Effect of different doses of recombinant human growth hormone therapy on children with growth hormone deficiency: a retrospective observational study.

OBJECTIVE: The aim of this study was to explore the effects of different doses of recombinant human growth hormone (rhGH) treatment on children with growth hormone deficiency (GHD). PATIENTS AND METHODS: Medical records of 174 GHD patients admitted to our hospital from June 2019 to January 2022 were retrospectively evaluated. A total of 136 patients met the inclusion criteria, of which 70 received 0.1 U/ (kg·d) (low-dose group) and 66 received 0.2 U/ (kg·d) dose of rhGH treatment (high-dose group). Growth and development status [height, weight, height standard deviation (HtSDS), growth rate], bone age, bone density, speed of sound (SOS) as distal radius bone mass, biochemical indicators of growth and development [insulin-like growth factor-1 (IGF-1), insulin-like growth factor binding protein 3 (IGFBP-3)], growth hormone (GH) levels and incidence of adverse reactions were collected and compared between the two groups before and after one year of the treatment. RESULTS: After the treatment, height, weight, HtSDS, and growth rate of the two groups increased compared to before the treatment and were significantly higher in the high-dose group than in the low-dose group (p<0.05). After one year of treatment, the following observations were made: the bone age of the two groups increased compared to the baseline values and was higher in the high-dose group compared to the low-dose group (p<0.05). The SOS of the two groups decreased but was significantly higher in the high-dose group compared to the low-dose group (p<0.05). Serum levels of IGF-1, IGFBP-3, and GH in both groups increased compared to the baseline values and were higher in the high-dose group than in the low-dose group (p<0.05). There was no significant difference in the incidence of adverse reactions between the high-dose group (8.6%) and the low-dose group (6.1%) (p>0.05). CONCLUSIONS: High-dose rhGH treatment for GHD is safe and can more effectively upregulate IGF-1, IGFBP-3, and GH, and promote the growth and development of children.

[The effect of Wendler Glottoplasty to elevate vocal pitch in transgender women].

Objective: To evaluate the effect of Wendler Glottoplasty to elevate vocal pitch in transgender women. Methods: The voice parameters of pre-and 3-month post-surgery of 29 transgender women who underwent Wendler Glottoplasty in department of otorhinolaryngology head and neck surgery of Beijing Friendship Hospital from January, 2017 to October, 2020 were retrospectively analyzed. The 29 transgender women ranged in age from 19-47 (27.0±6.3) years old. Subjective evaluation was performed using Transsexual Voice Questionnaire for Male to Female (TVQMtF). Objective parameters included fundamental frequency (F0), highest pitch, lowest pitch, habitual volume, Jitter, Shimmer, maximal phonation time (MPT), noise to harmonic ratio (NHR) and formants frequencies(F1, F2, F3, F4). SPSS 25.0 software was used for statistically analysis. Results: Three months after surgery, the score of TVQMtF was significantly decreased [(89.9±14.7) vs. (50.4±13.6), t=11.49, P<0.001]. The F0 was significantly elevated [(152.7±23.3) Hz vs. (207.7±45.9) Hz, t=-6.03, P<0.001]. Frequencies of F1, F2 and F3 were significantly elevated. No statistical difference was observed in the frequencies of F4. The highest pitch was not significantly altered while the lowest pitch was significantly elevated [(96.8±17.7) Hz vs. (120.0±28.9) Hz, t=-3.71, P=0.001]. Habitual speech volume was significantly increased [(60.0±5.2) dB vs. (63.6±9.6) dB, t=-2.12, P=0.043]. Jitter, Shimmer, NHR and MPT were not obviously altered (P>0.05). Conclusions: Wendler Glottoplasty could notably elevate the vocal pitch, formants frequencies and degree of vocal femininity in transgender women without affecting phonation ability and voice quality. It can be an effective treatment modality for voice feminization.

Site-directed mutation of ß-galactosidase from Streptococcus thermophilus for galactooligosaccharide-enriched yogurt making.

ß-Galactosidase is one of the most important enzymes used in dairy processing. It converts lactose into glucose and galactose, and also catalyzes galactose to form galactooligosaccharides (GOS), so-called prebiotics. However, most of the ß-galactosidases from the starter cultures have low transgalactosylation activities, the process that results in galactose accumulation in yogurt. Here, a site-directed mutation strategy was attempted, to genetically modify ß-galactosidase from Streptococcus thermophilus. Out of 28 Strep. thermophilus strains, a ß-galactosidase gene named bgaQ, encoded for high ß-galactosidase hydrolysis activity (BgaQ), was cloned from the strain Strep. thermophilus SDMCC050237. It was 3,081 bp in size, with 1,027 deduced amino acid residuals, which belonged to the GH2 family. After replacing the Tyr801 and Pro802 around the active sites of BgaQ with His801 and Gly802, the GOS synthesis of the generated mutant protein BgaQ-8012 increased from 20.5% to 26.7% at 5% lactose, and no hydrolysis activity altered obviously. Subsequently, the purified BgaQ or BgaQ-8012 was added to sterilized milk inoculated with 2 starters from Strep. thermophilus SDMCC050237 and Lactobacillus delbrueckii ssp. bulgaricus ATCC11842. The GOS yields with added BgaQ or BgaQ-8012 increased to 5.8 and 8.3 g/L, respectively, compared with a yield of 3.7 g/L without enzymes added. Meanwhile, the addition of the BgaQ or BgaQ-8012 reduced the lactose content by 49.3% and 54.4% in the fermented yogurt and shortened the curd time. Therefore, this study provided a site-directed mutation strategy for improvement of the transgalactosylation activity of ß-galactosidase from Strep. thermophilus for GOS-enriched yogurt making.

Gender Concept, Work Pressure, and Work-Family Conflict.

Based on the data of the 2015 China General Social Survey (CGSS), this article empirically analyzed the influence of gender concept, work pressure, and work flexibility on work-family conflict (work interfering family (WIF) and family interfering work (FIW)) from three perspectives (gender, age, and urban and rural areas in China) and tested its significance. The empirical results show that individuals holding the concept of gender inequality produced lower WIF and FIW, which only exists between sexual relations, older working people, and urban and rural areas. Multicultural exchange and integration only made it easier for working people under the age of 30 to accept the concept of gender equality, but it increased their WIF and FIW. Second, with the development of the economy and society of China, the work pressure of workers is the most important factor causing WIF and FIW. Lastly, in order to cope with the pressure of employment and the cost of living, it is difficult to ease the conflict between work and family.

[A historical review of general medicine].

The first official general medicine was established in the United States, and society of general medicine established in 1947. After that the European and American countries began to study of general medicine and construct system. In 1966, the commonwealth launched the first global residency training program in general medicine.At present, many countries have formed a perfect general practitioner training system. In 1988, the concept of general medicine was introduced into China. In 1989, the Chinese Medical Association established the General Medicine Education Committee, marked the beginning of general medical education in China. In 1993, General Medicine Branch of Chinese Medical Association was set up, was a symbol of the birth of general medicine in China. Compared with some European and American countries, China's general medicine was a late starter, and the training of general practitioners has experienced the development of diversification, at present, it is in line with the international training mode.

[Trend of cancer mortality in Hebei province, 1973-2013].

Objective: To analyze the data of malignant tumor mortality and change in disease burden in Hebei province from 1973 to 2013. Methods: Cancer mortality rate, age-standardized mortality rate and the years of life lost due to premature mortality (YLLs) were calculated by using the data from three rounds of all death causes survey and database of cancer registry in Hebei during 1973-2013. Results: From 1973 to 2013, a linear upward of malignant tumor mortality was observed, with a 51.57% increase. The mortality rate during 1973-1975 was 98.52/100 000 and it was 149.33/100 000 during 2011-2013. During 1973-1975, the YLLs was 17.0/1 000 in males and 12.8/1 000 in females. While during 2011-2013, the YLLs was 23.2/1 000 in males and 15.9/1 000 in females. During 1973-1975, esophagus cancer, stomach cancer and liver cancer were top three leading causes of deaths. During 2011-2013, lung cancer, stomach cancer and liver cancer were main leading causes of deaths. During the past 40 years, the deaths of esophagus cancer and cervix cancer decreased dramatically, but the deaths of lung cancer and breast cancer increased sharply. Conclusions: The disease burden caused by malignant tumor is becoming more serious in Hebei. It is necessary to strengthen the primary prevention and screening of malignant tumor.

The global regulator CodY responds to oxidative stress by the regulation of glutathione biosynthesis in Streptococcus thermophilus.

CodYst is a global transcriptional regulator that modulates the metabolic network in Streptococcus thermophilus ST2017. In this study, experimental data showed that the cell survival of the codYst defective mutant obviously declined at the presence of 10 mM H2O2, suggesting CodYst was involved in response to the oxidative stress. To investigate this phenomenon, transcriptome analysis and real time-quantitative PCR were performed and the results indicated that the transcriptional level of a bifunctional glutathione synthetase gene (gshF) was downregulated by about 3-fold in the codYst defective mutant, along with a decrease by 20% of the glutathione yield compared with the wild-type in minimal chemical defined medium, whereas half of the viable cells remained after H2O2 challenge. In vitro gel shift assays showed that the purified CodYst could bind to the promoter region of gshF, with a conserved CodYst box, confirming the regulation of CodYst on the gshF gene. To our knowledge, this is first report of CodYst in response to oxidative stress mediated by the regulation of gshF in S. thermophilus.

The complete mitochondrial genome sequence of the dwarf blue sheep, Pseudois schaeferi haltenorth in China.

The dwarf blue sheep (Pseudois schaeferi haltenorth) belongs the subfamily Caprinae, which is distributed in Sichuan, Tibet, Yunnan, and Qinghai in China. In this study, the complete mitochondrial genome of Pseudois schaeferi haltenorth was sequenced. The mitogenome was 16 741 bp in length, consisting of 13 protein-coding genes, 22 transfer RNA (tRNA) genes, 2 ribosomal RNA (rRNA) genes, and a non-coding control region (D-loop region). As in other mammals, most mitochondrial genes are encoded on the heavy strand, except for ND6 and eight tRNA genes which are encoded on the light strand. The overall base composition of the Pseudois schaeferi haltenorth is 33.54% A, 26.37% T, 26.91% C, and 13.18% G, A + T (59.91%) was higher than G + C (40.09%). The phylogenetic relationships was analyzed using the complete mitogenome sequence, results show that P. schaeferi haltenorth should be a different species differ from the Genus pseudois hodgson. These information provide useful data for further study on the protection of genetic resources and the taxonomy of Caprinae.

The complete mitochondrial genome sequence of the wild Huoba Tibetan sheep of the Qinghai-Tibetan Plateau in China.

The wild Huoba Tibetan sheep belongs to the subfamily Caprinae, which distributes in Huoba Town of Tibet Autonomous Region, China. In the present work, we report the complete mitochondrial genome sequence of wild Huoba Tibetan sheep for the first time. The total length of the mitogenome is 16 621 bp, consisting of 13 protein-coding genes, 22 transfer RNA (tRNA) genes, two ribosomal RNA (rRNA) genes, and a non-coding control region (D-loop region). As in other mammals, most mitochondrial genes are encoded on the heavy strand. Its overall base composition is A: 33.64%, T: 27.32%, C: 25.90%, and G: 13.14%, A + T (61.96%) was higher than G + C (39.04%). The phylogenetic relationships was analyzed using the complete mitogenome sequence, results show that wild Huoba Tibetan sheep should be a different species differ from the Ovis aries. These information provide an important data for further study on protection of genetic resources and the taxonomy of Caprinae.

Reduced expression of miR-503 is associated with poor prognosis in cervical cancer.

OBJECTIVE: We wished to evaluate the association between expression of microRNA (miR) -503 and prognosis in patients with cervical cancer. PATIENTS AND METHODS: 96 paired specimens of cervical cancer and adjacent normal cervical epithelial tissues were obtained. qPCR was used to evaluate expression levels of miR-503. We analyzed the associations between miR-503 expression levels and clinicopathological parameters, as well as recurrence-free and overall survival with Kaplan-Meier survival curves and proportional hazards model. RESULTS: miR-503 levels were significantly (p < 0.001) lower in cervical cancer tissue compared with adjacent normal cervical epithelial tissue. We further observed significant associations of expression of this miR and recurrence of cervical cancer, lymph node metastasization, and International Federation of Gynecology and Obstetrics (FIGO) stage. In addition, in multivariate analysis, miR-503 expression level was found to be an independent prognostic factor for both recurrence-free and overall survival. CONCLUSIONS: Reduced expression of miR-503 is an independent prognostic factor in cervical cancer indicating poor prognosis.

Analysis of agouti signaling protein (ASIP) gene polymorphisms and association with coat color in Tibetan sheep (Ovis aries).

Tibetan sheep, an indigenous breed, have a wide variety of phenotypes and a colorful coat, which make this breed an interesting model for evaluating the effects of coat-color gene mutations on this phenotypic trait. The agouti signaling protein (ASIP) gene is a positional candidate gene, as was inferred based on previous study. In our research, ASIP gene copy numbers in genomic DNA were detected using a novel approach, and the exon 2 g.100-104 mutation and copy number variation (CNV) of ASIP were associated with coat color in 256 sheep collected from eight populations with different coat colors by high-resolution melting curve assay. We found that the relative copy numbers of ASIP ranged from one to eight in Tibetan sheep. All of the g.100-104 genotypes in the populations were in Hardy-Weinberg equilibrium, and there was no relationship between the g.100-104 genotype and coat color (P > 0.05). The single ASIP CNV allele was found to be almost entirely associated with solid-black coat color; however, not all solid-black sheep displayed the putative single ASIP CNV genotype. From our study, we speculate that the ASIP CNV is under great selective pressure and the single ASIP CNV allows selection for black coat color in Tibetan sheep, but this does not explain all black phenotypes in Tibetan sheep.

De novo assembly and characterization of skin transcriptome using RNAseq in sheep (Ovis aries).

Wool is produced via synthetic processes of wool follicles, which are embedded in the skin of sheep. The development of new-generation sequencing and RNA sequencing provides new approaches that may elucidate the molecular regulation mechanism of wool follicle development and facilitate enhanced selection for wool traits through gene-assisted selection or targeted gene manipulation. We performed de novo transcriptome sequencing of skin using the Illumina Hiseq 2000 sequencing system in sheep (Ovis aries). Transcriptome de novo assembly was carried out via short-read assembly programs, including SOAPdenovo and ESTScan. The protein function, clusters of orthologous group function, gene ontology function, metabolic pathway analysis, and protein coding region prediction of unigenes were annotated by BLASTx, BLAST2GO, and ESTScan. More than 26,266,670 clean reads were collected and assembled into 79,741 unigene sequences, with a final assembly length of 35,447,962 nucleotides. A total of 22,164 unigenes were annotated, accounting for 36.27% of the total number of unigenes, which were divided into 25 classes belonging to 218 signaling pathways. Among them, there were 17 signal paths related to hair follicle development. Based on mass sequencing data of sheepskin obtained by RNA-Seq, many unigenes were identified and annotated, which provides an excellent platform for future sheep genetic and functional genomic research. The data could be used for improving wool quality and as a model for human hair follicle development or disease prevention.

Analysis of geographic and pairwise distances among sheep populations.

This study investigated geographic and pairwise distances among seven Chinese local and four introduced sheep populations via analysis of 26 microsatellite DNA markers. Genetic polymorphism was rich, and the following was discovered: 348 alleles in total were detected, the average allele number was 13.38, the polymorphism information content (PIC) of loci ranged from 0.717 to 0.788, the number of effective alleles ranged from 7.046 to 7.489, and the observed heterozygosity ranged from 0.700 to 0.768 for the practical sample, and from 0.712 to 0.794 for expected heterozygosity. The Wright's F-statistic of subpopulations within the total (FST) was 0.128, the genetic differentiation coefficient (GST) was 0.115, and the average gene flow (Nm) was 1.703. The phylogenetic trees based on the neighbor-joining method by Nei's genetic distance (DA) and Nei's standard genetic distance (DS) were similar. Sheep populations clustered into group 1 (Ta, M, L, H, O, G, and Q breeds) and group 2 (PD, WS, B, and T breeds). These results will have an important value applied and directive significance for sheep breeding in the future.

Limitation of high-resolution melting curve analysis for genotyping simple sequence repeats in sheep.

Variation in microsatellite or simple sequence repeat (SSR) loci has, until recently, relied heavily on the use of gel-based methods that can be both time consuming and difficult to genotype. Non gel-based systems are therefore important to increase simplicity and improve turn-around time without compromising assay sensitivity and accuracy. In this report, we assessed the latest of the non-gel-based methods, high-resolution melting (HRM) curve analysis. HRM is a technique that monitors exactly the decreasing fluorescence of intercalating dye in the process of dissociation of double-stranded DNA. The measurement immediately follows polymerase chain reaction in a one-step, closed-tube method. Four SSR loci of different complexity in sheep, namely MAF209, MCM140, CB226, and SRCRSP5, were assessed using the LightScanners System with LC Greens PLUS DNA binding dye. In order to improve the accuracy of genotyping, we applied internal oligo nucleotide calibrators while performing HRM. DNA polymorphisms were previously identified using capillary electrophoresis analysis (CE). The result showed that CE detected more genotypes than HRM in the same loci regardless of the level of polymorphism at the SSR loci. We demonstrate current limitations of the HRM method for the analysis of SSR loci.