Objective:The characteristics of women with false elevated testosterone were analyze and the literature was reviewed to provide reference for clinical laboratory identification of false elevated testosterone.Methods:The characteristics of three patients with false elevated testosterone in Peking Union Medical College Hospital were analyzed retrospectively, and the results of different detection platforms and methods for the determination of testosterone levels were compared. International and domestic literatures related to false elevation of testosterone and detection methods of testosterone were searched for a comprehensive analysis from PUBMED and CNKI.Results:The levels of testosterone in 3 female patients were elevated by immunoassay and normal by mass spectrometry. They were excluded from the diagnosis of hyperandrogenemia. A total of 38 literatures related to testosterone detection were retrieved, of which 9 case reports of pseudohyperandrogenemia, among which 12 cases of pseudohyperandrogenemia were reported in 2 domestic literatures in 2021. All cases were confirmed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Previous studies have clearly indicated that the result of routine immunoassay in clinical laboratory for the determination of female testosterone have poor correlation with the results of LC-MS/MS, with varying degrees of deviation.Conclusions:Immunoassay tests for female testosterone is susceptible to interference and lead to elevated false results. It is suggested that clinical laboratories evaluate the detection methods used and establish a identification program, and confirm samples with suspected pseudoelevated testosterone elevation using other immune platforms or LC-MS/MS.

There remains a significant gap in our quantitative understanding of crosstalk between apoptosis and necroptosis pathways. By employing the SWATH-MS technique, we quantified absolute amounts of up to thousands of proteins in dynamic assembling/de-assembling of TNF signaling complexes. Combining SWATH-MS-based network modeling and experimental validation, we found that when RIP1 level is below ~1000 molecules/cell (mpc), the cell solely undergoes TRADD-dependent apoptosis. When RIP1 is above ~1000 mpc, pro-caspase-8 and RIP3 are recruited to necrosome respectively with linear and nonlinear dependence on RIP1 amount, which well explains the co-occurrence of apoptosis and necroptosis and the paradoxical observations that RIP1 is required for necroptosis but its increase down-regulates necroptosis. Higher amount of RIP1 (>~46,000 mpc) suppresses apoptosis, leading to necroptosis alone. The relation between RIP1 level and occurrence of necroptosis or total cell death is biphasic. Our study provides a resource for encoding the complexity of TNF signaling and a quantitative picture how distinct dynamic interplay among proteins function as basis sets in signaling complexes, enabling RIP1 to play diverse roles in governing cell fate decisions.
Animals ; Apoptosis ; Caspase 8/metabolism* ; GTPase-Activating Proteins/metabolism* ; HEK293 Cells ; Humans ; Mice ; Mice, Knockout ; Necroptosis ; Receptor-Interacting Protein Serine-Threonine Kinases/metabolism*

Objective:To explore the correlations of α-melanocyte stimulating hormone ( α-MSH) levels in serum and synovial fluid with progression of primary knee osteoarthritis (KOA). Methods:A retrospective analysis was conducted of the 96 patients who had been diagnosed as primary KOA at Department of Orthopedics, The First Hospital of Huizhou from October 2018 to October 2019. Radiographic severity of KOA was determined by Kellgren-Lawrence (K-L) grades; α-MSH levels were measured by enzyme-linked immunosorbent assay (ELISA). Levels of pro-inflammatory cytokine interleukin-1 β (IL-1 β) and matrix metalloproteinase-3 (MMP-3) were also detected. Another 64 patients with patellar dislocation, matched in age and gender, were enrolled as controls. The Numeric Pain Scale (NPS) and revised Oxford Knee Score (OKS) were employed to evaluate their symptomatic severity. Receiver operating characteristics (ROC) curve was used to compare α-MSH, IL-1 β and MMP-3 with regard to their diagnostic values in the K-L grading. Results:There were no statistically significant difference in age, gender and body mass index between the 2 groups, showing they were comparable ( P> 0.05). The α-MSH levels in synovial fluid were significantly lower in the KOA patients than in the controls [(16.9±3.8) pg/mL versus (18.8±2.7) pg/mL] ( P<0.001); there were no significant differences between the KOA patients and the controls in the serum α-MSH levels [(24.9±1.8) pg/mL versus (24.8±1.7) pg/mL] ( P>0.05). The α-MSH levels in synovial fluid were negatively correlated with K-L grades ( r=-0.382, P<0.001) and negatively correlated with NPS ( r=-0.382, P<0.001) but positively correlated with OKS ( r=0.339, P<0.001). Moreover, the α-MSH levels in synovial fluid were negatively correlated with the IL-1 β levels in synovial fluid ( r=-0.483, P<0.001) and with the MMP-3 levels in synovial fluid ( r=-0.336, P< 0.001). Conclusions:The level of serum α-MSH may not be correlated with the progression of KOA but the synovial fluid α-MSH is negatively correlated with the progression of KOA. Therefore, the expression level of α-MSH in joint synovial fluid can be used as a potential biomarker for assessment of severity of knee osteoarthritis.

Pheochromocytoma and paraganglioma are rare neuroendocrine tumors. Because of the abnormal secretion of catecholamine, the risk of disease is high. At present, the choice of drug treatment for these diseases is still controversial. The further understanding of the research has showed that the different molecular subtypes have different carcinogenic mechanism and therapeutic response. And a variety of corresponding targeted drugs have entered the clinical trial stage, showing a certain therapeutic potential. This article reviews the current treatment and the progress of targeted drugs for pheochromocytoma and paraganglioma.

Objective:To investigate the correlation of mRNA and protein levels of Ghrelin in shoulder tissue and synovial fluid with severity of rotator cuff tear(RCT) and frozen shoulder(FS).Methods:Recruited for this study were 66 RCT and 66 FS patients who had been definitely diagnosed at Department of Orthopedics, The First Hospital of Huizhou from January 2018 to September 2019. Another 60 patients with rotator instability were recruited as a control group. After the severity of RCT was evaluated by ultrasonographic images, the RCT group was further divided into 3 subgroups according to the severity of RCT: a massive full thickness tear (MFTT) subgroup, a non massive full thickness tear (MFTT) subgroup, and a partial thickness tear (PTT) subgroup. The FS group was conventionally divided into 31 cases of acute phase and 35 cases of adhesive phase. Samples of subacromial bursa and shoulder joint bursa tissues and shoulder joint synovial fluid were collected. The expression of Ghrelin mRNA was detected by RT-PCR and the expression of Ghrelin protein in joint synovial fluid was detected by ELISA. The symptoms and functions of shoulder joint were evaluated by visual analogue scale (VAS) and Constant-Murley functional score.Results:There were no significant differences in gender or age between the RCT, FS and control groups, showing compatibility ( P>0.05).The expression of Ghrelin mRNA in subacromial synovial capsule and shoulder joint capsule and the expression of Ghrelin protein in shoulder synovial fluid in the RCT and FS groups were significantly lower than those in the control group ( P<0.05).The expression of Ghrelin mRNA in subacromial synovial capsule and shoulder joint capsule and the expression of Ghrelin protein in shoulder synovial fluid in the PTT subgroup were the highest, followed sequentially by NMFTT and MFTT subgroups, with significant differences between subgroups ( P<0.05). For FS patients, the expression levels of Ghrelin mRNA and protein in the acute phase were significantly lower than in the adhesive phase ( P<0.05). The relative expression of Ghrelin mRNA in joint capsule and the expression of Ghrelin protein in shoulder synovial fluid were negatively correlated with VAS scores and IL-6 levels (all P<0.05), and positively correlated with the Constant-Murley scores (all P<0.05). Conclusions:The expression of Ghrelin in shoulder tissue and synovial fluid is negatively correlated with the progress of rotator cuff tear and frozen shoulder.Local supplementation of Ghrelin may be a potential therapy for rotator cuff tear and frozen shoulder.

OBJECTIVE: To diagnose a fetus with Papillorenal syndrome by prenatal ultrasonography and genetic testing, and to correlate its genotype with phenotype. METHODS: Ultrasound finding of the fetus was reviewed. Muscle sample of the abortus was taken, and genetic variant related to the clinical phenotype was screened by whole exome sequencing (WES). Suspected pathogenic variant was verified by Sanger sequencing. RESULTS: Prenatal ultrasound revealed severe dysplasia of the fetal kidneys and oligohydramnios. WES revealed that the fetus has carried a c.736G>T (p.Glu246Ter) nonsense variant of the PAX2 gene, which was unreported previously. The result of Sanger sequencing was consistent with that of WES. Both parents of the fetus were of the wild-type, suggesting a de novo origin of the fetal variant. CONCLUSION The novel heterozygous c.736G>T (p.Glu246Ter) variant of the PAX2 gene probably underlay the Papillorenal syndrome in the fetus. Above finding has provided a basis for genetic counseling and clinical decision-making.

Objective To investigate the changes of prevalence of hyperuricemia ( HUA) and its correlations with blood glucose and lipid in healthy adults receiving physical examination at Peking Union Medical College Hospital (PUMCH) from 2012 to 2017. Meth-ods An observational approach was adopted for the data analysis.The test results of uric acid (UA),fasting blood glucose (FBG),to-tal cholesterol (TC),triacylglycerol (TG),low density lipoprotein cholesterol (LDL-C),high density lipoprotein cholesterol (HDL-C), creatinine (Cr) and Urea of 399 089 cases (206 881 males and 192 208 females) at PUMCH from January 2012 to December 2017 were collected and statistically analyzed.Results The total prevalence of HUA was 17.4% in which the prevalence of males was signif-icantly higher than that of females (25.6% vs 8.5%,χ2＝20 234.850,P＜0.01).During the years of 2012 to 2017,the prevalence of HUA was 26.5%,24.7%,28.6%,23.9%,24.8% and 24.5% in males,and 13.8%,6.3%,7.9%,6.1%,6.2% and 6.8% in females for each year respectively.The prevalence of HUA in males aged 18 to 64 years old was significantly higher than that in the age-matched fe-males (all P＜0.05).However, the prevalence of HUA in males aged≥65 years old was similar to the age-matched females.There was no statistically significant difference of HUA prevalence between males and females aged ≥65 in 2013,2015,2016 and 2017 ( χ2＝1.792,0.017,1.440 and 0.205 respectively;all P＞0.05).The percentages of hyperlipidemia in both males and females of HUA group were higher than those of non-HUA group respectively (all P＜0.01).The percentage of hyperglycemia in males of non-HUA group was higher than that of HUA group,but the percentage of hyperglycemia in females of non-HUA group was lower than that of HUA group ( all P＜0.01).High levels of TC,TG and FBG were risk factors of HUA with increased OR values in increased concentrations of TC,TG and FBG,respectively.Conclusion During the recent 6 years, in healthy adults receiving physiced examination at PVMCH, the preva-lence of male HUA diagnosed was at overall high level,but the prevalence of female HUA was in decreasing and relatively stable trend. Hyperlipidemia and hyperglycemia should be the risk factors of HUA.

Objective To examine perinatal complications and outcomes of twin pregnancies in women aged over 40 years.Methods A retrospective study was performed on the clinical data of 3 127 twin pregnancies,managed in 12 national hospitals from January2013-December 2013,to analyze differences in perinatal complications and outcomes between women aged over 40 years,and those aged 35 to ＜40 years and 18 to ＜35 years.Results For twin pregnancies,the incidence of postpartum hemorrhage,abortion,early preterm birth,termination of gestation,very low birth weight infants,mild neonatal asphyxia,and preterm births in women aged over 0 years was significantly higher than in women aged 35 to ＜40 years and 18 to ＜35 years (P ＜ 0.05).Among women aged over 40 years and those aged 35 to ＜40 years,the incidence of gestational hypertension was not significantly higher than in women aged 18 to ＜35 years for twin pregnancies (P ＞ 0.05).Conclusion Women aged over 40 years with twin pregnancies were more likely to develop maternal complications and poor perinatal outcomes.Therefore,twin pregnancies in women aged over 40 years should receive comprehensive perinatal management to extend the gestation and improve the perinatal prognosis.

Objective To research the important of prenatal diagnosis and effect of intervention to fetal hydrothorax. Methods The cases of fetal hydrothorax (n=5) were obtained from the Shengjing Hospital,China Medical University between December 2014 and May 2015. All pregnancies were uncomplicated, excluded congenital organic and chromosomal abnormalities during prenatal diagnosis and with a 37 average gestational weeks. The case 1, 2, 4 were unilateral hydrothorax and the case 3, 5 were bilateral. We performed an antenatal thracocentesis to case 1, 2, 3. In case1, the hydrothorax increased rapidly after 5 days, and the patient underwent a cesarean section and ex utero intrapartum treatment (EXIT);in case 2, the fetal heart rate was decreased to 40-50 bpm suddenly during thracocentesis, and we performed an emergent cesarean section and EXIT for the patient; in case 3, the patient underwent thracocentesis and a meanwhile cesarean section and EXIT procedure. We performed a conservative management to case 4, 5, the hydrothorax resolved spontaneously during the pregnancy and after birth, both patients underwent cesarean section. Results All fetuses were survived, the neonates of case 1, 2 and 3 underwent assited mechanical ventilation, thoracic close drainage, then discharged after hydrothorax resolved and feeding tolerance;in case 4, there was no respiratory distress and hospital treatment;in case 5, the neonate underwent assited mechanical ventilation and conservative management, the hydrothorax has resolved gradually. Conclusions The prenatal diagnosis and antenatal intervention (thracocentesis) may play an important role in fetal hydrothorax treatment. In clinical, we should choose different plan according to the gestation weeks and classification of hydrothorax of the patient.

Objective To analyze the clinical outcome and impact factors of twin-to-twin transfusion syndrome (TTTS) with anterior placenta treated by fetoscopic selective laser coagulation of placental vessels(SLCPV). Methods Ten cases of TTTS with anterior placenta and 8 cases with posterior placenta were treated by SLCPV in Shengjing Hospital from July 2011 to April 2014. Clinical data were analyzed retrospectively. Some cases were at Quintero stageⅡor higher stage, others were at Quintero stageⅠbut with cardiovascular score≥5 according to the scoring system of Children′s Hospital of Philadelphia. The anterior placenta cases were treated by curve fetoscopy and the posterior placenta cases were treated by straight fetoscopy. Results (1) Of all the 18 cases, the mean gestational age at SLCPV was 24.1 weeks (17+5 to 27+4 weeks). There were 2 cases at Quintero stageⅠ, 4 at stageⅡand 12 at stageⅢ. The mean gestational age of anterior placenta cases at SLCPV was 25.2 weeks (22 to 27+4 weeks), with 2 cases at Quintero stageⅠ, 2 cases at stage Ⅱ and 6 at stage Ⅲ;5 cases had preterm prelabour rupture of the membranes (PPROM)and 1 case had maternal intestinal obstruction after the operation;the average operation time was 40 minutes. Of the posterior placenta cases, the mean gestational age at SLCPV was 22.7 weeks (17+5 to 27+4 weeks);2 cases were at Quintero stageⅡand 6 cases at stageⅢ. PPROM happened in one case;one case had maternal enterobacter cloacae septicemia;the average operation time was 28 minutes. All the 18 cases could tolerate the operations. There was no intraoperative complication. (2) One anterior placenta case had maternal intestinal obstruction and miscarriage; and one posterior placenta case had enterobacter cloacae septicemia. Karyotype analyses of the all the twins were normal. (3) 17 cases delivered already, including all the 10 anterior placenta cases and 7 posterior placenta cases. One infant had corpus callosum agenesis, but its co-twin was normal. The average gestational age at delivery for anterior placenta cases was 32.6 weeks (24 to 37+1 weeks), an was 28.2 weeks (25+6 to 36+2 weeks) for posterior placenta cases. The fetuses survival rate was 13/17 (one case was still in pregnancy) for at least one twin, and 10/17 for both twins. Both twins survival rates were 5/10, 5/7 for anterior placenta cases and posterior placenta cases, respectively. At least one twin survival rates were 8/10, 5/7 for the two groups respectively. Conclusion SLCPV is suitable for the treatment of TTTS, no matter the placenta is on the anterior wall or posterior wall. The treatment had good outcomes, but more PPROM happened in the anterior placenta cases, which may be associated with operation time and the range of operation.