[Characteristics and clinical analysis of MLH1 c.463dupC gene mutation in a Lynch syndrome family].

In this study, a case of Lynch syndrome (LS) family line with a novel mutation site in the MLH1 c.463dupC gene was reported and the clinical and pathogenic genetic features of this family were analyzed. A 40-year-old female patient with colon cancer diagnosed at the First Affiliated Hospital of Kunming Medical University on October 2, 2020 was retrospectively included. The clinical data of the family were collected and the family lineage was drawn. The family tumor history met the Amsterdam Criteria Ⅱ and the diagnostic criteria of LS in Chinese, which was a typical LS family lineage. A germline code-shift missense mutation c.463dupC in the MLH1 gene located in exon 6, a possible pathogenic variant, was detected by second-generation sequencing (NGS) in the patient. Subsequently, Sanger sequencing was performed on a total of 20 direct lineage members of the family of the MLH1 gene, 7 cases were found to harbor the mutation and included in the LS high-risk control. Follow-up to October 2023 showed that the patient had endometrial and cervical polyps, one case had colorectal cancer, and two cases had intestinal polyps, all were treated with early intervention and therapy; two cases did not show any clinical symptoms. This study is the first to report a new mutation site for the potentially pathogenic MLH1 c.463dupC, providing a rationale for the pathogenicity of the mutation and standardized health management for familial carriers.

Copy number variation in HOXB7 and HOXB8 involves in the formation of beard trait in chickens.

The derived feathering phenotype beard in domestic birds is an ideal resource to investigate the genetic mechanisms controlling feather development and differentiation. In the present study, we performed a GWAS and QTL linkage analysis on the trait of beard in Beijing fatty chicken. One major QTL (1.2-1.9 Mb) was identified that could explain 34% of the phenotypic variation. The copy number variation that was copied from the region (GGA27:3 578 409-3 592 890 bp) containing homebox B7 (HOXB7) and homebox B8 (HOXB8) was validated to be only exhibited in the genome of bearded chickens. Protein-protein interaction analysis indicated that HOXB7 and HOXB8 proteins could highly interact with the HOXB family members, including HOXB4, HOXB5 and HOXB6, whose genomic locations near HOXB7 and HOXB8 suggested that they may regulate their family members to involve in the formation of the beard trait in chickens. Overall, our work provides basic data for understanding the mechanisms regulating beard development and differentiation.

[Association between parental socioeconomic status and preschoolers' consumption of sugar-sweetened beverages].

Objective: To explore the association between parental socioeconomic status (SES) and preschoolers' consumption of sugar-sweetened beverages (SSB). Methods: In June 2018, all preschoolers from 15 kindergartens were selected from the jurisdiction of Education Commission in Dongcheng District of Beijing by using an equal-proportion stratified cluster sampling method in the study. A self-designed questionnaire was used to investigate the parents of preschoolers to obtain the basic information of preschoolers and parents, the consumption situation of preschoolers' sugar-sweetened beverages and the perception of parents to SSB. A tatol of 3 217 preschoolers were finally included in the analysis. A generalized structural equation model was used to analyze the relationship between preschoolers' consumption of sugar-sweetened beverages and their parents' socioeconomic status and the mediating effect of their cognition of sugar-sweetened beverages. The size of mediating effect was estimated by using deviation correction non-parameter percentile Bootstrap method. Results: The age of 3 217 preschoolers was (4.23±0.67) years, of which 52.6% (n=1 692) were boys, and 77.62% (n=2 497) were SSB consumers. Among the parents of 3 217 preschoolers, fathers and mothers accounted for 24.90% (n=801) and 75.10% (n=2 416), and the M (P25, P75) scores of SES were 66.7 (62.5, 69.5) and 69.5 (64.6, 71.4), respectively. The proportion of parents who took the initiative to learn about their children's consumption of SSB, lacked confidence in restricting preschooler's consumption of SSB and read nutrition labels before purchasing food was 74.08% (n=2 383), 82.90% (n=2 667) and 36.24% (n=1 166), respectively. The generalized structural equation model showed that after adjusting for preschoolers' gender, age, body mass index (BMI) of preschoolers and their parents, preschoolers' consumption of SSB was negatively associated with their parents' SES score [path coefficient (95%CI):-4.69×10-2 (-6.56×10-2,-2.69×10-2) ]. The mediating effect of parents' perception of SSB consumption could explain 48.71% of the total effect [path coefficient (95%CI):-2.28×10-2 (-3.54×10-2, -1.10×10-2)]. Conclusion: The consumption of SSB in preschoolers is negatively associated with their parent's SES, and this relationship is partially mediated by parent's perception of SSB consumption.

Dual-channel compressed ultrafast photography for Z-pinch dynamic imaging.

The compressed ultrafast photography (CUP) can capture non-repetitive time-evolving events at 7 × 1013 fps, which is anticipated to find a diverse range of applications in physics, biomedical imaging, and materials science. The feasibility of diagnosing ultrafast phenomenon of Z-pinch by using the CUP has been analyzed in this article. Specifically, a dual-channel CUP design has been adopted for acquiring high quality reconstructed images and the strategies of identical masks, uncorrelated masks, and complementary masks have been compared. Furthermore, the image of the first channel was rotated by 90° to balance the spatial resolution between the sweep direction and the non-sweep direction. Both five synthetic videos and two simulated Z-pinch videos were chosen as the ground truth to validate this approach. The average peak signal to noise ratio of the reconstruction results is 50.55 dB for the self-emission visible light video and 32.53 dB for the laser shadowgraph video with unrelated masks (rotated channel 1). The simulation results show that the time-space-evolving process of plasma distribution can be well retold, and the phenomenon of plasma instability can be accurately diagnosed by the dual-channel CUP with unrelated masks (rotated channel 1). This study may promote the practical applications of the CUP in the field of accelerator physics.

Building phenotype networks to improve QTL detection: a comparative analysis of fatty acid and fat traits in pigs.

Models in QTL mapping can be improved by considering all potential variables, i.e. we can use remaining traits other than the trait under study as potential predictors. QTL mapping is often conducted by correcting for a few fixed effects or covariates (e.g. sex, age), although many traits with potential causal relationships between them are recorded. In this work, we evaluate by simulation several procedures to identify optimum models in QTL scans: forward selection, undirected dependency graph and QTL-directed dependency graph (QDG). The latter, QDG, performed better in terms of power and false discovery rate and was applied to fatty acid (FA) composition and fat deposition traits in two pig F2 crosses from China and Spain. Compared with the typical QTL mapping, QDG approach revealed several new QTL. To the contrary, several FA QTL on chromosome 4 (e.g. Palmitic, C16:0; Stearic, C18:0) detected by typical mapping vanished after adjusting for phenotypic covariates in QDG mapping. This suggests that the QTL detected in typical mapping could be indirect. When a QTL is supported by both approaches, there is an increased confidence that the QTL have a primary effect on the corresponding trait. An example is a QTL for C16:1 on chromosome 8. In conclusion, mapping QTL based on causal phenotypic networks can increase power and help to make more biologically sound hypothesis on the genetic architecture of complex traits.

The effects of haemodilution with succinylated gelatin solution on coagulation in vitro as assessed by thromboelastometry and impedance (multiple electrode) aggregometry.

We investigated the in vitro viscoelastic changes of progressive haemodilution with succinylated gelatin (SG) solution compared with normal saline (NS) using rotational thromboelastometry (ROTEM®). Whole blood (WB) samples obtained from 20 healthy volunteers were diluted in vitro with SG solution or NS by 10%, 20% and 40%. Fibrinogen concentration and ROTEM (EXTEM, FIBTEM) variables including coagulation time (CT), clot formation time (CFT), α-angle, and maximum clot firmness (MCF) were measured in the undiluted sample and at each degree of haemodilution. Haemodilution with SG decreased FIBTEM MCF by 34.8% at 20% dilution (SG 20% haemodilution mean 9.1 [standard deviation, SD 2.7] mm versus WB, mean 13.9 [SD 3.4] mm) whereas this was observed only at 40% haemodilution with NS (mean 8.5 [SD 2.7] mm, 38.7% decrease). We found that 40% haemodilution with SG slowed clot formation (EXTEM CFT; SG 40%, mean 179 [SD 39] seconds versus WB mean 87.9 [SD 13.7] seconds; increased CFT by 103%), reduced clot strength by 23.5% (EXTEM MCF; SG 40% mean 47.7 [SD 3.4] mm versus WB mean 62.4 [SD 2.5] mm), and decreased fibrin formation (FIBTEM MCF; SG 40% mean 5.8 [SD 1.6] mm versus WB mean 13.9 [SD 3.4] mm); 58.4% decrease). The platelet contribution to clot strength (EXTEM MCF-FIBTEM MCF) was not changed by SG. We found that haemodilution of more than 20% with SG impaired coagulation greater than that observed with NS haemodilution in this in vitro study. This suggests that at 40% haemodilution with SG, a clinical scenario that could occur during resuscitation of a patient in grade IV haemorrhagic shock, impaired coagulation could occur. Frequent monitoring of coagulation is advised when SG solutions are administered rapidly during volume resuscitation.

Relationship between Hashimoto's thyroiditis and papillary thyroid carcinoma in children and adolescents.

OBJECTIVE: We investigated the relationship between Hashimoto's thyroiditis (HT) and papillary thyroid carcinoma (PTC) in children and adolescents. PATIENTS AND METHODS: We carried out a retrospective study of thyroidectomies performed from 2004 to 2017 at The First People's Hospital and the Tumor Hospital of Yunnan Province (Kunming, China). The occurrence and features of PTC and benign thyroid disease (BTD) in children and adolescents (age ≤ 20 years) were compared. RESULTS: We evaluated 258 consecutive thyroidectomies. Among children and adolescents with PTC, 23 cases were histopathologically confirmed as HT. Mean tumor diameter was smaller in children and adolescents with PTC than in those with BTD. Thyroid-stimulating hormone (TSH) level was abnormally elevated in a greater proportion of children and adolescents with PTC as compared to those with BTD or youths with PTC. The proportion of thyroglobulin antibody (TGAb)- and thyroid peroxidase antibody (TpoAb)-positive children and adolescents was higher in the PTC than in the BTD group. Among children and adolescents with PTC, 23 had HT as compared to two in the BTD group. The proportion of children/adolescents with abnormally elevated TSH levels was higher for the PTC combined with HT group than for the PTC without HT group. A multivariate conditional logistic regression analysis showed that elevated TGAb was an independent risk factor for PTC in children and adolescents. CONCLUSIONS: HT is associated with an increased occurrence of PTC in children and adolescents.

Protein kinase C induced changes in human airway smooth muscle tone: the effects of Ca2+ and Na+ transport.

Activation of protein kinase C by phorbol 12,13-dibutyrate (PDB) (1 nM-3 microM) caused a concentration-dependent contractile response in human isolated bronchus. The mean maximal contraction was 26 +/- 4.4% (n = 11) of that induced by acetylcholine (1 mM). The contraction was increased by the presence of the Ca2+ ionophore (A23187) to 47 +/- 6% (n = 7, P < 0.05) by the Ca2+ channel agonist, Bay K 8644 to 59.5 +/- 4.5% (n = 4, P < 0.05) and by KCl to 47.4 +/- 6%, while it was unaffected by carbachol (28.7 +/- 6.8%, n = 4, P > 0.05). The Ca2+ channel antagonist, verapamil (1 microM) significantly reduced the contraction from 32.3 +/- 4.9 to 12.5 +/- 1% (n = 4, P < 0.05) and in the presence of nifedipine (1 microM), the contractile response was abolished. A single concentration of 10 microM PDB produced a biphasic response-relaxation (6 +/- 1%) followed by contraction (76 +/- 4%, n = 4) which was greater than that produced when responses were obtained cumulatively. The relaxation response was inhibited by the addition of a Na-/K+ exchange antagonist, ouabain (10 microM) which also markedly potentiated the contractile response to 110 +/- 10% (n = 4, P < 0.05). These results suggest that the protein kinase C-mediated contraction in human airway smooth muscle is dependent on extracellular Ca2+ influx. Protein kinase C may also phosphorylate Na+/K(+)-ATPase resulting in a relaxation response.

The involvement of protein kinase C in the contraction of human airway smooth muscle.

The involvement of protein kinase C in the contraction of airway smooth muscle has been investigated in human isolated bronchus. Phorbol 12,13-dibutyrate (PDB) (10 microM) produced aw biphasic response--relaxation followed by contraction. The protein kinase C inhibitor, staurosporine (0.1 microM) reduced the contractile response to PDB from 89 +/- 2.9% to 53 +/- 4.5% of the response to 1 mM acetylcholine (P < 0.05, n = 6) but increased the relaxation response from 12 +/- 6.1% to 29 +/- 5% (P < 0.05, n = 6). Staurosporine also reduced the maximal contractile response to a single dose of histamine (10 microM) from 121 +/- 13% to 91 +/- 10% (P < 0.05, n = 4) and the sustained phase tension from 94 +/- 4% to 85 +/- 5% at 30 min (P < 0.05, n = 4). However, GF 109203X, a more selective inhibitor of protein kinase C at 0.1 microM, 1 microM and 10 microM had no effect on the maximal contractile response and reduced only the sustained phase of the contraction to histamine. These results suggest that protein kinase C plays a role in maintenance of contraction in human airway smooth muscle.

Correlations between fat depot traits and fatty acid composition in abdominal subcutaneous adipose tissue and longissimus muscle: results from a White Duroc × Erhualian intercross F2 population.

The aim of this study was to quantify the partial correlation coefficients (r(p)) between fat depot traits (FDT) and the fatty acid composition of abdominal subcutaneous adipose tissue and LM intramuscular fat in 639 F(2) pigs derived from a White Duroc × Chinese Erhualian cross. Fat depot traits are classified into 2 groups: 1 is adipose tissues (abdominal subcutaneous adipose tissue weight, mesenteric adipose tissue weight, perirenal adipose tissue weight, and backfat thickness at 4 locations); the other is LM [intramuscular fat content (IMF) and marbling score]. Correlations of FDT within classification groups were markedly greater (P < 0.001) than those observed between the 2 groups (r(p) = 0.62 vs. 0.26), indicating variability in fat content of muscle is relatively independent of amount of carcass fat. In general, fatter pigs had greater (P < 0.05) proportions of SFA and MUFA, and less PUFA, than leaner pigs. However, the relationships of individual fatty acids with FDT varied. We found that the amounts of some fatty acids regarded as neutral (e.g., stearic acid) or beneficial (e.g., palmitoleic acid and linolenic acid) for human health were associated with smaller amount of adipose tissues, or merely with greater IMF (P < 0.05). Therefore, we conclude that increasing the proportions of these neutral or healthy fatty acids can be achieved without reducing the IMF of LM, which is positively related to eating quality.

Genome-wide identification of quantitative trait loci for pork temperature, pH decline, and glycolytic potential in a large-scale White Duroc x Chinese Erhualian resource population.

The pH values and temperatures at 45 min, and 3, 9, 15, and 24 h postmortem in the LM and semimembranosus muscle (SM) and glycolytic potential in LM were measured in 1,030 F(2) animals from a White Duroc x Erhualian resource population. A whole genome scan was performed with 183 microsatellites covering 19 porcine chromosomes to detect QTL for traits measured. A total of 73 QTL have been identified, including 1% genome-wise significant QTL for 24-h pH in LM and SM on SSC 15, and for glycolytic potential, total glycogen, and residual glycogen on SSC3, 6, and 7. Six 5% genome-wise significant QTL were detected for 9-h pH in SM on SSC3, pH decline from 3/9 h to 24 h in SM on SSC7, glycolytic potential on SSC1, and total glycogen on SSC1 and 6. This study confirmed QTL previously identified for pH except those on SSC1, 11, 12, and X, and found 11 new 5% genome-wise significant QTL for glycogen-related traits. This is the first time to report QTL for pH development during post-slaughter and for glycolytic potential at 5% genome-wise significance level. In addition, the observed different QTL for pH and pH decline at different times show that causal genes for pH postmortem play distinct roles at specific stages, in specific muscles, or both. These results provide a starting point for fine mapping of QTL for the traits measured and improve the understanding of the genetic basis of pH metabolism after slaughter.

[Theories and practical problems of population facing four modernizations being conscientiously studied].

PIP: The Second National Symposium on Population Theory focused on the problems of population and their solution associated with the 4 modernizations. The following issues discussed by 7 Sumposium panels are summarized: population development theory in the socialist society; population problems in China and their solution; population policies and legislation relating to population control; population distribution and migration; population estimation and population planning; and population research and the establishment of population theory. Discussants agreed that the comprehensive investigation of population principle in a socialist society is of great importance to decisionmaking in the area of China's population development policy. Several different issues arose concerning the content and critical areas in the development of a socialist population principle. More than 1 principle is operating in socialist population theory, but the most important is the principle of population reproduction. The point was made that in addition to the population principle specific to individual society, there exists principles that are common to every society. The consensus was that population growth is associated with all the economical, political, and idelogical developments and that among these the association between population growth and economic development is the most significant. The current major population problem in China was identified as maladjustment between population growth and economic development. This maladjustment has led to problems in the areas of education, employment, transportation, and housing. The fundamental solution was identified as improving economical development to increase the material reproduction and controlling the population reproduction. In addition to birth control policies, it was suggested that population policies should include the geographical distribution and migration of the population. There was wide support for the proposal to legislate population control. It was agreed that such legislation would promote the progress of population control and assure its success. Discussion of the problems of population distribution and migration concentrated on the population problems of the urban area and minority ethnic groups. It was suggested that a nationwide census be conducted in population planning, population legislation, and population theory investigation. In order to establish the socialist population theory, it is essential to clarify the subjects, scopes, and methods of population research.^ieng

Characterization of a tunable optical parametric oscillator laser system for multielement flame laser excited atomic fluorescence spectrometry of cobalt, copper, lead, manganese, and thallium in buffalo river sediment.

A pulsed (10 Hz) optical parametric oscillator (OPO) laser system based on beta-barium borate (BBO) crystals and equipped with a frequency-doubling option (FDO) was characterized for use in laser excited atomic fluorescence spectrometry (LEAFS). This all-solid-state laser has a narrow spectral line width, a wide spectral tuning range (220-2200 nm), and a rapid, computer-controlled slew scan of wavelength (0.250 nm s-1 in the visible and infrared, and 0.125 nm s-1 in the ultraviolet). The output power characteristics (15-90 mJ/pulse in the visible, 1-40 mJ in the infrared, and 1-11 mJ in the ultraviolet), laser pulse-to-pulse variability (3-13% relative standard deviation, RSD, of the laser pulses), conversion efficiency of the FDO (2-17%), and spectral bandwidth in the visible spectrum (0.1-0.3 cm-1) were measured. The laser was used as the excitation source for a flame LEAFS instrument for which rapid, sequential, multielement analysis was demonstrated by slew scan of the laser. The instrument allowed about 640 measurements to be made in about 6 h, with triplicate measurements of all solutions and aqueous calibration curves, which yielded accurate analyses of a river sediment (National Institute of Standards and Technology, Buffalo River Sediment, 2704) for five elements with precisions < 5% RSD. Comparable or improved flame LEAFS detection limits over literature values were obtained for cobalt (2 ng mL-1), copper (2 ng mL-1), lead (0.4 ng mL-1), manganese (0.2 ng mL-1), and thallium (0.9 ng mL-1) by flame LEAFS.

Microwave assisted digestion of atmospheric aerosol samples followed by inductively coupled plasma mass spectrometry determination of trace elements.

A microwave digestion method in a closed vessel was developed for the determination of trace metals in atmospheric aerosols using inductively coupled plasma mass spectrometry (ICP-MS). A recovery study for the elements V, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Se, Cd, Sb, and Pb was conducted using multi-elemental standard solutions, NIST 1633b Trace Elements in Coal Fly Ash, and NIST 1648 Urban Particulate Matter. A simple digestion method using only HNO3/H2O2 gave good recoveries (90%-108%) for all elements except Cr in SRM 1648, but yielded low recoveries for SRM 1633b. A more robust method using HNO3/H2O2/HF/H3BO3 yielded higher recoveries (82%-103%) for the lighter elements (V-Zn) in SRM 1633b, and improved the Cr recovery in SRM 1648, but decreased the Se recovery in both SRMs. A comparative analysis of aerosol samples obtained at a remote mountain location Nathiagali, Pakistan (2.5 km above mean sea level), and Mayville, New York, downwind from the highly industrialized Midwestern United States, was carried out using Instrumental Neutron Activation Analysis (INAA) for the elements Cr, Mn, Fe, Co, Zn, As, Se, and Sb. The simple digestion method yielded excellent agreement for Cr, Fe, Zn, As, Se, and Sb, with slopes of the ICP-MS vs. INAA regressions of 0.90-1.00 and R2 values of 0.96-1.00. The regressions for Mn and Co had slopes of 0.82 and 0.84 with R2 values of 0.83 and 0.82, respectively. Addition of HF/H3BO3 did not improve the correlation for any of the elements and degraded the precision somewhat. The technique provides sensitivity and accuracy for trace elements in relatively small aerosol samples used in atmospheric chemistry studies related to SO2 oxidation in cloud droplets. The ability to determine concentrations of a very large number of elements from a single analysis will permit source apportionment of various trace pollutants and hence strategies to control the sources of air pollution. This is particularly important as the health effects of particulate matter are increasingly recognized.

Protein kinase C isoforms in human airway smooth muscle cells: activation of PKC-zeta during proliferation.

Protein kinase C (PKC) is implicated in the regulation of smooth muscle contractility and growth. We have previously described the pattern of isoform expression of PKC in canine airway smooth muscle. This study identified the isoforms present in human cultured airway smooth muscle cells and also addressed the question of whether mitogenesis in these cells is associated with changes in a specific isoform, PKC-zeta. Western blot analysis revealed the presence of PKC-alpha, -betaI, and -betaII of the conventional group; PKC-delta, -theta, -epsilon, and -eta of the novel group; and PKC-zeta, -mu, and -iota of the atypical group. There was a significant increase in density of the Western blot for PKC-zeta in cells proliferating in response to 10% fetal bovine serum (FBS) to 372 +/- 115% of control values (P < 0.05; n = 3 patients) in the cytosolic fraction. Platelet-derived growth factor (PDGF) produced increases in PKC-zeta in both the cytosolic and membrane fractions to 210 +/- 49 and 443 +/- 227%, respectively, of control values (P < 0.05; n = 4 patients). There was no change in expression of PKC-alpha, -betaI, -betaII, -theta, -epsilon, -eta, -delta, or -iota in response to the same stimuli. PGE2 (1 microM) added to the cells 30 min before PDGF reduced incorporation of [3H]thymidine from 5,580 +/- 633 (SE) to 3, 980 +/- 126 dpm (P < 0.05; n = 3 patients) and, in addition, reduced expression of PKC-zeta in the membrane fraction as determined by Western blotting from 266 +/- 66 to 110 +/- 4% of control values (P < 0.05; n = 3 patients). PKC-zeta activity in stimulated cells (10% FBS), as assessed by immunoprecipitation and phosphorylation of glycogen synthase peptide, was approximately 3-fold greater than that in unstimulated cells, and the amount of PKC-zeta protein correlated with isoenzyme activity (r2 = 0.91; P < 0.02; n = 4 patients). In conclusion, this study 1) provides the first description of which isoforms of PKC are present in human cultured airway smooth muscle cells and 2) shows that proliferation of these cells is associated with upregulation of PKC-zeta. Whether activation of PKC-zeta is a primary or secondary event in airway smooth muscle cell proliferation remains to be determined.