OBJECTIVE: To retrospectively analyze the genetic differences of thalassemia gene mutations among ethnic groups in Hechi, Guangxi. METHODS: A total of 15 595 whole blood samples of residents of Hechi from January 1, 2020 to June 30, 2023 were screened for thalassemia, and the Gap-PCR method and RDB-PCR method were used to perform genetic testing on the positive samples. Gene sequencing was performed on the samples with positive screening results but negative genotyping results. RESULTS: Among the 15 595 samples, 10 501 cases were screened positively, and 8 506 cases were thalassemia gene carriers among the positive samples, with a positive coincidence rate of 81.00%. Among them, there were 5 374 cases of α-thalassemia, 2 531 cases of β-thalassemia, and 601 cases of α+β compound thalassemia. A total of 13 mutant types were detected in α-thalassemia, including --^SEA (48.57%), -α ^3.7 (31.31%), α ^CS (8.57%) and -α ^4.2 (8.07%). A total of 17 mutant types were detected in β-thalassemia, mainly CD17 (48.27%) and CD41-42 (41.24%). The thalassemia gene carriers were mainly from the Zhuang (6 106 cases), Han (969 cases), Yao (793 cases), Mulam (275 cases), and Maonan (228 cases) ethnic groups. The comparison of constituent ratios within the above five ethnic groups demonstrated that there were differences in the proportions of -- ^SEA, -α ^3.7, α ^CS , and -α ^4.2 among the Zhuang, Han, and Yao ethnic groups (P < 0.005). The proportion of α ^CS in the Mulam ethnic group was not significantly different from -α ^3.7 and -α ^4.2. The proportions of -- ^SEA, -α^3.7, and α ^CS in the Maonan ethnic group were not significantly different. There were no significant differences in the proportion of CD17 and CD41-42 among the Han, Yao, Mulam and Maonan ethnic groups. The proportion of --^SEA was the highest in the Mulam ethnic group (56.68%), which was statistically different from 35.92% in the Maonan ethnic group. The proportion of -α ^3.7 was the highest in the Zhuang ethnic group (33.25%), and the difference was statistically significant compared to the Mulam ethnic group which had the lowest proportion (18.72%). The proportion of α ^CS was the highest in the Maonan ethnic group (27.46%), and the differences were statistically significant compared with other ethnic groups. The proportions of CD17 in the Zhuang and Maonan ethnic groups (50.79%, 55.68%) were higher than those in the Han (39.12%), Yao (39.63%) and Mulam (30.00%), and the differences were statistically significant. There was no significant difference in the proportion of CD41-42 among the above five ethnic groups. CONCLUSIONS The mutation type and distribution differences of genes causing thalassemia among main ethnic groups in the minority inhabited areas of Hechi, Guangxi, show the characteristics of ethnic differentiation. The result is helpful to develop a special prevention and control plan for thalassemia in line with the population distribution characteristics, and provide reference for revealing the genetic background and geographical distribution of thalassemia in this area.
Humans ; China ; beta-Thalassemia/genetics* ; Ethnicity/genetics* ; alpha-Thalassemia/genetics* ; Mutation ; Genotype ; Retrospective Studies ; Asian People/genetics* ; Thalassemia/genetics* ; Male

Objective:To investigate the association of single nucleotide polymorphism at the estrogen receptor 1(ESR1) gene rs1801132 with the risk of brick-tea type skeletal fluorosis.Methods:The typical brick-tea type fluorosis areas in Qinghai, Xinjiang, and Inner Mongolia were selected as the survey sites for a cross-sectional study. An epidemiological questionnaire was conducted by the staffs on the sites for participants older than 16 years, and physical examination and X-ray diagnosis were performed. Brick tea, blood, and urine samples were collected at the same time. The diagnosis of skeletal fluorosis through X-ray was based on the "Diagnostic Criteria for Endemic Skeletal Fluorosis" (WS/T 192-2008); The determination of tea's fluoride and urinary fluoride was performed by fluoride ion-selective electrode method; gene sequencing analysis of rs1801132 locus of ESR1 gene was done by Sequenom MassARRAY flight mass spectrometry system.Results:A total of 994 patients were included in this study. The total prevalence of skeletal fluorosis was 23.9% (238/994). The prevalence of skeletal fluorosis in Tibetans(39.9%, 123/308) was higher than those of Mongolian and Han nationality [22.2% (58/261), 13.4% (57/425), χ 2=20.435, 67.811, P < 0.05]. Based on binary logistic analysis, the daily tea fluoride intake ≤ 3.5 mg, urinary fluoride content ≤1.6 mg/L, and age ≤45 years were used as the reference groups, and then, when the daily tea fluoride intake > 7.0 mg ( OR=2.865, 95% CI: 1.923-4.268), urinary fluoride content > 1.6-3.2 mg/L ( OR=2.368, 95% CI: 1.686-3.326) and > 3.2 mg/L ( OR=3.559, 95% CI: 2.401-5.276), the age > 45-65 years old ( OR=2.361, 95% CI: 1.603-3.477) and > 65 years old ( OR=4.556, 95% CI: 2.845-7.296), the risk of fluorosis was higher than that of the reference group, respectively. When the daily tea fluoride intake was > 3.5-7.0 mg and the level of urinary fluoride was > 1.6-3.2 mg/L, G allele had a protective effect on skeletal fluorosis in Mongolian population (adjusted OR=0.207, 95% CI: 0.044-0.974); when the daily tea fluoride intake was > 3.5-7.0 mg, gender was male group, G allele had a protective effect on skeletal fluorosis in Han population (adjusted OR=0.315, 95% CI: 0.112-0.887). Conclusion:The single nucleotide polymorphism of the rs1801132 locus at the ESR1 gene may be associated with the risk of susceptibility to brick-tea type skeletal fluorosis in Mongolian and Han nationality.

The paper dilates upon purpose and meaning of the building of multipath remote consultation platform based on medical alliance,introduces its building scheme,which includes implementation method,technology roadmap and technology feasibility analysis,compares the domestic and overseas situations in the area and discusses its future.

BACKGROUNDNontraumatic osteonecrosis of the femoral head (NONFH) is a debilitating disease that represents a significant financial burden for both individuals and healthcare systems. Despite its significance, however, its prevalence in the Chinese general population remains unknown. This study aimed to investigate the prevalence of NONFH and its associated risk factors in the Chinese population.

METHODSA nationally representative survey of 30,030 respondents was undertaken from June 2012 to August 2013. All participants underwent a questionnaire investigation, physical examination of hip, and bilateral hip joint X-ray and/or magnetic resonance imaging examination. Blood samples were taken after overnight fasting to test serum total cholesterol, triglyceride, and high-density lipoprotein (HDL) and low-density lipoprotein (LDL) levels. We then used multivariate logistic regression analysis to investigate the associations between various metabolic, demographic, and lifestyle-related variables and NONFH.

RESULTSNONFH was diagnosed in 218 subjects (0.725%) and the estimated NONFH cases were 8.12 million among Chinese people aged 15 years and over. The prevalence of NONFH was significantly higher in males than in females (1.02% vs. 0.51%, χ2 = 24.997, P < 0.001). Among NONFH patients, North residents were subjected to higher prevalence of NONFH than that of South residents (0.85% vs. 0.61%, χ 2 = 5.847, P = 0.016). Our multivariate regression analysis showed that high blood levels of triglycerides, total cholesterol, LDL-cholesterol, and non-HDL-cholesterol, male, urban residence, family history of osteonecrosis of the femoral head, heavy smoking, alcohol abuse and glucocorticoid intake, overweight, and obesity were all significantly associated with an increased risk of NONFH.

CONCLUSIONSOur findings highlight that NONFH is a significant public health challenge in China and underscore the need for policy measures on the national level. Furthermore, NONFH shares a number of risk factors with atherosclerosis.

Adult ; Age Distribution ; Aged ; Asian Continental Ancestry Group ; China ; epidemiology ; Female ; Femur Head Necrosis ; epidemiology ; Humans ; Male ; Middle Aged ; Prevalence ; Risk Factors ; Young Adult

Objective To evaluate the predictive values of ABCD,ABCD2 ,SPI-Ⅱ and ESSEN score models for the patients with high-risk transient ischemic attack (TIA)to develop to cerebral infarction in short and long term. Methods The ABCD, ABCD2 , SPI-Ⅱ and ESSEN scores of 235 cases of TIA patients were retrospectively analyzed.The incidence of cerebral infarction was followed up for 7 d and 1 year, and the receiver operating characteristic curve (ROC)was drawn to calculate the area under curve (AUC)to assess the accuracy of the score models,and compared with the original model and the relative risk (RR)value was calculated.Results The 7 d-incidence and 1 year-incidence of cerebral infarction in the 235 TIA patients were 9.36 % and 20.43%.The AUC of ABCD,ABCD2 ,SPI-Ⅱ and ESSEN models for 7 d were 0.70,0.74,0.67,and 0.62.The AUC of 1 year were 0.62,0.62,0.64,and 0.65.Compared with the orginal models,the RRs for 7 d of ABCD score model of the TIA patients in low,middle,and high risk groups were 0.09,0.92,and 0.72;the RRs of ABCD2 score model were 0.49,0.59,and 0.65;the RRs of SPI-Ⅱ score model were 0.58,0.87,and 0.55;the RRs of ESSEN score model were 0.11,0.18,and 0.55.Conclusion ABCD,ABCD2 ,SPI-Ⅱ and ESSEN score models can be used to assess the risk of cerebral infarction after TIA in Chinese population.The ABCD2 score model is of great value for short-term risk prediction,and the ESSEN score model is more value for long-term risk prediction.

BACKGROUND:The immunological rejection between host and graft is the leading cause of organ
transplantation failure. The traditional immunosuppressive agents have been unable to meet the needs of clinical treatment. Antibody-drug conjugate, as a type of new drugs, may be hope for the treatment of immune rejection. OBJECTIVE:To comprehensively analyze the composition of antibody-drug conjugates, mechanism of action, clinical research progress as wel as the development trend.
METHODS:A computer-based online retrieval was performed to search papers in CNKI and PubMed database using the key words of ADCs, immunosuppressive agents, immunotoxins, organ transplantation, graft rejection in Chinese and English. Recently published or published in the prestigious journals were selected in the same field. After excluding objective-independent papers and repeated studies, 42 papers were included for further analysis. RESULTS AND CONCLUSION:Antibody-drug conjugates, as highly effective and lowly toxic immunosuppressant, have achieved a breakthrough in treatment of targeting tumor, while the role of it in anti-immune rejection is stil at the exploratory stage. For islet transplantation, novel antibody-drug conjugates are required to block CD8+T effector by CD103/E-Cadherin pathway, and wil probably serve as a potential drug intervention for al ograft rejection.

OBJECTIVETo explore HEPACAM mutations in a Chinese family with megalencephalic leukoencephaloptathy with subcortical cysts (MLC).

METHODGenomic DNA samples were extracted from peripheral blood of the proband and her parents. All exons and exon-intron boundaries of HEPACAM and MLC1 were amplified in the MLC family by polymerase chain reaction (PCR) followed by direct DNA sequencing.

RESULTTwo heterozygous mutations of HEPACAM located in exon 2, c.203A > T(p.K68M) and c.395C > A(p.T132N), were identified in the proband. The proband's mother had the heterozygous mutations c.203A > T(p.K68M), and her father had the heterozygous mutation-c.395C > A(p.T132N). There was no variation found in MLC1 gene.

CONCLUSIONThe proband was heterozygous compound MLC patient carrying on one allele with the c.203A > T(p.K68M) mutation inherited from her mother, and the other allele with the c.395C > A(p.T132N) mutation inherited from her father. The parents both are heterozygous carriers with normal phenotype. The disease-causing gene for this family was resulted in HEPACAM mutation other than MLC1 mutation.

Asian Continental Ancestry Group ; genetics ; Base Sequence ; Child ; Cysts ; genetics ; pathology ; DNA Mutational Analysis ; Exons ; Female ; Genotype ; Hereditary Central Nervous System Demyelinating Diseases ; genetics ; pathology ; Heterozygote ; Humans ; Membrane Proteins ; genetics ; Mutation ; Pedigree ; Phenotype ; Proteins ; genetics

To investigate the protective effects of recombinant human tumor necrosis factor receptor II: IgG Fc fusion protein (rhu TNFR: Fc) against the lipopolysaccharide (LPS) induced intestinal damage of rats and its underlying mechanism. SD rats were randomly divided into four groups: control group, rhuTNFR: Fc group, LPS group and rhu TNFR: Fc + LPS group. Mean arterial pressure (MAP) was continuously monitored and the mortality rates were assessed. The levels of TNF-alpha and its bioactivity in the serum were assessed by ELISA and flow cytometry respectively. Pathologic changes of intestinal tissue were observed by HE staining. The rats of control and rhu TNFR: Fc group all survived with stable MAP, and the low level and bioactivity of TNF-alpha in the serum were maintained. While 83% of the rats in LPS group died by 6 h with the levels and bioactivity of TNF-alpha increasing significantly. In rhu TNFR: Fc + LPS group, the mortality rate of rats dropped to 33%. The TNF-alpha level increased compared with control group but its bioactivity decreased significantly compared with LPS group. The MPO activity and content of MDA decreased significantly. The status of pathological manifestation in the intestine was also ameliorated. These data suggest that rhu TNFR: Fc could protect rats from the acute intestine injury induced by LPS through ablating the rise in serum TNF-alpha level and bioactivity as well as anti-oxidation.
Animals ; Disease Models, Animal ; Etanercept ; Female ; Humans ; Immunoglobulin G ; pharmacology ; Intestines ; drug effects ; metabolism ; pathology ; Lipopolysaccharides ; adverse effects ; Male ; Rats ; Rats, Sprague-Dawley ; Receptors, Tumor Necrosis Factor ; Receptors, Tumor Necrosis Factor, Type II ; pharmacology ; Recombinant Fusion Proteins ; pharmacology ; Tumor Necrosis Factor-alpha ; metabolism

Objective To investigate the role of nasal mucosa fibrosis on radiation induced nasal mucosa injury. Methods Seventy two male rats were randomly divided into two groups, control group and irradiation injured group (radiation dose were 40 Gy);the rats were killed 1 week, 2 weeks, 4 weeks, 8 weeks, 3 months and 6 months after the finish of radiation. The middle turbinates of the animals were removed. The pathological change of the nasal mucosa were observed with scanning electron microscope, transmission electron microscope, hematoxylin and eosin (HE), alcian blue-periodic acid-Sehif (AB-PAS), and Masson Trichrome (MT). The Hyp content in nasal mucosa was measured with chemo-chromatometry. Results After radiation, the pathological characteristics in early stage (within 4 weeks) was acute inflammatory reaction. The repair of nasal mucosa started 4 weeks after radiation, lasted to 6 months. The deposition of collagen in nasal mucosa could be found 1 week after irradiation and increased gradually. Conclusion Irradiation could induce a serials of pathological changes on nasal mucosa. The nasal mucosa fibrosis may be one of the reasons of persistent irradiation induced nasal mucosa injury.

OBJECTIVESTo block the synthesis of ryanodine receptor 2 (RyR2) in myocardial cells by RNA interference and to investigate its biological impact on ischemia-reperfusion (I/R) in rat myocardial cells.

METHODSRat myocardial cells were isolated and cultured for an I/R model in vitro. RNA interference technique was used to block the synthesis of RyR2 in myocardial cells. Changes of LDH level, apoptosis, RyR2 mRNA expression and cytosolic Ca(2+) concentration were analyzed accordingly.

RESULTSMyocardial cells after I/R manipolation were severely injuried (LDH leakage, 125 IU/L vs 12 IU/L, P < 0.05), apoptosis (60.1% vs 5.5%, P < 0.05), significant cytosolic Ca(2+) overload (21.2 vs 7.6, P < 0.05) and remarkable mitochondrial membrane potential loss (37.2 vs 85.1, P < 0.05). However, no visible change of RyR2 was observed (20.1 vs 22.7, P > 0.05). Pre-treatment with RyR2 specified siRNA demonstrated suppressed expression of RyR2 (6.8 vs 20.1, P < 0.05), increased mitochondrial membrane potential (55.8 vs 37.2, P < 0.05), attenuated cytosolic Ca(2+) overload (8.6 vs 21.2) and cellular apoptosis (31.2% vs 60.1%, P < 0.05).

CONCLUSIONRyR2 gene silencing enables to protect myocardial cells from I/R injury in vitro.

Animals ; Apoptosis ; drug effects ; genetics ; Cells, Cultured ; Gene Silencing ; immunology ; physiology ; Membrane Potential, Mitochondrial ; drug effects ; immunology ; Myocardial Reperfusion Injury ; immunology ; pathology ; Myocytes, Cardiac ; drug effects ; pathology ; Oxygen ; metabolism ; RNA Interference ; RNA, Small Interfering ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; immunology ; pathology ; Ryanodine Receptor Calcium Release Channel ; drug effects ; genetics