[Efficacy of oral testosterone undecanoate in children with androgen insensitivity syndrome].

Objective: To investigate the efficacy and safety of oral testosterone therapy in individuals diagnosed with androgen insensitivity syndrome (AIS). Methods: A self-controlled study design was utilized, focusing on individuals with AIS who were genetically diagnosed at the Department of Endocrinology, Genetics, and Metabolism of Beijing Children's Hospital between 2009 and 2021. These patients underwent treatment involving the administration of testosterone. The primary observed indexes include the measurement of penis length, which should meet the minimal surgical standard (penis length≥2.5 cm) or greater than or equal to -2.5 s (lower limit of normal). Secondary observed indexes include penile length standard deviation score (PL-SDS), an increase in penis longitude (ΔPL), medication dosage, the course of therapy, and safety indicators, among others. There were 4 courses of treatment. After each course, patients were evaluated to determine whether termination of treatment was appropriate. Patients who exhibited inadequate post-treatment penile length growth were advised to continue with further treatment. The statistical methodology included t-test, and a Wilcoxon rank sum test to describe efficacy and safety. The patients were followed up until 2023. Results: The study comprised a total of 51 individuals with AIS, comprising 33 males and 18 females (gender of registered permanent residence). Among these patients, 10 were diagnosed with complete androgen insensitivity syndrome (CAIS) and 41 were diagnosed with partial androgen insensitive syndrome (PAIS). There were 2 children with CAIS were diagnosed by doctors and prescribed testosterone undecanoate, but the children did not really take medicine.The penile length of CAIS patients could not be measured (penile length<0.5 cm) before and after treatment. For PAIS patients, baseline penile length and PL-SDS were (2.3±0.6) cm and -3.7±1.3, respectively. The measurements for penile length and PL-SDS after each treatment course were recorded as follows: (2.7±0.8), (2.8±0.6), (2.6±0.4), (2.6±0.4) cm and -2.8±1.6, 2.5±1.6, 2.9±1.2, -3.2±0.9, respectively. Both penile length and PL-SDS interventions showed statistically significant gains when compared to the baseline performance of the 4 courses (t=4.05、3.56、2.55、2.23 and 3.88、3.50、2.50、2.19, all P<0.05). Before treatment, 13 PAIS patients (32%) reached 2.5 cm and seven (17%) reached greater than or equal to -2.5 s. Following the initial, subsequent, third, and fourth therapeutic interventions, 18 cases (44%), 24 cases (59%), 25 cases (61%), and 26 cases (63%) reached 2.5 cm, respectively. Additionally, A total of 12 cases (29%), 15 cases (37%), 20 cases (49%), and 21 cases (51%), respectively, were found to reach greater than or equal to -2.5 s. The study involved the longitudinal monitoring of patients with the highest recorded age being 13.7 years. The weight, height, body mass index, bone age/age, cholesterol, hemoglobin and so on were all within the normal range and the difference were not statistically significant (all P>0.05). All 49 patients were no abnormalities in blood electrolyte, liver and kidney function and thyroid function and no changes in precocious puberty, pubic hair growth, aggressive behavior, vulvar skin darkening, diarrhea or other conditions. Conclusions: Testosterone undecanote in children with CAIS was no effective. The initial course of treatment for patients with PAIS demonstrates observable enhancements in penile length and PL-SDS. For patients with inadequate penile length growth, continued treatment in subsequent courses (such as the second, third, and fourth courses) is recommended toenhance outcomes gradually. Testosterone undecanoate was safe and effective for the majority of individuals with PAIS patients, with few adverse effects and good treatment tolerance.

Ergonomic risk factors and work-related musculoskeletal disorders in clinical physiotherapy.

Objectives: The purpose of this study was to objectively quantify and evaluate the ergonomic risk of clinical physiotherapy practices and evaluate physiotherapists for work-related musculoskeletal disorders and pain. Methods: Twenty-nine physiotherapists in the rehabilitation department of a large-scale tertiary hospital were recruited in this study. The sampling period lasted for 2 weeks for each physiotherapist and interval sampling was adopted to avoid duplication of cases. Therapist posture during physiotherapy was captured, tracked and analyzed in real time using structured light sensors with an automated assessment program. The quantification of ergonomic risk was based on REBA (Rapid Entire Body Assessment) and the RPE (perceived physical exertion) scores of the therapists were recorded before and after treatment, respectively. Results: Two hundred and twenty-four clinical physiotherapy cases were recorded, of which 49.6% were high risk and 33% were very high risk, with none of the cases presenting negligible risk. The positioning (p < 0.001) of physiotherapist had a considerable impact on ergonomic risk and pediatric physiotherapy presented a higher risk to physiotherapists than adults (p < 0.001). The RPE score of physiotherapist after performing physiotherapy was greater than before physiotherapy and was positively correlated with the REBA distribution. Conclusion: Our study creates an automatic tool to assess the ergonomic risk of physiotherapy practices and demonstrates unacceptable ergonomic risk in common practices. The high prevalence of musculoskeletal disorders and pains recommends that rehabilitation assistance devices should be optimized and standard ergonomic courses should be included in physiotherapists' training plans.

[Clinical and genetic analysis of Noonan syndrome in 20 children].

Objective: To explore the clinical and genetic characteristics of Noonan syndrome in children. Methods: The clinical characteristics,genetic analysis and follow-up data of 20 children diagnosed with Noonan syndrome who were admitted to Department of Endocrinology, Genetics and Metabolism, Beijing Children's Hospital, Capital Medical University from March 2016 to December 2020 were retrospectively analyzed. Results: Among 20 children with Noonan syndrome, 13 were males and 7 were females. The age at diagnosis was 5.9 years (1.1 years to 12.2 years). The most common clinical complaints were delayed height growth, followed by hypospadias or cryptorchidism in 2 cases, and special facial appearance in 1 case. Physical examination revealed 12 cases of Noonan syndrome with facial features, 9 cases with cryptorchidism and hypospadias, 10 cases with abnormal cardiac structure, and 10 cases with mental retardation; Twelve patients were detected with PTPN11 variations, 4 patients carried SOS2 variations, 2 cases were confirmed with variations in SHOC2 and SOS1. Six children received recombinant human growth hormone treatment, and their height increased by 4.0 (2.5-6.0) cm to varying degrees at 9 months. No adverse events occurred. Conclusions: Male Noonan syndrome is more frequently found with external genitalia. In addition to the high frequency of PTPN11 variation, the frequency of gene variation in SOS2 gene is higher than previously reported. All of the SOS2 variations are de novo. The syndrome phenotype profiles could vary with the admitted clinical departments. To understand the full picture of the syndrome, it is necessary to collect medical information from different departments.

[Feasibility study of contrast injection scheme based on body mass and iodine flow rate in coronary computed tomography angiography with wide detector CT].

Objective: To investigate the feasibility of coronary computed tomography angiography (CCTA) with the individualized contrast medium injection scheme based on body mass and iodine flow rate by using wide detector CT at 100 kV. Methods: From May 2018 to July 2018,270 patients with clinically suspected coronary artery disease underwent CCTA in TEDA International Cardiovascular Hospital. They were randomly divided into three groups, 90 cases in each group: group A was 0.5 ml/kg, group B was 0.6 ml/kg, the flow rate of contrast medium injection in group A and group B was (body mass×25 mg)/the concentration of contrast medium,group C was 0.8 ml/kg and the flow rate of contrast medium was 5 ml/s. Iohexol (iodine concentration 350 mgI/ml) was used in all three groups. The CT values of the aorta root in the three groups, the CT value of the middle segment of LAD and RCA, SNR、CNR、SD of the aortic root, subjective score of coronary artery and effective dose (ED) were compared. Results: There was no significant difference in CT value of aortic root, CT value of middle LAD and RCA, SNR、CNR、SD of the aortic root, subjective score of coronary artery among group A, group B and group C (all P>0.05). The flow rates of the three groups of contrast agents were statistically different (4.5±0.5 vs 4.5±0.5 vs 5, P=0.015), and there was no statistical difference between group A and group B (P>0.05) but lower than group C (P=0.015); the amount of contrast agent in the three groups was statistically different (32±3 vs 38±4 vs 53±7, P<0.001), group A

Promoted diffusion mechanism of Fe2.7wt.%Si-Fe10wt.%Si couples under magnetic field by atomic-scale observations.

Diffusion behavior of newly designed Fe2.7wt.%Si-Fe10wt.%Si couples at 1100 °C for up to 12 h has been investigated under the 0, 0.8 and 3 T magnetic fields. Diffusion thickness of solid solution layer and weight percent of Si on Fe2.7wt.%Si side increase significantly under a magnetic field. Application of a magnetic field promotes the diffusion of solid solution layer through the possible diffusion of vacancies mainly due to the appearance of defects, which has been demonstrated by the increased dislocation density and broadening of the typical XRD peaks. Replacement of Si sits by Fe atoms in the crystal structure leads to the appearance of Fe diffraction peaks, which has been confirmed by the increased interplanar spacings under a magnetic field. The magnetic field benefits the depinning of dislocations and leads to higher dislocation density because of the magnetoplastic effect which has been confirmed by the significantly reduced thickness of Fe2.7wt.%Si. Nano-sized Fe3Si particles precipitate in the matrix with an orientation relationship on Fe10wt.%Si side as {220}Fe3Si || {220}matrix & < 1-10 >Fe3Si || < 1-10 >matrix. Fe3Si particles pin dislocation moving and lead to higher dislocation density.

[The comparative study of endoscope versus open surgery on nipple sparing mastectomy with immediate reconstruction using prosthesis implantation].

Objective: To compare the clinical efficacy between endoscopic nipple-sparing mastectomy with immediat reconstruction using prosthesis implantation and open surgery. Methods: Totally 189 early-stage breast cancer patients admitted at Department of Breast and Thyroid Surgery, Southwest Hospital, Third Military Medical University from January 2013 to December 2017 were enrolled. Among them, 104 patients underwent endoscopic nipple sparing mastectomy with immediat reconstruction using prosthesis implantation (endoscopic group), with an age of (41.7±6.1) years (range: 25 to 51 years), and 85 patients underwent traditional open surgery (open group), with an age of (41.6±7.7) years (range: 27 to 67 years). The operative duration, the volume of intraoperative blood loss, the volume of drainage in 3 days after surgery, postoperative complications and patients' satisfaction of breast reconstruction were compared between the two groups using t test, Mann-Whitney U test, χ(2) test or non-parametric test. Results: There were no statistically significant differences in postoperative complications, the rates of recurrence and overall survival between the two groups (P>0.05). The operative duration (sentinel lymph node biopsy: (178± 80) minutes vs. (198±42) minutes, t=-2.082, P=0.039; axillary lymph node dissection: (204±79) minutes vs. (233±49) minutes, t=-2.952, P=0.004), the volume of drainage in three days postoperative ((183±141)ml vs. (237±104) ml, t=- 2.938, P=0.004) in the open group were lower than endoscopic group. The volume of intraoperative blood loss in the endoscopic group was lower than that in the open group ((87±64) ml vs. (62± 36) ml, t=3.210, P=0.002). Patients' satisfaction of breast reconstruction in the endoscopic group was higher than that in the open group. Conclusions: Both endoscopic nipple sparing mastectomy with immediat reconstruction using prosthesis implantation and open surgery are safe in oncology. Endoscopic surgery maybe more suitable alternative in breast reconstruction for early-stage breast cancer patients.

[Clinical phenotype and gene analysis of 86 cases of 5 alpha reductase deficiency].

Objective: Molecular genetics and clinical phenotypic characteristics of 5 alpha reductase deficiency were analyzed. Methods: The genetic results and clinical features classied as Prader grade of external genitalia of 86 children with SRD5A2 mutation seen from 2007 to 2017 at Department of Endocrinology of Beijing Children's Hospital were analyzed, and the mutation differences in different were compared regions according to the literatures. Results: Among the 86 children, 15 had were homozygous mutations, accounting for 17%, and 71 cases of compound heterozygous mutations accounted for 83%. Totally 172 alleles mutations in this series. The mutation was mainly located on exon 1 and exon 4, in which the mutation frequency of exon 1 was 23.8% (41/172), and the frequency of exon 4 mutation was 55.8% (96/172). A total of 19 mutation types of the SRD5A2 gene in this group were detected, of which 5 were new mutations (p.A228F, p.E57D, p.V124D, p.A117D, p.E197K); 65 patients had p.R227Q mutation, accounting for 76%, while 31 had p.Q6* mutation, accounting for 36%. Other rare types such as p.R246W, p.R103* and so on were also seen in the present study, there was no significant difference between north China and south China (P>0.05). The clinical phenotypes of p.R227Q variation varied, mainly in Prader 3-4, accounting for 82%, while (Prader 0-1) were less, accounting only 2%. The variation of p.Q6* was mainly manifested in Prader 3, accounting for 50%. p.R246Q mainly presented Prader 3. The variation of p.G203S appeared to have Prader 2 and Prader 4-5, accounting for 20% and 73% respectively. There was no significant difference in clinical phenotype corresponding to each protein type (P>0.05) . Conclusion: Among the 86 children have identified 19 SRD5A2 mutation types, p.R227Q is a hotspot mutation in Chinese. Variations at different types may have different clinical phenotypes, while the same variations may have different clinical features. There was no significance different in the variation types between the north and the south.

Unbalanced lateral mandibular deviation associated with TMJ sound as a sign in TMJ disc dysfunction diagnosis.

The aim was to study the characteristics of lateral mandibular horizontal deviations during opening-closing movements and their association with TMJ sounds of the clicking type. Subjects were 28 healthy volunteers and 38 patients diagnosed with MRI imaging as having TMJ disc dysfunction, 22 with disc displacement without (DD) and 16 as having disc displacement with reduction (DDR). TMJ sounds were recorded with miniature microphones placed in the ear canals, and jaw movements were documented with a kinesiograph. A sign, unbalanced lateral deviation (ubd) was defined as a rapid, short duration, change in jaw movement direction from, and back to, a smooth deviation path in the horizontal plane. The hypotheses were that degrees of maximal deviations, proportions of unbalanced deviation (ubd) and such deviation associated with TMJ sounds (ubdS), differ between healthy subjects and patients with DD or DDR. Comparisons between groups were made using one-way anova and chi-square analysis, as appropriate. No differences were found between groups regarding degree of lateral deviation per se. The proportions of ubd and ubdS were significantly higher in patients with DDR than in healthy subjects and than in patients with DD (P < 0·001), but no such differences were found between healthy subjects and patients with DD. For prediction of DDR, the sensitivity and specificity of the sign ubdS were found to be 68·8% and 89·3%, respectively. For the sign ubd, they were 100·0% and 64·3%. This indicates that the sign ubdS has diagnostic value in screening for DDR.

Aberrant promoter methylation of the CD4 gene in peripheral blood cells of mastitic dairy cows.

Bovine mastitis is the most common and costly disease of dairy cattle. Cluster of differentiation 4 (CD4) is closely related to the immune response in mastitis. We quantified promoter CpG methylation levels of the CD4 gene in Chinese Holsteins with clinical mastitis (CM) and in healthy controls; these levels were quantitatively detected with bisulfite pyrosequencing assays and confirmed by cloning sequencing. We found that the bovine CD4 promoter had 16% more methyl groups in the cows with CM (75.0 ± 5.8%) compared to the controls (59.0 ± 8.5%). The decreased expression level of CD4 in CM cows may be downregulated by the increased DNA methylation levels in the CD4 promoter. Two-dimensional hierarchical clustering analyses showed large differences in promoter CD4 methylation between mastitic and healthy cows; the dendrogram clearly distinguished the cows with clinical mastitis from healthy controls based on methylation levels. The DNA methylation level of the CD4 gene was strongly influenced by mastitis status in all comparisons. We suggest that the DNA methylation level of the CD4 promoter can be used as a molecular marker for clinical mastitis in dairy cows.

Livin and caspase-3 expression are negatively correlated in cervical squamous cell cancer.

OBJECTIVE: Overexpression in cancer cells of inhibitor of apoptosis proteins like livin appears to promote tumorigenesis by regulating expression of proteins involved in apoptosis signaling. Here, the authors investigated expression of livin and an apoptosis protein that is known to inhibit, caspase-3, in cervical squamous cell carcinoma. MATERIALS AND METHODS: Their expression was assessed for correlation with tumor invasiveness. Immunohistochemistry for livin and caspase-3 was used in 36 normal cervical tissues and in 98 samples of cervical squamous cell carcinoma. The percentage of cells expressing these proteins was compared between normal and cancer samples. Their expression rates in cancer samples were subsequently compared with one another and with the clinical and pathological characteristics of the samples. RESULTS: Livin was more commonly expressed in tumor samples than in normal tissues, while the opposite pattern was observed for caspase-3. Expression of livin was significantly associated with advanced clinical stage, higher pathological grade, and lymph node metastasis (p < 0.05). Expression of caspase-3 was significantly associated with lower clinical stage, lower pathological grade, and lack of lymph node metastasis (p < 0.05). Finally, expression of livin was negatively correlated to caspase-3 expression in cervical squamous cell carcinoma tissue (r = -0.57, p < 0.05). CONCLUSIONS: Livin may inhibit apoptosis in cervical squamous cell carcinoma by downregulating caspase-3, thereby promoting disease progression.

NEXAFS study of 1-butanethiol adsorbed on Cu(111) and square root of 7 x square root of 7 R19.1 degrees S/Cu(111).

The adsorption of 1-butanethiol on Cu(111) and square root of 7 x square root of 7 R19.1 degrees S/Cu(111) surfaces has been studied by S K-edge near edge X-ray absorption fine structure (NEXAFS) spectroscopy and thermal desorption spectroscopy. Upon adsorption on clean Cu(111) surface at room temperature, butanethiolate as well as atomic sulfur is formed. For the butanethiolate, the S-C bond is found predominately perpendicular to the surface as revealed by polarization analysis. In contrast, on square root of 7 x square root of 7 R19.1 degrees S/Cu(111) surface, the S-H and S-C bonds of the butanethiol stay intact, resulting in a weakly chemisorbed butanethiol.

[Developmental genetic analysis of brown rice thickness of indica rice (Oryza sativa L.)].

Analysis of developmental genetic effects for brown rice thickness (BRT) trait in indica rice (Oryza sativa L.) at four different filling stages was conducted and a developmental genetic model and corresponding statistical approaches for quantitative traits of triploid endosperm in cereal crops was used. The results indicated that the diploid maternal plant, triploid endosperm and cytoplasmic genetic effects were important for BRT trait at all filling stages of rice and those effects were the major effect at initial medium, filling period and mature period respectively. The additive and dominance effects were the major effect alternatively at four filling stages of rice. Significant endosperm and maternal dominance effects for BRT suggest that the utilization of heterosis for BRT is viable. The results of conditional genetic variance components shown that the expression of new quantitative genes in endosperm, cytoplasm and maternal plant for BRT was found at most filling stages of rice. The gene expression was most active at the early filling stages, especially at the second stage (8-14 days after flowering). Near to mature period (22-28 days after flowering), however, the expression of genes decreased sharply and even closed. The phenomena that the genes expressed spasmodically, i.e. the net genetic effects equaled to zero in some filling stages were detected for some genetic effects. Dominance and cytoplasmic correlation coefficients were significant at 0.05 or 0.01 probability level in some filling stages meanwhile there were the most strong relationship between mature period and other periods for BRT.

Effect of bis(beta-chloroethyl)sulfide (BCES) on base mismatch repair of DNA in monkey kidney cells.

Sulfur mustard, bis(beta-chloroethyl)sulfide (BCES), a bifunctional alkylating agent, is a vesicant whose mode of action involves interference with the integrity of cellular DNA. Alkylation of DNA is responsible for some of the biological effects of BCES in tissue. Another possible mechanism by which BCES could exert its toxic effect is interference with high fidelity repair of damaged DNA. This study evaluated the possible effects of BCES on the repair of specific errors, i.e., mismatched bases, in the DNA. Heteroduplex (ht) DNA, formed between two temperature-sensitive mutants of SV40 virus, tsA239 and tsA255, each having a different point mutation in the gene for large T antigen, was used to study the effect of BCES on mismatched base repair in African green monkey kidney (AGMK) cells. AGMK cells were exposed to dilute solutions of BCES in methylene chloride (MC) prior to cationic lipofection with ht DNA. In order for the cells to produce wild type (wt) SV40 DNA at a nonpermissive temperature (41 degrees C), repair of at least one of the two mismatches in the DNA had to occur. It was observed that (a) as the concentration of BCES was increased, a proportionally longer delay in the appearance of wt DNA at 41 degrees C was observed in treated cells transfected with ht DNA as compared with cultures exposed to MC alone and then transfected with ht DNA, (b) there was no such effect in exposed AGMK cells transfected with wt DNA, (c) wt and ht DNA were transfected at similar rates in unexposed cells, and (d) BCES did not affect the rate of transfection of wt cells. These observations are consistent with the hypothesis that BCES affects mismatched base repair.

Paramedian reticular nucleus: a thermolytic area in the rat medulla oblongata.

The effects of stimulation or ablation of the paramedian reticular nucleus (PRN) of the rat medulla oblongata on the thermal responses induced by ambient temperature changes, a pyrogen, or a hypothermic substance were assessed. Electrical stimulation of the PRN elicited thermolytic reactions (including decreased metabolism, cutaneous vasodilation and hypothermia) which could be mimicked by micro-injection of kainic acid (an excitotoxic amino acid) into the same region. Bilateral electrolytic lesions in the PRN prevented the animals from responding to heat stress (35 degrees C for 30 min) to some extent, but did not prevent responses to cold stress (4 degrees C for 60 min). In addition, the thermogenic reactions induced by intrahypothalamic injection of polyriboinosinic acid: polyribocytidylic acid (a pyrogenic substance), or the thermolytic reactions induced by intraperitoneal administration of chlorpromazine (a tranquilizer), were antagonized respectively by activation or ablation of the PRN. This suggests that the PRN of the caudal medulla may function as a thermolytic area.

Cold stress or a pyrogenic substance elevates thyrotropin-releasing hormone levels in the rat hypothalamus and induces thermogenic reactions.

Both thyrotropin-releasing hormone (TRH) levels in the hypothalamus and thermoregulatory responses were assessed in rats after they had been equilibrated to each of three ambient temperatures (Ta: 8, 22 and 30 degrees C) tested. Cold exposure, in addition to elevating TRH levels in the hypothalamus, led to increased metabolism and cutaneous vasoconstriction in rats at Ta = 8 degrees C. In contrast, heat exposure resulted in decreased metabolism and cutaneous vasodilatation in rats accompanied by no change in hypothalamic TRH levels at Ta = 30 degrees C. In addition, rats were chronically implanted with a cerebroventricular cannula to allow administration of the pyrogenic substance polyriboinosinic acid-polyribocytidylic acis (Poly I:C) into the brain at Ta = 22 degrees C. Intracerebroventricular administration of Poly I:C, in addition to elevating hypothalamic TRH levels, produced a fever with a latency of onset of about 30 min. The fever induced by Poly I:C was brought about by increased metabolism and cutaneous vasoconstriction in rats. The results suggest that either cold stress or Poly I:C injection elevates TRH levels in rat hypothalamus and thus induces thermogenic reactions.

Somatostatin: a hypothalamic transmitter for thermoregulation in rats.

The changes in both the thermoregulatory responses and brain somatostatin (SS) levels produced by ambient temperature (Ta) changes were assessed in rats after they had been equilibrated to each of the Ta for a period of about 90 min. Cold exposure, in addition to elevating hypothalamic SS-levels, led to increased metabolism and cutaneous vasoconstriction at Ta = 8 degrees C. In contrast, heat exposure, in addition to lowering hypothalamic SS-levels, resulted in decreased metabolism and cutaneous vasodilation at Ta = 30 degrees C. Rats were chronically implanted with a hypothalamic cannula to allow intrahypothalamic injection of SS on the conscious rats. Direct administration of SS (0.1-0.3 micrograms) into the preoptic anterior hypothalamic area caused a dose-related rise in colon temperature at three Ta tested. The SS-induced hyperthermia was produced by increased metabolism at Ta = 8 degrees C, whereas at Ta = 30 degrees C, it was caused by cutaneous vasoconstriction. At Ta = 22 degrees C, the hyperthermia was caused by increased metabolism and cutaneous vasoconstriction. Systemic administration of cysteamine, in addition to lowering hypothalamic SS-levels, produced a dose-related fall in colon temperature at Ta of 8 degrees C and 22 degrees C. The hypothermia induced by cysteamine was produced by decreased metabolism at Ta = 8 degrees C, whereas at Ta = 22 degrees C, it was caused by both decreased metabolism and cutaneous vasodilation. The data indicate that the hypothalamic SS-levels mediate normal body temperature responses in rats.