correlated with death during hospitalisation. CS is the only predictor of long-term overall mortality.

Adult ; Aged ; Angiography ; Angioplasty, Balloon, Coronary ; Coronary Artery Disease ; pathology ; therapy ; Coronary Vessels ; pathology ; Female ; Follow-Up Studies ; Hospitalization ; Humans ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Multivariate Analysis ; Myocardial Infarction ; diagnosis ; therapy ; Odds Ratio ; Percutaneous Coronary Intervention ; Prognosis ; Proportional Hazards Models ; Regression Analysis ; Retrospective Studies ; Shock, Cardiogenic ; Young Adult

BACKGROUNDThis meta-analysis evaluated the effect of noninvasive, positive pressure ventilation on severe, stable chronic obstructive pulmonary disease (COPD).

METHODSPUBMED, CNKI, Wanfang, EMBASE and the Cochrane trials databases were searched. Randomized controlled trials of patients with severe, stable COPD and receiving noninvasive positive pressure ventilation, compared with sham ventilation or no ventilation, were reviewed. The mortality, physiological and health related parameters were pooled to yield odds ratio (OR), weighted mean differences or standardized mean differences (SMD), with 95% confidence interval (CI).

RESULTSEight parallel and three crossover randomized controlled trials met the inclusion criteria. Pooled analysis for parallel, randomized controlled trials showed noninvasive positive pressure ventilation: (1) Did not affect the 12- or 24-month mortality (OR 0.82, 95%CI: 0.48 to 1.41); (2) Improved the arterial carbon dioxide tension (SMD -0.88, 95%CI: -1.43 to -0.34); (3) Did not improve forced expiratory volume in one second (SMD 0.20, 95%CI: -0.06 to 0.46), maximal inspiratory pressure (SMD 0.01, 95%CI: -0.28 to 0.29) or 6-minute walk distance (SMD 0.17, 95%CI: -0.16 to 0.50); (4) Subgroup analysis showed noninvasive positive pressure ventilation improved the arterial carbon dioxide tension in hypercapnic patients. Pooled analysis for crossover randomized controlled trials did not show improvement in arterial blood gas or forced expiratory volume in one second with noninvasive positive pressure ventilation.

CONCLUSIONSNoninvasive positive pressure ventilation improves the arterial carbon dioxide tension but does not improve the mortality, pulmonary function, or exercise tolerance and should be cautiously used in severe stable chronic obstructive pulmonary disease.

Carbon Dioxide ; blood ; Forced Expiratory Volume ; Humans ; Positive-Pressure Respiration ; Pulmonary Disease, Chronic Obstructive ; physiopathology ; psychology ; therapy ; Quality of Life ; Randomized Controlled Trials as Topic

Adult ; Anastomosis, Surgical ; Esophagus ; surgery ; Humans ; Male ; Stents ; Stomach ; surgery ; Tracheoesophageal Fistula ; surgery

Background This meta-analysis evaluated the effect of noninvasive,positive pressure ventilation on severe,stable chronic obstructive pulmonary disease (COPD).Methods PUBMED,CNKI,Wanfang,EMBASE and the Cochrane trials databases were searched.Randomized controlled trials of patients with severe,stable COPD and receiving noninvasive positive pressure ventilation,compared with sham ventilation or no ventilation,were reviewed.The mortality,physiological and health related parameters were pooled to yield odds ratio (OR),weighted mean differences or standardized mean differences (SMD),with 95％ confidence interval (C/).Results Eight parallel and three crossover randomized controlled trials met the inclusion criteria.Pooled analysis for parallel,randomized controlled trials showed noninvasive positive pressure ventilation:(1) Did not affect the 12-or 24-month mortality (OR 0.82,95％ C/:0.48 to 1.41); (2) Improved the arterial carbon dioxide tension (SMD-0.88,95％C/:-1.43 to-0.34); (3) Did not improve forced expiratory volume in one second (SMD 0.20,95％ C/:-0.06 to 0.46),maximal inspiratory pressure (SMD 0.01,95％ C/:-0.28 to 0.29) or 6-minute walk distance (SMD 0.17,95％ C/:-0.16 to 0.50); (4) Subgroup analysis showed noninvasive positive pressure ventilation improved the arterial carbon dioxide tension in hypercapnic patients.Pooled analysis for crossover randomized controlled trials did not show improvement in arterial blood gas or forced expiratory volume in one second with noninvasive positive pressure ventilation.Conclusions Noninvasive positive pressure ventilation improves the arterial carbon dioxide tension but does not improve the mortality,pulmonary function,or exercise tolerance and should be cautiously used in severe stable chronic obstructive pulmonary disease.

OBJECTIVEHerein, the synthesis, component, microstructure and pharmacological and toxicology researches of the Synthetic Mercury Sulfide (S-HgS) a kind of common drug in Chinese, Mongolia, Tibetan medicine, and Indian medicine system were summarized. The similar cognition about mercury toxicity & pharmacological action from some Asian regions was analyzed, and it can supply some useful direction for the traditional Asian medicine system.

METHODRecent literatures both domestic and abroad were summarized and analyzed.

RESULTS-HgS is the basis of Vermilion, Mongolia-Vermilion, Zuotai, and Ras-sindoor. Athough the processes of synthesis are very different, but the microstructure and pharmacological & toxicology of S-HgS is similar.

CONCLUSIONS-HgS has a far-ranging application,and unique curative effect. New technology such as nanotechnology can be used for improving the advancement of traditional Asian medicine.

Humans ; Medicine, Traditional ; Mercury Compounds ; adverse effects ; chemistry ; pharmacology ; Sulfates ; adverse effects ; chemistry ; pharmacology

BACKGROUNDChromosomal abnormalities have been shown to play an important prognostic role in multiple myeloma (MM). Interphase fluorescence in situ hybridization (i-FISH) has been much more effective to identify cytogenetic aberrations in MM than conventional cytogenetic technique (CC). To clearly determine the cytogenetic features of Chinese MM patients and identify their prognostic implications, we designed a multicenter study based on i-FISH including 672 patients from 52 hospitals in China.

METHODSAll 672 patients were systematically screened for the following genomic aberrations: del(13q), IgH rearrangement, del(p53) and 1q21 amplifications.

RESULTSThe analysis showed that the chromosomal changes were detected in 22.1% patients by CC and in 82.3% patients by i-FISH. The most common abnormalities by CC were chromosome 1 aberrations (48.4%), -13/13q- (37.6%), hyperdiploidy (36.6%), hypodiploidy (30.1%) and IgH rearrangements (23.7%). The most frequent abnormalities by FISH was del(13q), which was found in 60.4% patients, whereas IgH rearrangement, 1q21 amplification and p53 deletions were detected in 57.6%, 49.0% and 34.7% cases, respectively. By statistical analysis, -13/13q- by CC was associated with low level of platelet (P = 0.015), hyperdiploidy was associated with low level of serum albumin (P = 0.028), and IgH rearrangement by FISH was associated with high level of β2 microglobulin (P = 0.019). Moreover, 1q21 amplification and del(p53) by FISH conferred a high incidence of progressive disease (PD) after initial therapy. Metaphase detection of IgH rearrangements and chromosome 1 aberrations concurrently was associated with a short progression free survival (PFS) (P = 0.036). No significant prognostic implications of other cytogenetic abnormalities were found associated with overall survival and PFS.

CONCLUSIONSChinese MM patients had similar cytogenetic abnormalities compared with the previous reported studies. However, the prognostic significance of FISH aberrations were not clearly determined and further study is required.

Adult ; China ; Chromosome Aberrations ; Chromosomes, Human, Pair 1 ; genetics ; Cytogenetic Analysis ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Karyotyping ; Male ; Middle Aged ; Multiple Myeloma ; genetics ; pathology

OBJECTIVETo investigate the optimum proportion of Mosaicplasty and genes-enhanced tissue engineering for the repair of acute osteochondral defects.

METHODSWestern blot test was conducted to detect the expression of hTGF-beta1, Col II and Aggrecan in 3 groups, including hTGF-beta1, transduction group, Adv-betagal transduction group and control group without transduction. Eighteen 6-month-old Shanghai male goats (weight: 22 to 25 kg) were used. BMSCs were isolated from the autologous bone marrow, and were subcultured to get the cells at passage 3. Thirty-six medial femoral condyles were used and divided into 6 groups named AR, AL, BR, BL, CR, and CL. Acute cylindrical defects (9 mm in diameter and 3 mm in depth)were created in the weight bearing area of the medial femoral condyle of hind limbs. In the single group, the autologous osteochondral mosaicplasty was performed to repair the defect; in the combination group, besides the mosaicplasty, the dead space between the cylindrical grafts and the host cartilage were injected with the suspension of hTGF-beta1, gene enhanced autogenous BMSCs in sodium alginate, and CaCl2 was dropped into it to form calcium alginate gels. The autologous osteochondral transplantation cover rates of group AR was 44.44% single group, AL was 44.44% combination group, BR was 33.33% single group, BL was 33.33% combination group, CR was 22.22% single group, and CL was 22.22% combination group. The goats were killed 24 weeks after operation to receive gross and histology observation, which was evaluated by the histological grading scale of O'Driscoll, Keeley and Salter. Immunohistochemistry and TEM observation were also performed.

RESULTSWestern blot test showed the expression of the hTGF-beta1, Col II and the Aggrecan in the hTGF-beta1 transduction group were significantly higher than that of the Adv-betaga1 transduction and the blank control groups. The gross and histology observation revealed that each defects of six groups had different degrees of repairing. There was no significantly difference among the BL, AR, and AL groups. But the scores of the other three groups (BR, CR, and CL) were significantly poorer than the former three groups.

CONCLUSIONMosaicplasty associated with genes enhanced tissue engineering could repair the osteochondral defects effectively. With the autologous osteochondral transplantation coverage reducing, the advantage of the combination could have a better representation.

Animals ; Blotting, Western ; Bone Diseases ; metabolism ; pathology ; therapy ; Cell Line ; Goats ; Humans ; Immunoprecipitation ; Male ; Tissue Engineering ; methods