Objective : To investigate the effects of microRNA-29a(miR-29a) in mediating the regulation of dihydroartemisinin(DHA) on the immune checkpoint molecule B7H3 in lung adenocarcinoma(LUAD). Methods: The expression level and prognostic significance of B7H3 in LUAD were analyzed by public database. Small interfering RNA(siRNA) was used to knock down B7H3 in LUAD cell lines A549 and HCC827, and cell proliferation was detected by CCK-8 method. A549 and HCC827 cells were treated with gradient concentrations of DHA(0, 5, 10, 25, 50, 100 μmol/L) for 48 h, and the half maximal inhibitory concentrate(IC50) was calculated. A549 and HCC827 cells were treated with IC50concentration of DHA for 1, 2 and 3 days, and the cell proliferation was detected by CCK-8 method. A549 and HCC827 cells were transfected with miR-29a inhibitor. After DHA treatment, the expression level of miR-29a was detected by RT-qPCR, and the expression level of B7H3 was detected by Western blot. Results : B7H3 was overexpressed in LUAD and associated with poor prognosis. After knocking down of B7H3, the proliferation ability of A549 and HCC827 cells significantly decreased(allP<0.001). DHA inhibited the proliferation of A549 and HCC827 cells in both dose-and time-dependent manners, with IC50values of 30.16 μmol/L and 7.50 μmol/L, respectively. DHA up-regulated the expression of miR-29a in A549 and HCC827 cells(P<0.001,P<0.01), and down-regulated the expression of B7H3 in both cell lines(P<0.01,P<0.001). After transfection of miR-29a inhibitor into A549 and HCC827 cells, the expression of B7H3 was up-regulated, and the down-regulation of B7H3 by DHA was partially reversed. Conclusion miR-29a mediates the molecular regulation of DHA on B7H3 in LUAD.

Objective To investigate the regulatory effect of artemisinin derivative dihydroartemisinin(DHA)on anti-tumor immune function of CD8+T cells induced by non-small cell lung cancer(NSCLC)cells.Methods NSCLC A549 cells were divided into DMSO control group and DHA treatment group.A549 cells were treated with DMSO and DHA at different concentrations(25,50 and 100 μmol/L),and the optimal concentration of DHA was selected to treat A549 cells for 0,24,48 and 72 h according to half maximal inhibitory concentrate(IC50).CCK-8 method and colony formation test were used to detect the effect of DHA on the proliferation and colony formation ability of A549 cells.Peripheral blood mononuclear cells(PBMCs)of healthy individuals were isolated by density gradient centrifugation.After monocytes were removed by adhesion method,A549 cells pretreated with mitomycin C were co-cultured with PBMCs at 10:1 ratio.After 2 weeks,flow cytometry was used to detect the proportion of CD8+T cells and the expression levels of perforin and granzyme B.Results Compared with the control group,the proliferation inhibition rates of A549 cells increased after treatment with 25,50 and 100 μmol/L DHA for 24 h(P<0.01).The IC50 of DHA on A549 cells was46.26 μmol/L.According to IC50 concentration analysis,the inhibi-tion rates of A549 cells treated with 50 μmol/L DHA for 0,24,48 and 72h were 1.53%,53.50%,63.84%and 69.91%,and the cells inhibition rates of A548 cells increased compared with the previous observation time point,namely 0,24 and 48 h(P<0.01).The colony formation assay showed that the colony formation number of A549 cells in DHA treated group decreased compared with the control group(P<0.01).Flow cytometry results showed that compared with the control group,the proportion of CD8+T cells induced by A549 cells in the co-culture system and the proportion of CD8+T cells expressing perforin and granzyme B were higher in DHA pretreatment group(P<0.01).Conclusion DHA inhibits the growth of NSCLC cells and promotes anti-tumor immune response of CD8+T cells induced by NSCLC cells.

Objective:To investigate the expression level of miR-21 in patients with septic acute respiratory distress syndrome, and analyze its correlation with inflammatory factors and its value in evaluating clinical prognosis.Methods:Patients with sepsis admitted to the intensive care unit (ICU) of the First Affiliated Hospital of Hebei North University from October 2020 to March 2022 were prospectively recruited. The patients were divided into an ARDS group and a non-ARDS group according to whether ARDS occurred within 3 days after admission. The ARDS group was divided into a low-risk group and a high-risk group according to the oxygenation index, and the ARDS group was divided into a survival group and a death group according to their 28-day survival status. In addition, 50 healthy volunteers who underwent physical examination during the same period were included in the control group. The expression levels of serum miR-21 and inflammatory factors [tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6)] were compared in each group at admission. To analyze the relationship between miR-21 expression and inflammatory factors and explore the value of miR-21 in predicting the prognosis of sepsis patients with ARDS.Results:A total of 106 patients with sepsis were included. Compared with the healthy control group, the levels of serum miR-21, TNF-α and IL-6 in the ARDS group and non-ARDS group were significantly increased (all P<0.05). Compared with the low-risk group, the levels of serum miR-21, TNF-α and IL-6 in the high-risk group were significantly increased (all P<0.05). Compared with the survival group, the serum miR-21 expression level and TNF-α and IL-6 levels in the death group were significantly increased (all P<0.05). Pearson correlation analysis showed that the serum miR-21 expression level in the ARDS group was positively correlated with IL-6 and TNF-α levels ( r=0.842, 0.697, P<0.001). ROC curve analysis showed that the AUC of serum miR-21 in predicting death from sepsis complicated with ARDS was 0.876 (95% CI: 0.761-0.942), the best cut-off value was 2.25, and its sensitivity and specificity were 92.9% and 71.7%, respectively. Conclusions:The expression level of serum miR-21 is significantly increased in patients with sepsis ARDS, is positively correlated with the level of inflammatory factors, is closely correlated with the severity and prognosis of the disease, and has great value in evaluating the prognosis of patients with sepsis ARDS.

OBJECTIVE: To explore the genetic basis for fetus with bilateral lateral ventriculomegaly. METHODS: Fetus umbilical cord blood and peripheral blood samples of its parents were collected. The fetus was subjected to chromosomal karyotyping, whilst the fetus and its parents were subjected to array comparative genomic hybridization (aCGH). The candidate copy number variation (CNV) were verified by qPCR, Application goldeneye DNA identification system was used to confirm the parental relationship. RESULTS: The fetus was found to have a normal karyotype. aCGH analysis indicated that it has carried a 1.16 Mb deletion at 17p13.3, which partially overlapped with the critical region of Miller-Dieker syndrome (MDS), in addition with a 1.33 Mb deletion at 17p12 region, which is associated with hereditary stress-susceptible peripheral neuropathy (HNPP). Its mother was also found to harbor the 1.33 Mb deletion at 17p12. qPCR analysis confirmed that the expression levels of genes from the 17p13.3 and 17p12 regions were about the half of that in the normal control, as well as the maternal peripheral blood sample. Parental relationship was confirmed between the fetus and its parents. Following genetic counseling, the parents has chosen to continue with the pregnancy. CONCLUSION The fetus was diagnosed with Miller-Dieker syndrome due to the de novo deletion at 17p13.3. Ventriculomegaly may be an important indicator for prenatal ultrasonography in fetuses with MDS.
Pregnancy ; Female ; Humans ; Classical Lissencephalies and Subcortical Band Heterotopias ; Comparative Genomic Hybridization ; DNA Copy Number Variations ; Fetus ; Hydrocephalus ; Prenatal Diagnosis ; Chromosome Deletion

OBJECTIVE: To explore the genetic etiology of two patients with developmental delay and intellectual disability. METHODS: Two children who were respectively admitted to Henan Provincial People's Hospital on August 29, 2021 and August 5, 2019 were selected as the study subjects. Clinical data were collected, and array comparative genomic hybridization (aCGH) was carried out on the children and their parents for the detection of chromosomal microduplication/microdeletions. RESULTS: Patient 1 was a 2-year-and-10-month female and patient 2 was a 3-year-old female. Both children had featured developmental delay, intellectual disability, and abnormal findings on cranial MRI. aCGH revealed that patient 1 has harbored arr[hg19] 6q14.2q15(84621837_90815662)×1, a 6.19 Mb deletion at 6q14.2q15, which encompassed ZNF292, the pathogenic gene for Autosomal dominant intellectual developmental disorder 64. Patient 2 has harbored arr[hg19] 22q13.31q13.33(46294326_51178264)×1, a 4.88 Mb deletion at 22q13.31q13.33 encompassing the SHANK3 gene, haploinsufficiency of which can lead to Phelan-McDermid syndrome. Both deletions were classified as pathogenic CNVs based on the guidelines of American College of Medical Genetics and Genomics (ACMG) and were not found in their parents. CONCLUSION The 6q14.2q15 deletion and 22q13-31q13.33 deletion probably underlay the developmental delay and intellectual disability in the two children, respectively. Haploinsufficiency of the ZNF292 gene may account for the key clinical features of the 6q14.2q15 deletion.
Humans ; Child ; Female ; Child, Preschool ; Intellectual Disability/genetics* ; Comparative Genomic Hybridization ; Chromosome Disorders/genetics* ; Chromosome Deletion ; Magnetic Resonance Imaging ; Chromosomes, Human, Pair 22 ; Developmental Disabilities/genetics* ; Carrier Proteins/genetics* ; Nerve Tissue Proteins/genetics*

Objective:To investigate the relationship between dosimetric parameters and tumor volume change after 125I implantation for thyroid cancer and obtain better dosimetric parameters that predict the curative effect more accurately. Methods:A total of 22 consecutive patients with thyroid cancer (23 targets) who received 125I interstitial brachytherapy in Department of Oncology, Hebei General Hospital were retrospectively analyzed. All the patients received post-operative dose verification, and the D 90 (Minimum dose received by 90% target volume) was calculated. After a regular follow-up, the tumor volume reduction ratio after t months (R t) , actual absorbed dose (D 1m) , efficacy corrected absorbed dose (D 1e) , and sensitivity corrected absorbed dose (D 1s) of the first month were calculated according to the actual follow-up CT images. The statistical test was carried out by SPSS21.0. The Spearman linear analysis was applied to analyze the relationship between D 90, D 1m, D 1e, D 1s and R t, and the curve fitting was also completed. Results:The post-operative D 90, D 1m, D 1e, D 1s and R t were (129.73±14.22) Gy, (36.95±7.35) Gy, (43.45±11.32) Gy, (41.78±13.39) Gy, and (32.00±19.00) %, respectively. And the correlation coefficient were 0.692, 0.551, 0.728, and 0.858, respectively, which showed significant positive relevance between dosimetric parameters and tumor volume change ( P<0.01) , the curve fitting presented cubic function. Conclusion:The post-operative D 90, D 1m, D 1e, and D 1s can be predictors for curative effect, and D 1s is the best predictor.

Objective:To explore the value of octreotide suppression test(OST) in predicting the efficacy of somatostatin receptor ligands(SRLs) in the treatment of active acromegaly.Methods:The clinical data of 76 patients with active acromegaly from 2011 to 2020 was retrospectively analyzed. OST was carried out as follows: After an overnight fasting and baseline sampling of growth hormone(GH), 100 μg octreotide was subcutaneously injected, and sampling for GH was obtained every 2 hours for 8 hours. All patients were treated with SRLs for at least 3 months. A good GH response is defined as a post-treatment random GH<1 μg/L or >80% fall compared with the baseline GH. A good insulin-like growth factor Ⅰ(IGF-Ⅰ) response is defined as IGF-Ⅰ<1.3 upper limit of normal(ULN) or >50% reduction compared with the baseline. If both GH and IGF-Ⅰ fulfill the criteria of a good response, it is defined as a good GH and IGF-Ⅰ response.Results:The baseline level of GH during OST was 15.00(6.38, 34.20) μg/L, the median time to reach the nadir GH was(3.65±1.65) hours, and the nadir GH level was 1.47(0.50, 4.19) μg/L. The median GH suppression rate was 89.12%(72.71%, 95.09%). When the cutoff value of GH suppression rate in predicting a good GH response was 89.32%, the area under the curve(AUC) was 0.74, with a sensitivity of 81.80% and specificity of 66.00%. When the cutoff value of GH suppression rate in predicting a good IGF-Ⅰ response was 93.14%, the AUC was 0.64, with a sensitivity of 50.00% and specificity of 75.60%. When the GH suppression rate was 90.71%, the AUC was 0.78, with the sensitivity of 83.30% and specificity of 70.00% in predicting a good GH and IGF-Ⅰ response. Compared with GH/IGF-Ⅰ non-responders, GH/IGF-Ⅰ responders displayed lower nadir GH during OST, higher GH suppression rate and IGF-Ⅰ reduction rate, and lower ratio of IGF-1 to ULN( P<0.05). Conclusion:GH suppression rate during the OST is a valuable predictor to evaluate the efficacy of SRLs in patients with acromegaly, with the highest sensitivity and specificity when the cutoff value is 90.71%.

DECIDE-Diet trial was taken as a case to introduce the methods of blinding and blinding assessment for feeding trials, report the details of blinding, conduct a blinding survey and calculate Jame's BI and Bang's BI. Jame's BI was 0.683 (95% CI: 0.593~0.772). The Bang's BI for the intervention group was 0.340 (95% CI: 0.199~0.481), and for the control group was 0.086 (95% CI: -0.060~0.231). The blinding of the DECIDE)-Diet was generally successful, but the intervention group may infer their group to a certain extent. Feeding trials should report the details of blinding and consider blinding assessment.

Objective:To explore the clinical value of heparin binding protein (HBP) in bronchoalveolar lavage fluid (BALF) for diagnosis and differential diagnosis of bacterial pneumonia.Methods:Eighty eight patients with pulmonary infection from the respiratory department of the Fourth Affiliated Hospital of Anhui Medical University from January 2019 to January 2021 were enrolled in the study, including 48 cases of bacterial pneumonia and 40 cases of non-bacterial pneumonia; meanwhile, 40 non-pulmonary infection patients were also enrolled as the control group. The BALF levels of HBP, procalcitonin (PCT), interleukin-6 (IL-6) were measured, and the clinical values of the above indexes in differential diagnosis of bacterial and non-bacterial pneumonia were analyzed.Results:The BALF levels of HBP and IL-6 in bacterial pneumonia group were significantly higher than those of the non-bacterial pneumonia group and the control group ( P<0.05). ROC curve showed that the areas under the curve (AUC) of HBP and IL-6 were 0.930 and 0.893 for the early diagnosis of bacterial pneumonia; and the sensitivity was 88.5% and 82.7%, the specificity was 92.5% and 92.5%, respectively. Combined detection of HBP and IL-6, the AUC was 0.942 and the sensitivity was 94.2% and the specificity was 95.0%. When they were used to distinguish bacterial pneumonia, the AUC of HBP and IL-6 were 0.890 and 0.777, and the sensitivities were 80.8% and 71.2%, and the specificity were 91.7% and 75.0%, respectively. Combined detection of HBP and IL-6, the AUC was 0.902, and the sensitivity was 96.2% and the specificity was 79.2%. Conclusions:BALF HBP and IL-6 have good clinical value in the early diagnosis and distinguishing bacterial pulmonary infection and the joint value of the two is better.

Objective To compare the effect of different enteral nutritional support methods in elderly patients with severe pneumonia.Methods Elderly patients (average age over 65 years) with severe pneumonia admitted to our hospital from June 2015 to June 2018 were selected as the study subjects,and 86 patients finally completed the study.The patients were randomly divided into the control group and observation group with 43 patients in each group,and nasojejunal tubes were placed for patients in both groups.Patients in the observation group were fed with enteral nutrition emulsion through continuously-heated nutritional pump,while patients in the control group was meal served with enteral nutrition emulsion.Changes in blood biochemical parameters,immune indexes,inflammation indexes,oxygenation indexes,the GIDF and SOFA scores as well as curative effect (mechanical ventilation time and effective rate of treatment) were monitored and compared before and after 10 days of nutritional support treatment.SPSS 20.0 statistical software package was used for data analysis,and self paired t-test was used for comparison before and after intervention in the same group,x2 test was used in comparison between different groups,and the counting data was expressed as the rate (n,％).Results There was no significant difference in baseline data between patients in the two groups (P＞0.05).After ten days of intervention,compared with the control group,the levels of serum albumin and prealbumin in the observation group were higher [(31.22±2.36) g/L and (0.29±0.24) g/L,P=0.015 and P=0.023],the immune indexes were higher [IgG (13.24±0.70) g/L,P=0.020;IgM (1.43±0.19) g/L,P=0.011;CD4+/CD8+ 1.55±0.49,P=0.043],the inflammation indexes were lower [IL-6 (312.54±42.53) pg/mL,P=0.031;PCT (1.56±0.81) ng/mL,P=0.017],the oxygenation indexes were better [PaO2/FiO2 (315.58±20.37) mmHg,P=0.019],and the GIDF and SOFA scores were significantly lower[(10.6±l.2) and (8.5±1.7),P=0.041 and P=0.038].The clinical outcome showed that the mechanical ventilation time in the observation group was significantly shorter [(6.01±1.48) d vs (8.12 ± 1.17)d,P=0.039],and the total effective rate of treatment was better than the control group (67.44％ vs 41.86％,P=0.027).Conclusions Enteral nutrition support through continuously-heated nutritional pump can improve the nutritional status of elderly patients with severe pneumonia,reduce the incidence of gastrointestinal dysfunction,maintain stable organ fuction,thus resulting in better prognosis in elderly patients with severe pneumonia.