OBJECTIVE: This study was aimed at investigating the carrier rate of, and molecular variation in, α- and β-globin gene mutations in Hunan Province. METHODS: We recruited 25,946 individuals attending premarital screening from 42 districts and counties in all 14 cities of Hunan Province. Hematological screening was performed, and molecular parameters were assessed. RESULTS: The overall carrier rate of thalassemia was 7.1%, including 4.83% for α-thalassemia, 2.15% for β-thalassemia, and 0.12% for both α- and β-thalassemia. The highest carrier rate of thalassemia was in Yongzhou (14.57%). The most abundant genotype of α-thalassemia and β-thalassemia was -α ^3.7/αα (50.23%) and β ^IVS-II-654/β ^N (28.23%), respectively. Four α-globin mutations [CD108 (ACC>AAC), CAP +29 (G>C), Hb Agrinio and Hb Cervantes] and six β-globin mutations [CAP +8 (C>T), IVS-II-848 (C>T), -56 (G>C), beta nt-77 (G>C), codon 20/21 (-TGGA) and Hb Knossos] had not previously been identified in China. Furthermore, this study provides the first report of the carrier rates of abnormal hemoglobin variants and α-globin triplication in Hunan Province, which were 0.49% and 1.99%, respectively. CONCLUSION Our study demonstrates the high complexity and diversity of thalassemia gene mutations in the Hunan population. The results should facilitate genetic counselling and the prevention of severe thalassemia in this region.
Humans ; beta-Thalassemia/genetics* ; alpha-Thalassemia/genetics* ; Hemoglobinopathies/genetics* ; China/epidemiology* ; High-Throughput Nucleotide Sequencing

Objective: To explore the etiological diagnostic value of metagenomic next-generation sequencing (mNGS) in peritoneal dialysis (PD)-related peritonitis. Methods: The study was a retrospective cohort study. The clinical data of patients with PD-related peritonitis who were treated and underwent microbial cultivation and mNGS test at the same time from June 2020 to July 2021 in the Affiliated Drum Tower Hospital, Medical School of Nanjing University were analyzed. The positive rate, detection time and consistency between mNGS test and traditional microbial culture were compared. Results: A total of 18 patients with age of (50.4±15.4) years old and median dialysis time of 34.0 (12.4, 62.0) months were enrolled in the study, including 11 males and 7 females. Pathogenic microorganisms were isolated in 17 patients by mNGS test, with a positive rate of 17/18, which was higher than 13/18 of microbial culture, but the difference was not statistically significant (P=0.219). Both mNGS test and microbial culture isolated positive pathogenic bacteria in 12 patients, and mNGS test isolated the same types of pathogenic bacteria as microbial cultivation did in 11 patients. In five patients with negative microbial culture, mNGS test also isolated pathogenic microorganisms, including 3 cases of Staphylococcus epidermidis, 1 case of Mycobacterium tuberculosis and 1 case of Ureaplasma urealyticum. In 1 patient, microbial culture isolated pathogenic bacteria (Escherichia coli) whereas mNGS test did not. The detection time of mNGS was 25.0 (24.0, 27.0) h, which was significantly shorter than 89.0 (72.8, 122.0) h of microbial culture (Z=3.726, P<0.001). Conclusions: mNGS test can improve the detection rate of pathogenic microorganisms in PD-related peritonitis and greatly shorten the detection time, and has good consistency with microbial culture. mNGS may provide a new approach for pathogen identification of PD-related peritonitis, especially refractory peritonitis.
Female ; Male ; Humans ; Adult ; Middle Aged ; Aged ; Retrospective Studies ; Peritoneal Dialysis/adverse effects* ; High-Throughput Nucleotide Sequencing ; Peritonitis/diagnosis* ; Sensitivity and Specificity

Objective: To explore the prognostic factors of extracellular NK/T cell lymphoma (ENKTL) treated with pegaspargase/L-asparaginase. Methods: The clinical data of 656 ENKTL patients diagnosed at 11 medical centers in the Huaihai Lymphoma Working Group from March 2014 to April 2021 were retrospectively analyzed. The patients were randomly divided into two groups: a training set (460 cases) and a validation set (196 cases) at 7∶3, and the prognostic factors of the patients were analyzed. A prognostic scoring system was established, and the predictive performance of different models was compared. Results: Patients' median age was 46 (34, 57) years, with 456 males (69.5% ) and 561 nasal involvement (85.5% ). 203 patients (30.9% ) received a chemotherapy regimen based on L-asparaginase combined with anthracyclines, and the 5-year overall survival rate of patients treated with P-GEMOX regimen (pegaspargase+gemcitabine+oxaliplatin) was better than those treated with SMILE regimen (methotrexate+dexamethasone+cyclophosphamide+L-asparaginase+etoposide) (85.9% vs 63.8% ; P=0.004). The results of multivariate analysis showed that gender, CA stage, the Eastern Cooperative Oncology Group performance status (ECOG PS) score, HGB, and EB virus DNA were independent influencing factors for the prognosis of ENKTL patients (P<0.05). In this study, the predictive performance of the prognostic factors is superior to the international prognostic index, Korean prognostic index, and prognostic index of natural killer lymphoma. Conclusion: Gender, CA stage, ECOG PS score, HGB, and EB virus DNA are prognostic factors for ENKTL patients treated with pegaspargase/L-asparaginase.
Male ; Humans ; Middle Aged ; Asparaginase/therapeutic use* ; Prognosis ; Retrospective Studies ; Lymphoma, Extranodal NK-T-Cell/drug therapy* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Etoposide ; Cyclophosphamide ; Methotrexate/therapeutic use* ; DNA/therapeutic use* ; Treatment Outcome

OBJECTIVES: To compare the application effect of microwave digestion - vacuum filtration - automated scanning electron microscopy (MD-VF-Auto SEM) method and plankton gene multiplex PCR system in the diagnosis of drowning. METHODS: Lung, liver and kidney tissue of 10 non-drowning cases and 50 drowning cases were prepared for further MD-VF-Auto SEM method analysis and plankton gene multiplex PCR system analysis. The positive detection rate of the two methods in each tissue was calculated. RESULTS: The positive rate of the MD-VF-Auto SEM method detecting diatoms in drowning cases was 100%, and few diatoms were detected in the liver and kidney tissues of 6 non-drowning cases. By using the plankton gene multiplex PCR system, the diatom positive rate of drowning cases was 84%, and all the non-drowning cases were negative. There were significant differences in the positive rate of the liver, kidney tissues between MD-VF-Auto SEM method and plankton gene multiplex PCR system (P<0.05), as well as the total positive rate of cases. However, no significant differences were found in the positive rates of lung tissues (P>0.05). CONCLUSIONS MD-VF-Auto SEM method is more sensitive than plankton gene multiplex PCR system in diatom test. But the plankton gene multiplex PCR system can also detect plankton other than diatoms. Combination of the two methods can provide a more reliable basis for the diagnosis of drowning.
Diatoms/genetics* ; Drowning/diagnosis* ; Humans ; Liver ; Lung ; Microscopy, Electron, Scanning ; Multiplex Polymerase Chain Reaction ; Plankton/genetics*

italic>Rehmannia glutinosa belongs to the Scrophulariaceae family with important medicinal value. In order to effectively explore the transcriptome information of R. glutinosa and identify the genes encoding enzymes involved in phenylethanol glycoside (PhGs) biosynthesis, the leaves, stems and tuberous roots of R. glutinosa were used for transcriptome sequencing using Pacific Biosiences RS II platform. A total of 27 773 transcripts were generated with an average length of 2 380 bp, and 27 236 coding sequences (CDS) were predicted. Using BLAST software, non-redundant transcript sequences were annotated with NR, NT, GO, COG, KEGG, SwissProt and Interpro databases and a total of 27 399 annotated genes were obtained. Among them, the number of genes related to Sesamum indicum in the NR database was the highest (81.44%), which is consistent with their evolutionary relationship. Enzymes likely involved in the biosynthesis of isoacteoside, echinacoside, cistanosides A, cistanosides F, 2′-acetylacteoside and leonoside F were identified, and 143 genes were identified in R. glutinosa full-length transcriptome. The expression levels of 19 genes correlated with acteoside content in twelve tissues of R. glutinosa, and most showed higher expression levels in leaf tissues and floral organs. This study provides more reliable transcriptome data for screening R. glutinosa for functional genes and provides a foundation for the study of the molecular mechanisms of PhGs biosynthesis.

Objective: To evaluate the association of lead exposure with stunting and underweight among children aged 3-5 years in China. Methods: Data was collected from China National Human Biomonitoring (CNHBM) between January 2017 and December 2018. A total of 3 554 children aged 3-5 years were included. Demographic characteristic, lifestyle and nutritional status were collected through questionnaires. Height and weight were measured by standardized method. Stunting and underweight status were determined by calculating height for age Z-score and weight for age Z-score. Blood and urine samples were collected to detect the concentrations of blood lead, urinary lead and urinary creatinine. Children were stratified into 4 groups (Q₁ to Q₄) by quartiles of blood lead level and corrected urinary lead level, respectively. Complex sampling logistic regression models were applied to evaluate the association of the blood lead level, urinary lead level with stunting and underweight. Results: Among 3 554 children, the age was (4.09±1.06) years, of which 1 779 (80.64%) were female and 1 948 (55.84%) were urban residents. The prevalence of stunting and wasting was 7.34% and 2.96%, respectively. The M (Q₁, Q₃) for blood lead levels and urinary lead levels in children was 17.49 (12.80, 24.71) μg/L, 1.20 (0.61, 2.14) μg/g Cr, respectively. After adjusting for confounding factors, compared with the lowest blood lead concentration group Q₁, the risk of stunting gradually increased in the Q₃ and Q₄ group (P_trend=0.010), with OR (95%CI) values of 1.40 (0.80-2.46) and 1.80 (1.07-3.04), respectively. Compared with the lowest urinary lead concentration group Q₁, the risk of stunting still increased in the Q₃ and Q₄ group (P_trend=0.012), with OR (95%CI) values of 1.69 (1.01-2.84) and 1.79 (1.05-3.06), respectively. The correlation between the lead exposure and underweight was not statistically significant (P>0.05). Conclusion: Lead exposure is positively associated with the risk of stunting among children aged 3-5 years in China.
Child ; Female ; Humans ; Infant ; Male ; Lead ; Thinness/epidemiology* ; Growth Disorders/epidemiology* ; Body Height ; Nutritional Status ; Prevalence ; China/epidemiology*

Objective: To develop a nomogram model for the differential diagnosis of benign and malignant breast BI-RADS (Breast Imaging Reporting and Data System) category 4 nodules based on serum tumor specific protein 70 (SP70) and conventional laboratory indicators and validate its predictive efficacy. Methods: A case-control study design was used to retrospectively analyze the data of 429 female patients diagnosed with BI-RADS category 4 breast nodules by breast color doppler flow imaging at the First Affiliated Hospital of Nanjing Medical University from January 2021 to April 2022 with an age range of 16 to 91 years and a median age of 50 years, and the patients were divided into a training cohort (314 patients) and a validation cohort (115 patients) according to the inclusion time successively. Using postoperative pathological findings as the"gold standard", univariate and multivariate logistic regression analyses were used to identify the predictor variables used for the model. The nomogram, receiver operating characteristic (ROC) curves and calibration curves were drawn for the prediction model, and the discrimination and calibration of the model were evaluated using the consistency index (C-index) and calibration plots. Results: The postoperative pathological results showed that 286 (66.7%) were malignant nodules and 143 (33.3%) were benign nodules of 429 breast BI-RADS category 4 nodules. The serum SP70 (OR=1.227,95%CI: 1.033-1.458,P=0.020), NLR (OR=1.545,95%CI: 1.047-2.280,P=0.028), LDL-C (OR=2.215, 95%CI: 1.354-3.622, P=0.002), GLU (OR=2.050,95%CI:1.222-3.438,P=0.007), PT (OR=1.383,95%CI: 1.046-1.828,P=0.023), nodule diameter (OR=1.042, 95%CI: 1.008-1.076, P=0.015) and age (OR=1.062,95%CI: 1.011-1.116,P=0.016) were independent risk factors which could be used to distinguish benign and malignant breast BI-RADS category 4 nodules (P<0.05). The nomogram was plotted by the above seven independent variables, and the concordance index (C-index) for the training cohort and validation cohort were 0.842 (95%CI:0.786-0.898) and 0.787 (95%CI:0.687-0.886), respectively. The sensitivity and specificity of using this model to identify benign and malignant breast BI-RADS category 4 nodules in the training and validation cohort were 83.5%, 72.5% and 79.2%, 73.6%, respectively. The calibration curves showed good agreement between the predicted and actual values in the nomogram. Conclusions: This study combined serum SP70, conventional laboratory indicators and breast color doppler flow imaging to develop a nomogram model for the differential diagnosis of benign and malignant breast BI-RADS category 4 nodules. The model may have good predictive efficacy and may provide a basis for clinical treatment options, which is beneficial for guiding breast cancer screening and prevention.
Female ; Humans ; Middle Aged ; Adolescent ; Young Adult ; Adult ; Aged ; Aged, 80 and over ; Diagnosis, Differential ; Retrospective Studies ; Case-Control Studies ; Breast/pathology* ; Breast Neoplasms/pathology*

ObjectiveTo explore the effect of Qishengwan on ileal flora during its treatment of Alzheimer's disease （AD） under the guidance of the theory of "interior-exterior relationship between heart and small intestine". MethodThe AD model was established by bilateral intraventricular injection of β-amyloid 1-42 （Aβ_1-42）. The rats were then randomly divided into the blank group， sham-operated group， model group， low-， medium-， and high-dose （5.6， 11.2，22.4 g·kg^-1·d^-1） Qishengwan groups， and donepezil （0.46 mg·kg^-1·d^-1） group. After medication for 28 successive days， the spatial memory ability of rats was observed in water maze test， and the levels of Aβ_1-42， nuclear transcription factor-κB （NF-κB）， tumor necrosis factor-α （TNF-α）， and interleukin-6 （IL-6） in the hippocampus were analyzed by enzyme-linked immunosorbent assay （ELISA）. Additionally， the contents of the ileum were collected and subjected to 16SrRNA-sequencing analysis for figuring out the changes in ileal flora. ResultCompared with the blank group and sham-operated group， the model group exhibited significantly reduced stay time in the target quadrant and number of target quadrant and platform crossings （P<0.05， P<0.01） and elevated Aβ_1-42 content in the hippocampus （P<0.01） and central inflammatory factors NF-κB， TNF-α， and IL-6 （P<0.05， P<0.01）. Compared with the model group， Qishengwan at each dose significantly alleviated the impaired spatial memory function （P<0.05， P<0.01）， improved the deposition of Aβ_1-42 in the hippocampus of rats （P<0.05， P<0.01）， and reduced the expression of central nervous system inflammatory factors （P<0.05， P<0.01）， thus exerting a good therapeutic effect on AD rats. The 16SrRNA-sequencing analysis results showed that the structure of the ileal flora in the model group was significantly separated from those in the blank group and sham-operated group. The abundance of Lachnospiraceae NK4A136 group was significantly increased （P<0.01）， while that of Escherichia-Shigella was reduced （P<0.05， P<0.01）. Qishengwan at each dose significantly changed the ileal flora structure and regulated the relative abundance of Lachnospiraceae NK4A136 group， Escherichia-Shigella， and Ruminococcaceae. ConclusionQishengwan has a positive therapeutic effect on AD. It can significantly enhance the memory and cognitive abilities in AD rats， which may be related to its regulation of the structure of rat ileal flora and the relative abundance of Lachnospiraceae NK4A136 group， Escherichia-Shigella， and Ruminococcaceae， the attenuation of the central neuroinflammatory response， and the reduction of central Aβ_1-42 deposition.

Objective: To evaluate the success rate of His-Purkinje system pacing (HPSP) in patients with various sites of atrioventricular block (AVB) and provide clinical evidence for the selection of HPSP in patients with AVB. Methods: This is a retrospective case analysis. 637 patients with AVB who underwent permanent cardiac pacemaker implantation and requiring high proportion of ventricular pacing from March 2016 to September 2021 in the Department of Cardiology, General Hospital of Northern Theater Command were enrolled. The site of AVB was determined by electrophysiological examination. His bundle pacing (HBP) was performed in the first 130 patients (20.4%) who were classified as the HBP group and HPSP included HBP and/or left bundle branch pacing (LBBP) was performed in later 507 patients (79.6%) and these patients were classified as the HPSP group. The basic clinical information such as age and sex of the two groups was compared, and the success rates of HBP or HPSP in patients with different sites of AVB and QRS intervals were analyzed. Results: The age of HBP group was (66.4±15.9) years with 75 males (57.7%). The age of HPSP group was (66.8±13.6) years with 288 (56.8%) males. Among 637 patients, 63.0% (401/637) had atrioventricular node block; 22.9% (146/637) had intra-His block; 14.1% (90/637) had distal or inferior His bundle block. Totally, the success rate of HPSP was higher than that of HBP [93.9% (476/507) vs. 86.9% (113/130), P<0.05]. In each group of patients with various AVB sites, the success rate of HPSP was higher than that of HBP respectively and both success rates of HBP and HPSP showed a declining trend with the distant AVB site. The success rate of HBP in patients with atrioventricular node block and intra-His block was higher than that in patients with distal or inferior His bundle block [95.2% (79/83) vs. 47.1% (8/17), P<0.001; 86.7% (26/30) vs. 47.1% (8/17), P=0.010]. The success rate of HPSP was higher than that of HBP in patients with distal or inferior His bundle block [87.7% (64/73) vs 47.1% (8/17), P=0.001]. In patients with QRS<120 ms, 94.9% (520/548) of AVB sites were in atrioventricular node or intra-His, and HBP had a similar high success rate with HPSP [95.6% (109/114) vs. 96.3% (418/434), P=0.943] in these patients. In patients with QRS ≥ 120 ms, 69.7% (62/89) of AVB sites were at distal or inferior His bundle, and the success rate of HBP was only 25.0% (4/16), while the success rate of HPSP was as high as 79.5% (58/73), P<0.001. Conclusions: In patients with QRS<120 ms and atrioventricular node block or intra-His block, success rates of HBP and HPSP are similarly high and HBP might be considered as the first choice. In patients with QRS ≥ 120 ms and AVB site at distal or inferior His bundle, the success rate of HPSP is higher than that of HBP, suggesting LBBP should be considered as the first-line treatment option.
Aged ; Aged, 80 and over ; Atrioventricular Block/therapy* ; Bundle of His/physiology* ; Cardiac Pacing, Artificial ; Electrocardiography ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Treatment Outcome

Objective:The clinical characteristics and prognosis of 20 patients with small B-lymphocyte proliferative disease with t (14;19) (q32; q13) were analyzed to improve the understanding of such rare cases.Methods:The clinical data of 20 patients with t (14; 19) (q32; q13) small B lymphocyte proliferative disease treated in the First Affiliated Hospital of Nanjing Medical University from April 2013 to December 2020 were retrospectively collected and analyzed. Among them, 10 cases were chronic lymphocytic leukemia (CLL) and 10 cases were other small B-cell malignancies.Results:Among the 20 cases, 10 were male and 10 were female, and the median age at diagnosis was 53.5 (35-88) years old. All patients had absolute lymphocytosis, 19 patients had lymphadenopathy, and 10 patients had splenomegaly. With a median follow-up of 36 (4-163) months, three patients died, and 11 patients had a time to treatment (TTT) ≤12 months. Ten patients (50%) were accompanied by +12, two patients (2/17, 12%) were accompanied by 13q-. Moreover, we found that t (14;19) was associated with unmutated immunoglobulin heavy-chain variable (IGHV) somatic mutation (17/19, 89%) and a biased use of IGHV4-39 (7/17, 41%) was observed. Next-generation sequencing detected one or more gene mutations in 14 (14/17, 82%) cases and a total of 25 gene mutations had been revealed, of which the most frequent were NOTCH1 (35%) , followed by SF3B1 (24%) and KMT2D (18%) . For 10 CLL patients, five (50%) were defined as Rai Ⅲ/Binet C. It is noteworthy that among the 20 cases, two cases actually involved Richter transformation.Conclusions:Small B-cell malignant tumors with abnormal t (14; 19) show unique clinical biological characteristics, often accompanied by a variety of adverse prognostic factors, and tend to have an aggressive clinical course.