Background::Cluster of differentiation 8 (CD8 T) cells play critical roles in eradicating human immunodeficiency virus (HIV)-1 infection, but little is known about the effects of T cells expressing CD8 at low levels (CD8 low) or high levels (CD8 high) on HIV-1 replication inhibition after HIV-1 invasion into individual. Methods::Nineteen patients who had been acutely infected with HIV-1 (AHI) and 20 patients with chronic infection (CHI) for ≥2 years were enrolled in this study to investigate the dynamics of the quantity, activation, and immune responses of CD3 +CD8 low T cells and their counterpart CD3 +CD8 high T cells at different stages of HIV-1 infection. Results::Compared with healthy donors, CD3 +CD8 low T cells expanded in HIV-1-infected individuals at different stages of infection. As HIV-1 infection progressed, CD3 +CD8 low T cells gradually decreased. Simultaneously, CD3 +CD8 high T cells was significantly reduced in the first month of AHI and then increased gradually as HIV-1 infection progressed. The classical activation of CD3 +CD8 low T cells was highest in the first month of AHI and then reduced as HIV-1 infection progressed and entered the chronic stage. Meanwhile, activated CD38 -HLA-DR +CD8 low T cells did not increase in the first month of AHI, and the number of these cells was inversely associated with viral load ( r = -0.664, P = 0.004) but positively associated with the CD4 T-cell count ( r = 0.586, P = 0.014). Increased programmed cell death protein 1 (PD-1) abundance on CD3 +CD8 low T cells was observed from the 1st month of AHI but did not continue to be enhanced, while a significant T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif (ITIM) domains (TIGIT) abundance increase was observed in the 12th month of infection. Furthermore, increased PD-1 and TIGIT abundance on CD3 +CD8 low T cells was associated with a low CD4 T-cell count (PD-1: r = -0.456, P = 0.043; TIGIT: r = -0.488, P = 0.029) in CHI. Nonetheless, the nonincrease in PD-1 expression on classically activated CD3 +CD8 low T cells was inversely associated with HIV-1 viremia in the first month of AHI ( r = -0.578, P = 0.015). Notably, in the first month of AHI, few CD3 +CD8 low T cells, but comparable amounts of CD3 +CD8 high T cells, responded to Gag peptides. Then, weaker HIV-1-specific T-cell responses were induced in CD3 +CD8 low T cells than CD3 +CD8 high T cells at the 3rd and 12th months of AHI and in CHI. Conclusions::Our findings suggest that CD3 +CD8 low T cells play an anti-HIV role in the first month of infection due to their abundance but induce a weak HIV-1-specific immune response. Subsequently, CD3 +CD8 low T-cell number decreased gradually as infection persisted, and their anti-HIV functions were inferior to those of CD3 +CD8 high T cells.

Objective: To analyze the clinical characteristics of children with Burkitt lymphoma (BL) and to summarize the mid-term efficacy of China Net Childhood Lymphoma-mature B-cell lymphoma 2017 (CNCL-B-NHL-2017) regimen. Methods: Clinical features of 436 BL patients who were ≤18 years old and treated with the CNCL-B-NHL-2017 regimen from May 2017 to April 2021 were analyzed retrospectively. Clinical characteristics of patients at disease onset were analyzed and the therapeutic effects of patients with different clinical stages and risk groups were compared. Survival analysis was performed by Kaplan-Meier method, and Cox regression was used to identify the prognostic factors. Results: Among 436 patients, there were 368 (84.4%) males and 68 (15.6%) females, the age of disease onset was 6.0 (4.0, 9.0) years old. According to the St. Jude staging system, there were 4 patients (0.9%) with stage Ⅰ, 30 patients (6.9%) with stage Ⅱ, 217 patients (49.8%) with stage Ⅲ, and 185 patients (42.4%) with stage Ⅳ. All patients were stratified into following risk groups: group A (n=1, 0.2%), group B1 (n=46, 10.6%), group B2 (n=19, 4.4%), group C1 (n=285, 65.4%), group C2 (n=85, 19.5%). Sixty-three patients (14.4%) were treated with chemotherapy only and 373 patients (85.6%) were treated with chemotherapy combined with rituximab. Twenty-one patients (4.8%) suffered from progressive disease, 3 patients (0.7%) relapsed, and 13 patients (3.0%) died of treatment-related complications. The follow-up time of all patients was 24.0 (13.0, 35.0) months, the 2-year event free survival (EFS) rate of all patients was (90.9±1.4) %. The 2-year EFS rates of group A, B1, B2, C1 and C2 were 100.0%, 100.0%, (94.7±5.1) %, (90.7±1.7) % and (85.9±4.0) %, respectively. The 2-year EFS rates was higher in group A, B1, and B2 than those in group C1 (χ²=4.16, P=0.041) and group C2 (χ²=7.21, P=0.007). The 2-year EFS rates of the patients treated with chemotherapy alone and those treated with chemotherapy combined with rituximab were (79.3±5.1)% and (92.9±1.4)% (χ²=14.23, P<0.001) respectively. Multivariate analysis showed that stage Ⅳ (including leukemia stage), serum lactate dehydrogenase (LDH)>4-fold normal value, and with residual tumor in the mid-term evaluation were risk factors for poor prognosis (HR=1.38,1.23,8.52,95%CI 1.05-1.82,1.05-1.43,3.96-18.30). Conclusions: The CNCL-B-NHL-2017 regimen show significant effect in the treatment of pediatric BL. The combination of rituximab improve the efficacy further.
Adolescent ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Burkitt Lymphoma/drug therapy* ; Child ; Disease-Free Survival ; Female ; Humans ; Lactate Dehydrogenases ; Lymphoma, B-Cell/drug therapy* ; Male ; Prognosis ; Retrospective Studies ; Rituximab/therapeutic use* ; Treatment Outcome

Objective:Establishment of a new model of human primary colon cancer transplantation tumor in normal immune mice and to provide a reliable experimental animal model for studying the pathogenesis of colon cancer under normal immunity.Methods:Human colon cancer cells come from colon cancer patients who underwent surgery in the Affiliated Hospital of Jining Medical College in 2017. The mice in the cell control group were inoculated with phosphate buffered solution (PBS) containing colon cancer cells, the microcarrier control group was inoculated with PBS containing microcarrier 6, and the cell-microcarrier complex group was inoculated with the PBS containing colon cancer cell-microcarrier complex. The cells of each group were inoculated under the skin of the right axilla of mice by subcutaneous injection, and the time, size, tumor formation rate and pathological changes under microscope were recorded. The transplanted tumor tissue was immunohistochemically stained with the EnVisiion two-step method, and the tumor formation rate of the transplanted tumor was judged according to the proportion of positive cells in the visual field. The polymerase chain reaction (PCR) method was used to detect the expression of human-specific Alu sequence in mice tumor tissue.Results:After inoculation with tumor cells, the mice in the cell control group and the microcarrier control group did not die and did not form tumors; the mice in the cell-microcarrier complex group had palpable subcutaneous tumors in the right axillary subcutaneously on the 5th to 7th days after inoculation, and tumor formation rate is 67% (10/15), and the tumor volume can reach about 500 mm 3 2 to 3 weeks after vaccination. The immunohistochemistry results showed that CK20, CDX-2 and carcinoembryonic antigen were all positively expressed. The PCR results showed that the expression of human-specific Alu sequence can be detected in the transplanted tumor tissue of tumor-bearing mice. Conclusion:Human primary colon cancer cells used microcarrier 6 as a carrier to form tumors in normal immunized mice, and successfully established a new model of human colon cancer transplantation tumor in normal immune mice.

Objective:Establishment of a new model of human primary colon cancer transplantation tumor in normal immune mice and to provide a reliable experimental animal model for studying the pathogenesis of colon cancer under normal immunity.Methods:Human colon cancer cells come from colon cancer patients who underwent surgery in the Affiliated Hospital of Jining Medical College in 2017. The mice in the cell control group were inoculated with phosphate buffered solution (PBS) containing colon cancer cells, the microcarrier control group was inoculated with PBS containing microcarrier 6, and the cell-microcarrier complex group was inoculated with the PBS containing colon cancer cell-microcarrier complex. The cells of each group were inoculated under the skin of the right axilla of mice by subcutaneous injection, and the time, size, tumor formation rate and pathological changes under microscope were recorded. The transplanted tumor tissue was immunohistochemically stained with the EnVisiion two-step method, and the tumor formation rate of the transplanted tumor was judged according to the proportion of positive cells in the visual field. The polymerase chain reaction (PCR) method was used to detect the expression of human-specific Alu sequence in mice tumor tissue.Results:After inoculation with tumor cells, the mice in the cell control group and the microcarrier control group did not die and did not form tumors; the mice in the cell-microcarrier complex group had palpable subcutaneous tumors in the right axillary subcutaneously on the 5th to 7th days after inoculation, and tumor formation rate is 67% (10/15), and the tumor volume can reach about 500 mm 3 2 to 3 weeks after vaccination. The immunohistochemistry results showed that CK20, CDX-2 and carcinoembryonic antigen were all positively expressed. The PCR results showed that the expression of human-specific Alu sequence can be detected in the transplanted tumor tissue of tumor-bearing mice. Conclusion:Human primary colon cancer cells used microcarrier 6 as a carrier to form tumors in normal immunized mice, and successfully established a new model of human colon cancer transplantation tumor in normal immune mice.

Objective To investigate the effect of cisternostomy on the prognosis of patients with traumatic brain injury (TBI).Methods A retrospective case control study was conducted to analyze the clinical data of 46 patients with TBI admitted to Shanxi Dayi Hospital from May 2017 to September 2018.There were 37 males and nine females,aged 24-80 years [(49.8 ± 15.7)years].The injury severity score (ISS) was 6-42 points [(25.0 ± 8.2)points],and the Glasgow Coma score (GCS) was 3-14 points [(3.4 ± 1.7) points].Twenty-three patients underwent routine surgery only (control group),and 23 patients underwent cisternostomy (cisternostomy group) on the basis of routine surgery.Intracranial pressure monitoring was performed in both groups before surgery.The postoperative intracranial pressure,intracranial pressure 1 week after operation,postoperative mechanical ventilation time,neurosurgical ICU (NICU) time,postoperative dehydration dose,decompressive craniectomy rate,postoperative infection rate,mortality rate,length of hospital stay,GCS at discharge,and Glasgow outcome score (GOS) of 3 months of follow-up were compared between the two groups.Results Compared with the control group,the cistemostomy group had lower postoperative intracranial pressure [(7.1 ± 5.7) mmHg vs.(14.2 ± 12.0) mmHg)],intracranial pressure 1 week after operation [(11.8 ± 0.5) mmHg vs.(14.0 ± 0.7) mmHg],postoperative dosage of dehydrating agent [0 (0-500.0) ml vs.1 275 (787.5-3 812.5) ml] and decompression rate (57％ ∶ 91％) (P ＜ 0.05).There were no significant differences between the cistemostomy group and control group in postoperative mechanical ventilation time [120 (42.0-225.0)hours vs.89(65.5-203.5)hours],NICU time [236(182.0-340.5)hoursvs.281 (114-400)hours],postoperative infection rate (4％ vs.0),mortality rate (13％ vs.39％) and hospital stay [32 (20.0-44.5) hours vs.25 (12.0-30.5)hours] (P ＞ 0.05).The cisternostomy group had higher GCS score at discharge than the control group [(10.7 ± 4.2) points vs.(7.9 ± 4.2) points] (P ＜ 0.05).After 3 months of follow-up,18 patients in the cisternostomy group showed good prognosis,better than that in the control group (11 patients) (P ＜ 0.05).Conclusion For TBI patients,cisternostomy can clear the blood cerebrospinal fluid,reduce harmful metabolic products in the brain,reduce intracranial pressure and hence improve the prognosis of patients.

OBJECTIVE: To investigate the effects of millimeter wave (MMW) exposure on apoptosis of human melanoma A375 cells and explore the mechanisms. METHODS: Through electromagnetic field calculation we simulated MMW exposure in cells and calculated the specific absorption rate (SAR). The optimal irradiation parameters were determined according to the uniformity and intensity of the SAR. A375 cells were then exposed to MMV for 15, 30, 60, or 90 min, with or without pretreatment with the caspase-3 inhibitor AC-DEVD-fmk (10 μmol/L) for 1 h at 90 min before the exposure. CCK-8 assay was used to assess the changes in the viability and Annexin-V/ PI staining was used to detect the apoptosis of the cells following the exposures; Western blotting was used to detect the expression of caspase-3 in the cells. RESULTS: The results of electromagnetic field calculation showed that for optimal MMV exposure, the incident field needed to be perpendicular to the bottom of the plastic Petri dish with the antenna placed below the dish. CCk-8 assay showed that MMW exposure significantly inhibited the cell viability in a time-dependent manner ( < 0.05); exposures for 15, 30, 60, and 90 min all resulted in significantly increased apoptosis of the cells ( < 0.05). The cells with MMW exposure showed significantly increased expression of caspase-3. The inhibitory effect of MMW on the cell viability was antagonized significantly by pretreatment of the cells with AC-DEVD-fmk ( < 0.05), which increased the cell viability rate from (36.7±0.09)% to (59.8±0.06)% ( < 0.05). CONCLUSIONS 35.2 GHz millimeter wave irradiation induces apoptosis in A375 cells by activating the caspase-3 protein.
Apoptosis ; Caspase 3 ; metabolism ; Caspase Inhibitors ; pharmacology ; Cell Line, Tumor ; Cell Survival ; Electromagnetic Fields ; Enzyme Activation ; Humans ; Magnetic Field Therapy ; Melanoma ; enzymology ; pathology ; therapy ; Time Factors

Objectives To explore the correlation between the heteroplasmy level of mt5178C＞A mutation in ND2 gene of mitochondria DNA and essential hypertension(EH)in middle-aged and elderly adults.Methods EH patients and normotensive controls were recruited consecutively from 2014-2015 from general population.Demographics,clinical characteristics and blood leukocytes were collected.The mt5178C＞A mutation heteroplasmy level was quantified by the rapid and sensitive realtime polymerase chain reaction(PCR) method for each participant.Results A total of 108 EH patients and 109 controls were recruited.The mt5178C＞A mutation heteroplasmy level was(42 ± 11％)in EH patients and (54± 13)％ in control subjects,with statistically significant difference between the two groups(P＜0.01).Using a two-step cluster analysis,the mt5178C＞A heteroplasmy level exceeding 44％ was associated with a decreased risk of EH(OR=0.18,95％,CI:0.10-0.31,P＜0.01).Correlation analysis showed mt5178C＞ A heteroplasmy level was significantly negatively correlated with both systolic blood pressure (r =-0.38,P＜ 0.001) and diastolic blood pressure (r =-0.49,P＜ 0.01)in 109 controls.Logistic regression analysis demonstrated that in single-factor analysis,mt5178C ＞ A heteroplasmy level (OR =0.82,95 ％ CI:0.77 0.87,P ＜ 0.01) was protective factor for EH,however,BMI(OR=1.30,95％CI:1.12-1.45,P＜0.01),total cholesterol(OR=2.13,95％CI:1.39-3.28,P=0.00),triglyceride(OR=7.62,95％CI:3.45-16.84,P＜0.01)and blood urea nitrogen(OR =1.35,95 ％ CI,P =0.03) were risk factors for EH.And a multiple logistic regression analysis showed that mt5178C＞ A heteroplasmy level (OR =0.83,95 ％ CI:0.78-0.89,P＜ 0.01) was independent protective factor for E H,however,only total cholesterol (OR =2.17,95 ％ CI:1.58-2.98,P =0.02) and low density lipoprotein cholesterol (OR =0.06,95％ CI:0.01-0.83,P =0.04) were independent risk factors for EH,and the P at critical 0.05 value.Conclusions Mitochondrial ND2 gene 5178C＞ A mutation heteroplasmy level exerts protective role against EH in middle-aged and elderly adults in Chinese population.

Objective To investigate the cytotoxicity of γδ T cells to HIV-1 latency cells in patients with early HIV-1 infection.Methods Sixteen early HIV-1-infected patients were enrolled in this study.Peripheral blood mononuclear cells (PBMCs) of patients were isolated and γδ T cells were expanded using zoledronate (5 μmol/L) and interleukin (IL)-2 (1 000 IU/mL) ex vivo.Lactic dehydrogenase (LDH) was used to detect the cytotoxic role of γδ T cells to HIV-1 latency cells(J-Lat Full Length Clonel0.6).The phenotype of γδ T cells before and after expansion and the intensity of GFP in HIV-1 latency cells were detected by flow cytometry.Results Zoledronate plus IL-2 stimulated rapid and large γδ T cells proliferation ex vivo (P＜0.001).γδ T cells showed high cytotoxici ty to latency cells,and the intensity of GFP in latency cells was decreased significantly (P＜0.05).Moreover,expanded γδ T cells displayed cytotoxic NK-like phenotype,the frequency of CD56+ Vδ2 T cells in patients with early HIV-1 infection was significantly higher than that of healthy controls.Conclusions γδ T cell has an ability to eradicate HIV-1 latency,and γδ T cell-based autologous or xenogenous adoptive immunotherapy will have promise prospects to cure HIV-1 infection.

OBJECTIVETo investigate the outcomes and relative risk factors in subjects with impaired fasting glucose in Inner Mongolia, China.

METHODA total number of 32 villages in Kezuohou Banner and Naiman areas in Inner Mongolia were selected as the baseline surveys study fields from 2002 to 2003. Patients with IFG (5.6 mmol/L≤FPG<7.0 mmol/L) but without history of diabetes were selected as the study subjects. A follow-up study was conducted in 2013. Multinomial logistic regression analysis was used to evaluate the correlated factors.

RESULTSThere were 384 patients with IFG recruited in the study. Out of them, 150 (39.1%) progressed to normoglycaemia, 174 (45.3%) remained as IFG, and 60 (15.6%) developed into type 2 diabetes mellitus. Through adjustment multivariately, patients that returning to the status of normoglycaemia were significantly associated under the function of TG (OR = 0.692, 95%CI:0.502-0.952, P < 0.05)and those developed to diabetes were significantly associated with factors as age(OR = 1.052, 95%CI:1.014-1.090, P < 0.05) or obesity (OR = 2.924, 95% CI:1.353-6.320, P < 0.05).

CONCLUSION15.6% of the IFG patients developed diabetes mellitus among the Inner Mongolian population. Elevated TG was an inhibition factor for patients returning to normoglycaemia while both age and abdominal obesity were risk factors for the development of diabetes in the Inner Mongolian population.

Blood Glucose ; analysis ; China ; epidemiology ; Diabetes Mellitus, Type 2 ; epidemiology ; Fasting ; blood ; Follow-Up Studies ; Humans ; Obesity ; epidemiology ; Prediabetic State ; epidemiology ; Risk Factors

Ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF/MS) was developed to identify the absorbed parent components and metabolites in rat bile, plasma and urine after oral administration of Radix Paeoniae Alba extract (RPAE). A total of 65 compounds were detected in rat bile, plasma and urine samples, including 11 parent compounds and 54 metabolites. The results indicated that glucuronidation, hydroxylation and methylation were the major metabolic pathways of the components of RPAE. Furthermore, the results of this work demonstrated that UPLC-Q-TOF/MS combined with MetaboLynx? software and mass defect filtering (MDF) could provide unique high throughput capabilities for drug metabolism study, with excellent MS mass accuracy and enhanced MSE data acquisition. With the MSE technique, both precursor and fragment mass spectra can be simultaneously acquired by alternating between high and low collision energy during a single chromatographic run.