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Introduction: Relapse remained the major obstacle to improving the prognosis of children with acute lymphoblastic leukemia (ALL). This study aimed to investigate the changing patterns of Ig/TCR gene rearrangements between diagnosis and relapse and the clinical relevance and to explore the mechanism of leukemic relapse. Methods: Clonal Ig/TCR gene rearrangements were screened by multiplex PCR amplification in 85 paired diagnostic and relapse bone marrow (BM) samples from children with ALL. The new rearrangements presented at relapse were quantitatively assessed by the RQ‐PCR approach targeting the patient‐specific junctional region sequence in 19 diagnostic samples. The relapse clones were further back‐traced to diagnostic and follow‐up BM samples from 12 patients. Results: Comparison of Ig/TCR gene rearrangements between diagnosis and relapse showed that 40 (57.1%) B‐ALL and 5 (33.3%) T‐ALL patients exhibited a change from diagnosis to relapse, and 25 (35.7%) B‐ALL patients acquired new rearrangements at relapse. The new relapse rearrangements were present in 15 of the 19 (78.9%) diagnostic samples as shown by RQ‐PCR, with a median level of 5.26 × 10−2. The levels of minor rearrangements correlated with B immunophenotype, WBC counts, age at diagnosis, and recurrence time. Furthermore, back‐tracing rearrangements in 12 patients identified three patterns of relapse clone dynamics, which suggested the recurrence mechanisms not only through clonal selection of pre‐existing subclones but also through an ongoing clonal evolution during remission and relapse. Conclusion: Backtracking Ig/TCR gene rearrangements in relapse clones of pediatric ALL revealed complex patterns of clonal selection and evolution for leukemic relapse. [ABSTRACT FROM AUTHOR]

Biological invasion refers to the process that organisms invade into another new environment through natural or man-made way from the original habitat, causing economic losses or ecological disasters to biodiversity, agriculture, forestry, animal husbandry and fishery production and human health. Human activities and the development of global integration accelerate the occurrence of biological invasion, which poses a serious threat to the global biodiversity and economy. Since entering the 21st century, biological invasion has continued. Pomacea canaliculata Lam, native to the Amazon River Basin of South America, was introduced into southern China as an aquatic economic animal in the 1980s because of its rich protein content and high nutrient content. Later, it was abandoned in the fields due to excessive blind breeding, too strong fishy smell and poor taste, and spread to the aquatic environment such as rice fields through canals and rivers. Because of its strong fecundity, adaptability and stress resistance, miscellaneous food habits and lack of natural enemies, the snail has become a disaster in many areas of southern China, which poses a major threat to the biodiversity, ecosystem, crops and aquatic plants in the invaded areas. In addition, Pomacea canaliculata is the intermediate host of Angiostrongylus cantonensis, which causes eosinophilic meningitis, and has indirect potential harm to human health. In 2000, the IUCN Expert Committee on alien invasive species listed Pomacea canaliculata as one of the world's 100 malignant alien invasive species. In March 2003, the State Environmental Protection Administration listed the first batch of 16 alien species to invade China. The control methods of Pomacea canaliculata can be divided into four aspects. First of all, physical methods are used to collect snails and eggs manually. During the peak breeding period, human resources are concentrated to collect snails in fields, canals and other areas. During the spawning period, bamboo chips and wooden sticks are inserted in the rice fields to attract the snails to lay eggs and destroy the collected eggs. However, this method has the characteristics of high frequency spawning, strong sustainability of prevention and control, rapid spread with the current, and it is difficult to control. In addition, the artificial fishing cost is high and the timeliness cannot be met for the large area where the Pomacea snail occurs. The second is chemical control. Though the molluscicides, such as spiromethane, tetraacetaldehyde and copper sulfate, are put in the rice fields, rice fields and channels at the same time. Although the effect is obvious, it is easy to cause serious environmental pollution if it is not used properly, and the snail is easy to produce drug resistance. The secondary biological method is to make use of the thin shell and meat of Fushou snail, which is high in protein, low in fat and has more in the areas where snails occur, ducks, fish and crabs are cultivated. However, in the process of biological control, it is necessary to strictly control the number of biological population to avoid animal feces polluting the water environment and damaging people's water sanitation. Finally, in order to prevent and control Pomacea canaliculata with camellia seed cake, saponins and other plant sources, it has become a hot spot in the field of snail control due to its long-term, economic and ecological safety to non target cells. However, there are few studies on the extraction and preparation of botanical toxicants and their toxic effects on Pomacea canaliculata. The results showed that castor seed was highly toxic, and the main toxic components were ricinine and ricin. Among them, ricin was one of the most toxic plant toxin proteins, which has a strong insecticidal and bactericidal effect. When it entered the animal body, it would be decomposed by the object itself, and it would not accumulate in the biological chain and produce drug resistance. Ricinine is a kind of alkaloid with low toxicity, which can cause vomiting and various toxic reactions. It can lead to liver and kidney damage, convulsion, hypotension and death. At present, there is no report on the toxicity of castor oil extract to Pomacea canaliculata. The biological soaking method was used to prepare the botanical toxicant from the extract of Ricinus communis L. seed. The toxic effects of different extract concentrations (0, 0.5, 1.5, 3.0, 4.5, 6.0 g/L) on the snails were studied. The liver tissue physiological and biochemical indexes of the snails treated with sublethal concentrations of 1.58 (LC25), 3.82 (LC50) and 6.05 (LC75) g/L and their correlation were further studied analysis of the mechanism of its toxic action. The results showed that after 48h treatment, the mortality of Pomacea canaliculata increased with the increase of time and concentration, and the mortality of Pomacea canaliculata was significantly different under different concentrations (P<0.05). The protein content (TP), malondialdehyde (MDA) content and catalase (CAT) activity in hepatopancreatic tissue were significantly different from those in the control group after 48h of sublethal concentration treatment. There was a significant negative correlation between catalase (CAT) activity and malondialdehyde (MDA) content (P<0.05). The extract of Ricinus communis L. seed can cause damage of liver tissue and disorder of metabolism by affecting the content of protein (TP), malondialdehyde (MDA) and the activity of catalase (CAT) in the liver tissue, so as to achieve the toxic effect. The results of molluscicidal test and physiological and biochemical indexes showed that castor seed had potential molluscicidal effect on Pomacea canaliculata. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the combined impact of IKZF1 deletions/high expression of CRLF2 on the prognosis of pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL). IKZF1 deletions and CRLF2 expression were assessed in bone marrow samples from 117 children with newly diagnosed BCP-ALL. Sixteen (13.7%) patients were found to harbor IKZF1 deletions, which was associated with inferior outcomes. The event-free survival (EFS) for patients with high -CRLF2 expression was significantly worse than that for low -CRLF2 expression. Moreover, combined modeling of IKZF1+/CRLF2high identified 7.8% of cases as the highest risk subgroup (7-year EFS 33.3 ± 15.7%). In a multivariate analysis, IKZF1+/CRLF2high remained a strong independent prognostic factor for EFS (HR: 14.263, p = 0.019). IKZF1 deletions and high -CRLF2 expression were associated with inferior outcomes, and the coexistence of IKZF1+/CRLF2high had a significant impact on an integrated prognostic model for high-risk BCP-ALL. [ABSTRACT FROM AUTHOR]

Abstract: We previously observed that disruption of FK506‐binding protein 12.6 (FKBP12.6) gene resulted in cardiac hypertrophy in male mice. Studies showed that overexpression of FKBP12.6 attenuated thoracic aortic constriction (TAC)‐induced cardiac hypertrophy in mice, whereas the adenovirus‐mediated overexpression of FKBP12.6 induced hypertrophy and apoptosis in cultured neonatal cardiomyocytes, indicating that the role of FKBP12.6 in cardiac hypertrophy is still controversial. In this study, we aimed to investigate the roles and mechanisms of FKBP12.6 in angiotensin II (AngII)‐induced cardiac hypertrophy using various transgenic mouse models in vivo and in vitro. FKBP12.6 knockout (FKBP12.6−/−) mice and cardiac‐specific FKBP12.6 overexpressing (FKBP12.6 TG) mice were infused with AngII (1500 ng/kg/min) for 14 days subcutaneously by implantation of an osmotic mini‐pump. The results showed that FKBP12.6 deficiency aggravated AngII‐induced cardiac hypertrophy, while cardiac‐specific overexpression of FKBP12.6 prevented hearts from the hypertrophic response to AngII stimulation in mice. Consistent with the results in vivo, overexpression of FKBP12.6 in H9c2 cells significantly repressed the AngII‐induced cardiomyocyte hypertrophy, seen as reductions in the cell sizes and the expressions of hypertrophic genes. Furthermore, we demonstrated that the protection of FKBP12.6 on AngII‐induced cardiac hypertrophy was involved in reducing the concentration of intracellular Ca2+ ([Ca2+]i), in which the protein significantly inhibited the key Ca2+/calmodulin‐dependent signalling pathways such as calcineurin/cardiac form of nuclear factor of activated T cells 4 (NFATc4), calmodulin kinaseII (CaMKII)/MEF‐2, AKT/Glycogen synthase kinase 3β (GSK3β)/NFATc4 and AKT/mTOR signalling pathways. Our study demonstrated that FKBP12.6 protects heart from AngII‐induced cardiac hypertrophy through inhibiting Ca2+/calmodulin‐mediated signalling pathways. [ABSTRACT FROM AUTHOR]

To characterize the genetic profiles and relationships between ancient ethnic populations, we analyzed polymorphisms in mitochondrial DNA (mtDNA) isolated from the blood of 753 members of 12 ethnic groups (Buyi, Dong, Gelao, Hui, Man, Miao, Menggu, Mulao, Maonan, Qiang, She and Zhuang) living in the Guizhou Province of China. The 9-bp deletion of mtDNA was detected by the polymerase chain reaction (PCR) and PCR-PAGE, and 11 SNPs by restriction fragment length polymorphism and mini-sequencing. Thereafter, these genotyping results were verified by PCR-DNA sequencing. The mtDNA of these populations exhibited considerable diversity, both with respect to the haplogroups M and N, and subgroups thereof. The differences between the major ethnic groups reflected the maternal inheritance. These ethnic groups in Guizhou demonstrated a genetic profile that differed considerably from that of other Asian populations. Our findings indicate that the matrilineal genetic profiles of Guizhou groups are relatively complex and distinct, showing relationships that reflect national history and geography. [ABSTRACT FROM AUTHOR]

Context.—: Langerhans cell histiocytosis (LCH) is a rare myeloid neoplasm that predominantly affects young children., Objective.—: To investigate genetic alterations and their correlation with clinical characteristics and prognosis in pediatric LCH., Design.—: We performed targeted sequencing to detect mutations in LCH lesions from pediatric patients., Results.—: A total of 30 genomic alterations in 5 genes of the MAPK pathway were identified in 187 of 223 patients (83.9%). BRAF V600E (B-Raf proto-oncogene, serine/threonine kinase) was the most common mutation (51.6%), followed by MAP2K1 (mitogen-activated protein kinase kinase 1) alterations (17.0%) and other BRAF mutations (13.0%). ARAF (A-Raf proto-oncogene, serine/threonine kinase) and KRAS (KRAS proto-oncogene, GTPase) mutations were relatively rare (2.2% and 0.9%, respectively). Additionally, FNBP1 (formin-binding protein 1)::BRAF fusion and MAP3K10 (mitogen-activated protein kinase kinase 10) mutations A17T and R823C were identified in 1 case each, with possible constitutive activation of ERK1/2 phosphorylation. BRAF V600E was more frequent in patients with risk organ involvement, while MAP2K1 mutation was more prevalent in patients with single-system LCH (P = .001). BRAF V600E was associated with craniofacial bone, skin, liver, spleen, and ear involvement (all P < .05). Patients with other BRAF mutations had a higher proportion of spinal column involvement (P = .006). Univariate analysis showed a significant difference in progression-free survival among the 4 molecular subgroups for patients treated with first-line therapy (P = .02). According to multivariate analysis, risk organ involvement was the strongest independent adverse prognostic factor (hazard ratio, 8.854; P < .001); BRAF or MAP2K1 mutation was not an independent prognostic factor., Conclusions.—: Most pediatric patients with LCH carry somatic mutations involving the MAPK pathway, correlating with clinical characteristics and outcomes for first-line chemotherapy., Competing Interests: The authors have no relevant financial interest in the products or companies described in this article., (© 2024 College of American Pathologists.)

We previously observed that disruption of FK506-binding protein 12.6 (FKBP12.6) gene resulted in cardiac hypertrophy in male mice. Studies showed that overexpression of FKBP12.6 attenuated thoracic aortic constriction (TAC)-induced cardiac hypertrophy in mice, whereas the adenovirus-mediated overexpression of FKBP12.6 induced hypertrophy and apoptosis in cultured neonatal cardiomyocytes, indicating that the role of FKBP12.6 in cardiac hypertrophy is still controversial. In this study, we aimed to investigate the roles and mechanisms of FKBP12.6 in angiotensin II (AngII)-induced cardiac hypertrophy using various transgenic mouse models in vivo and in vitro. FKBP12.6 knockout (FKBP12.6 -/- ) mice and cardiac-specific FKBP12.6 overexpressing (FKBP12.6 TG) mice were infused with AngII (1500 ng/kg/min) for 14 days subcutaneously by implantation of an osmotic mini-pump. The results showed that FKBP12.6 deficiency aggravated AngII-induced cardiac hypertrophy, while cardiac-specific overexpression of FKBP12.6 prevented hearts from the hypertrophic response to AngII stimulation in mice. Consistent with the results in vivo, overexpression of FKBP12.6 in H9c2 cells significantly repressed the AngII-induced cardiomyocyte hypertrophy, seen as reductions in the cell sizes and the expressions of hypertrophic genes. Furthermore, we demonstrated that the protection of FKBP12.6 on AngII-induced cardiac hypertrophy was involved in reducing the concentration of intracellular Ca 2+ ([Ca 2+ ]i), in which the protein significantly inhibited the key Ca 2+ /calmodulin-dependent signalling pathways such as calcineurin/cardiac form of nuclear factor of activated T cells 4 (NFATc4), calmodulin kinaseII (CaMKII)/MEF-2, AKT/Glycogen synthase kinase 3β (GSK3β)/NFATc4 and AKT/mTOR signalling pathways. Our study demonstrated that FKBP12.6 protects heart from AngII-induced cardiac hypertrophy through inhibiting Ca 2+ /calmodulin-mediated signalling pathways., (© 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

To characterize the genetic profiles and relationships between ancient ethnic populations, we analyzed polymorphisms in mitochondrial DNA (mtDNA) isolated from the blood of 753 members of 12 ethnic groups (Buyi, Dong, Gelao, Hui, Man, Miao, Menggu, Mulao, Maonan, Qiang, She and Zhuang) living in the Guizhou Province of China. The 9-bp deletion of mtDNA was detected by the polymerase chain reaction (PCR) and PCR-PAGE, and 11 SNPs by restriction fragment length polymorphism and mini-sequencing. Thereafter, these genotyping results were verified by PCR-DNA sequencing. The mtDNA of these populations exhibited considerable diversity, both with respect to the haplogroups M and N, and subgroups thereof. The differences between the major ethnic groups reflected the maternal inheritance. These ethnic groups in Guizhou demonstrated a genetic profile that differed considerably from that of other Asian populations. Our findings indicate that the matrilineal genetic profiles of Guizhou groups are relatively complex and distinct, showing relationships that reflect national history and geography.

Objective: To analyze the population genetics characteristics of mitochondrial DNA (mtDNA) in Gelao, Mulao, Maonan ethnic groups from Guizhou., Methods: Minisequenceing and restriction fragment length polymorphism (RFLP) were used to analyze 12 single nucleotide polymorphism (SNPs) of mitochondrial DNA in the 3 ethnic groups., Results: A total of 30 haplotypes were detected in 156 samples. The distribution of H1, H23 had differed between Mulao, Maonan and Gelao, respectively, and so did M7 among the three groups. The difference was statistically significant (P < 0.05). Mulao, Maonan had respectively differed from Gelao and the difference was also statistically significant (P < 0.05)., Conclusion: There was a great similarity in the distribution of haplotypes of the mtDNA among the three ethnic groups, except for some difference in the distribution of certain haplotypes.

Objective: To study the frequency of a 9 bp deletion polymorphism of mitochondrial DNA (mtDNA) in ethnic Miao, Buyi and Dong populations from Guizhou province., Methods: Polymerase chain reaction-polyacrylamide gel electrophoresis (PCR-PAGE) was used to detect the 9 bp deletion. The result was verified with DNA sequencing., Results: Two polymorphisms, including a standard pattern and a short pattern (the 9 bp deletion), were found among the three ethnic groups. The frequency of short pattern in 304 males was 23.0%. Respectively, those of Miao, Buyi and Dong ethnics were 28.6%, 26.8% and 13.7%. A statistically significant difference was detected among the three groups (P<0.05)., Conclusion: The frequencies of the 9 bp polymorphism were relatively high among ethnic Miao, Buyi and Dong populations from Guizhou, and there was a significant difference between the three.

Objective: To investigate allelic frequencies of interluekin-10 (IL-10) gene promoter in Miao, Dong and Buyi ethnics of Guizhou., Methods: TaqMan MGB-based real-time PCR was used to determine the genotypes of IL-10 -819 and IL-10 -592 in 589 Miao, Dong and Buyi ethnics of Guizhou., Results: The allelic frequency of IL-10 -819 in Miao ethnics was significantly different from those in Dong or Buyi ethnics. Allelic frequencies of IL-10 -592 in Miao ethnics was significantly different from those in Dong or Buyi ethnics. In Miao, Dong and Buyi ethnics, the distributions of genotype frequencies of IL-10 -819 and IL-10 -592 were statistically different from Han ethnics from Guizhou and Taiwan of China as well as South Koreans., Conclusion: There is a heterogeneity in the frequencies of polymorphisms of IL-10 promoter among different ethnic groups.

Objective: To investigate the association between both regulated upon activation normal T cell expressed and secreted (RANTES) -403G/A, -28C/G gene polymorphism and the susceptibilities to hepatitis B virus (HBV) infection, among people with Dong and Han ethnicities, in Guizhou., Methods: A total of 229 individuals with HBV persistence infection, 161 HBV clearanced patients and another 200 controls were recruited to conduct a case-control study among residents with Dong or Han ethnicities. Allelic frequencies of both RANTES-403G/A and -28C/G were identified by TaqMan-MGB probe., Results: Both RANTES-403G/A and -28C/G polymorphism in the HBV-persistent group, when compared to the HBV-clearances group, no significant difference was found (P > 0.05)., Results: from the univariate analysis showed that subjects carrying -403AG and -28GG genotype had higher risk on the susceptibility to HBV persistence infection. The distributions of RANTES-28C/G gene polymorphism between Dong minority and Han ethnicities regarding HBV persistence showed statistically significant difference (P < 0.05). There was no difference on the distributions of RANTES-403G/A gene polymorphism between Dong minority and Han ethnicities., Conclusion: Patients that carrying both RANTES-403AG and -28GG genotype had higher risk on the persistence to HBV, while RANTES-403A had contributed to the clearance of HBV infection.

Objective: To investigate the association between interleukin-10 (IL-10) gene promoter microsatellite polymorphisms and the susceptibility to hepatitis B virus infection in Han, Yi and Yao ethnicities in GuiZhou province., Methods: 500 volunteers were selected from Guizhou province. Allelic frequency of IL-10.G and IL-10.R loci was identified by short tandom repeat polymerase chain reaction. The relativity between allelic frequency and HBV infection was analyzed., Results: Genotype data from H-W analysis on all the IL-10 polymorphisms indicated that it was a random distribution. Very high HBV infection rates were found in the native ethnic minorities of Guizhou province. The overall HBV infection rate among the total population was 67.00%, with the HBV infection rates of Yi nationality in Weining, Yi nationality in Qianxi, Yao nationality in Libo and Han nationality in Libo as 51.85%, 42.86%, 79.52% and 84.30%, respectively. The polymorphisms distribution of IL-10.G and IL-10.R were statistically different among the ethnic groups (P < 0.05). The polymorphisms distribution of IL-10.R had no significant difference between HBV infection group and non-infection group, as well as among HBV natural removal group and non-infected group in all the ethnic groups. The frequency of IL-10.G 459 bp (19CA) was significantly higher in non-infection group than in the infected group (P < 0.05). The frequency of IL-10.G 471 bp (25CA) was significantly higher in the non-infection group than in the HBV natural removal group (P < 0.05). The polymorphisms distribution of IL-10.G did not show significant difference between the HBV infection group and the HBV natural removal group in all the ethnic groups. We did not find any differences in allelic and genotypic frequencies of IL-10.G between infection group and non-infection group in Yi nationality in Weining, and Yao nationality in Libo (P > 0.05), as well as HBV natural removal group and non-infected group (P > 0.05)., Conclusion: The polymorphisms distribution of IL-10.R and IL-10.G did not show significant difference in Yi, Yao and Han ethnics population living in Guizhou province. IL-10.G seemed to influence the susceptibility of HBV infection in Han, Yao and Yi ethnics population of Guizhou province.

Objective: To investigate the association of IL-10 gene promoter polymorphism with susceptibility to hepatitis B viral infection in Han, Yi and Yao ethnic groups from Guizhou province., Methods: Five hundred volunteers from Guizhou province were selected to undertake PCR-RFLP for detection of IL-10 gene promoter -592 polymorphism., Results: The genotypic distributions of IL-10-592 were 32.53%-51.43% (AA), 40.74%-54.82% (AC), 5.79%-18.52% (CC) whereas the allelic frequencies were 59.94%-72.38% for the A allele, and 27.62%-40.06% for the C allele in Han, Yi and Yao ethnic from Guizhou. The distributions of allele and genotype frequencies of IL-10-592 were statistically different between Yao ethnic in Libo and Yi ethnic in Qianxi, Yao ethnic in Libo and Han ethnic in Libo,Yi ethnic in Qianxi and Yi ethnic in Weining,Yi ethnic in Weining and Han ethnic in Libo (P < 0.05). IL-10-592 polymorphism was associated with HBV infection in Yi ethnic in Qianxi and the whole population., Conclusion: IL-10-592 gene polymorphisms influenced the susceptibility to HBV infection in Han, Yao, Yi sub-populations in Guizhou. Result of the study suggested that IL-10-592 gene polymorphisms might serve as a risk factor to HBV infection.