Objective To investigate the clinical features and prognosis of childhood acute lymphoblastic leukemia (ALL) with CREBBP gene mutation. Methods A retrospective analysis was performed for the clinical data of 14 ALL children with CREBBP gene mutation who were admitted to Children's Hospital of the First Affiliated Hospital of Zhengzhou University from January 2016 to December 2023. Results The ALL patients with CREBBP gene mutation accounted for 1.5％ (14/963) among all children diagnosed with ALL during the same period of time,among whom there were 4 boys (29％) and 10 girls (71％),with a median age of 4 years and 3.5 months. All children had an immunological type of B-cell ALL and concurrent mutations in other genes including NRAS,KRAS,ETV6,FLT3,PAX5,SH2B3,CDKN2A,and CDKN2B,and 4 children had karyotype abnormality. All 14 children received induction therapy with the VDLP regimen,with a complete remission (CR) rate of 79％ (11/14) after the first course of treatment. Three children experienced bone marrow recurrence alone,with a recurrence rate of 21％ (3/14),among whom 1 child achieved CR after blinatumomab therapy and 2 received bridging hematopoietic stem cell transplantation after chemotherapy for recurrence. Among the 14 children,1 died due to treatment discontinuation and 13 achieved disease-free survival. The 5-year overall survival rate was 92％±7％,and the event-free survival rate was 73％±13％. Conclusions ALL with CREBBP gene mutation is more common in girls and has a low induction remission rate and a high recurrence rate,and it is often accompanied by other types of gene mutations and abnormal karyotypes. Most children with recurrence can achieve long-term survival after immunotherapy or hematopoietic stem cell transplantation.

Objective To explore the correlation of glucose and lipid metabolism indicators combined with antiphospholipid antibodies with the prognosis of patients with atherosclerosis.Methods A total of 128 patients with atherosclerosis treated in our hospital from April 2021 to March 2023 were selected as study group,and 48 healthy individuals as control group.Glycolipid metabolism indexes and antiphospholipid antibody level of the two groups were compared,and the predictive value of glycolipid metabolism indexes,antiphospholipid antibodies and combined detection for the prognosis of patients with atherosclerosis were analyzed by ROC.Results TC,TG,ACL,and anti-β2-GP1 in the study group was higher than that in the control group(P＜0.05).The study group was divided into two sub-groups according to the prognosis.The expression level of TC,TG,ACL,and anti-β 2-GP1 in poor prognosis group was higher than that in good prognosis group(P＜0.05).TC,TG,ACL,and anti-β 2-GP1 was positively correlated with the poor prognosis of patients with atherosclerosis(P＜0.05).ROC curve showed that the predictive value of six combined tests for the prognosis of patients with atherosclerosis was higher than that of single test of TC,TG,ACL,and anti-β2-GP1(P＜0.05).Conclusion The combined detection of TC,TG,ACL,and anti-β2-GP1 has high predictive value for the prognosis of patients with atherosclerosis.

Objective To investigate the spatiotemporal distribution characteristics and potential influencing factors of newly diagnosed echinococcosis cases in Qinghai Province from 2016 to 2022, so as to provide insights into the formulation of the echinococcosis control strategy in Qinghai Province. Methods The number of individuals screened for echinococcosis, number of newly diagnosed echinococcosis cases, number of registered dogs and number of stray dogs were captured from the annual reports of echinococcosis control program in Qinghai Province from 2016 to 2022, and the detection of newly diagnosed echinococcosis cases was calculated. The number of populations, precipitation, temperature, wind speed, sunshine hours, average altitude, number of year-end cattle stock, number of year-end sheep stock, gross domestic product (GDP) per capita, and number of village health centers in each county (district) of Qinghai Province were captured from the Qinghai Provincial Statistical Yearbook, and county-level electronic maps in Qinghai Province were downloaded from the National Platform for Common Geospatial Information Services. The software ArcGIS 10.8 was used to map the distribution of newly diagnosed echinococcosis cases in Qinghai Province, and the spatial autocorrelation analysis of newly diagnosed echinococcosis cases was performed. In addition, the spacetime scan analyses of number of individuals screened for echinococcosis, number of newly diagnosed echinococcosis cases and geographical coordinates in Qinghai Province were performed with the software SaTScan 10.1.2, and the spatial stratified heterogeneity of the detection of newly diagnosed echinococcosis cases was investigated with the software GeoDetector. Results A total of 6 569 426 residents were screened for echinococcosis in Qinghai Province from 2016 to 2022, and 5 924 newly diagnosed echinococcosis cases were found. The detection of newly diagnosed echinococcosis cases appeared a tendency towards a decline over years from 2016 to 2022 (χ² = 11.107, P < 0.01), with the highest detection in Guoluo Tibetan Autonomous Prefecture in 2017 (82.12/10⁵). There were spatial clusters in the detection of newly diagnosed echinococcosis cases in Qinghai Province from 2016 to 2018 (Moran’s I = 0.34 to 0.65, all Z values > 1.96, all P values < 0.05), and the distribution of newly diagnosed echinococcosis cases appeared random distribution from 2019 to 2022 (Moran’s I = −0.09 to 0.04, all Z values < 1.96, all P values > 0.05). Local spatial autocorrelation analysis showed high-high clusters and low-low clusters in the detection of new diagnosed echinococcosis cases in Qinghai Province from 2016 to 2022, and space-time scan analysis showed that the first most likely cluster areas of newly diagnosed echinococcosis cases in Qinghai Province from 2016 to 2022 were mainly distributed in Yushu Tibetan Autonomous Prefecture and Guoluo Tibetan Autonomous Prefecture. GeoDetector-based analysis of the driving factors for the spatial stratified heterogeneity of detection of newly diagnosed echinococcosis cases in Qinghai Province showed that average altitude, number of village health centers, number of cattle and sheep stock, GDP per capita, annual average sunshine hours, and annual average temperature had a strong explanatory power for the spatial distribution of newly diagnosed echinococcosis cases, with q values of 0.630, 0.610, 0.600, 0.590, 0.588, 0.537 and 0.526, respectively. Conclusions The detection of newly diagnosed echinococcosis cases appeared a tendency towards a decline in Qinghai Province over years from 2016 to 2022, showing spatial clustering. Targeted control measures are required in cluster areas of newly diagnosed echinococcosis cases for further control of the disease.

During the development of whole-cell microbial sensors,factors such as cellular metabolic activity and signal output modes play pivotal roles in the stability and repeatability of the sensors,presenting numerous challenges for the standardization of sensor applications. This research focused on the arsenic ion sensor based on the RepL amplifier,adjusting the reporter genes,culture media,growth stages,and induction times of arsenic ions,aiming to investigate how these factors affect the sensor's detection performance. The results indicated that the cell's culturing environment,growth status (e.g.,different growth phases),type of reporter,and induction time all had significant impacts on the performance of the arsenic ion sensor. First,the stability of the sensors varied greatly in different media,all the three sensors displayed greater stability in LB culture medium. Meanwhile,the cells in different growth stages also exhibited different performance advantages. Cells at the stationary growth phase exhibited better detection sensitivity and linearity,while cells in the logarithmic growth phase had lower limit of detection (LOD) . Moreover,there was an optimal induction time for the response of the sensor,overly long or short induction time could interfere with its response. The optimal induction time for the arsenic sensor in this work was about 2-3 h. By comparing three types of fluorescent protein reporters,it was found that although their detection limits were fairly similar,all within the range of 5-10μg/L,but their response times varied,ranging from 40 min to 2 h. The fluorescent proteins with higher brightness exhibited faster sensor response. These research outcomes provided a solid foundation for the practical application of microbes in detection. In practice,we could choose cells in specific states based on particular purpose,maximizing the performance of the cell sensors and further broadening the application scope of such sensors.

Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.

Objective: To explore the heterogeneity and correlation of clinical phenotypes and genotypes in children with disorders of sex development (DSD). Methods: A retrospective study of 1 235 patients with clinically proposed DSD in 36 pediatric medical institutions across the country from January 2017 to May 2021. After capturing 277 DSD-related candidate genes, second-generation sequencing was performed to analyzed the heterogeneity and correlation combined with clinical phenotypes. Results: Among 1 235 children with clinically proposed DSD, 980 were males and 255 were females of social gender at the time of initial diagnosis with the age ranged from 1 day of age to 17.92 years. A total of 443 children with pathogenic variants were detected through molecular genetic studies, with a positive detection rate of 35.9%. The most common clinical phenotypes were micropenis (455 cases), hypospadias (321 cases), and cryptorchidism (172 cases) and common mutations detected were in SRD5A2 gene (80 cases), AR gene (53 cases) and CYP21A2 gene (44 cases). Among them, the SRD5A2 mutation is the most common in children with simple micropenis and simple hypospadias, while the AMH mutation is the most common in children with simple cryptorchidism. Conclusions: The SRD5A2 mutation is the most common genetic variant in Chinese children with DSD, and micropenis, cryptorchidism, and hypospadias are the most common clinical phenotypes. Molecular diagnosis can provide clues about the biological basis of DSD, and can also guide clinicians to perform specific clinical examinations. Target sequence capture probes and next-generation sequencing technology can provide effective and economical genetic diagnosis for children with DSD.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics* ; Child ; China/epidemiology* ; Cryptorchidism/genetics* ; Disorders of Sex Development/genetics* ; Female ; Genital Diseases, Male ; Genotype ; Humans ; Hypospadias/genetics* ; Male ; Membrane Proteins/genetics* ; Penis/abnormalities* ; Phenotype ; Retrospective Studies ; Steroid 21-Hydroxylase/genetics*

Objective: Autologous peripheral blood stem cells (PBSC) derived from bone marrow can promote liver regeneration and improve the liver function of patients, but there are few studies on its effect on the long-term outcomes in patients with decompensated cirrhosis. Based on previous work, this study observed the clinical outcomes of PBSC treatment in patients with decompensated cirrhosis for 10 years, in order to provide more data support for the safety and efficacy of stem cells in clinical applications. Methods: Data of patients with decompensated liver cirrhosis who completed PBSC treatment in the Department of Gastroenterology of the First Affiliated Hospital of Air Force Military Medical University from August 2005 to February 2012 were included. The follow-up endpoint was death or liver transplantation, and patients who did not reach the follow-up endpoint were followed-up for at least 10 years. The patients with decompensated liver cirrhosis who met the conditions for PBSC treatment but did not receive PBSC treatment in our hospital during the same period were used as controls. Results: A total of 287 cases with decompensated liver cirrhosis had completed PBSC treatment, and 90 cases were lost to follow-up within 10 years after surgery. A total of 151 cases with complete survival follow-up data were included in the control group. There were no statistically significant differences in baseline information such as gender, age, etiological composition and liver function score between the two groups. The 10-year survival rate was higher in PBSC than control group (37.56% vs. 26.49%, P<0.05). Cholinesterase, albumin, international normalized ratio, Child-Turcotte-Pugh score, model for end-stage liver disease score, and other indicators were gradually recovered within 3 months to 1 year after PBSC treatment, and stabilized at a more desirable level in the long-term after follow-up for up to 10 years. There was no statistically significant difference in the incidence of liver cancer between the two groups (25.22% vs.31.85%, P=0.267). The age of onset of hepatocellular carcinoma was later in PBSC than control group [(56.66±7.21) years vs. (52.69±8.42) years, P<0.05]. Conclusions: This long-term observational follow-up study of more than ten years confirms that PBSC treatment can bring long-term benefits to patients with decompensated cirrhosis, with good long-term safety, thus providing more data support on the safety and efficacy of stem cells for clinical applications.
End Stage Liver Disease ; Follow-Up Studies ; Humans ; Liver Cirrhosis/drug therapy* ; Middle Aged ; Peripheral Blood Stem Cells ; Severity of Illness Index ; Treatment Outcome

Objective: We evaluated the safety and efficacy of lipoprotein apheresis (LA) in patients with familial hypercholesterolemia (FH) who can't reach low-density lipoprotein cholesterol(LDL-C) target goals with the maximal tolerated dose of lipid-lowering agents. Methods: This was a retrospective cross-sectional study. Between February 2015 and November 2019, patients with FH who were admitted in Fuwai hospital and treated with LA were consecutively enrolled. Based on intensive lipid-lowering agents, these patients received LA by double filtration plasma pheresis (DFPP) method. The changes of lipid levels such as LDL-C and lipoprotein(a)[Lp(a)] were compared before and after LA treatment, and the changes of immunoglobulin (Ig) concentration and LA-related adverse effects were also discussed. Results: A total of 115 patients with FH were enrolled in this study, of which 8 cases were homozygous FH and 107 cases were heterozygous FH. The age was (43.9±12.2) years and there were 75 (65.2%) males, and 108 (93.8%) with coronary artery disease. For pre-and immediately after LA treatment, the LDL-C was (5.20±2.94) mmol/L vs. (1.83±1.08) mmol/L, Lp(a) concentration was 428.70(177.00, 829.50)mg/L vs. 148.90(75.90, 317.00) mg/L (P<0.001), with a decrease of 64.2% and 59.8% respectively. The levels of IgG and IgA measured 1 day after LA treatment were both in the normal range and IgM concentration was below the reference value, the reductions of which were 15.1%, 25.0% and 58.7% respectively (P<0.001). Six patients had mild symptoms of nausea, hypotension dyspnea and palpitation, the symptoms were relieved by symptomatic treatment. Conclusion: For patients with FH who do not achieve LDL-C target goal with the maximal tolerated lipid-lowering agents, especially those with elevated Lp(a) levels, LA, which can significantly further reduce LDL-C and Lp(a) levels, is an effective and safe option.
Adult ; Blood Component Removal/methods* ; Cholesterol, LDL ; Cross-Sectional Studies ; Female ; Humans ; Hyperlipoproteinemia Type II/therapy* ; Lipoprotein(a)/chemistry* ; Lipoproteins/chemistry* ; Male ; Middle Aged ; Retrospective Studies

Objective: To investigate the prevalence of allergic rhinitis (AR) in 3 central cities (Chifeng, Hohhot, Ordos) and the surrounding rural areas of Inner Mongolia region, and to look for possible risk factors related to the disease. Methods: From March to October of 2019, a multi-stage stratified random sampling epidemiological survey was conducted in Chifeng, Hohhot, Ordos and rural areas. The AR-related factors of the population were obtained in the form of face-to-face questionnaire survey, and the skin prick test (SPT) was taken for the participants. AR disease was diagnosed according to the "Guidelines for the Diagnosis and Treatment of Allergic Rhinitis (2015, Tianjin)". The daily airborne pollen situation in the three regions was monitored during the same period. SPSS 23.0 was used to analyze all survey results. Results: A total of 6 818 questionnaires were recovered, with 6 393 valid questionnaires. The self-reported prevalence of AR was 27.72% (1 772/6 393) and the confirmed prevalence of AR was 17.10% (1 093/6 393). The prevalence of perennial AR was 1.83% (117/6 393) while the prevalence of seasonal AR was 15.27% (976/6 393). The prevalence of AR diagnosed in females was higher than that in males (19.19% vs 15.34%, χ²=16.594, P<0.001) and the prevalence of females in the two age groups of 36-45 years and 46-55 years was significantly higher than that of males (18.17% vs 9.73%, 14.13% vs 7.25%, χ² value was 23.848, 18.772, respectively, all P<0.001). The prevalence of confirmed diagnoses in ethnic minorities was higher than that of Han nationality, and the prevalence of confirmed diagnoses in urban areas was higher than that in rural areas (23.13% vs 16.20%, 27.27% vs 9.71%, χ² value was 24.516, 336.024, respectively, all P<0.001). The main nasal symptoms of AR patients were sneezing (91.31%), nasal congestion (85.91%) and nasal itching (85.00%). The most common concomitant disease of AR was allergic conjunctivitis (73.99%). Asthma (OR=6.629), food allergy (OR=3.236), drug allergy (OR=1.786), application of antibiotics (OR=1.553), recent home decoration (OR=2.307), and smoking (OR=1.322) were the AR related risk factors. The highest proportion of SPT positive reactions was Artemisia annua (80.15%). The peak period of clinical symptoms of AR patients in Inner Mongolia region was July to September, which was consistent with the second peak period of airborne pollen monitoring. Conclusions: The prevalence of AR in central cities and the surrounding rural areas of Inner Mongolia region is 17.10%, and Artemisia species is the most important pollen allergen in this area. History of asthma, food allergy, drug allergy, antibiotic use, home decoration and smoking history are the related risk factors for AR.
Adult ; Allergens ; China/epidemiology* ; Female ; Humans ; Male ; Middle Aged ; Pollen ; Prevalence ; Rhinitis, Allergic/epidemiology* ; Rhinitis, Allergic, Seasonal ; Urbanization

Objective:To assess the correlation between frailty and cardiac autonomic nervous system function in elderly patients.Methods:Elderly hospitalized patients aged 65 years and over were enrolled and assessed for frailty by using the clinical frailty scale.Cardiac autonomic modulation was evaluated by heart rate variability analysis through 24 h electrocardiogram recording.Results:A total of 180 elderly patients were enrolled in this study, including 66 patients with frailty and 114 patients without frailty.The mean age of the frailty group was higher than that of the non-frailty group(79.8±6.0 vs.75.0±6.3, t=5.030, P<0.001). The proportions of patients with hypertension, stroke/transient cerebral ischemia attack(TIA), heart failure and osteoarthritis were higher in the frailty group than in the non-frailty group(all P<0.05). Compared with the non-frailty group, the standard deviation of normal-to-normal intervals(SDNN)[103.0(76.0, 121.2) vs.107.5(92.0, 136.0), Z=-2.108, P=0.035], the standard deviation of the averages of NN intervals in all 5-min segments(SDANN)[86.0(67.7, 106.5) vs.97.5(78.0, 126.0), Z=-2.694, P=0.007], normalized low frequency(LFnorm)(53.1±13.0 vs.59.3±13.9, t=-3.024, P=0.003)and low frequency/high frequency(LF/HF)ratio[1.2(1.0, 1.4) vs.1.4(1.1, 1.7), Z=-3.041, P=0.002]were decreased and normalized high frequency(HFnorm)(36.8±9.2 vs.32.2±10.7, t=3.033, P=0.003)was increased in the frailty group.HFnorm in the frailty group was significantly higher than that in the non-frailty group.The incidents of SDANN<92 ms, LFnorm<50 nU, HFnorm>32 nU and LF/HF ratio<1.5 were higher in the frailty group than in the non-frailty group(59.1% or 39/66 vs.41.2% or 47/114, 42.4% or 28/66 vs.22.8% or 26/114, 72.7% or 48/66 vs.49.1% or 56/114, 84.8% or 56/66 vs.65.8% or 75/114, χ2=5.346, 7.660, 9.547, 7.664, P=0.021, 0.006, 0.002, 0.006). Logistic multivariate regression analysis showed that LFnorm, HFnorm and LF/HF ratio were correlated with frailty( OR=0.971, 1.039 and 0.333, all P<0.05), and HFnorm>32 nU and LF/HF ratio<1.5 were risk factors for frailty( OR=2.401 and 2.773, both P<0.05). Conclusions:Cardiac autonomic nerve system function is impaired in elderly frail patients, with the imbalance between the sympathetic and vagus nerves.Therefore particular attention should be paid to heart rate variability in elderly patients with frailty.