Objective:To analyze the clinical characteristics and prognosis of patients with myelodysplastic syndrome (MDS) with a bone marrow nucleated erythroid cell proportion of greater than or equal to 50% (MDS-E) .Methods:The clinical characteristics and prognostic factors of patients with MDS-E were retrospectively analyzed by collecting the case data of 1 436 newly treated patients with MDS diagnosed in the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences from May 2014 to June 2023.Results:A total of 1 436 newly diagnosed patients with complete data were included in the study, of which 337 (23.5%) patients with MDS-E had a younger age of onset and lower neutrophil and platelet counts compared with those in patients with an erythroid cell proportion of less than 50% (MDS-NE) (all P<0.05). The proportion of MDS cases with ring sideroblasts (MDS-RS) was higher in the MDS-E group than in the MDS-NE group, and multi-hit TP53 mutations were more enriched in the MDS-E group than in the MDS-NE group (all P<0.05). Among patients with MDS-RS, the frequency of complex karyotypes and the TP53 mutation rate were significantly lower in the MDS-E group than in the MDS-NE group (0 vs 11.9%, P=0.048 and 2.4% vs 15.1%, P=0.053, respectively). Among patients with TP53 mutations, the frequencies of complex karyotypes and multi-hit TP53 mutations were significantly higher in the MDS-E group than in the MDS-NE group (87.5% vs 64.6%, P=0.003 and 84.0% vs 54.2%, P<0.001, respectively). Survival analysis of patients with MDS-RS found that the overall survival (OS) in the MDS-E group was better than that in the MDS-NE group [not reached vs 63 (95% CI 53.3-72.7) months, P=0.029]. Among patients with TP53 mutations and excess blasts, the OS in the MDS-E group was worse than that in the MDS-NE group [6 (95% CI 2.2-9.8) months vs 12 (95% CI 8.9-15.1) months, P=0.022]. Multivariate analysis showed that age of ≥65 years ( HR=2.47, 95% CI 1.43-4.26, P=0.001), mean corpuscular volume (MCV) of ≤100 fl ( HR=2.62, 95% CI 1.54-4.47, P<0.001), and TP53 mutation ( HR=2.31, 95% CI 1.29-4.12, P=0.005) were poor prognostic factors independent of the Revised International Prognostic Scoring System (IPSS-R) prognosis stratification in patients with MDS-E. Conclusion:Among patients with MDS-RS, MDS-E was strongly associated with a lower proportion of complex karyotypes and TP53 mutations, and the OS in the MDS-E group was longer than that in the MDS-NE group. Among patients with TP53 mutations, MDS-E was strongly associated with complex karyotypes and multi-hit TP53 mutations, and among TP53-mutated patients with excess blasts, the OS in the MDS-E group was shorter than that in the MDS-NE group. Age of ≥65 years, MCV of ≤100 fl, and TP53 mutation were independent adverse prognostic factors affecting OS in patients with MDS-E.

Objective:To assess the ultrasonographic features and potential diseases of fetal abnormal sylvian fissure(SF), and to explore the value of whole-genome sequencing (WGS) in prenatal detection.Methods:A total of 28 fetuses with a sonographic diagnosis of abnormal SF in Shenzhen Maternal and Child Health Hospital Affiliated to Southern Medical University between October 2018 and October 2020 were prospectively included. The fetal brain was evaluated by neuroultrasound and intrauterine MRI in detail. Amniotic fluid/cord blood obtained by amniocentesis or tissue samples from umbilical cord after birth were collected for WGS. Pregnancy outcomes and postnatal MRI were recorded, and neurodevelopment of live-born infants was followed up for more than 24 months after delivery.Results:During the study period, 28 fetuses with abnormal SF were identified, with a gestational age of 21.3-30.0 (24.8±2.0) weeks. Abnormal SF presented in MCD ( n=15, 53.6%), chromosomal anomalies ( n=3, 10.7%) or single-gene genetic syndromes ( n=3, 10.7%) with the affected fetuses showing developmental delay, hydrocephalus or leukomalacia ( n=4, 14.2%), corpus callosal agenesis with large interhemispheric cysts ( n=1, 3.6%), benign subarachnoid space enlargement with arachnoid cysts ( n=1, 3.6%), and multiple malformations ( n=1, 3.6%). Among the 15 cases with MCD, the most common pathology was lissencephaly/pachygyria, followed by schizencephaly, severe microcephaly, hemimegalencephaly with paraventricular heterotopia, and polymicrogyria. Abnormal SF presented bilaterally in 23 fetuses and unilaterally in 5. All cases were categorized into six types depending on SF morphology in the transthalamic section: no plateau-like or a small insula, linear type, irregular corrugated SF, Z-shaped, and cyst occupying type. In addition to abnormal SF, associated anomalies or mild variations were identified in all fetuses. There were 17 cases underwent intrauterine MRI, and 13 cases underwent postnatal MRI examination.And 25 pregnancies were terminated; 3 were born alive, and 2 had typical syndromic changes with poor neurodevelopmental prognosis. A related pathogenic genetic variant was detected in 57.1% (16/28) fetus, and the incidence of single nucleotide variants(SNVs) was 42.9% (12/28), among which de novo SNVs accounted for 91.7% (11/12). Conclusions:Fetal abnormal SF could be classified based on the ultrasonographic features of transthalamic section. Fetal abnormal SF may indicate MCD, some chromosomal abnormalities or single-gene genetic syndromes that may lead to poor neurodevelopmental outcomes, and may be affected by extra-cortical factors. It is suggested to carry out targeted prenatal genetic diagnosis for fetuses with abnormal SF.

Objective:To observe the morphological changes of the sylvian fissure on the transthalamic section of fetal brain at 20-32 weeks, and grade the fetal sylvian fissure development by means of a simple scoring system and explore its clinical feasibility.Methods:From September 2018 to June 2020, 487 normal single fetuses of 20-32 weeks were examined in Shenzhen Maternal and Child Health Hospital Affiliated to Southern Medical University. The sylvian fissure maturation was analyzed on the transthalamic section of fetal brain at 20-32 weeks and was graded from 0 to 5: un-visualized (grade 0), shallow arc (grade 1), obtuse-angled platform (grade 2), right-angled platform (grade 3), acute-angled platform (grade 4), and closed operculum (grade 5). The pregnancy outcomes and gestational age were recorded.Statistical analysis was performed by SPSS 20.0 software using box plot, Mann-Whitney U test, Weighted Kappa coefficient. Results:Left sylvian fissuer grades were obtained in 280 fetuses and right sylvian fissure grades were obtained in 247 fetuses. The fetal sylvian fissure maturation at 20-32 weeks was graded from 0 to 5, which increased with advancing gestation. Grade 0 only appeared in 3 fetuses at 20 weeks, and 99.4% fetuses at 20 weeks had grade ≥1. Grade 1 appeared in 20-22 weeks, grade 2 in 20-25 weeks, grade 3 in 22-26 weeks, grade 4 in 25-32 weeks, and grade 5 in 27-32 weeks. Box-plot and Mann-Whitney U test showed that gestational week distribution of sylvian fissure at all grades was symmetric on both sides ( P>0.05). The Weighted Kappa coefficients were 0.857(95% CI=0.750-0.957) and 0.939 (95% CI=0.859-1.000), respectively, with strong consistency regarding inter- and intra-observer agreements. Conclusions:Fetal sylvian fissure maturation at 20-32 weeks can be evaluated by means of a simple scoring system with symmetrical grading of both sides.

: AbstractObjective: To investigate the effect of γδ T cells on the proliferation, apoptosis and autophagy of multiple myeloma cells. METHODS: Peripheral blood mononuclear cells (PBMNC) were isolated from healthy volunteers, and stimulated with zoledronic acid (Zol) in combination with rhIL-2. Flow cytometry analysis was used to detected the purity of γδ T cells. γδ T cells were collected and co-cultured with RPMI-8226 or U-266 cells at different effector target ratios. The proliferation of RPMI-8226 or U-266 cell lines were detected by CCK-8. Cell cycle and cell apoptosis were detected by flow cytometry and Western blot．The expressions of autophagy-related proteins were detected by Western blot. RESULTS: γδ T cells can be expanded in vitro. γδ T cells could inhibit the proliferation of RPMI-8226 or U-266 cells, induced cell cycle arrest and promoted apoptosis in an effector target-dependent manner. In addition, γδ T cells could induce autophagy of myeloma cells, inhibited the expression of autophagy-related PI3K, P-AKT and P-mTOR, while increased the expression of AMPK and Beclin-1. CONCLUSION γδ T cells can inhibit the proliferation of RPMI-8226 and U-266 myeloma cells, induce cell cycle arrest, promote apoptosis, and enhance autophagy in vitro. The mechanism may be related to inhibition of PI3K/AKT/mTOR signaling pathway and/or activation of AMPK/Beclin-1 signaling pathway.
AMP-Activated Protein Kinases/pharmacology* ; Apoptosis ; Autophagy ; Beclin-1/pharmacology* ; Cell Proliferation ; Humans ; Leukocytes, Mononuclear/metabolism* ; Multiple Myeloma/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; T-Lymphocytes ; TOR Serine-Threonine Kinases/metabolism*

Objective To observe the intervention effect of typical hot spring bathing in Guizhou province on joint pain, serum anti-keratin antibody(AKA), anti-perinuclear factor antibody(APF)and anti-cyclic citrullinated peptide antibody(CCP). Methods A total of 160 people with joint pain symptoms from five typical hot spring areas in Guizhou province were selected as the subjects. They were treated with hot spring bathing intervention for 4 weeks, once a day, 5 times a week, 40 to 50 minutes each time. According to the evaluation index of physiotherapy natural mineral water in the Code for Geological Exploration and Evaluation of Natural Warm Mineral Water Resources(GB/T 13727-2016)and geological types, the five typical hot springs were divided into three different types, namely water temperature type hot springs(water temperature > 36 ℃), metasilicate type hot springs(metasilicate > 50 mg/L)and warm mineral spring type hot springs(total dissolved solids > 1 000 mg/L). WHO pain grading standard was used to score the degree of joint pain before and after hot spring bathing intervention. Serum APF, AKA and CCP antibodies were detected by ELISA kit before and after hot spring bathing. Results The joint pain score of the subjects was 2.60±0.60, and the joint pain score of the total population decreased after intervention(0.61±0.57, P < 0.05). Before intervention, the joint pain scores of water temperature type, metasilicic acid type and warm mineral spring type were 2.78±0.96, 1.98±1.15 and 3.31±0.57, respectively. After intervention, the scores of joint pain of the three kinds of hot spring bathing patients all decreased(P < 0.05), and were 0.50±0.65, 0.48±0.74 and 0.85±0.90, respectively. Before intervention, AKA(ng/L)and CCP(μg/mL)antibody levels of the observed subjects were 34.89±16.06 and 107.58±10.40, respectively, which significantly decreased after intervention(both P < 0.05), namely 26.06±10.68 and 102.93±6.01, respectively. AKA(ng/L)was 35.04±20.01 before intervention, but decreased significantly after intervention(26.61±7.54, P < 0.05). AKA(ng/L)and CCP(μg/mL)were 31.09±17.26 and 106.51±10.13 before intervention, respectively. After intervention, the above two antibody indexes significantly decreased(all P < 0.05)to 24.53±13.98 and 98.57±5.68, respectively. Before intervention, the AKA(ng/L), APF(ng/mL)and CCP(μg/mL)antibody levels were 38.40±8.66, 349.46±118.43 and 104.96±9.66, respectively. After intervention, the above three antibody indexes significantly decreased(all P < 0.05). The values were 34.00±7.55, 269.38±127.55 and 101.65±3.04, respectively. Conclusion The typical hot spring bathing intervention in Guizhou province can relieve the symptoms of joint pain, and the three types of hot springs can reduce the levels of AKA, APF and CCP antibodies to different degrees, and the warm mineral spring type of hot spring is better than the other types of hot spring.

Objective:To investigate the correlations of human leukocyte antigen (HLA)-A, B, C, and DRB1 genotypes with cross-reactivity caused by aromatic antiepileptic-drugs.Methods:A case-control association study was carried out on subjects who accepted treatments/physical examination in our hospitals from September 2016 and September 2020; 31 patients with aromatic antiepileptic drugs (carbamazepine, phenytoin, oxcarbazepine, lamotrigine and phenobarbital)-induced cross-reactivity were enrolled as patient group, 52 tolerant subjects who took the 5 antiepileptic drugs for more than 3 months without cross-reactivity were chosen as tolerant control group, and 500 healthy volunteers were recruited as normal control group. The ethnicity of all patients and controls was Han Chinese. High-resolution genotyping was performed to compare the HLA-A, B, C, and DRB1 genotypes in subjects of the 3 groups. χ2 test or Fisher's exact test were used to analyze the correlations of HLA genes with cross-reactivity caused by aromatic antiepileptic-drugs. Results:The presence of HLA-B*13:01 genotype in the patient group, the tolerant control group, and the normal control group was 45.2% (14/31), 15.4% (8/52) and 14.6% (73/500), respectively. The presence of HLA-B*13:01 genotype in the patient group was significantly higher as compared with that in the tolerant control group and normal control group ( Pc<0.017). No other HLA genotypes were found to be associated with cross-reactivity caused by aromatic antiepileptic-drugs. Conclusion:HLA-B*13:01 is the risk genotype for cross-reactivity caused by aromatic antiepileptic-drugs.

Objective To investigate the detection results and epidemiological characteristics of hu﹣man adenovirus (HAdV) among children with community acquired pneumonia ( CAP) in Hunan province. Methods A descriptive retrospective survey was conducted to investigate the clinical epidemiological data of 33 056 children with CAP admitted to the Children′s Medical Center of Hunan People′s Hospital from May 1st,2014 to April 30th,2019. The seasonal distribution and demographic characteristics of HAdV infection were analyzed. Results (1) A total of 33 056 children with CAP were included in this study. A total of 3 770 children with HAdV positive were detected,with a total detection rate of 11. 40% (3 770/33 056). From May 2014 to April 2019,the detection rates of adenovirus in different years were 13. 76%,8. 57%, 7. 94%,9. 53%,12. 36% and 24. 75% respectively. Adenovirus detection rate reached its peak in 2019. (2) The detection rate of HAdV among male children were higher than that among female children (χ2 ＝ 6. 374, P＝0. 012). Among 3 770 children with HAdV infection,3 036 (80. 53%) were from 6 months to 5 years old. The detection rate of adenovirus were different in different age groups. The highest detection rate was 16. 65% in 3 to 5 years old group (χ2 ＝526. 494,P<0. 001). Among children with severe pneumonia,the detection rate of adenovirus was 18. 43% (415/2 252). The detection rate of adenovirus was the highest in the age group of 6 months to 1 years, and the difference was statistically significant ( χ2 ＝71. 485, P <0. 001). (3) The detection rate of adenovirus was the lowest in autumn,and the other three seasons were all high﹣incidence seasons (χ2 ＝ 268. 744,P<0. 001). (4) The hospitalization days of adenovirus pneumonia were longer than those of non﹣adenovirus pneumonia (Z＝ －10. 419,P<0. 001). Conclusion The preva﹣lence of HAdV infection is related to age,season and sex. The susceptibility of adenovirus varies with severity of pneumonia. We should be vigilant against the outbreak of adenovirus infection characterized by years.

Objective: To investigate the detection results and epidemiological characteristics of human adenovirus (HAdV) among children with community acquired pneumonia (CAP) in Hunan province. Methods: A descriptive retrospective survey was conducted to investigate the clinical epidemiological data of 33 056 children with CAP admitted to the Children′s Medical Center of Hunan People′s Hospital from May 1st, 2014 to April 30th, 2019.The seasonal distribution and demographic characteristics of HAdV infection were analyzed. Results: (1) A total of 33 056 children with CAP were included in this study.A total of 3 770 children with HAdV positive were detected, with a total detection rate of 11.40% (3 770/33 056). From May 2014 to April 2019, the detection rates of adenovirus in different years were 13.76%, 8.57%, 7.94%, 9.53%, 12.36% and 24.75% respectively.Adenovirus detection rate reached its peak in 2019.(2) The detection rate of HAdV among male children were higher than that among female children (χ²= 6.374, P=0.012). Among 3 770 children with HAdV infection, 3 036 (80.53%) were from 6 months to 5 years old.The detection rate of adenovirus were different in different age groups.The highest detection rate was 16.65% in 3 to 5 years old group (χ²=526.494, P<0.001). Among children with severe pneumonia, the detection rate of adenovirus was 18.43% (415/2 252). The detection rate of adenovirus was the highest in the age group of 6 months to 1 years, and the difference was statistically significant(χ²=71.485, P<0.001). (3) The detection rate of adenovirus was the lowest in autumn, and the other three seasons were all high- incidence seasons (χ²= 268.744, P<0.001). (4) The hospitalization days of adenovirus pneumonia were longer than those of non-adenovirus pneumonia (Z=-10.419, P<0.001). Conclusion The prevalence of HAdV infection is related to age, season and sex.The susceptibility of adenovirus varies with severity of pneumonia.We should be vigilant against the outbreak of adenovirus infection characterized by years.

Objective To summarize and analyze the perioperative complications of irreversible electroporation (IRE) ablation in treating tumors at different locations and to discuss their managements. Methods A total of 200 patients with tumors, including pancreatic tumor (n=71), liver tumor (n=64) and other tumors (n =65), were enrolled in this study. All patients received IRE ablation treatment. The perioperative complications were recorded and the data were statistically analyzed. The causes of severe complications and the treatment of complications were discussed. Results None of the patients died during the course of IRE ablation procedure. Severe postoperative complications occurred in the patients with pancreatic tumor or liver tumor, including duodenal artery bleeding in 3 patients with pancreatic tumor, which occurred at 10 days, 11 days and 15 days after IRE ablation respectively, and gastrointestinal bleeding (n =1) and biliary septic shock (n=1) in 2 patients with liver tumor, which occurred at 9 days after IRE ablation, the clinical symptoms were controlled after interventional embolization and/or vascular ligation together with anti-infective therapy. All minor complications were relieved after symptomatic treatment within 14 days. Conclusion IRE ablation has less systemic inflammatory response, and both the intraoperative and postoperative adverse reactions can be easily controlled, besides, IRE ablation has higher clinical safety. Although IRE ablation procedure may damage the internal or peripheral vessels of the pancreatic tumor, this severe complications can be effectively avoided if proper measures are adopted based on the causes of complications. (J Intervent Radiol, 2018, 27: 223-227)

OBJECTIVE:To establish a method for simultaneous determination of gamabufotalin,arenobufagin,telocinobufa-gin,desacetylcinobufotalin,bufotalin,cinobufotalin,bufalin,cinobufagin and resibufogenin in Liushen pills. METHODS:HPLC method was adopted. The determination was performed on ODS-2 C18 column with mobile phase consisted of acetonitrile-0.15%phosphoric acid(gradient elution)at the flow rate of 1.0 mL/min. The detection wavelength was set at 296 nm,and column temper-ature was 40 ℃. The sample size was 10 μL. RESULTS:The linear ranges of gamabufotalin,arenobufagin,telocinobufagin,de-sacetylcinobufotalin, bufotalin, cinobufotalin,bufalin, cinobufagin and resibufogenin were 1.10-70.39 μg/mL(r=0.9996), 4.03-257.78 μg/mL(r=0.9999),4.09-261.89 μg/mL(r=0.9999),0.67-42.96 μg/mL(r=0.9999),3.36-214.73 μg/mL(r=0.9999), 5.73-366.44 μg/mL(r=0.9999),3.77-241.56 μg/mL(r=0.9999),7.31-468.11 μg/mL(r=0.9999),5.18-331.56 μg/mL(r=0.9999). The limits of quantitation were 1.10,0.85,1.02,0.34,0.84,1.43,0.94,3.66,2.59 μg/mL;the limits of detection were 0.27, 0.21,0.51,0.17,0.42,0.72,0.47,0.91,1.30 μg/mL,respectively. RSDs of precision,stability and reproducibility tests were all lower than 3.0%. The recoveries were 96.35%-103.10%(RSD=2.72%,n=6), 96.76%-103.24%(RSD=2.49%,n=6), 97.01%-101.39%(RSD=1.64%,n=6),97.32%-104.01%(RSD=2.61%,n=6),95.76%-103.60%(RSD=2.92%,n=6), 95.07%-102.59%(RSD=2.92%,n=6),95.77%-101.43%(RSD=2.03%,n=6),95.11%-103.72%(RSD=3.19%,n=6), 95.23%-103.34%(RSD=3.24%,n=6),respectively. CONCLUSIONS:The method is simple,rapid,accurate,reliable and can be used for the determination of bufadienolide in Liushen pills .