[Characteristics of overnight obstructive apnea events in patients with obstructive sleep apnea hypopnea syndrome].

Objective: To compare the overnight variation trends in the duration of obstructive apnea events, and to explore the adaptive capacity to the pathophysiological consequences of periodic sleep disordered-breathing and its underlying mechanism in patients with obstructive sleep apnea hypopnea syndrome (OSAHS). Methods: A retrospective analysis were performed of the polysomnographic (PSG) results of 89 snoring patients including 10 non-OSAHS, 15 mild, 29 moderate and 35 severe OSAHS. The total record time was divided into four equal phases, and the variation trends of the mean apnea duration (MAD) and the longest apnea duration (LAD) were compared with the progression of sleep phases in different groups. Correlation analysis was conducted with demographic indicators, pulse oxygen saturation (SpO2) and sleep related indicators. In addition, the number of apneas-time variability curve was plotted for fitting analysis. Results: In patients with severe OSAHS, both MAD [26.1(20.9, 31.4) s] and LAD [56.5(46.5, 82.0) s] were significantly higher than those of non-OSAHS, mild and moderate OSAHS (P<0.001). In addition, the MAD in the third and fourth quartiles were significantly higher than that in the first quartile [(28.4±9.0) s, (27.3±9.8) s, (22.3±9.9) s, respectively, P=0.046], and the LAD in the third quartile was significantly higher than that in the first quartile [56.5(38.5, 71.0) s, 41.0(28.0, 53.0) s, respectively, P=0.018]. In all subjects, the MAD and LAD in the third and fourth quartiles were significantly higher than those in the first quartile [MAD: 20.3(10.3, 29.2) s, 18.5(11.3, 24.2) s, 12.9(0.0, 21.8) s, respectively, P<0.001; LAD: 28.0(10.3, 50.5) s, 28.0(12.0, 44.5) s, 14.5(0.0, 32.3) s, respectively, P<0.001]. There was no statistical difference in the lowest SpO2 (LSpO2), the mean SpO2 (MSpO2), and the percent of sleep time oxygen saturation below 90% (T90%) of all subjects in different sleep phases (P>0.05). The LAD was positively correlated with obstructive apnea index (OAI, OR=1.660, P=0.025), but no correlation was observed with other indicators (P>0.05). The MAD increased 0.22 s per episode at the onset of sleep (1-31 apnea events), then dropped to 0.04 s of increase per episode, with a dynamics change of 5.5-fold slower. Conclusions: The MAD and LAD show a gradual prolongation trend with the progression of sleep phases, and the prolongation trend is the most obvious in patients with severe OSAHS, while the dynamic change trend of SpO2 is not obvious. There may be multiple adaptation mechanisms for recurrent hypoxic episodes, and the adaptation occurr in stages, with a rapid increase in MAD at the onset of sleep, follow by a markedly slower increase. Patients with severe OSAHS express the most complete pattern, suggesting the most severe pathophysiological outcomes.

DSP-enabled reconfigurable and transparent spectral converters for converging optical and mobile fronthaul/backhaul networks.

Dynamically reconfigurable and transparent signal spectral conversion is expected to play a vital role in seamlessly integrating traditional metropolitan optical networks and mobile fronthaul/backhaul networks. In this paper, a simple digital signal processing (DSP)-enabled spectral converter is proposed and extensively investigated, for the first time, which just utilizes a single standard dual-parallel Mach-Zehnder modulator (DP-MZM) driven by SDN-controllable RF signals and DC bias currents. As an important thrust of the paper, optimum operating conditions of the proposed converter are analytically identified, statistically examined and experimentally verified. Optimum operating condition-supported spectral converter performances in IMDD-based network nodes are explored both theoretically and experimentally in terms of frequency detuning range-dependent conversion efficiency, spectral conversion-induced OSNR/power penalty and transparency to input signal characteristics. The proposed spectral converter has unique advantages including low configuration complexity, strict transparency, SDN-controllable performance reconfigurability and flexibility, as well as negligible spectral conversion-induced latency.

Permanent neonatal diabetes caused by abnormalities in chromosome 6q24.

BACKGROUND: Methylation defects at chromosome 6q24 usually induce transient neonatal diabetes mellitus. There are few reports of permanent neonatal diabetes mellitus caused by abnormalities of 6q24. We report the first case of permanent neonatal diabetes mellitus to be associated with confirmed methylation defects at chromosome 6q24. CASE REPORT: A baby girl, small for her gestational age, was found to have high blood glucose 1 day after birth, with no systematic congenital anomalies. She showed no remission of diabetes and has hitherto been reliant on insulin (now aged of 5.5 years), which supports a diagnosis of permanent neonatal diabetes mellitus. The single nucleotide polymorphism array and highly polymorphic short tandem repeat analysis identified paternal uniparental disomy of chromosome 6, and a genome-wide analysis ruled out mutations in coding and non-coding regions. CONCLUSION: This report expands the varieties of neonatal diabetes known to be induced by methylation defects at chromosome 6q24, and suggests that the diagnostic evaluation of permanent neonatal diabetes mellitus should be expanded to include testing for 6q24.

miR-182 selectively targets HOXA10 in goat endometrial epithelium cells in vitro.

Proper HOXA10 expression was essential for endometrial receptivity what was crucial for successful embryo implantation in mammalian. This study confirmed that miR-182 regulated the expression levels of HOXA10 by binding to its 3' UTR, selectively downregulated HOXA10 in goat endometrial epithelium cells (gEECs) but not stromal cell (gESCs) in vitro. However, HOXA10 and miR-182 both up-expressed in the goat endometrium at gestational day 15 (D15) compared with gestational day 5 (D5), suggesting that there were some other factors regulated the expression of HOXA10 during the development of goat endometrium in vivo. What's more, HOXA10 gene silencing (HOXA10-siRNA) resulted in gEECs apoptosis in vitro, and it regulated the protein levels of oestrogen receptor a (ERa), progesterone receptor B (PRb), insulin-like growth factor 1 receptor (IGF1R), BCL-2, pleiotrophin (PTN), AKT and p-JNK in gEECs. Furthermore, HOXA10 might regulate the protein levels of endometrial receptivity biomarker genes, including vascular endothelial growth factor (VEGF), osteopontin (OPN), cyclooxygenase-2 (COX-2) and prolactin receptor (PRLR) in gEECs. In conclusion, miR-182 targeted HOXA10 selectively in EECs in vitro, and HOXA10 played an important role in maintaining the function of EECs in dairy goats.

Robust and tunable 16.375Gb/s dual-band optical OFDM transmissions over directly modulated VCSEL-based 200m OM2 MMFs.

Utilizing low-cost, 2.2GHz modulation bandwidth, uncooled and standalone directly modulated VCSEL (DM-VCSEL)-based real-time dual-band optical OFDM (OOFDM) transmitters, aggregated 16.375Gb/s transmissions of OOFDM signals having bandwidths approximately 3.8 times higher than the VCSEL manufacturer-specified modulation bandwidths, are experimentally demonstrated, for the first time, over 200m OM2 MMF links based on intensity modulation and direct detection. The aggregated signal transmission capacities of the aforementioned links vary by just 8% for various OM2 MMFs ranging from 100m to 500m, and by just 10% over a 1GHz passband carrier frequency detuning range. Such dual-band OOFDM adaptability-induced excellent performance robustness and large passband frequency tunability can significantly relax the requirements on VCSEL modulation bandwidth for achieving specific transmission performances for cost-sensitive application scenarios such as data centers.

Two missense mutations in exon 9 of caprine PRLR gene were associated with litter size.

Guanzhong (n = 321) and Boer (n = 191) goat breeds were used to detect single nucleotide polymorphisms (SNPs) in the coding regions of the prolactin receptor (PRLR) gene by DNA sequencing and PCR-RFLP. Two SNPs (c.1457G>A and c.1645G>A) were identified that caused amino acid variations p.Ser485Asn and p.Val548Met respectively. Statistical results indicated that the c.1457G>A and c.1645G>A SNPs were significantly associated with litter size in Boer and Guanzhong goat breeds. Further analysis revealed that combined genotype C4 (GGGG) and haplotype G-G were better than the others for litter size in both goat breeds. These results might contribute to goat genetic resources and breeding.

Two mutations in the 5'-flanking region of the KITLG gene are associated with litter size of dairy goats.

In this study, Xinong Saanen (SN) and Guanzhong (GZ) dairy goat breeds were used to detect single nucleotide polymorphisms (SNPs) in the 5'-flanking region of the KITLG gene by DNA sequencing and primer-introduced restriction analysis-polymerase chain reaction. Two novel SNPs (g.13090G>T and g.13664C>A) were identified (GenBank Accession no. KM658964). Furthermore, g.13090G>T and g.13664C>A loci were closely linked in SN and GZ breeds (r(2) > 0.33). Association analysis results showed that g.13090G>T and g.13664C>A SNPs significantly affected litter size (P < 0.05). The litter size of individuals with the combined genotype GG/CC from both dairy goat breeds was greater than that of individuals with TT/AA in average parity (P < 0.05). Known biochemical and physiological functions, along with our results, indicated that GG/CC could be used in marker-assisted selection to choose individuals with greater litter size from both breeds. These results extend the spectrum of genetic variation in the caprine KITLG gene and may contribute to genetic resources and breeding of goats.

Polymorphisms of PRLR and FOLR1 genes and association with milk production traits in goats.

We investigated the polymorphisms of PRLR and FOLR1 genes in Xinong Saanen, Guanzhong, and Boer goat breeds by DNA sequencing and PCR-RFLP. Two novel SNPs were identified: KC109741: g.62130C>T in the 3ꞌ-UTR of goat gene PRLR, and KC136296: g.7884A>C in exon 3 of goat gene FOLR1. In the three goat breeds, the polymorphism information content was 0.20-0.27 at the g.62130C>T locus. At the g.7884A>C locus, it was 0.36 in Boer goats. The three goat breeds were in Hardy-Weinberg disequilibrium at the g.62130C>T locus. The g.62130C>T SNP was found to be significantly associated with milk production traits in Xinong Saanen and Guanzhong breeds. These results are consistent with the regulatory function of PRLR in mammary gland development, milk secretion, and expression of milk protein genes; they extend the spectrum of genetic variation of the goat PRLR gene, which could be useful for breeding programs.

[Effect and safety of Burosumab in the treatment of 4 children with X-linked hypophosphatemia].

Objective: To evaluate the effectiveness and safety of treatment with Burosumab in pediatric X-linked hypophosphatemia (XLH) patients. Methods: In this retrospective case study, 4 children with pediatric XLH, who were treated with Burosumab in Beijing Children's Hospital, Capital Medical University and Shandong Provincial Hospital affiliated to Shandong First Medical University from July 2022 to December 2023, were selected as the study objects. We collected and analyzed their clinical characteristics, biochemical indicators, imaging results, and treatment. The children were followed up every 3 months until December 2023, and the clinical outcomes and adverse drug reactions after treatment were evaluated. Results: Of the 4 patients, 3 were males and 1 was female; they were aged 6.7, 2.9, 2.1, and 2.3 years, respectively. Three patients had previously received treatment with phosphate supplements and active vitamins, but their wadding gait and lower limb deformities did not improve significantly, neither did their imaging changes of active richets. The initial dose of Burosumab in the 4 patients was 0.8 mg/kg, administered subcutaneously every 2 weeks, with a treatment course of 0.8-1.3 years. The fasting serum phosphorus and tubular maximum reabsorption of phosphate/glomerular filtration rate (TmP/GFR) of the 4 patients before treatment were 0.72, 0.95, 0.81, 0.66 mmol/L and 0.67, 0.85, 0.87, 0.61 mmol/L, respectively. At the last follow-up, the fasting serum phosphorus and TmP/GFR levels were significantly increased (0.96, 1.09, 1.09, 0.90 mmol/L, and 0.85, 0.79, 1.03, 0.98 mmol/L, respectively). Among them, only the TmP/GFR level (1.17 mmol/L) in case 2 achieved normal values at 3 months post-therapy, while the rest did not reach the normal range for children of the same age. After treatment, the alkaline phosphatase levels of all patients gradually decreased (the values were 461, 240, 423, and 237 U/L, respectively), and the ALP levels in cases 2 and 4 returned to normal at the last visit. Case 4 showed a slight increase in parathyroid hormone (PTH) levels after 9 months of treatment, while the PTH levels in the rest 3 cases remained normal. Case 1 underwent a 6-minute walking test, and the walking distance increased from 245 m to 570 m. Abnormal gait, lower limb deformity, and the severity of rickets in the 4 patients had all improved. No adverse drug reactions such as nephrocalcinosis, local skin injection reaction, hyperphosphatemia, or vitamin D deficiency were observed. Conclusion: Burosumab can improve clinical symptoms in children with XLH with a good safety profile.

[Clinical characteristics and prognosis of 5 children with maturity onset of diabetes of the young 12 subtype].

Objective: To analyze the genetic and clinical characteristics, treatment and prognosis of patients diagnosed with maturity onset of diabetes of the young (MODY) 12 subtype. Methods: This retrospective study collected and analyzed data from 5 children with MODY12 subtype caused by ABCC8 gene variants who underwent inpatient and outpatient genetic testing at Beijing Children's Hospital from January 2016 to December 2023. Their clinical and genetic features, treatment, and follow-up results were analyzed. Results: Among the 5 patients with MODY12 subtype, 4 were male and 1 was female, with an age of 13.4 (5.5, 14.6) years. Four of the patients were born large for gestational age, while one was born small for gestational age. Two patients were overweight or obese. Three patients exhibited typical symptoms of diabetes, while 2 were incidentally found to have elevated blood glucose level. One patient was found to have diabetic ketoacidosis at onset, who was diagnosed with congenital hyperinsulinism during the neonatal period and received diazoxide treatment, and experienced intellectual developmental delay. All 5 patients had autosomal dominant inherited diabetes within 3 generations. The fasting blood glucose at onset was 7.5 (6.5, 10.0) mmol/L, the haemoglobin A1c (HbA1c) was 11.8% (7.5%, 13.5%), and the fasting C-peptide was 1.2 (1.1, 2.2) µg/L. The duration of follow-up was 15 (9, 32) months. One patient underwent lifestyle intervention, 2 received metformin orally, 1 received insulin therapy, and the other received subcutaneous injection of insulin combined with sulfonylurea orally. At the last follow-up, the median fasting blood glucose was 6.1 (5.1, 7.0) mmol/L, the HbA1c was 5.9% (5.7%, 7.1%), and the fasting C-peptide was 1.7 (0.9, 2.9) µg/L. One patient developed diabetic retinopathy. There were 4 missense variations in ABCC8 gene and one in-frame deletion, all of which were maternally inherited heterozygotes. Conclusions: MODY12 subtype is a heterogeneous disorder with the age of onset from infancy to adolescence. It can present as mild hyperglycemia or diabetic ketoacidosis, and has a high incidence of obesity. Definitive diagnosis can be achieved through genetic test, and individualized treatment is recommended based on glucose levels.

[Preparation of chitin/hyaluronic acid/collagen hydrogel loaded with mouse adipose-derived stem cells and its effects on wound healing of full-thickness skin defects in rats].

Objective: To prepare the chitin/hyaluronic acid/collagen hydrogel loaded with mouse adipose-derived stem cells and to explore its effects on wound healing of full-thickness skin defects in rats. Methods: The research was an experimental research. Chitin nanofibers were prepared by acid hydrolysis and alkaline extraction method, and then mixed with hyaluronic acid and collagen to prepare chitin/hyaluronic acid/collagen hydrogels (hereinafter referred to as hydrogels). Besides, the hydrogels loaded with mouse adipose-derived stem cells were prepared. Thirty male 12-week-old guinea pigs were divided into negative control group, positive control group, and hydrogel group according to the random number table, with 10 guinea pigs in each group. Ethanol, 4-aminobenzoic acid ethyl ester, or the aforementioned prepared hydrogels without cells were topically applied on both sides of back of guinea pigs respectively for induced contact and stimulated contact, and skin edema and erythema formation were observed at 24 and 48 h after stimulated contact. Adipose-derived stem cells from mice were divided into normal control group cultured routinely and hydrogel group cultured with the aforementioned prepared hydrogels without cells. After 3 d of culture, protein expressions of platelet-derived growth factor-D (PDGF-D), insulin-like growth factor-Ⅰ (IGF-Ⅰ), and transforming growth factor ß1 (TGF-ß1) were detected by Western blotting (n=3). Eight male 8-week-old Sprague-Dawley rats were taken and a circular full-thickness skin defect wound was created on each side of the back. The wounds were divided into blank control group without any treatment and hydrogel group with the aforementioned prepared hydrogels loaded with adipose-derived stem cells applied. Wound healing was observed at 0 (immediately), 2, 4, 8, and 10 d after injury, and the wound healing rate was calculated at 2, 4, 8, and 10 d after injury. Wound tissue samples at 10 d after injury were collected, the new tissue formation was observed by hematoxylin-eosin staining; the concentrations of interleukin-1α (IL-1α), IL-6, IL-4, and IL-10 were detected by enzyme-linked immunosorbent assay method; the expressions of CD16 and CD206 positive cells were observed by immunohistochemical staining and the percentages of positive cells were calculated. The sample numbers in animal experiment were all 8. Results: At 24 h after stimulated contact, no skin edema was observed in the three groups of guinea pigs, and only mild skin erythema was observed in 7 guinea pigs in positive control group. At 48 h after stimulated contact, skin erythema was observed in 8 guinea pigs and skin edema was observed in 4 guinea pigs in positive control group, while no obvious skin erythema or edema was observed in guinea pigs in the other two groups. After 3 d of culture, the protein expression levels of PDGF-D, IGF-I, and TGF-ß1 in adipose-derived stem cells in hydrogel group were significantly higher than those in normal control group (with t values of 12.91, 11.83, and 7.92, respectively, P<0.05). From 0 to 10 d after injury, the wound areas in both groups gradually decreased, and the wounds in hydrogel group were almost completely healed at 10 d after injury. At 4, 8, and 10 d after injury, the wound healing rates in hydrogel group were (38±4)%, (54±5)%, and (69±6)%, respectively, which were significantly higher than (21±6)%, (29±7)%, and (31±7)% in blank control group (with t values of 3.82, 3.97, and 4.05, respectively, Pvalues all <0.05). At 10 d after injury, compared with those in blank control group, the epidermis in wound in hydrogel group was more intact, and there were increases in hair follicles, blood vessels, and other skin appendages. At 10 d after injury, the concentrations of IL-1α and IL-6 in wound tissue in hydrogel group were significantly lower than those in blank control group (with tvalues of 8.21 and 7.99, respectively, P<0.05), while the concentrations of IL-4 and IL-10 were significantly higher than those in blank control group (with tvalues of 6.57 and 9.03, respectively, P<0.05). The percentage of CD16 positive cells in wound tissue in hydrogel group was significantly lower than that in blank control group (t=8.02, P<0.05), while the percentage of CD206 positive cells was significantly higher than that in blank control group (t=7.21, P<0.05). Conclusions: The hydrogel loaded with mouse adipose-derived stem cells is non-allergenic, can promote the secretion of growth factors in adipose-derived stem cells, promote the polarization of macrophages to M2 phenotype in wound tissue in rats with full-thickness skin defects, and alleviate inflammatory reaction, thereby promoting wound healing.

Polymorphism identification in goat GNRH1 and GDF9 genes and their association analysis with litter size.

This study investigated the polymorphisms of GNRH1 and GDF9 genes in 641 goats of three breeds: Xinong Saanen, Guanzhong and Boer. Two allelic variants were identified in the GNRH1 gene (JN645280:g.3548A>G and JN645281:g.3699G>A) and one allelic variant was found in the GDF9 gene (JN655693:g.4093G>A). Furthermore, g.4093G>A was a missense mutation (p.Val397Ile of GDF9). Results of an association analysis indicated that SNPs g.3548A>G and g.4093G>A had significant effects on litter size (P < 0.05). The combination genotypes of SNPs g.3548A>G, g.3699G>A and g.4093G>A also affected litter size with the C5 genotype having the highest litter size in the first, third, fourth and average parity. Hence, the biochemical and physiological functions, together with the results obtained in our investigation, suggest that the GNRH1 and GDF9 genes could serve as genetic markers for litter size in goat breeding.

Transcriptional activity of an ovarian-specific promoter from rat in dairy goat granulosa cells.

Ovarian-specific promoter 1 (OSP-1) is a retrovirus-like element isolated from the complementary DNA library of rat that has been thought to be specifically expressed in ovary. To exploit this promoter in dairy goat ovary granulosa cells (GCs), OSP-1 from rat was used to construct the reporter vector pOSP-1-EGFP, in which egfp coding for enhanced green fluorescent protein (EGFP) was used as a reporter to examine the activity of OSP-1 in GCs. EGFP was successfully expressed in dairy goat GCs transfected with pOSP-1-EGFP. Reverse transcriptase-polymerase chain reaction analysis confirmed the tissue-specific transcription of EGFP messenger RNA in dairy goat GCs transfected with pOSP-1-EGFP. We concluded that OSP-1 promoter from rat can specifically drive foreign gene expression in dairy goat GCs. Thus, we obtained a tissue-specific regulation element and provided a potential tool for the research of regulation and development of the ovary in dairy goats.

Molecular cloning and characterization of KISS1 promoter and effect of KISS1 gene mutations on litter size in the goat.

Kisspeptins, the product of the KISS1 gene, play an essential role in the regulation of reproductive functions, acting primarily at the hypothalamic level of the gonadotropic axis. We detected polymorphisms of the goat KISS1 gene in 723 individuals from three goat breeds (Xinong Saanen, Guanzhong, and Boer) by DNA pooling, PCR-RFLP, and DNA sequencing methods. We cloned the promoter sequence of this gene and found it to share high similarity with that of the bovine KISS1 promoter. Six TATA boxes were found in the goat KISS1 promoter region. Two novel SNPs (g.2124T>A and g.2270C>T) were identified in the intron 1 of the KISS1 gene of all three goat breeds. The three goat breeds were in Hardy-Weinberg disequilibrium at g.2124T>A and g.2270C>T loci. The g.2124T>A and g.2270C>T loci were closely linked in the three goat breeds (r2 > 0.33). The g.2124T>A and g.2270C>T SNPs were significantly associated with litter size, and the C1 female goats had a larger litter size than did those with the other genotypes. These results extend the spectrum of genetic variation of the goat KISS1 gene, which contributes to our knowledge of goat genetic resources for breeding programs.

Polymorphism identification in the goat KITLG gene and association analysis with litter size.

This study reported the analysis of KIT ligand (KITLG) gene polymorphisms in 681 goats of three breeds: Xinong Saanen (SN), Guanzhong (GZ), and Boer (BG). In addition, the study identified three allelic variants: g.769T>C and g.817G>T in SN and GZ breeds, and g.9760G>C in the three goat breeds. The g.769T>C and g.817G>T loci were closely linked (r(2) > 0.33). All the single nucleotide polymorphism loci were in Hardy-Weinberg disequilibrium (P < 0.05). Significant associations were found for litter size with all three loci. Therefore, these results suggest that the KITLG gene is a strong candidate gene affecting litter size in goats.

Analysis of differentially expressed genes in ovaries of polytocous versus monotocous dairy goats using suppressive subtractive hybridization.

In this study, suppressive subtractive hybridization (SSH) was performed to screen differentially expressed genes in ovarian tissues between polytocous and monotocous goats. From the SSH cDNA library, we obtained 29 differentially expressed sequence tags (ESTs) that have high similarity with known genes in the public database, which were involved in signal transduction, transcriptional regulation, cellular molecular dynamics, cytoskeleton, metabolism and oxidation-reduction. In addition, one novel EST that has no similarity with known genes in the public database was obtained. Eight ESTs, TIMP1, NUCB1, OAZ1, CXXC5, CAPNS2, ATP5A1, Z and RPL5, were further examined for the reproducibility of the SSH data by the real-time quantitative PCR. The results confirmed an increased expression of respective mRNA in ovarian tissues of polytocous goats compared with those of monotocous goats. The study has identified several genes (known or unknown) that may have effect on follicular development, ovulation and egg activation in goats.

[Clinical analysis of 4 children with hereditary hypercholesterolemia].

Objective: To investigate the clinical characteristics of hereditary hypercholesterolemia in childhood. Methods: The clinical data including general conditions, clinical manifestations, laboratory tests, and genetic testing results of 4 children with hereditary hypercholesterolemia who admitted to Henan Children's Hospital from January 2020 to December 2020 were retrospectively analyzed. Results: There were 4 female children aged 5.5,1.5,6.3,3.1 years, all presented with skin xanthoxoma as the chief complaint. Plasma total cholesterol (range 11.8 to 20.9 mmol/L) and low density lipoprotein-cholesterol (range 8.2 to 13.7 mmol/L) were significantly elevated. The serum ß-glutamate levels in case 1 (241.2 µmol/L) and case 2 (164.2 µmol/L) increased significantly. Genetic analysis revealed compound heterozygous variants of ABCG8 gene in case 1 and ABCG5 gene in case 2 who were diagnosed with sitosterolemia. Case 3 and 4 who all had family history of hypercholesterolemia and compound heterozygous variants of LDLR gene were diagnosed with familial hypercholesterolemia. After diet treatment, the blood lipids returned normal and the skin xanoma subsided in case 1 and 2. In case 3 and 4, the blood lipids gradually decreased after diet and rosuvastatin treatment. Conclusions: Xanthomatosis is the common clinical manifestation of sitosterolemia and familial hypercholesterolemia. Family history, blood plant sterol profile, genetic variation, and changes in blood lipids after early dietary treatment are helpful for disease identification.

[Consistency evaluation of 2 methods in detecting serum insulin-like growth factorâ in children].

Objective: To evaluate the consistency of mass spectrometry (MS) and chemiluminescence immunoassay (CLIA) in detecting serum insulin-like growth factor-1 (IGF-1) and IGF-1 standard deviation score (SDS). Methods: This cross-sectional parallel control study prospectively collected the serum samples of 115 children with short stature disorders who were admitted in the Department of Endocrinology, Beijing Children's Hospital, Capital Medical University from February 2020 to December 2021. The serum IGF-1 level was detected by CLIA and MS, and converted to SDS for consistency analysis. Pearson analysis was used to analyze the correlation between the 2 methods, and Deming regression equation was established. Bland-Altman diagram and weighted Kappa coefficient were used to evaluate the consistency of the 2 methods. Results: There were 46 boys (40.0%) and 69 girls (60.0%), aged (8±3) years. Among the 115 cases, 37 were Turner syndrome, 59 were small for gestational age (SGA) at term, 1 was growth hormone deficiency (GHD) and 18 were other diseases. Pearson correlation analysis showed a preferable correlation between IGF-1 measured by the 2 detection methods (r=0.94, P<0.01), and IGF-1 SDS was also significantly correlated (r=0.92, P<0.01). Bland-Altman analysis showed that the consistency of serum IGF-1 levels detected by the 2 methods was poor, and the mean difference between CLIA and MS was 33.38 µg/L. The result detected by CLIA was significantly higher than that by MS, with SDS of 43.51 µg/L (95%CI -51.89-118.7 µg/L). After converting the results to SDS and removing 3 outliers (including 1 GHD patient), the weighted Kappa showed acceptable consistency (κ=0.68). Conclusion: In clinical application, after converting to IGF-1 SDS, IGF-1 detected by MS and CLIA can be used for cross-reference, but too high or too low levels should be cautious about.

[Efficacy of recombinant human growth hormone treatment in children born small for gestational age with syndromic and non-syndromic short stature].

Objective: To analyse the efficacy of recombinant human growth hormone (rhGH) treatment in children born small for gestational age (SGA) with syndormic and non-syndormic short stature. Methods: The clinical data of 59 children born SGA who were diagnosed as short stature and admitted to the Center of Endocrinology, Genetics and Metabolism, Beijing Children's Hospital from July 2012 to June 2021 were collected and analyzed. According to the 2019 consensus on short stature, they were divided into syndromic group and non-syndromic group. Before treatment and 6, 12, 18 and 24 months after treatment, height standard deviation score (Ht-SDS), difference of height standard deviation (∆Ht-SDS) and homeostasis model assessment-insulin resistance index (HOMA-IR) were compared between groups, while Ht-SDS and HOMA-IR were compared before and after treatment. Independent t test or Kruskal-Wallis test were used for comparison between the 2 groups, and paired t test or Mann-Whitney U test were used for the intra-group comparison. Results: Among the 59 cases, 37 were males and 22 females, aged (5.5±2.3) years. There was no significant difference in Ht-SDS after 12 months of treatment between 2 groups (0.9±0.4 vs. 1.2±0.4, t=1.68, P=0.104) or in height SDS after 24 months of treatment (1.4±0.7 vs. 1.9±0.5, t=1.52, P=0.151). After 12 months of treatment, the insulin resistance index of the non-syndromic group was significantly higher than that of the syndromic group (2.29 (1.43, 2.99) vs. 0.90 (0.55, 1.40), Z=-2.95, P=0.003). There were significant differences in Ht-SDS between 6 months and before treatment, 12 months and 6 months in syndromic type (Z=7.65, 2.83 P<0.001, P=0.020), but all were significant differences in non-syndromic type between 6 months and before treatment, 12 months and 6 months, 18 months and 12 months, 24 months and 18 months (Z=11.95, 7.54, 4.26, 3.83, all P<0.001). Conclusion: The efficacy of rhGH treatment in children born SGA is comparable between syndromic and non-syndromic short stature cases, but non-syndromic children treated with rhGH need more frequent follow-up due to the risk of insulin resistance.

A new approach for cloning hLIF cDNA from genomic DNA isolated from the oral mucous membrane.

Complementary DNA (cDNA) is valuable for investigating protein structure and function in the study of life science, but it is difficult to obtain by traditional reverse transcription. We employed a novel strategy to clone human leukemia inhibitory factor (hLIF) gene cDNA from genomic DNA, which was directly isolated from the mucous membrane of mouth. The hLIF sequence, which is 609 bp long and is composed of three exons, can be acquired within a few hours by amplifying each exon and splicing all of them using overlap-PCR. This new approach developed is simple, time- and cost-effective, without RNA preparation or cDNA synthesis, and is not limited to the specific tissues for a particular gene and the expression level of the gene.