Exposure to Progestin 17-OHPC Induces Gastrointestinal Dysfunction through Claudin-1 Suppression in Female Mice with Increased Anxiety-Like Behaviors.

INTRODUCTION: Progestin, commonly used in oral contraception and preventing preterm birth, elicits various off-target side effects on brain and gastrointestinal (GI) functions, yet the precise mechanisms remain elusive. This study aims to probe progestin's impact on GI function and anxiety-like behaviors in female mice. METHODS: Colon stem cells were utilized to explore the mechanism underlying progestin 17-hydroxyprogesterone caproate (17-OHPC)-mediated suppression of claudin-1 (CLDN1), crucial for epithelial integrity. Chromatin immunoprecipitation and luciferase assays identified potential progestin-response elements on the CLDN1 promoter, with subsequent assessment of oxidative stress and pro-inflammatory cytokine release. Manipulation of vitamin D receptor (VDR) or estrogen receptor ß (ERß) expression elucidated their roles in 17-OHPC-mediated effects. Intestine-specific VDR deficient mice were generated to evaluate 17-OHPC's impact on GI dysfunction and anxiety-like behaviors in female mice. Additionally, gene expression was analyzed in various brain regions, including the amygdala, hypothalamus, and hippocampus. RESULTS: Exposure to 17-OHPC suppressed CLDN1 expression via epigenetic modifications and VDR dissociation from the CLDN1 promoter. Furthermore, 17-OHPC intensified oxidative stress and pro-inflammatory cytokine release. VDR knockdown partly mimicked, while overexpression of either VDR or ERß partly restored 17-OHPC-mediated effects. Intestinal VDR deficiency partly mirrored 17-OHPC-induced GI dysfunction, with minimal impact on 17-OHPC-mediated anxiety-like behaviors. CONCLUSIONS: 17-OHPC suppresses CLDN1 expression through VDR, contributing to GI dysfunction in female mice, distinct from 17-OHPC-induced anxiety-like behaviors. This study reveals a new mechanism and potential negative impact of progestin exposure on the GI tract, alongside inducing anxiety-like behaviors in female mice.

Identification of the lateral organ boundary domain gene family and its preservation by exogenous salicylic acid in Cerasus humilis.

The gene family known as the Lateral Organ Boundary Domain (LBD) is responsible for producing transcription factors unique to plants, which play a crucial role in controlling diverse biological activities, including their growth and development. This research focused on examining Cerasus humilis'ChLBD gene, owing to its significant ecological, economic, and nutritional benefits. Examining the ChLBD gene family's member count, physicochemical characteristics, phylogenetic evolution, gene configuration, and motif revealed 41 ChLBD gene family members spread across 8 chromosomes, with ChLBD gene's full-length coding sequences (CDSs) ranging from 327 to 1737 base pairs, and the protein sequence's length spanning 109 (ChLBD30)-579 (ChLBD35) amino acids. The molecular weights vary from 12.068 (ChLBD30) to 62.748 (ChLBD35) kDa, and the isoelectric points span from 4.74 (ChLBD20) to 9.19 (ChLBD3). Categorizing them into two evolutionary subfamilies: class I with 5 branches, class II with 2, the majority of genes with a single intron, and most members of the same subclade sharing comparable motif structures. The results of collinearity analysis showed that there were 3 pairs of tandem repeat genes and 12 pairs of fragment repeat genes in the Cerasus humilis genome, and in the interspecific collinearity analysis, the number of collinear gene pairs with apples belonging to the same family of Rosaceae was the highest. Examination of cis-acting elements revealed that methyl jasmonate response elements stood out as the most abundant, extensively dispersed in the promoter areas of class 1 and class 2 ChLBD. Genetic transcript analysis revealed that during Cerasus humilis' growth and maturation, ChLBD developed varied control mechanisms, with ChLBD27 and ChLBD40 potentially playing a role in managing color alterations in fruit ripening. In addition, the quality of calcium fruit will be affected by the environment during transportation and storage, and it is particularly important to use appropriate means to preserve the fruit. The research used salicylic acid-treated Cerasus humilis as the research object and employed qRT-PCR to examine the expression of six ChLBD genes throughout storage. Variations in the expression of the ChLBD gene were observed when exposed to salicylic acid, indicating that salicylic acid could influence ChLBD gene expression during the storage of fruits. This study's findings lay the groundwork for additional research into the biological role of the LBD gene in Cerasus humilis. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-024-01438-5.

Prevalence and genetic analysis of thalassemia in childbearing age population of Hainan, The Free Trade Island in Southern China.

BACKGROUND: Hainan has one of the high incidences of thalassemia in China, but the epidemiological data in the whole province has not been reported yet. The objective of our study was to reveal the true prevalence and molecular mutation spectrum of thalassemia in the population of Hainan who are of childbearing age. METHODS: We screened 166,936 individuals from 19 cities and counties in Hainan by hematological parameters analysis, and further conducted genetic analysis for individuals whose MCV was less than 82fL. RESULTS: In total, 21,619 (12.95%) subjects were diagnosed as thalassemia carriers or patients. The overall prevalence of α-thalassemia, ß-thalassemia, and α+ß-thalassemia were 10.39%, 1.38%, and 1.18%, respectively. Eleven α-thalassemia mutations and sixteen ß-thalassemia mutations were identified. The high-frequent genotypes of α-thalassemia were -α3.7 /αα (19.70%), -α4.2 /αα (19.39%), αα/--SEA (15.60%), αWS α/αα (9.24%), and -α3.7 /-α4.2 (8.90%), and those of ß-thalassemia were ßCD41/42(-TTCT) /ßN (58.92%), ß-28(A>G) /ßN (16.05%), ßIVS-Ⅱ-654(C>T) /ßN (8.42%), ßCD71/72(+A) /ßN (6.03%), ßCD17(A>T) /ßN (5.47%), and ßCD26 (GAG>AAG) /ßN (2.69%). In addition, the frequencies and hematological profiles of many rare mutations of α- [Fusion, HKαα, αααanti4.2 , IVS-II-55 (T>G), IVS-II-119 (-G,+CTCGGCCC)] and ß-globin genes [-50 (G>A), IVS-Ⅱ-81 (C>T)] in Hainan were reported for the first time. CONCLUSION: Our study revealed the high prevalence and extensive molecular spectrum of thalassemia in childbearing age population of Hainan, suggesting thalassemia in Hainan ranks second in prevalence among all regions in China. The findings will be useful for genetic counseling and prevention of thalassemia.

Noninvasive prenatal diagnosis of common aneuploidies by semiconductor sequencing.

Massively parallel sequencing (MPS) of cell-free fetal DNA from maternal plasma has revolutionized our ability to perform noninvasive prenatal diagnosis. This approach avoids the risk of fetal loss associated with more invasive diagnostic procedures. The present study developed an effective method for noninvasive prenatal diagnosis of common chromosomal aneuploidies using a benchtop semiconductor sequencing platform (SSP), which relies on the MPS platform but offers advantages over existing noninvasive screening techniques. A total of 2,275 pregnant subjects was included in the study; of these, 515 subjects who had full karyotyping results were used in a retrospective analysis, and 1,760 subjects without karyotyping were analyzed in a prospective study. In the retrospective study, all 55 fetal trisomy 21 cases were identified using the SSP with a sensitivity and specificity of 99.94% and 99.46%, respectively. The SSP also detected 16 trisomy 18 cases with 100% sensitivity and 99.24% specificity and 3 trisomy 13 cases with 100% sensitivity and 100% specificity. Furthermore, 15 fetuses with sex chromosome aneuploidies (10 45,X, 2 47,XYY, 2 47,XXX, and 1 47,XXY) were detected. In the prospective study, nine fetuses with trisomy 21, three with trisomy 18, three with trisomy 13, and one with 45,X were detected. To our knowledge, this is the first large-scale clinical study to systematically identify chromosomal aneuploidies based on cell-free fetal DNA using the SSP and provides an effective strategy for large-scale noninvasive screening for chromosomal aneuploidies in a clinical setting.

Obstacles to the coordination of delivering integrated prenatal HIV, syphilis and hepatitis B testing services in Guangdong: using a needs assessment approach.

BACKGROUND: Integration of services for Prevention of Mother-To-Child Transmission of HIV (PMTCT) into routine maternal and child health care is promoted as a priority strategy by the WHO to facilitate the implementation of PMTCT. Integration of services emphasizes inter-sectoral coordination in the health systems to provide convenient services for clients. China has been integrating prenatal HIV, syphilis and hepatitis B testing services since 2009. However, as the individual health systems are complex, effective coordination among different health agencies is challenging. Few studies have examined the factors that affect the coordination of such complex systems. The aim of this study is to assess the effectiveness of and examine challenges for integrated service delivery. Findings will provide the basis for strategy development to enhance the effective delivery of integrated services. METHODS: The research was conducted in Guangdong province in 2013 using a needs assessment approach that includes qualitative and quantitative methods. Quantitative data was collected through a survey and from routine monitoring for PMTCT and qualitative data was collected through stakeholder interviews. RESULTS: Routine monitoring data used to assess key indicators of coordination suggested numerous coordination problems. The rates of prenatal HIV (95%), syphilis (47%) and hepatitis B (47%) test were inconsistent. An average of only 20% of the HIV positive mothers was referred in the health systems. There were no regular meetings among different health agencies and the clients indicated complicated service processes. The major obstacles to the coordination of delivering these integrated services are lack of service resource integration; and lack of a mechanism for coordination of the health systems, with no uniform guidelines, clear roles or consistent evaluation. CONCLUSIONS: The key obstacles that have been identified in this study hinder the coordination of the delivery of integrated services. Our recommendations include: 1) Facilitate integration of the funding and information systems by fully combining the service resources of different health agencies into one unit; 2) Establish regular meetings to facilitate exchange of information and address problems; 3) Establish a client referral network between different health agencies with agreed guidelines, clear roles and consistent evaluation.

[Comparison of the effect of three ß-thalassemia prenatal screening strategies using in Guangdong province].

OBJECTIVE: To compare the effect of three ß-thalassemia prenatal screening strategies in Guangdong province. METHODS: A total of 13 284 hospital-delivered couples and 13 369 newborns were recruited from 91 hospitals in 21 counties or districts of Guangdong province from June to December 2012. Mean cell volume (MCV), mean corpuscular hemoglobin (MCH) and hemoglobin A2 (Hb A2) were tested for all the couples, and all the couples and newborns were detected by 17 types of ß-globin gene mutations. The effect of three ß-thalassemia prenatal screening strategies were compared as following: (1) MCV/MCH with Hb A2 serial screening (SS): Hb A2 was tested if the woman's MCV < 82 fl and (or) MCH < 27 pg. If the woman's Hb A2 > 3.5, it meant positive. And if the woman was ß-thalassemia carrier and her husband's Hb A2 > 3.5, it meant couple positive. (2) MCV/MCH with Hb A2 parallel screening (PS): if the woman's MCV < 82 fl and (or) MCH < 27 pg and (or) Hb A2 > 3.5 pg, it meant couple positive. And the husband would be tested for ß-globin gene mutations if the woman was ß-thalassemia carrier. (3) MCV/MCH with Hb A2 serial screening for couples (SSC): if one of the couple or both of them had MCV < 82 fl and (or) MCH < 27 pg, the couple would be tested for Hb A2, and if one of the couple got Hb A2 > 3.5, it meant couple positive. RESULTS: (1) For the SS strategy, the sensitivity was 92.69% (583/629); the specificity was 99.87% (12 638/12 655); the positive predictive value was 97.17% (583/600); and the negative predictive value was 99.64% (12 638/12 684). The results of ß-globin gene mutations tested showed that the rate of ß-thalassemia carriers was 4.74% (629/13 284) in the 13 284 pregnant women, and it was 4.29% (570/13 284) in their husbands. (2) The SS strategy detected 27 (0.20%, 27/13 284) ß-thalassemia carrier couples. For the SS strategy detecting ß-thalassemia carrier couples, the missed diagnosis rate was 11.11% (3/27); the sensitivity was 88.89% (24/27); the specificity was 100.00% (27/27); the positive predictive value was 100.00% (24/24); and the negative predictive value was 99.98% (13 257/13 260). (3) When using the SS strategy for 13 369 offsprings, there were 582 ß-thalassemia carriers (4.35%, 582/13369), including 578 (99.31%, 578/582) minor ß-thalassemia, 3 (0.52%, 3/582) intermedia ß-thalassemia and 1 (0.17%, 1/582) major ß-thalassemia. The SS strategy detected 25 fetuses who needed ß-thalassemia prenatal diagnosis. (4) For the PS strategy, the sensitivity was 98.09% (617/629); the specificity was 88.73% (11 229/12 655); the positive predictive value was 30.20% (617/2 043); and the negative predictive value was 99.89% (11 229/11 241). (5) When using the PS strategy for the ß-thalassemia carrier couples, the sensitivity was 100.00% (27/27); the specificity was 95.55% (12 667/13 257); the positive predictive value was 4.38% (27/617); and the negative predictive value was 100.0% (12 667/12 667). (6) The PS strategy detected 28 fetuses who needed ß-thalassemia prenatal diagnosis in 13 369 offsprings. (7) For the SSC strategy, the sensitivity was 93.80% (590/629); the specificity was 95.75% (12 117/12 655); the positive predictive value was 52.30% (590/1 128); and the negative predictive value was 99.68% (12 117/12 156). When the SSC strategy was used for the husbands, the sensitivity was 92.28% (526/570); the specificity was 95.27% (12 112/12 714);the positive predictive value was 46.63% (526/1 128); and the negative predictive value was 99.64% (12 112/12 156). (8) When the SSC strategy was used in ß-thalassemia carrier couples, the sensitivity was 100.00% (27/27); the specificity was 91.69% (12 156/13 257); the positive predictive value was 2.39% (27/1 128); and the negative predictive value was 100.00% (12 156/12 156). (9) The SSC strategy detected 28 fetuses who needed ß-thalassemia prenatal diagnosis. CONCLUSIONS: All the three ß-thalassemia prenatal screening strategies had good effect in clinical practice and public health. While in the high-prone area of ß-thalassemia, MCV/MCH with Hb A2 parallel screening and MCV/MCH with Hb A2 serial screening for couples stratigies were better.

Maternal deaths among rural-urban migrants in China: a case-control study.

BACKGROUND: Disparity in maternal mortality exists between rural-urban migrant and urban resident women in China, but little research has provided evidence for related policy development. The objective of this study was to identify associations with and risks for maternal death among rural-urban migrant women in order to improve health services for migrant women and reduce maternal mortality in China. METHODS: We conducted a prospective case-control study in urban areas of Guangdong, Zhejiang and Fujian provinces and Beijing municipality. In each, migrant women who died between July 1, 2010 and October 1, 2011 were identified through reports from China's Maternal and Child Mortality Surveillance System. For each, four matched controls were selected from migrant women who delivered in local hospitals during the same period. We compared socio-demographic characteristics, health status and health service variables between cases and controls, and used bivariate and multivariate conditional logistic regression analyses to determine associations with and risk factors for maternal death. RESULTS: 109 cases and 436 controls were assessed. Family income <2000 yuan per month (OR = 4.5; 95% CI 1.7-11.7) and lack of health insurance (OR = 1.3; 95% CI 1.1-1.6) were more common amongst women who died, as were lack of antenatal care (ANC) (OR = 22.3; 95% CI 4.3-116.0) and attending ANC only 1-4 times (OR = 5.0; 95% CI 1.6-15.5). Knowledge of danger signs during delivery was less common in this group (OR = 0.3; 95% CI 0.1-0.8). CONCLUSION: Differences existed between migrant women who died in pregnancy and surviving controls. The identified risk factors suggest strategies for health sector and community action on reducing maternal mortality among migrant women in China. A systematic approach to maternity care for rural-urban migrant women is recommended.

High prevalence of thalassemia in migrant populations in Guangdong Province, China.

BACKGROUND: The objectives of this study were to estimate the prevalence of thalassemia and to analyze the need for public health services for migrant populations in different cities in Guangdong Province, China. METHODS: A cross-sectional survey was conducted in 21 cities of Guangdong Province. Twenty-three types of a- and ß-globin gene mutations were detected in a total of 14,230 pregnant women and 14,249 husbands. RESULTS: There was a 16.45% prevalence of thalassemia among the 28,479 individuals, and the prevalences of α-, ß-, and combined α-/ß- thalassemia were 12.03%, 3.80%, and 0.63%, respectively. Compared with the native city residents in the province, the migrants from within the province and the immigrants from outside the province had lower prevalences of thalassemia, but the prevalence values were >11%. CONCLUSIONS: The prevalence values for thalassemia gene mutations were high in all three population groups studied in Guangdong Province. The results indicate that all segments of the Guangdong population should be screened for thalassemia.

[Gene diagnosis for a child with tuberous sclerosis].

OBJECTIVE: To identify the pathogenic mutation in a family affected with tuberous sclerosis. METHODS: For the proband and its parents, mutational hotspots in the 11 exons of TSC1 and TSC2 gene were analyzed with DNA sequencing and bioinformatics tools. RESULTS: A heterozygous c.4493G>C missense mutation was identified in the proband. The same mutation was however not found in the parents. CONCLUSION: The missense mutation c.4493G>C probably underlie the tuberous sclerosis complex seen in the child.

A review of the botany, phytochemistry, pharmacology, synthetic biology and comprehensive utilization of Silybum marianum.

Silybum marianum (L.) Gaertn, a herbaceous plant with a long history in traditional medicine for the treatment of hepatobiliary diseases, particularly in Europe, which has attracted attention for its remarkable therapeutic effect. This review systematically summarizes the research progress in the botany, phytochemistry, pharmacology, comprehensive utilization and synthetic biology of S. marianum. Up to now, more than 20 types of flavonolignan components have been isolated from S. marianum. In addition, the rearch on fatty acids and triterpenoids is also constantly improving. Among them, silybin is the most active compound in flavonolignans components. Its pharmacological effects in vivo and in vitro include anti-inflammatory, antioxidant, anti-tumour, hypoglycaemic, neuroprotective and immunoregulatory properties. The use of coniferyl alcohol and taxifolin as substrates to produce silybin and isosilybin under the action of enzyme catalysis is the commonly used biosynthetic pathway of silymarin, which provides support for a comprehensive analysis of the synthetic pathway of silymarin. In addition to medicinal use, the extracts of plants also have broad application prospects in the production of food, healthcare products, cosmetics and other aspects. In addition, the chemical composition, pharmacological mechanism and synthetic biology of S. marianum need to be further studied, which is very important for its clinical efficacy and resource development.

The carrier rate and mutation spectrum of genes associated with hearing loss in South China hearing female population of childbearing age.

BACKGROUND: Given that hearing loss occurs in 1 to 3 of 1,000 live births and approximately 90 to 95 percent of them are born into hearing families, it is of importance and necessity to get better understanding about the carrier rate and mutation spectrum of genes associated with hearing impairment in the general population. METHODS: 7,263 unrelated women of childbearing age with normal hearing and without family history of hearing loss were tested with allele-specific PCR-based universal array. Further genetic testing were provided to the spouses of the screened carriers. For those couples at risk, multiple choices were provided, including prenatal diagnosis. RESULTS: Among the 7,263 normal hearing participants, 303 subjects carried pathogenic mutations included in the screening chip, which made the carrier rate 4.17%. Of the 303 screened carriers, 282 harbored heterozygous mutated genes associated with autosomal recessive hearing loss, and 95 spouses took further genetic tests. 8 out of the 9 couples harbored deafness-causing mutations in the same gene received prenatal diagnosis. CONCLUSIONS: Given that nearly 90 to 95 percent of deaf and hard-of-hearing babies are born into hearing families, better understanding about the carrier rate and mutation spectrum of genes associated with hearing impairment in the female population of childbearing age may be of importance in carrier screening and genetic counseling.

An easy operating pathogen microarray (EOPM) platform for rapid screening of vertebrate pathogens.

BACKGROUND: Infectious diseases emerge frequently in China, partly because of its large and highly mobile population. Therefore, a rapid and cost-effective pathogen screening method with broad coverage is required for prevention and control of infectious diseases. The availability of a large number of microbial genome sequences generated by conventional Sanger sequencing and next generation sequencing has enabled the development of a high-throughput high-density microarray platform for rapid large-scale screening of vertebrate pathogens. METHODS: An easy operating pathogen microarray (EOPM) was designed to detect almost all known pathogens and related species based on their genomic sequences. For effective identification of pathogens from EOPM data, a statistical enrichment algorithm has been proposed, and further implemented in a user-friendly web-based interface. RESULTS: Using multiple probes designed to specifically detect a microbial genus or species, EOPM can correctly identify known pathogens at the species or genus level in blinded testing. Despite a lower sensitivity than PCR, EOPM is sufficiently sensitive to detect the predominant pathogens causing clinical symptoms. During application in two recent clinical infectious disease outbreaks in China, EOPM successfully identified the responsible pathogens. CONCLUSIONS: EOPM is an effective surveillance platform for infectious diseases, and can play an important role in infectious disease control.

Effectiveness of a prevention of mother-to-child HIV transmission program in Guangdong province from 2007 to 2010.

BACKGROUND: To achieve the goal of United Nations of elimination of new HIV infections, a program of prevention of mother-to-child transmission (PMTCT) was launched in Guangdong province. The objective of this study is to evaluate the effectiveness of the PMTCT program. METHODS: The retrospective cross-section analysis was conducted using the data of case reported cards of HIV positive mothers and their infants from 2007 to 2010 in Guangdong province, and 108 pairs of eligible subjects were obtained. We described the data and compared the rates of MTCT by various PMTCT interventions respectively. RESULTS: The overall rate of HIV MTCT was 13.89% (15) among 108 pairs of HIV positive mothers and their infants; 60.19% (65) of the mothers ever received ARVs, 80.56% (87) of infants born to HIV positive mothers ever received ARVs, but 16.67% (18) of the mothers and infants neither received ARVs. Among all the mothers and infants, who both received ARVs, received triple ARVs, mother received ARVs during pregnancy, and both received ARVs and formula feeding showed the lower rates of HIV MTCT, and the rates were 8.06%, 2.50%, 5.77%, and 6.67% respectively. In infants born to HIV positive mother, who received mixed feeding had a higher HIV MTCT up to 60.00%. Delivery mode might not relative to HIV MTCT. CONCLUSIONS: The interventions of PMTCT program in Guangdong could effectively reduce the rate of HIV MTCT, but the effectiveness of the PMTCT program were heavily cut down by the lower availability of the PMTCT interventions.

Corrigendum: Prevalence of iron-deficiency anemia in pregnant women with various thalassemia genotypes: thoughts on iron supplementation in pregnant women with thalassemia genes.

[This corrects the article DOI: 10.3389/fnut.2022.1005951.].

Prevalence and Genetic Analysis of Thalassemia and Hemoglobinopathy in Different Ethnic Groups and Regions in Hainan Island, Southeast China.

Background: There are limited studies on the molecular profile of thalassemia in Hainan, the free trade island in China. Our aim was to reveal the prevalence and molecular mutation spectrum of thalassemia in different ethnic groups and regions of Hainan through a large sample study for the first time. Methods: A total of 231,596 individuals from 19 cities and counties in Hainan were screened by hematological parameter analysis, and further genetic analysis was performed on individuals with MCV less than 82 fL. Results: Totally, 31,780 (13.72%) subjects were diagnosed as thalassemia carriers. The overall prevalence of α-thalassemia, ß-thalassemia, and α+ß-thalassemia were 11.04%, 1.48%, and 1.20%, respectively. We further analyzed the molecular profiles of thalassemia in various ethnic groups and mainly compared the difference between Han and Li. The results showed that the frequency of thalassemia in the Li population (47.03%) was much higher than that in Han (9.37%). Except for ß-thalassemia (1.31% of Li vs. 1.47% of Han), the frequencies of α-thalassemia (39.59% of Li vs. 7.35% of Han) and α+ß-thalassemia (6.13% of Li vs. 0.56% of Han) in the Li were obviously higher than those in Han. The high-frequent genotypes of α-thalassemia in Han were αα/--SEA (25.55%), -α3.7/αα (22.17%), -α4.2/αα (21.59%), αWSα/αα (8.93%), and -α3.7/-α4.2 (4.17%) and those of Li were -α4.2/αα (17.24%), -α3.7/αα (17.16%), -α3.7/-α4.2 (15.09%), αWSα/αα (9.69%), and αWSα/-α3.7 (8.06%), respectively. The αα/--SEA was the highest genotype of α-thalassemia in Han but only accounted for 1.87% in Li. For ß-thalassemia, the top three high-frequent genotypes in both Han and Li were ßCD41/42(-TTCT)/ßN, ß-28(A>G)/ßN, and ßIVS-Ⅱ-654(C>T)/ßN, but the frequency of ßCD41/42(-TTCT)/ßN in Li (90.96%) was much higher than that in Han (56.32%) and the data reported in other provinces of China. Additionally, the prevalence of thalassemia ranged from 8.16% to 34.35% in Hainan, Wuzhishan, Baoting, Qiongzhong, and Baisha have a higher prevalence than other areas. Conclusion: Our study revealed the characteristics of ethnic and regional differences in the prevalence of thalassemia in the childbearing age population of Hainan for the first time, indicating that the prevalence of thalassemia among Li nationality is the highest in China. Those findings will be useful for genetic counseling and the prevention of thalassemia.

Prevalence of iron-deficiency anemia in pregnant women with various thalassemia genotypes: Thoughts on iron supplementation in pregnant women with thalassemia genes.

Background: There are limited studies on iron-deficiency anemia (IDA) in carriers of various thalassemia genotypes. However, for pregnant women (PW) with high iron demand, ignoring the phenomenon of carrying the thalassemia genes combined with IDA may lead to adverse pregnancy outcomes. Methods: The hematological phenotype indexes of 15,051 PW who received a prenatal diagnosis of thalassemia in our hospital were analyzed, and the plasma ferritin (PF) of 714 anemic pregnant women (APW) was determined. Results: The results showed that 87.43% of APW without thalassemia suffered from IDA. Among APW with various thalassemia genotypes, we found that 40.00∼77.78% of subjects with α-thalassemia silent genotypes [αCS (or QS)α/αα (40.00%), -α3.7(or 4.2)/αα (57.65%), and αWSα/αα (77.78%)] and 18.18∼84.21% of subjects with α-thalassemia minor genotypes [αCS (or QS)α/-α3.7(or 4.2) (18.18%), -α3.7(or 4.2)/-α3.7(or 4.2) (40.00%), αα/-SEA (44.55%), and αWSα/-α3.7(or 4.2) (84.21%)] developed IDA, while in subjects with α-thalassemia intermedia genotypes, only αWSα/-SEA was associated with IDA, with an incidence of 16.67%. However, the incidence of IDA in APW with common ß-thalassemia minor genotypes (ßCD17(A>T)/ß, ßCD41/42 (-TTCT)/ß, ßCD71/72(+A)/ß, ßIVS-II-654(C>T)/ß, and ß-28(A>G)/ß) was less than 10.85%. In addition, the APW with ß-thalassemia minor had a higher PF level than the APW without thalassemia. Conclusion: Our study is the first to reveal differences in the prevalence of IDA among PW with various thalassemia genotypes, indicating that the possibility of IDA should be fully considered when managing PW with α-thalassemia silent or minor genotypes in high-risk areas, and that iron supplementation should be monitored dynamically for PW with ß-thalassemia minor genotypes.

Characterization of human cytomegalovirus UL145 and UL136 genes in low-passage clinical isolates from infected Chinese infants.

BACKGROUND: Human cytomegalovirus (HCMV) is a leading cause of morbidity and mortality in immunocompromised individuals. The unique long b' (ULB') region of HCMV contains at least 19 open reading frames (ORFs); however, little is known about the function of UL145 and UL136. We characterized UL145 and UL136 in low-passage clinical isolates from Chinese infants. MATERIAL/METHODS: The clinical strains of HCMV were recovered from the urine from HCMV-infected infants. Human embryonic lung fibroblasts (HELFs) were infected with clinical isolates of HCMV, and the viral DNA and mRNA for UL145 and UL136 were analyzed by polymerase chain reaction (PCR) and sequencing techniques. We also predicted the structure and function of UL145 and UL136 proteins. RESULTS: Sixty-two Chinese infants infected with HCMV were recruited into this study and the clinical isolates were recovered from the urine. Two strains among the low-passage isolates, D2 and D3, were obtained. The UL145 and UL136 sequences were deposited with GenBank under accession numbers of DQ180367, DQ180381, DQ180377, and DQ180389. The mRNA expression of both UL145 and UL136 was confirmed by reverse transcription (RT-PCR) assays. UL145 was predicted to contain 1 protein kinase C phosphorylation site, 2 casein kinase II phosphorylation sites and a zinc finger structure. UL136 was predicted to contain a protein kinase C phosphorylation site, N-myristoylation site, cAMP- and cGMP-dependent protein kinase phosphorylation site and tyrosine kinase II phosphorylation site. Both UL145 and UL136 are highly conserved. CONCLUSIONS: UL145 may act as an intranuclear regulating factor by direct binding to DNA, while UL136 may be a membrane receptor involving signal transduction.

New insights into the structural characteristics and functional relevance of the human cytochrome P450 2D6 enzyme.

To date, the crystal structures of at least 12 human CYPs (1A2, 2A6, 2A13, 2C8, 2C9, 2D6, 2E1, 2R1, 3A4, 7A1, 8A1, and 46A1) have been determined. CYP2D6 accounts for only a small percentage of all hepatic CYPs (< 2%), but it metabolizes approximately 25% of clinically used drugs with significant polymorphisms. CYP2D6 also metabolizes procarcinogens and neurotoxins, such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, 1,2,3,4-tetrahydroquinoline, and indolealkylamines. Moreover, the enzyme utilizes hydroxytryptamines and neurosteroids as endogenous substrates. Typical CYP2D6 substrates are usually lipophilic bases with an aromatic ring and a nitrogen atom, which can be protonated at physiological pH. Substrate binding is generally followed by oxidation (5-7 A) from the proposed nitrogen-Asp301 interaction. A number of homology models have been constructed to explore the structural features of CYP2D6, while antibody studies also provide useful structural information. Site-directed mutagenesis studies have demonstrated that Glu216, Asp301, Phe120, Phe481, and Phe483 play important roles in determining the binding of ligands to CYP2D6. The structure of human CYP2D6 has been recently determined and shows the characteristic CYP fold observed for other members of the CYP superfamily. The lengths and orientations of the individual secondary structural elements in the CYP2D6 structure are similar to those seen in other human CYP2 members, such as CYP2C9 and 2C8. The 2D6 structure has a well-defined active-site cavity located above the heme group with a volume of approximately 540 A(3), which is larger than equivalent cavities in CYP2A6 (260 A(3)), 1A2 (375 A(3)), and 2E1 (190 A(3)), but smaller than those in CYP3A4 (1385 A(3)) and 2C8 (1438 A(3)). Further studies are required to delineate the molecular mechanisms involved in CYP2D6 ligand interactions and their implications for drug development and clinical practice.