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 understand the survival status and its influencing factors of occupational pneumoconiosis patients in Shizuishan City, and to analyze the disease burden of occupational pneumoconiosis and its trend, so as to provide scientific basis for formulating comprehensive prevention and treatment measures of occupational pneumoconiosis. Methods: A retrospective survey was conducted during July to December 2020 to explore the survival status of occupational pneumoconiosis patients who had been reported from 1963 to 2020 in Shizuishan City. The Kaplan-Meier method and Life-table method were used for survival analysis, and Cox proportional hazards regression model was used to analyze the influencing factors of survival time. The disability adjusted life years (DALY) was applied to analyze the disease burden of occupational pneumoconiosis and its temporal trend. Results: From 1963 to 2020, a total of 3263 cases of occupational pneumoconiosis were reported in Shizuishan City, of which 1467 died, so that the fatality rate was 44.96%. The median survival time was 26.71 years, average age of death was (70.55±10.92) years old. There were significant differences in the survival rates of occupational pneumoconiosis patients among different types, diagnosis age, exposure time, industry, initial diagnosis stage and whether upgraded (P<0.05) . As the survival time increased, the survival rate of patients decreased gradually. When the survival time was ≥50 years, the cumulative survival rate of patients was 4.20%. Cox regression analysis suggested that the type of pneumoconiosis, industry, diagnosis age, exposure time, initial diagnosis stage and whether upgraded were the influencing factors for the survival time of patients with occupational pneumoconiosis (P<0.05) . The total DALY attributable to occupational pneumoconiosis from 1963 to 2020 in Shizuishan City was 48026.65 person years, of which the years of life lost (YLL) was 15155.39 person years, and the average YLL was 10.33 years/person, and the years lost due to disability (YLD) was 32871.26 person years, and the average YLD was 10.07 years/person. The DALY attributed to coal worker's pneumoconiosis and silicosis were 39408.51 person years and 6565.02 person years, respectively, and they accounted for 82.06% and 13.67% of the total disease burden in Shizuishan City, respectively. The DALY caused by occupational pneumoconiosis in the age group of 40-49 years old and the first diagnosis of stage I occupational pneumoconiosis were higher, which were 20899.71 and 36231.97 person years, respectively. The average YLL and average YLD showed a volatility downtrend over time. Conclusion: The disease burden of occupational pneumoconiosis cannot be ignored in Shizuishan City, and timely targeted measures should be taken for key populations and key industries. It is recommended that life-cycle health management and hierarchical medical should be taken to improve the life quality of patients and prolong their lifes.
Adult ; Aged ; Aged, 80 and over ; Anthracosis ; China/epidemiology* ; Coal Mining ; Cost of Illness ; Humans ; Middle Aged ; Pneumoconiosis/epidemiology* ; Retrospective Studies

BACKGROUND: Syndrome is one of the most important concepts in Chinese medicine (CM) theory. However, it was not well accounted in most of randomized controlled trials (RCTs). OBJECTIVES: To determine whether CM syndrome differentiation affects the treatment results, functional constipation (FC) was selected as a target disease, and MaZiRenWan (, MZRW), a classic CM formula commonly used for constipation with excessive heat syndrome, was selected for study. METHODS: It is an 18-week prospective double-blinded, doubledummy RCT, including 2-week run-in, 8-week treatment and 8-week post treatment follow-up. A total of 120 FC patients diagnosed as excessive heat syndrome will be recruited from the First Teaching Hospital of Tianjin University of Traditional Chinese Medicine and the Baokang Affiliated Hospital of Tianjin University of Traditional Chinese Medicine. Patients will be randomly allocated into fixed MZRW (f_MZRW) granule group, modified MZRW (m_MZRW) granule group or bisacodyl group. For m_MZRW group, no more than two herbal granules can be added according to the syndrome differentiation for individual participants. The primary end point is the mean of complete spontaneous bowel movements (CSBMs) per week during the treatment period. Secondary end points include mean of CSBMs per week during follow-up, stool form, global symptom improvement, constipation and constipation-related symptoms assessment, CM syndrome change, and reported adverse events. DISCUSSION This trial is designed to evaluate the effectiveness of these three interventions for FC patients with the CM syndrome of excessive heat, and to determine the change of CM syndrome and the progress of disease during the treatment course. The results are important to explore whether syndrome differentiation is important for the therapeutic effect of a formula on a disease. [Trial registration: Chinese Clinical Trial Registry (Reg No. ChiCTR-TRC-13003742); protocol version: MZRW/NSFC-81173363 (2015.05.04)].
Constipation ; diagnosis ; drug therapy ; Double-Blind Method ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Medicine, Chinese Traditional ; Outcome Assessment (Health Care) ; Prospective Studies ; Randomized Controlled Trials as Topic

Objective:To investigate the association of 24 h urinary glucose between blood glucose fluctuation and islet function.Methods:A cross-sectional survey of 124 inpatients with type 2 diabetes was conducted,the clinical data were collected,dynamic blood glucose monitoring system(CGMS)was applied to assess blood glucose fluctuation,the pancreatic β cell secretion function was calculated,aiming to investigate the association of 24 h urinary glucose between blood glucose fluctuation and islet function.Objective:The average of the renal threshold for glucose(RTG)was 11.8 mmol/L and of which 75％were elevated(>10 mmol/L).24 h urinary glucose was 30.54 g.Correlation analysis demonstrated that 24 h urinary glucose was positively associated with fasting blood glucose(FBG),2 h postprandial blood glucose(2 h PBG),the mean blood glucose(MBG),fasting plasma(preprandial)glucose area under the curve(AUC2),postprandial glucose area under the curve(AUC1)and glomerular filtration rate(eGFR),there was a significantly negative relationship between 24 h urinary glucose and the mean amplitude of glucose excursions(MAGE)and RTG,but not associated with course of disease,gender,age of patient,body mass index(BMI),blood pressure、absolute means of daily differences(MODD),the pancreatic β cell secretion function and HbA1c.Multiple stepwise regression analysis showed that 24 h urine sugar was correlated with MAGE,MBG,FBG,eGFR,RTG and AUC2(absolute value of β' was-0.668,0.437,0.148,0.116,-0.107,and 0.086,respectively;P<0.05).Conclusions:The average of the renal threshold for glucose in patients with type 2 diabetes was elevated.The 24 h urinary glucose was related to blood glucose level,blood glucose fluctuations assessed by CGMS,eGFR and RTG,among which,MAGE influenced 24 h urinary glucose most.MAGE may be the most predictive risk factor for 24 h urinary glucose.

Female ; Hernia, Inguinal ; surgery ; Humans ; Incidence ; Infant ; Infant, Newborn ; Laparoscopy ; methods ; Male ; Pyloric Stenosis, Hypertrophic ; epidemiology ; surgery ; Retrospective Studies

Ketamine is a phencyclidine derivative acting primarily as a noncompetitive antagonist of N-methyl-D-aspartate (NMDA) excitatory glutamate receptors. As a common intravenous anaesthetic in clinic, it is also increasingly abused because of its hallucination and addiction effects. Based on the pharmacological and toxicologic characteristics of ketamine and the acknowledged addiction mechanism of other abused drugs, this article reviews the possible addiction mechanism of the ketamine in the aspects of its enhanced effects and reward systems, the anatomic structures, the related receptors and the individual differences.
Anesthetics, Dissociative/adverse effects* ; Animals ; Brain/drug effects* ; Humans ; Illicit Drugs ; Ketamine/adverse effects* ; Mental Disorders/chemically induced* ; Rats ; Receptors, Dopamine/drug effects* ; Receptors, N-Methyl-D-Aspartate/drug effects* ; Substance-Related Disorders

Objective To elucidate the experience in hemioplasty in patients undergoing peritoneal dialysis. Metbods From January 2002 to July 2008, 45 patients having 48 hemias were studied. Inguinal (50.0%) and umbilical (39.6%) were the most common sites. Multiple hemias were detected in 3 patients. All patients were operated upon with tension-free hemioplasty technique using a polypropylene mesh. Automated peritoneal dialysis was reinstituted in 97.8% of the cases in 24 h postoperatively. Results Forty-eight hemias were detected in 45 patients. Mean operation time and post-operative hospital-stay were (63±38) minutes and 4 (1-26) days. Complications occurred in 7(14.6%) hemioplasties (2 wound infections, 2 wound bleeding, 2 seroma and 1 peritonitis). The average follow-up was (29±21) months. None of the patients had leakage or early hemia recurrence due to early resumption of automated peritoneal dialysis (APD); there were no long-term complications (leakage or recurrence). Conclusions Problems accompanying hernia in continuous ambulatory peritoneal dialysis patients can be safely solved by using a careful technique of tension-free hemioplasty. Postoperative dialysis with APD can be applied after operation.

OBJECTIVETo investigate the influence of long-term anoxic exposure on the sperm function of male adults at different altitudes.

METHODSA total of 28 male adults that had stayed at the altitude of 5 340 m for 1-3 years were included as a high-altitude group (HAG), 34 at the mean altitude of 3 800 m for 2-5 years as a middle-altitude group (MAG) and 31 permanently at the altitude of 1 300 m as controls. Semen specimens were collected and the real-time semen analysis was performed by using computer-assisted semen analysis (CASA) system.

RESULTSThe sperm density, VCL, VSL, VAP and LIN in the HAG were (51.12 +/- 14.61) x 10(6)/ ml, (48.17 +/- 13. 52) microm/s, (32.64 +/- 6.70) microm/s, (41.21 +/- 9.32) microm/s and 52.24 +/- 8.14, respectively, significantly lower than those of the control (P < 0.01 or P < 0.05). Compared with the control group, there was a progressive decrease in sperm concentration, sperm motility rate, VSL, VCL, LIN, VAP and ALH in the MAG.

CONCLUSIONThe higher the altitude, the more obvious was the negative effect of anoxic exposure on the sperm function of male adults.

Adult ; Altitude ; Control Groups ; Diagnosis, Computer-Assisted ; Humans ; Male ; Sperm Count ; Sperm Motility ; Spermatozoa ; physiology

The paper presents the development and design of an ultrasonic Doppler fetal heart rate monitoring system based on DSP, and explains the realization of a algorithm for detecting fetal heart rate. Clinical practice has proved that this system is able to pick up the real-time fetal heart rate correctly and rapidly.
Algorithms ; Fetal Monitoring ; instrumentation ; methods ; Heart Rate, Fetal ; physiology ; Humans ; Sensitivity and Specificity ; Signal Processing, Computer-Assisted ; Ultrasonography, Doppler ; instrumentation ; methods ; Ultrasonography, Prenatal ; instrumentation ; methods

OBJECTIVETo deliver the naked genes into cells through the bioeffects of cell membrane porous produced by low-frequency ultrasound (US) and to investigate the safety by determining the threshold of cell damage and membrane permeability.

METHODSThe suspension of red cells from chickens, rabbits, rats, and S180 cells was exposed to calibrated US field with different parameters in still and flowing state. Laser scanning confocal microscopy, fluorescent microscopy, scanning electron microscopy, flow cytometry and spectrophotometry were used to examine cell morphology, membrane permeability, enzymes, free radicals, naked gene expression efficiency, threshold of cell damage and cell viability.

RESULTSThe plasmid of green fluorescent protein (GFP) as a reporter gene was delivered into S180 cells under optimal conditions without cell damage and cytotoxicity. The transfection rate was (35.83 +/- 2.53)% (n = 6) in viable cells, and the cell viability was (90.17 +/- 1.47)% (n = 6). Also, malondialdehyde, hydroxyl free radical, alkaline phosphatase, and acid phosphatase showed a S-shaped growth model (r = 0.98 +/- 0.01) in response to the permeability change and alteration of cell morphology. The constant E of energy accumulation in US delivery at 90% cell viability was an optimal control factor, and at 80% cell viability was the damage threshold.

CONCLUSIONUS under optimal conditions is a versatile gene therapy tool. The intensity of GFP expression in US group has a higher fluorescent peak than that in AVV-GFP group and control group (P < 0.001). The optimal gene uptakes, expression of gene and safety depend on E, which can be applied to control gene delivery efficiency in combination with other parameters. The results are helpful for development of a novel clinical naked gene therapeutic system and non-hyperthermia cancer therapeutic system.

Animals ; Cell Membrane ; chemistry ; metabolism ; ultrastructure ; Cell Survival ; genetics ; Cells, Cultured ; Chickens ; DNA Damage ; genetics ; Free Radicals ; metabolism ; Genes, Reporter ; genetics ; Green Fluorescent Proteins ; genetics ; Malondialdehyde ; metabolism ; Permeability ; Plasmids ; genetics ; Porosity ; Rabbits ; Rats ; Risk Assessment ; Transfection ; methods ; Ultrasonics