Objective:To explore the distribution and hematological characteristics of rare thalassemia-associated mutations in Chenzhou region of Hunan Province with an aim to provide a basis for genetic counseling and effective prevention.Methods:A total of 37 370 individuals enrolled from January 2015 to December 2021 were screened by routine blood test and hemoglobin electrophoresis. The genotypes were determined with high-throughput sequencing.Results:A total of 8 455 thalassemia mutations (including 185 rare ones) were detected, which had involved 27 mutational types. Rare type α-Thalassemia --THAI and CD31 (AGG>AAG) have the typical microcytic hypochromic hematological features, whilst SEA-HPFH, CD14 (CTG>-TG), CD37 (TGG>TAG), -90(C>T), Codon 15 (G>A), IVS-Ⅰ-128 (T>G), CD86 (GCC>GC-) and Chinese Gγ+ (Aγδβ)0 had typical microcytic hypochromic and β-thalassemia-associated hematological features of elevated HbA2 or HbF. In addition, the -50(G>A)heterozygotes of β-thalassemia had normal or slightly decreased MCV and MCH without an increase in HbA2.Conclusion:Various forms of thalassemia-associated mutations have been identified in the Chenzhou region of Hunan Province. Above finding has facilitated development of preventive and control strategies for thalassemia as well as birth health programs.

This study was designed to explore the role of F.nucleatum in macrophage polarization and colorectal cancer metastasis.F.nucleatum and RAW264.7 cells were cocultured at the MOI of 100∶1,and then glucose uptake was measured by 2-NBDG,expression levels of M1 and M2 macrophage markers were determined by qPCR,glycosylation modification level and polarization marker expression of macrophages were tested by Western blotting,and STAT6 glycosylation modification was verified by Co-IP experiment.Meanwhile,F.nucleatum was co-cultured with RAW264.7(MOI=100∶1),and the supernatant was removed to treat RKO cells.The migration ability of colorectal cancer was detected by transwell experiment and scratch experiment.Data showed that F.nucleatum promoted M2 macrophage polarization and enhance the metastasis of colorectal cancer cells RKO;F.nucleatum also promoted the glucose intake of macrophages and enhanced the expression of M2-related markers.Taken together,F.nucleatum promotes the level of glycosylation in macrophages,which induces its polarization to M2 by modifying O-GlcNAc of STAT6,to regulate colorectal cancer metastasis.

OBJECTIVE: To assess the value of non-invasive prenatal testing (NIPT) for the identification of numerical and structural chromosomal abnormalities and copy number variations (CNVs) in fetuses. METHODS: 46 197 pregnant women undergoing NIPT at the Prenatal Diagnosis Center of Chenzhou First People's Hospital from January 2018 to December 2021 were selected as the study subjects. Positive cases were subjected to chromosomal karyotyping and copy number variation sequencing (CNV-seq) following amniocentesis. RESULTS: Nearly 50% of common chromosomal aneuploidies were found in the elder pregnant women. Among these, sex chromosome aneuploidies were mainly found in pregnant women with advanced age as well as borderline risks by serological screening. Rare autosomal aneuploidies and CNVs were mainly found in those with borderline or high risks by serological screening. The positive predictive values (PPV) for fetal chromosomal abnormalities indicated by NIPT were as follows: T21 (92.37%, 109/118), T18 (53.85%, 14/26), sex chromosome aneuploidies (45.04%, 59/131), T13 (34.62%, 9/26), CNVs (29.17%, 14/48), and rare autosomal aneuploidies (2.60%, 2/77). CONCLUSION NIPT has a high detection rate for T21, T18, T13 and sex chromosome aneuploidies. It can also detect rare autosomal aneuploidies and CNVs, including some rare structural abnormalities, though verification is required by analyzing amniotic fluid samples.
Pregnancy ; Female ; Humans ; DNA Copy Number Variations ; Chromosome Aberrations ; Chromosome Disorders/genetics* ; Aneuploidy ; Fetus

OBJECTIVE: To assess the diagnostic value of whole exome sequencing (WES) for patients with intellectual disability (ID) or global developmental delay (GDD). METHODS: 134 individuals with ID or GDD who presented at Chenzhou First People's Hospital between May 2018 and December 2021 were selected as the study subjects. WES was carried out on peripheral blood samples of the patients and their parents, and candidate variants were verified by Sanger sequencing, copy number variation sequencing (CNV-seq) and co-segregation analysis. The pathogenicity of the variants was predicted based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). RESULTS: A total of 46 pathogenic single nucleotide variants (SNVs) and small insertion/deletion (InDel) variants, 11 pathogenic genomic copy number variants (CNVs), and 1 uniparental diploidy (UPD) were detected, which yielded an overall detection rate of 43.28% (58/134). The 46 pathogenic SNV/InDel have involved 62 mutation sites in 40 genes, among which MECP2 was the most frequent (n = 4). The 11 pathogenic CNVs have included 10 deletions and 1 duplication, which have ranged from 0.76 to 15.02 Mb. A loss of heterozygosity (LOH) region of approximately 15.62 Mb was detected in 15q11.2q12 region in a patient, which was validated as paternal UPD based on the result of trio-WES. The patient was ultimately diagnosed as Angelman syndrome. CONCLUSION WES can detect not only SNV/InDel, but also CNV and LOH. By integrating family data, WES can accurately determine the origin of the variants and provide a useful tool for uncovering the genetic etiology of patients with ID or GDD.
Humans ; Exome Sequencing ; Intellectual Disability/genetics* ; DNA Copy Number Variations ; Mutation ; Loss of Heterozygosity

OBJECTIVE: To determine the carrier rate for common recessive genetic diseases in Chenzhou region in order to provide a reference for carrier screening in this region. METHODS: Targeted capture and high-throughput sequencing were carried out to detect potential variants of 79 genes associated with 88 recessive genetic diseases. Couples at risk were provided with prenatal diagnosis upon their subsequent pregnancies. RESULTS: A total of 1314 individuals were enrolled, among whom 355 (27.02%) were found to be carrier for at least one disease. The carrier rates for 8 diseases have exceeded 1%, with the most common two including thalassemia (11.72%, 154/1314) and autosomal recessive deafness (5.48%, 72/1314). Ten couples were found to be at risk for producing affected offspring. Among these, five females were carriers for X-linked recessive genetic diseases. Following genetic counseling, seven couples had accepted prenatal diagnosis, and 3 affected fetuses were diagnosed. CONCLUSION The disease types and pathogenic variants of Chenzhou region have differed from previously reported. Further research is required to validate the above finding with a larger populations.
Female ; Pregnancy ; Humans ; China ; Prenatal Diagnosis ; Fetus ; Genetic Counseling ; Genetic Diseases, X-Linked

OBJECTIVE: To analyze the current status of diagnosis and management of acute appendicitis (AA) in China. METHODS: Questionnaire survey was used to retrospectively collect data of hospitalized patients with AA from 43 medical centers nationwide in 2017 (Sort by number of cases provided: Jinling Hospital of Medical School of Nanjing University, The First Affiliated Hospital of Xinjiang Medical University, Lu'an People's Hospital, Tengzhou Central People's Hospital, Dalian Central Hospital, The Affiliated Hospital of Xuzhou Medical University, Dongying People's Hospital, Jinjiang Hospital of Traditional Chinese Medicine, Huangshan Shoukang Hospital, Xuyi People's Hospital, Nanjing Jiangbei People's Hospital, Lanzhou 940th Hospital of PLA, Heze Municipal Hospital, The First College of Clinical Medical Science of China Three Gorges University, Affiliated Jiujiang Hospital of Nanchang University, The Second People's Hospital of Hefei, Affiliated Central Hospital of Shandong Zaozhuang Mining Group, The Third People's Hospital of Kunshan City, Xuzhou First People's Hospital, The 81st Group Army Hospital of PLA, Linyi Central Hospital, The General Hospital of Huainan Eastern Hospital Group, The 908th Hospital of PLA, Liyang People's Hospital, The 901th Hospital of Joint Logistic Support Force, The Third Affiliated Hospital of Chongqing Medical University, The Fourth Hospital of Jilin University, Harbin Acheng District People's Hospital, The First Affiliated Hospital of Zhengzhou University, Nanjing Luhe People's Hospital, Taixing Municipal People's Hospital, Baotou Central Hospital, The Affiliated Hospital of Nantong University, Linyi People's Hospital, The 72st Group Army Hospital of PLA, Zaozhuang Municipal Hospital, People's Hospital of Dayu County, Taixing City Hospital of Traditional Chinese Medicine, Suzhou Municipal Hospital, Beijing Guang'anmen Hospital, Langxi County Hospital of Traditional Chinese Medicine, Nanyang Central Hospital, The Affiliated People's Hospital of Inner Mongolia Medical University).The diagnosis and management of AA were analyzed through unified summary. Different centers collected and summarized their data in 2017 and sent back the questionnaires for summary. RESULTS: A total of 8 766 AA patients were enrolled from 43 medical centers, including 4 711 males (53.7%) with median age of 39 years and 958 (10.9%) patients over 65 years old. Of 8 776 patients, 5 677 cases (64.6%) received one or more imaging examinations, and the other 3 099 (35.4%) did not receive any imaging examination. A total of 1 858 (21.2%) cases received medical treatment, mainly a combination of nitroimidazoles (1 107 cases, 59.8%) doublet regimen, followed by a single-agent regimen of non-nitroimidazoles (451 cases, 24.4%), a nitroimidazole-free doublet regimen (134 cases, 7.2%), a triple regimen of combined nitroimidazoles (116 cases, 6.3%), nitroimidazole alone (39 cases, 2.1%) and nitroimidazole-free triple regimen (3 cases, 0.2%). Of the 6 908 patients (78.8%) who underwent surgery, 4 319 (62.5%) underwent laparoscopic appendectomy and 2589 (37.5%) underwent open surgery. Ratio of laparotomy was higher in those patients under 16 years old (392 cases) or over 65 years old (258 cases) [15.1%(392/2 589) and 10.0%(258/2 589), respectively, compared with 8.5%(367/4 316) and 8.0%(347/4 316) in the same age group for laparoscopic surgery, χ²=91.415, P<0.001; χ²=15.915,P<0.001]. Patients with complicated appendicitis had higher ratio of undergoing open surgery as compared to those undergoing laparoscopic surgery [26.7%(692/2 589) vs. 15.6%(672/4 316), χ²=125.726, P<0.001].The cure rates of laparoscopic and open surgery were 100.0% and 99.8%(2 585/2 589) respectively without significant difference (P=0.206). Postoperative complication rates were 4.5%(121/2 589) and 4.7%(196/4 316) respectively, and the difference was not statistically significant (χ²=0.065, P=0.799). The incidence of surgical site infection was lower (0.6% vs. 1.7%, χ²=17.315, P<0.001), and hospital stay was shorter [6(4-7) days vs. 6(5-8) days, U=4 384 348.0, P<0.001] in the laparoscopic surgery group, while hospitalization cost was higher (median 12 527 yuan vs. 9 342 yuan, U=2 586 809.0, P<0.001). CONCLUSIONS The diagnosis of acute appendicitis is still clinically based, supplemented by imaging examination. Appendectomy is still the most effective treatment at present. Laparoscopic appendectomy has become the main treatment strategy, but anti-infective drugs are also very effective.
Acute Disease ; Adolescent ; Adult ; Aged ; Anti-Bacterial Agents ; therapeutic use ; Appendectomy ; Appendicitis ; diagnosis ; therapy ; China ; Female ; Health Care Surveys ; Humans ; Laparoscopy ; Male ; Middle Aged ; Retrospective Studies ; Treatment Outcome ; Young Adult

Objective To compare the clinical effects between laparoscopic radical resection combined with radiofrequency ablation (RFA) and open radical resection for colorectal liver metastases.Methods The retrospective cohort study was conducted.The clinicopathological data of 120 colorectal liver metastases patients who were admitted to the Mengchao Hepatobiliary Hospital of Fujian Medical University (80 patients) and the Third Mfiliated Hospital of Chongqing Medical University (40 patients) between September 2012 and April 2017 were collected.Sixty patients undergoing laparoscopic radical resection of colorectal cancer combined with RFA of liver metastases were allocated into the laparoscopy with RFA group,and 60 undergoing open radical resection of colorectal liver metastases were allocated into the open group.Observation indicators:(1) surgical and postoperative situations;(2) follow-up and survival situations.Follow-up using outpatient examination and telephone interview was performed to detect postoperative survival up to May 2017.Measurement data with normal distribution were represented as x±s,and comparisons between groups were analyzed using independent-sample t test.Measurement data with skewed distribution were described as M (range).Comparisons of count data were analyzed using chi-square test or Fisher exact probability.The repeated measures data were analyzed using the repeated measures ANOVA.The survival curve and rate were respectively drawn and calculated by the Kaplan-Meier method,and the Log-rank test was used for survival analysis.Results (1) Surgical and postoperative situations:① All the patients underwent successful surgery,without conversion to open surgery in the laparoscopy with RFA group.Operation time,volume of intraoperative blood loss,cases with overall complications,death,abdominal pain,nausea and vomiting,liver dysfunction,pleural effusion,non-calculus cholecystitis and peptic ulcer and duration of postoperative hospital stay were respectively (135±34)minutes,(451±197)mL,31,0,18,6,6,4,3,2,(13±4)days in the laparoscopy with RFA group and (165±49)minutes,(794±204)mL,42,1,15,9,10,11,5,5,(19±4)days in the open group,with statistically significant differences in operation time,volume of intraoperative blood loss,cases with overall complications and duration of postoperative hospital stay between groups (t =3.983,9.394,x2 =4.232,t =9.148,P＜0.05),and no statistically significant differences in cases with death,abdominal pain,nausea and vomiting,liver dysfunction,pleural effusion,non-calculus cholecystitis and peptic ulcer between groups x2 =0.376,0.686,1.154,3.733,0.134,0.607,P＞0.05).() Levels of alanine aminotransferase (ALT),total bilirubin (TBil) and prothronbin time (PT) before operation,at day 1 and 3 postoperatively were respectively (70±9)U/L,(399±36)U/L,(231±19) U/L,(21±3) μmol/L,(26±3) μmol/L,(23±5) μmol/L,(17.3±2.4) seconds,(20.2-±4.4) seconds,(18.9±2.8) seconds in the laparoscopy with RFA group and (68± 8) U/L,(412±39)U/L,(253±22)U/L,(21±4)μmol/L,(28±4)μmol/L,(27±8)μmol/L,(16.6±3.0)seconds,(22.1±5.2) seconds,(20.1± 4.4)seconds in the open group,with statistically significant differences in the levels of ALT,TBil and PT before operation,at day 1 and 3 postoperatively between groups (F=16.727,13.115,4.194,P＜0.05).(2) Follow-up and survival situations:120 patients were followed up for 7-24 months,with a median time of 20 months.The postoperative 1-and 2-year tumor-free survival rates,1-and 2-year overall survival rates were respectively 23.3％,11.9％,85.0％,40.0％ in the laparoscopy with RFA group and 20.0％,12.8％,83.3％,38.3％ in the open group,with no statistically significant difference in above indicators between groups (x2 =0.145,0.069,0.012,0.196,P＞0.05).Further analysis showed that postoperative 2-year overall survival rate of patients with 1,2,3 and ＞3 liver metastasis lesions were respectively 53.3％,38.2％,40.0％,16.7％ in the laparoscopy with RFA group and 50.0％,35.7％,40.0％,15.4％ in the open group,with a statistically significant difference in 2-year survival rate of patients with different liver metastasis lesions in the laparoscopy with RFA group (x2 =20.949,P＜0.05) and in the open group (x2 ＝ 21.349,P＜0.05).Conclusion There are some advantages of fewer traumas,less complications,faster postoperative recovery and minimally invasive in laparoscopic radical resection combined with RFA for colorectal liver metastases,meanwhile,less liver metastasis lesions and better prognosis are found.

Objective To evaluate the effect of anticoagulant therapy by pulmonary ventilation/perfusion (V/Q) imaging in chronic thromboembolic pulmonary hypertension (CTEPH) patients.Methods Thirtysix CTEPH patients (16 males,20 females,average age:(53.8±13.8) years) diagnosed by pulmonary angiography from January 2013 to December 2015 were included in this retrospective study.All patients received anticoagulant therapy for more than 6 months.They underwent pulmonary V/Q imaging before and 6 months after anticoagulant therapy.The numbers of pulmonary segments with perfusion defect,percentage of perfusion defect score (PPDs) and pulmonary arterial systolic pressure (PASP) before and after anticoagulant therapy were measured by echocardiography.Pair t test was used for data analysis.Results Before anticoagulant therapy,there were 319 pulmonary segments with perfusion defect in 36 CTEPH patients,8.9± 3.4 on average,and reduced to 8.4+3.6 after anticoagulant therapy (t =3.101,P＜0.01).The PPDs before and after anticoagulant therapy were (43.3±19.7)％ and (40.8±+20.5)％ (t=2.364,P＜0.05).In the subgroup of 9 patients with improved pulmonary perfusion,the PASP significantly decreased from (68.7±27.3)to (56.1 +±34.8) mmHg (1 mm Hg =0.133 kPa;t =2.465,P＜ 0.05) after anticoagulant therapy.In contrast,in the subgroup of 27 patients with no improved pulmonary perfusion,the PASP before and after anticoagulant therapy were (71.3±26.9) and (76.7±35.0) mmHg respectively (t=-1.511,P＞0.05).Conclusion Pulmonary V/Q imaging is a reliable method for evaluating the changes of pulmonary perfusion before and after anticoagulant therapy,and it is valuable for assessing the effect of anticoagulant therapy in CTEPH patients.

BACKGROUND:The aim of spinal mobilization and spinal manipulation is to correct vertebral subluxation. However, facet joint pressures are not clear during these two therapies.
OBJECTIVE:To compare human lumbar facet joint pressures during simulated high-velocity, low-amplitude spinal manipulationversuslow-velocity, low-amplitude spinal mobilization.
METHODS:Totaly 12 adult fresh lumbar spinal specimens (T12-S2) were divided into two groups randomly. Parameters of simulated spinal mobilization (n=6): preload angle 15° (speed 3°/s), maximum angle 20° (speed 1°/s), with 9 N horizontal force to L5 spinous process. Parameters of simulated spinal manipulation (n=6): preload angle 15° (speed 3°/s), impulse angle 20° (impulse speed 33°/s), with 22 N horizontal force to L5 spinous process. Pressures of bilateral L4-5/L5-S1 facet joints were measured with Tekscan system.
RESULTS AND CONCLUSION:(1) During two spinal manipulative therapies (rotation to the right and then back to the neutral position), pressures of right facet joints decreased first and then increased gradualy, while pressures of left facet joints changed oppositely. (2) Pressures of right facet joints were similar regardless of manipulation type (P > 0.05). The maximum pressure of left facet joints was larger during manipulation than that during mobilization (P < 0.05). (3) Descending speed of pressures of right joint was larger during manipulation than that during mobilization (P < 0.01), and no significant difference in ascending speed of pressure of right facet joints was detected (P > 0.05). Both ascending and descending speeds of the left facet joints were larger during manipulation than that during mobilization (P < 0.01). (4) During two spinal manipulative therapies, pressures of ipsilateral facet joints decreased first and then increased, while pressures of contralateral facet joints increased first and then decreased. Joint pressure after treatment restored to that before treatment. (5) Impulse speed and magnitude of pressures of facet joints during manipulation were larger than that during mobilization. Facet joints are more possible to be injured during manipulation than that during mobilization. During manipulation, we should pay attention to the speed and intensity of the impact.

Objective This paper attempts to explore the application of dizziness handicap inventory (DHI) in evaluation of health -related quality of life (QOL ) changes of patients with benign paroxysmal positional vertigo (BPPV) before and after the treatment with canalith repositioning procedure (CRP) .Methods The DHI was em-ployed to investigate and evaluate the dizziness handicap of 120 patients with BPPV before and after 3 months of CRP treatment (treatment group) and 60 healthy controls (control group) ,while the DHI scoring results were com-pared .Results As indicated by DHI evaluation ,the scoring of each DHI items of patients with BPPV before treatment was higher than that of control group ,treatment group before treatment :functional score 22 .60 ± 6 .54 ,emotional score 18 .50 ± 8 .28 ,physical score 17 .90 ± 5 .05 ,total composite score 59 .00 ± 14 .32 .For the control group:functional score 1 .35 ± 1 .74 ,emotional score 1 .00 ± 1 .01 ,physical score 1 .37 ± 1 .86 ,total composite score 3 .72 ± 3 .46 ,with the differ-ence statistically significant (P<0 .05) .The DHI scoring of treatment group of patients with BPPV after 3 months of CRP treatment was lower than that before the treatment (treatment group after 3 months CRP treatment :functional score 1 .10 ± 1 .42 ,emotional score 1 .50 ± 1 .70 ,physical score 1 .45 ± 1 .46 ,total composite score 4 .05 ± 3 .66) ,and the difference was statistically significant (P<0 .05) .There was no statistically significant difference comparing to the control group (P>0 .05) .Conclusion CRP is effective to treat BPPV .The DHI is available for the evaluation of QOL of BPPV patients .