Lymphatic metastasis is the main metastatic route for colorectal cancer, which increases the risk of cancer recurrence and distant metastasis. The properties of the lymph node metastatic colorectal cancer (LNM-CRC) cells are poorly understood, and effective therapies are still lacking. Here, we found that hypoxia-induced fibroblast activation protein alpha (FAPα) expression in LNM-CRC cells. Gain- or loss-function experiments demonstrated that FAPα enhanced tumor cell migration, invasion, epithelial-mesenchymal transition, stemness, and lymphangiogenesis via activation of the STAT3 pathway. In addition, FAPα in tumor cells induced extracellular matrix remodeling and established an immunosuppressive environment via recruiting regulatory T cells, to promote colorectal cancer lymph node metastasis (CRCLNM). Z-GP-DAVLBH, a FAPα-activated prodrug, inhibited CRCLNM by targeting FAPα-positive LNM-CRC cells. Our study highlights the role of FAPα in tumor cells in CRCLNM and provides a potential therapeutic target and promising strategy for CRCLNM.

Objective:To explore the genetic characteristics of a fetus with sex chromosome abnormality indicated by non-invasive prenatal testing (NIPT) at 25 + gestational weeks. Methods:A pregnant woman who was admitted to the Taizhou Hospital for abnormal NIPT result on January 6, 2023 was selected as the study subject. Relevant clinical data was collected. The fetus was subjected to chromosomal karyotyping analysis, copy number variation sequencing (CNV-seq), fluorescence in situ hybridization (FISH), and multiplex PCR assays. Results:NIPT had suggested monosomy of X chromosome. The fetus was found to have a chromosomal karyotype of 45, X[59]/46, X, del(Y)(q11.2)[17] at 30 + weeks of gestational age. CNV-seq suggested the presence a 7.98 Mb deletion at Yq11.222q12 and a mosaicism 16.92 Mb deletion. FISH suggested that the fetus harbored two SRY genes and a mosaicism sex chromosomal abnormality, and multiplex PCR revealed that its AZF b+ c region was completely deleted. C-banded karyotyping showed darkly stained dense mitotic granules at both ends of the Y chromosome. The fetus was ultimately determined as a 45, X/46, X, idic(Y)(q11.2) mosaicism. Following elected abortion, testing of the fetal tissue confirmed the presence of 45, X/46, XY mosaicism, and CNV-seq result of the placental tissue was compatible with that of NIPT. CNV-seq analysis of the couple revealed no obvious abnormality. Conclusion:With combined NIPT, karyotyping, CNV-seq, FISH and multiplex PCR assays, the fetus was diagnosed as a 45, X/46, X, idic(Y)(q11.2) mosaicism with deletion of the AZF b+ c region. Above finding has enabled prenatal diagnosis for the fetus.

OBJECTIVE To explore the moisture and components change law of Peucedani Radix slices during microwave vacuum drying, and effectively improve the drying efficiency and slice quality of Peucedani Radix slices, by carring out drying characteristics analysis and simulation of Peucedani Radix Slices during microwave vacuum drying. METHODS Microwave vacuum drying experiments of Peucedani Radix slices under different drying conditions (microwave power density, vacuum degree and slice thickness) were carried out. The changes of moisture ratio and drying rate during drying process were studied. The contents of three coumarin ingredients (praeruptorin A, praeruptorin B and praeruptorin E) in dried Peucedani Radix slices were determined by HPLC. Weibull function was used to simulate and analyze the moisture ratio curve during drying process. RESULTS Microwave vacuum drying process of Peucedani Radix slices has three stages: acceleration, constant speed and deceleration. Compared with vacuum degree and slice thickness, increasing microwave power density could shorten drying time and improve drying efficiency more effectively. In the range of experimental parameters, the optimum drying conditions were as follows: microwave power density was 3.0 W·g–1, vacuum degree was 800 Pa, and slice thickness was 2 mm. The changes of all drying conditions had no significant effect on the content of coumarins in dried Peucedani Radix slices. The results of Weibull function simulation and analysis showed that the scale parameters under different drying conditions ranged from 17.43 to 45.38, and the smaller the value, the shorter the drying time. The shape parameters ranged from 1.41 to 1.77 and were all greater than 1, indicating that the drying process was controlled by internal and external water diffusion. CONCLUSION The research work not only provides important theoretical basis and technical support for the process improvement and quality control of microwave vacuum drying process of Peucedani Radix slices, but also provides important reference for the standardization of Peucedani Radix slices drying and the formation of quality characteristics.

Abstract: It has long been thought that immune memory is an exclusive hallmark of adaptive immunity, but recent studies have shown that innate immunity also has characteristics similar to immune memory. Innate immune cells, upon being stimulated by pathogens such as lipopolysaccharide (LPS) and β-glucan, can develop a form of immune memory. Upon a secondary encounter with the stimulus, these innate immune cells can produce a stronger immune response, providing nonspecific protection. This immune phenomenon is termed "trained immunity". The mechanism of trained immunity mainly involves the epigenetic reprogramming and metabolic reprogramming of innate immune cells and the interaction between them. This article reviews the main research progress and mechanism of pathogen infection-induced trained immunity.

OBJECTIVE: To determine the chromosomal karyotype of a fetus with copy number variation (CNV) of the X chromosome signaled by non-invasive prenatal testing (NIPT). METHODS: NIPT was performed on the peripheral blood sample taken from the pregnant women. Amniotic fluid and cord blood samples were subjected to conventional G banded karyotyping, and were further analyzed by high-throughput sequencing for chromosome microdeletion/microduplication. The results were then verified by fluorescence in situ hybridization (FISH) on metaphase cells. RESULTS: The NIPT test of pregnant women suggested low risk for 21-trisomy, 18-trisomy, and 13-trisomy, whilst indicated the number of chromosome X to be low. The G banded karyotype of the amniotic fluid and cord blood cells was 46,XX. The result of high-throughput sequencing chromosome microdeletion/microduplication detection was seq[hg19](X)× 1, (Y)× 2. FISH showed a clear red signal at each end of a whole chromosome, and a green signal on the other chromosome, with a karyotype of 46,X,ish idic(Y) (q11.23) (SRY++, DXZ1+). C banding showed that there is a dense and a slightly loose centromere at both ends of the Y chromosome, and the parachromatin region was missing. The karyotype of amniotic fluid and cord blood cells was finally determined to be 46,X, pus idic(Y) (q11.23). CONCLUSION For chromosome anomalies suggested by auxiliary report of NIPT, conventional karyotyping combined with high-throughput sequencing for chromosome microdeletion/microduplication should be adopted for the prevention and reduction of the rate of chromosome microdeletion/microduplication syndromes.
Chromosome Aberrations ; DNA Copy Number Variations ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Pregnancy ; Prenatal Diagnosis ; X Chromosome

OBJECTIVE To provide prenatal diagnosis for families affected with tuberous sclerosis complex and explore the correlation between phenotype and genotype. METHODS For probands from 10 families, all exons and splicing regions of the TSC1 and TSC2 genes were analyzed with high throughput DNA sequencing. Suspected mutations were verified by Sanger sequencing. RESULTS All probands were found to have mutations, which included 1 case with TSC1 mutation and 9 cases with TSC2 mutations (missense mutations in 6, nonsense mutations in 2, and frameshifting mutation in 1 case). Prenatal diagnosis was provided for 9 cases, and 1 fetus was found to carry a mutation. Genetic analysis has identified a novel pathogenic mutation (TSC2 c.2415-2416 ins GT). CONCLUSION Identification of pathological mutations for tuberous sclerosis complex can facilitate genetic counseling and prenatal diagnosis for the affected families.

OBJECTIVETo analyze the deletion region for two fetal cases with large Yq deletions in order to provide genetic counseling and prenatal diagnosis.

METHODSFor both cases, amniotic fluid samples were cultured and analyzed with G banding and fluorescence in situ hybridization (FISH). Multiplex polymerase chain reaction was also carried out to amplify 15 sequence tagged sites (STS) of azoospermia factor (AZF) on the Y chromosome.

RESULTSFor both samples, the karyotypes were determined as 46,X,del(Y)(pter→q11:). No heterochromatin was found in C band. The karyotypes of their fathers were 46,XY, and heterochromatin was found in C band. STS analyses suggested that only sY82, sY84 and sY86 in AZFa were amplifiable while the other 12 STS were negative in amniotic fluid for the first case, which indicated deletions of AZFb, AZFd and AZFc. No AZF deletion was found in its father. For the second case, all 15 STS were amplifiable in the amniotic fluid, suggesting no AZF deletion. No AZF deletion was found in its father too.

CONCLUSIONConventional karyotyping combined with FISH and molecular genetics techniques can enable characterization of AZF microdeletions and facilitate genetic counseling and prenatal diagnosis.

Adult ; Azoospermia ; genetics ; Chromosome Deletion ; Chromosomes, Human, Y ; genetics ; Female ; Fetal Diseases ; diagnosis ; genetics ; Genetic Counseling ; Humans ; In Situ Hybridization, Fluorescence ; Karyotyping ; Male ; Pregnancy ; Prenatal Diagnosis

OBJECTIVETo investigate the major influence factors of child neglect among rural areas children aged 3-6 years in China.

METHODSAccording to multi-stage stratified cluster sampling, distribution characteristics and the level of economic development, we randomly sampled 10 provinces, 26 cities (8 capital cities, 16 prefecture-level cities and 2 municipalities) using lottery method. Depending on the different level of economic and cultural, we sampled one medium county from each city (municipalities sampled two counties), a total of 28 counties. All towns were divided into high, medium and low three levels in accordance with economic and cultural, each level sampled one town, each conty sampled three towns, a total of 84 towns were sampled. Each town sampled 40 children, including 20 boys and 20 girls (including each 10 children aged 3 to 6, half and half boys and girls). 4 096 rural children aged 3-6 years old were sampled and surveyed of China. Based on "the Neglect Norms for Children Aged 3 to 6 Years Old in Rural Areas of China" explored the risk factors of child neglect. SPSS 18. 0 for windows was employed for statistics analysis. Multifactorial analysis was conducted through multivariate Logistic Regression.

RESULTSThe total neglected rate of the rural children aged 3 to 6 was 53.7% (2,047/3,810), and the total neglected degree was 44.42±7.57. The multivariate logistic regression analysis showed that, neglected risk of the boys was higher than the girls (OR=1.30, 95% CI: 1.13-1.49), neglected risk of children were higher, when their mothers were migrant workers (OR=2.18, 95% CI: 1.59-3.00); the lower educational level of mothers, the higher neglected risk of children, the children in families that mothers only received primary education or was uneducated were most likely to be neglected (OR=2.92, 95% CI: 1.91-4.47), the second was the families that mothers received primary education (OR=1.86, 95% CI: 1.29-2.69); the lower the household income, the easier to be neglected the children, the easiest one was the household income less than 5000 RMB (OR=2.85, 95% CI: 2.14-3.79), the second was 5000-9,999 RMB (OR=1.76, 95% CI: 1.40-2.20); the relationship between children and mothers was distanced, neglect risk of children was higher (OR=3.88, 95% CI: 1.31-11.52); left behind children were easier to be neglected (OR=1.30, 95% CI: 1.09-1.54).

CONCLUSIONThe influence factors among children aged 3-6 years in the rural areas of China were boys, mother's occupation, maternal education level, the relationship between children and mothers, household income and left-behind children.

Child Abuse ; Child, Preschool ; China ; Demography ; Factor Analysis, Statistical ; Female ; Humans ; Male ; Mothers ; Risk Factors ; Rural Population ; Surveys and Questionnaires ; Transients and Migrants

OBJECTIVETo analyze pupils' neglect status aged 6-11 years in China's rural.

METHODSAccording to the principle of multi-stage stratified cluster sampling, to extract 7,943 pupils aged 6-11 years for the survey from 56 primary schools in 28 counties in nine provinces, from December 2012 to March 2013. Proceed questionnaire survey by the scale from "Neglect Evaluation Norms for pupils aged 6-8 years in Rural Areas of China" and "Neglect Evaluation Norms for pupils aged 9-11 years in Rural Areas of China". And analyze neglect rates and neglect degrees of the different grades, gender, family types and different levels of neglect.

RESULTSThe total neglect rate of China's rural pupils aged 6-8 and 9-11 years was 40.2% (1,258/3,130) and 42.5% (1,498/3,526) respectively, which differences had no statistical significant (χ2=3.59, P=0.058); the total neglect degree was 46.04±8.87 and 44.78±10.43 respectively, which differences had statistical significant (t=5.01, P<0.001); the differences of neglect rates and neglect degrees between male (41.4% (657/1,587) and 46.28±8.76) and female (39.0% (601/1,543) and 45.78±8.97) of aged 6-8 were all no statistical significant (χ2=1.87, P=0.171; t=1.49, P=0.136); the neglect rates and neglect degrees of male (46.3% (816/1,763) and 45.53±10.11) were higher than female (38.7% (682/1,763) and 44.06±10.69) in the group of aged 9-11, which differences were all statistical significant (χ2=20.84, t=3.97, P<0.001); the male neglect rate in the group of aged 6-8 in social neglect (11.7% (198/1,691)) and the neglect degree in educational neglect (48.09±9.70) were higher than female (9.4% (155/1,648) and 47.37±9.89), which differences were all statistical significance (χ2=14.55, P<0.001, t=2.22, P=0.026), the male neglect rate in the group of aged 9-11 in physical neglect (20.4% (398/1,954)) was higher than female (16.7% (326/1 957)), which differences had statistical significance (χ2=8.92, P=0.003).

CONCLUSIONThe neglect status of Chinese pupils aged 6-11 years in rural was serious, and we should find out risk factors and provide efficient prevention measures.

Child ; Child Abuse ; China ; Female ; Humans ; Male ; Physical Examination ; Pupil ; Risk Factors ; Rural Population ; Schools ; Surveys and Questionnaires

OBJECTIVETo develop a standard Neglect Evaluation Scale which is suitable for rural primary school students in China.

METHODSAccording to the principle of multi-stage stratified cluster sampling, a field investigation was conducted among primary school students in 28 counties from 7 provinces and 2 municipalities. The questionnaires were self-designed, and determined by multiple rounds of pilots and revisions. Among 5 862 students, 2 792 (6-8 years' old) and 3 070 (9-11 years' old) were investigated by using two kinds of Neglect Evaluation questionnaires, respectively. After project analysis, factor analysis, reliability and validity analysis, the reliability and stability of the scale were tested. Then percentile method was used to determine the evaluation standard to develop and finalize the formal scale.

RESULTSThe numbers of the remaining items for 6-8 year-old group and 9-11 year-old group is 69 and 58, respectively, both of which contain six levels of neglect, including body, emotion, health care, education, security, and society. 4 times of factor analysis were conducted in both of the two groups. The factor loadings in these two groups were 0.290-0.700 and 0.276-0.729 respectively. Reliability test results showed that the two kinds of scales' Cronbach alpha coefficient were 0.924 and 0.929 respectively, split-half reliability were 0.891 and 0.904 respectively, the retest reliability were 0.559 and 0.892 respectively, the differences were statistically significant (P < 0.05). The retest reliability among 6-8 year-old group in medical neglect level had no statistical significance, but was close to the cut-off point (P = 0.054). The test results of external validity indicated that both of the two scales could reflect the neglect status of the subjects (P < 0.05), but the subjective and objective evaluation towards neglect were not consistent. The cut-off points for judging whether the children were neglected or not among 6-8 year-old and 9-11 year-old groups were 159 and 137 respectively; and the adjusted values were 160 and 135 respectively.

CONCLUSIONThe two norm scales developed by this study showed good discriminability, reliability, validity, and stability. The norms developed on the basis of the scales was suitable for the situation of rural students in primary schools in China.

Child ; Child Abuse ; China ; Factor Analysis, Statistical ; Humans ; Reproducibility of Results ; Rural Population ; Schools ; Students ; Surveys and Questionnaires