Triceps skinfold thickness trajectories and the risk of all-cause mortality:A prospective cohort study

BACKGROUND The measurement of triceps skinfold(TSF)thickness serves as a noninvasive metric for evaluating subcutaneous fat distribution.Despite its clinical utility,the TSF thickness trajectories and their correlation with overall mortality have not been thoroughly investigated.AIM To explore TSF thickness trajectories of Chinese adults and to examine their associations with all-cause mortality.METHODS This study encompassed a cohort of 14747 adults sourced from the China Health and Nutrition Survey.Latent class trajectory modeling was employed to identify distinct trajectories of TSF thickness.Subjects were classified into subgroups reflective of their respective TSF thickness trajectory.We utilized multivariate Cox regression analyses and mediation examinations to explore the link between TSF thickness trajectory and overall mortality,including contributory factors.RESULTS Upon adjustment for multiple confounding factors,we discerned that males in the‘Class 2:Thin-stable’and‘Class 3:Thin-moderate’TSF thickness trajectories exhibited a markedly reduced risk of mortality from all causes in comparison to the‘Class 1:Extremely thin’subgroup.In the mediation analyses,the Geriatric Nutritional Risk Index was found to be a partial intermediary in the relationship between TSF thickness trajectories and mortality.For females,a lower TSF thickness pattern was significantly predictive of elevated all-cause mortality risk exclusively within the non-elderly cohort.CONCLUSION In males and non-elderly females,lower TSF thickness trajectories are significantly predictive of heightened mortality risk,independent of single-point TSF thickness,body mass index,and waist circumference.

Dipeptidyl peptidase-4 inhibitors and the risk of infection: A systematic review and meta-analysis of cardiovascular outcome trials

BACKGROUND Since adverse events during treatment affect adherence and subsequent glycemic control,understanding the safety profile of oral anti-diabetic drugs is imperative for type 2 diabetes mellitus(T2DM)therapy.AIM To evaluate the risk of infection in patients with T2DM treated with dipeptidyl-peptidase 4(DPP-4)inhibitors.METHODS Electronic databases were searched.The selection criteria included randomized controlled trials focused on cardiovascular outcomes.In these studies,the effects of DPP-4 inhibitors were directly compared to those of either other active anti-diabetic treatments or placebo.Six trials involving 53616 patients were deemed eligible.We calculated aggregate relative risks employing both random-effects and fixed-effects approaches,contingent upon the context.RESULTS The application of DPP-4 inhibitors showed no significant link to the overall infection risk[0.98(0.95,1.02)]or the risk of serious infections[0.96(0.85,1.08)],additionally,no significant associations were found with opportunistic infections[0.69(0.46,1.04)],site-specific infections[respiratory infection 0.99(0.96,1.03),urinary tract infections 1.02(0.95,1.10),abdominal and gastrointestinal infections 1.02(0.83,1.25),skin structure and soft tissue infections 0.81(0.60,1.09),bone infections 0.96(0.68,1.36),and bloodstream infections 0.97(0.80,1.18)].CONCLUSION This meta-analysis of data from cardiovascular outcome trials revealed no heightened infection risk in patients undergoing DPP-4 inhibitor therapy compared to control cohorts.

Study on the Expression Levels of CXCR4, CXCL12, CD44, and CD147 and Their Potential Correlation with Invasive Behaviors of Pituitary Adenomas

Objective To evaluate the factors of CXCR4, CXCL12, CD44, and CD147 as early potential diagnostic biomarkers by determining their expression levels in invasive and non-invasive pituitary adenomas. Methods Fresh pituitary adenoma specimens were collected from 35 pituitary adenoma （21 invasive and 14 non-invasive） patients who underwent surgical treatment in our Neurosurgery Department between January and April of 2009. The expression levels of CXCR4, CXCL12, CD44, and CD147 were evaluated firstly by flow cytometry, fluorescence microscopy in single cell suspensions, and then by immunohistochemical staining of paraffin tissue sections. Results Flow cytometric analyses showed that the percentage of CXCR4- and CXCL12-positive cells from invasive pituitary adenomas （IPA） was significantly higher in the single cell suspensions than that from non-invasive pituitary adenomas （nlPA） （P〈O.05）. Immunohistochemical staining revealed that CXCR4 and CXCL12 staining index scores of the invasive pituitary adenomas were significantly higher than those of the non-invasive pituitary adenomas （P〈O.05）. In contrast, neither flow cytometry nor immunohistochemical staining demonstrated significant difference between CD44 and CD147 expression levels, respectively. Conclusion Expression levels of CXCR4 and CXCL12 are correlated with the invasiveness of pituitary adenomas. Therefore, rather than CD44 and CD147, CXCR4 and CXCL12 may potentially serve as biomarkers for early detection of pituitary adenomas.

Clinical characteristics of non-alcoholic fatty liver disease in Chinese adult hypopituitary patients

BACKGROUND Patients with hypothalamic-pituitary disease have the feature of central obesity,insulin resistance, and dyslipidemia, and there is increased prevalence of liver dysfunction consistent with non-alcoholic fatty liver disease(NAFLD) in this population. The causes of hypopituitarism in the reported studies varied and combined pituitary hormone deficiency including central diabetes insipidus is much common in this population. This retrospective cross-sectional study was performed to analyze the clinical characteristics and related factors with NAFLD and cirrhosis in Chinese adult hypopituitary/panhypopituitary patients.AIM To analyze the clinical characteristics of and related risk factors for NAFLD in Chinese adult hypopituitary patients.METHODS Adult Chinese patients with hypopituitarism and/or panhypopituitarism were enrolled at the Pituitary Center of Peking Union Medical College Hospitalbetween August 2012 and April 2018. According to abdominal ultrasonography,these patients were divided into an NAFLD(-) group and an NAFLD(+) group,and the latter was further divided into an NAFLD group and a cirrhotic group.The data, such as patient characteristics, diagnosis, and treatment, were extracted from medical records, and statistical analysis was performed.RESULTS A total of 36 male and 14 female adult Chinese patients with hypopituitarism were included in this retrospective study; 43(87.0%) of these patients exhibited growth hormone(GH) deficiency, and 39(78.3%) had diabetes insipidus. A total of 27(54.0%) patients were diagnosed with NAFLD, while seven patients were cirrhotic. No significant differences were noted in serum GH or insulin-like growth factor 1 among patients with cirrhosis, subjects with NAFLD, and those without NAFLD. However, plasma osmolality and serum sodium concentration of the cirrhotic patients were 314.9 mOsm/kgH2 O and 151.0 mmol/L,respectively, which were significantly higher than those of the NAFLD patients(P = 0.036 and 0.042, respectively). Overweight/obesity and insulin resistance were common metabolic disorders in this population. The body mass index(BMI)and homeostasis model assessment of insulin resistance parameters of the cirrhotic patients were 27.7 kg/m2 and 9.57, respectively, which were significantly higher than those of the patients without NAFLD(P = 0.011 and0.044, respectively). A correlation analysis was performed, and fasting insulin concentration was positively associated with plasma osmolality in patients with NAFLD, after adjusting for gender, age, and BMI(r = 0.540, P = 0.046), but no correlation was noted in patients without NAFLD.CONCLUSION NAFLD is common in patients with hypopituitarism. Plasma osmolality and serum sodium levels of hypopituitary patients with cirrhosis are higher than those of subjects with NAFLD, and fasting insulin concentration is positively associated with plasma osmolality in patients with NAFLD, which suggests that hyperosmolality might be a contributor to the worsening of NAFLD in hypopituitary patients.

EFFECTS OF GLUCAGON ON ISLET β CELL FUNCTION IN PATIENTS WITH DIABETES MELLITUS

Objective To evaluate islet β cell response to intravenous glucagon （ a non-glucose secretagogue） stimulation in diabetes mellitus. Methods Nineteen patients with type 1 diabetes （T1 D） and 131 patients with type 2 diabetes （T2D） were recruited in this study. T2D patients were divided into two groups according to therapy： 36 cases treated with insulin and 95 cases treated with diet or oral therapy. The serum C-peptide levels were determined at fasting and six minutes after intra- venous injection of 1 mg of ghicagon. Results Both fasting and 6-minute post-ghicagon-stimulated C-peptide levels in T1D patients were significantly lower than those of T2D patients （0. 76±0. 36 ng/mL vs. 1.81±0. 78 ng/mL, P 〈 0.05 ; 0.88±0.42 ng/mL vs. 3.68±0. 98 ng/mL, P 〈 0. 05 ）. In T1D patients, the C-peptide level after injection of ghicagon was similar to the fasting level. In T2D, patients treated with diet or oral drug had a significantly greater fasting and stimulated C-peptide level than those patients received insulin therapy （2.45±0. 93 ng/mL vs. 1.61±0. 68 ng/mL, P 〈 0.05 ; 5.26±1.24 ng/mL vs. 2.15±0.76 ng/mL, P 〈 0.05 ）. The serum C-peptide level after ghicagon stimulation was positively correlated with C-peptide levels at fasting in all three groups （ r = 0.76, P 〈 0.05 ）. Conclusions The 6-minute ghicagon test is valuable in assessing the function of islet β cell in patients with diabetes mellitus. It is helpful for diagnosis and treatment of diabetes mellitus.

Heteroplasmy Level of the Mitochondrial tRNA^(Leu(UUR)) A3243G Mutation in a Chinese Family Is Positively Associated with Earlier Age-of-onset and Increasing Severity of Diabetes

Objective To investigate the mutations of mitochondrial genome in a pedigree with suspected maternally inherited diabetes and deafness and to explore the correlations between the mutations and clinical features. Methods Genomic DNA was isolated from blood leucocytes of each member of the pedigree. The mitochondrial genome was amplified with 24-pair primers that could cover the entire mitochondrial DNA. Direct sequencing of PCR products was used to identify any mitochondrial DNA mutations. Results Family members on the maternal side all harbored the tRNA^Lcu（UUR） A3243G mutation. The paternal side family members did not have the mutation. The age-of-onset of diabetes of the 4 maternal side family members was 15, 41, 44, and 65 years old, and their corresponding heteroplasmy level of the mutation was 34.5%, 14.9%, 14.6%, and 5.9%, respectively. The age-of-onset of diabetes and heteroplasmy level of A3243G mutation were negatively correlated with a correlation coefficient of -0.980（P=0.02）. Meanwhile, patient with high heteroplasmy level of A3243G mutation had relatively low severity of disease. Moreover, 6 reported polymorphisms and 2 new variants were found. Conclusions The main cause of diabetes in this pedigree is the tRNA^Lcu（UUR） A3243G mutation. However, other gene variants may contribute to its pathogenicity. The heteroplasmy level of the tRNA^Lcu（UUR） A3243G mutation is positively associated with earlier age-of-onset and increasing severity of diabetes.

MEK AND p38 MAPK-DEPENDANT PATHWAYS ARE INVOLOVED IN THE POSITIVE EFFECT OF INTERLEUKIN-6 ON HUMAN GROWTH HORMONE GENE EXPRESSION IN RAT MtT/S SOMATOTROPH CELLS

Objective To investigate the effect of interleukin-6(IL-6)on the human growth hormone(hGH)gene expression in a rat somatotropic pituitary cell line MtT/S.Methods The plasmids containing various lengths of hGH gene 5'-promoter fragments were constructed.Stably transfected MtT/S cells were created by cotransfecting the above plasmids and pcDNA3.1(+)with DMRIE-C transfection reagent.After the administration of these cells with IL-6 and/or various inhibitors of signaling transduction pathways,the luciferase activities in MtT/S cells lysis were assayed to demonstrate the effects of IL-6 on hGH gene promoter activity and possibly involved mechanism.Results The 103 U/mL IL-6 stimulated GH secretion and synthesis,and promoted the 5'-promoter activity of GH gene in stably transfected MtT/SGL cells with the action of 1.69 times above the control.Among inhibitors of signaling transduction pathways,mitogen-activated protein kinase kinase(MAPKK/MEK)inhibitor PD98059(40 μmol/L)and p38 mitogen-activated protein kinase(MAPK)inhibitor SB203580(5 μmol/L)completely blocked the stimulatory effect of IL-6.Western blot analysis further confirmed the activation of phosphorylated MEK and p38 MAPK in MtT/SGL cells.Neither over-expression of Pit-1 nor inhibition of Pit-1 expression affected IL-6 induction of hGH promoter activity.A series of deletion constructs of hGH promoter were created to identify the DNA sequence that mediated the effect of IL-6.The results showed that the stimulatory effect of IL-6 was abolished following deletion of the-196 to-132 bp fragment.Conclusions IL-6 promotes GH secretion and synthesis by rat MtT/S somatotroph cells.The stimulatory effect of IL-6 on hGH gene promoter appears to require the activation of MEK and p38 MAPK,and a fragment of promoter sequence that spans the-196 to-132 bp of the gene,but may be unlinked with Pit-1 protein.

EFFECT OF INTERLEUKIN-1β ON GROWTH HORMONE GENE EXPRESSION AND ITS POSSIBLE MOLECULAR MECHANISM IN RAT MtT/S SOMATOTROPH CELLS

Objective To elucidate the effect of interleukin-1β （IL- 1β） on human growth hormone （hGH） gene expression in a rat somatotropic pituitary cell line MtT/S. Methods Stably transfected MtT/S cells were firstly established by transfecting 484-Lucl plasmid which contained hGH gene promoter --484 to ＋30 bp and luciferase reporter gene. The effect of IL-1β on hGH gene expression was determined by assaying the luciferase activities. RT-PCR method was also used to determine whether IL-1 recepor mRNA was expressed in MtT/S cells. Results The 10^3 U/mL IL-1β stimulated secretion and synthesis of GH, and promoted the 5＇-promoter activity of GH gene in stably transfected MtT/SGL cells with the action of 1.38 times above the control. Among inhibitors of signaling transduction pathways, mitogen-activated protein kinase kinase （MAPKK/MEK） inhibitor PD98059 （40 μmol/L） and p38 mitogen-activated protein kinase （MAPK） inhibitor SB203580 （5 μmol/L） completely blocked the stimulatory effect of IL-1μ, and phosphatidylinositol-3-kinase （PI3-K） inhibitor LY294002 partly abolished the effect of IL-1μ. Western blot analysis further confirmed the activation of phosphorylated MEK and p38 MAPK in MtT/SGL cells. Neither over-expression of Pit- 1 nor inhibition of Pit- 1 expression affected induction of hGH promoter activity by IL-1μ. A series of deletion constructs of hGH promoter were created to identify the DNA sequence that mediated the effect of IL-1β, and results showed that the stimulatory effect of IL-1β was abolished following deletion of the --196 to -- 132 bp fragment. Conclusions IL-1β promotes GH secretion and synthesis in rat MtT/S somatotroph cells. The stimulatory effect of IL-1β on hGH gene promoter appears to require the activation of MEK, p38 MAPK, PI3-K, and a fragment of promoter sequence that spans the -196 to -132 bp of the gene, but it may be unlinked with Pit-1 protein.

Efficacy and Safety of SGLT2 Inhibitors in Patients with Type 1 Diabetes:A Meta-analysis of Randomized Controlled Trials

Objective To assess the efficiency and safety of a novel sodium-glucose co-transporter 2(SGLT2) inhibitor—SGLT2 inhibitors,in combination with insulin for type 1 diabetes mellitus(T1DM). Methods We searched Medline,Embase,and the Cochrane Collaboration Library to identify the eligible studies published between January 2010 and July 2016 without restriction of language. The Food and Drug Administration(FDA) data and Clinical Trials(http://www.clinicaltrials.gov) were also searched. The included studies met the following criteria:randomized controlled trials; T1DM patients aged between 18 and 65 years old; patients were treated with insulin plus SGLT2 inhibitors for more than 2 weeks; patients' glycosylated hemoglobin(HbA1c) levels were between 7% and 12%. The SGLT2 inhibitors group was treated with SGLT2 inhibitors plus insulin,and the placebo group received placebo plus insulin treatment. The outcomes should include one of the following items:fasting blood glucose,HbA1c,glycosuria,or adverse effects. Data were analyzed by two physicians independently. The risk of bias was evaluated by using the Cochrane Collaboration's Risk of Bias tool and heterogeneity among studies was assessed using Chi-square test. Random effect model was used to analyze the treatment effects with Revman 5.3. Results Three trials including 178 patients were enrolled. As compared to the placebo group,SGLT2 inhibitor absolutely decreased fasting blood glucose [mean differences(MD)-2.47 mmol/L,95% confidence interval(CI)-3.65 to-1.28,P<0.001] and insulin dosage(standardized MD-0.75 U,95%CI-1.17 to-0.33,P<0.001). SGLT2 inhibitors could also increase the excretion of urine glucose(MD 131.09 g/24 h,95%CI 91.79 to 170.39,P<0.001). There were no significant differences in the incidences of hyperglycemia [odds ratio(OR) 1.82,95%CI 0.63 to 5.29,P=0.27],urinary tract infection(OR 0.95,95%CI 0.19 to 4.85,P=0.95),genital tract infection(OR 0.27,95%CI 0.01 to 7.19,P=0.43),and diabetic ketoacidosis(OR 6.03,95%CI 0.27 to 135.99,P=0.26) between the two groups. Conclusion SGLT2 inhibitors combined with insulin might be an efficient and safe treatment modality for T1DM patients.

Bilateral Pheochromocytoma as First Presentation of von Hippel-Lindau Disease in a Chinese Family

Objective To investigate the clinical and genetic features of a Chinese family with yon Hippel- Lindau （VHL） disease revealed by bilateral pheochromocytoma. Methods The proband and other members in a Chinese family with familial pheochromocytoma were clinically evaluated and followed up. Genomic DNA extracted from the peripheral blood of 8 family members （including 3 patients） was amplified by polymerase chain reaction （PCR） and the PCR products were directly sequenced. Results The first presentation in the proband, his mother, and his sister was bilateral pheochromocytoma, and the missense mutation of 695G-A （Arg161Gln） in exon 3 of VHL gene was detected in the three patients. In the follow-up study, the proband and his mother were found to have other VHL tumors, induding retinal and cerebellar hemangioblastomas and pancreatic tumor. Neither clinical presentation of VHL disease nor gene mutation was found in other family members. Conclusion VHL disease should be suspected in some patients with familial pheochromocytoma, and VHL gene screening helps to achieve early diagnosis of the disease.

Professor Liu Shih-hao and the First Case Study of Insulinoma in China

INSULINOMA is the most common cause of hypoglycemia. Although it is a rare disease, there has been a significant progress in its diagnosis along with the technology development. A set of

Analysis of Cardiovascular Risk Factors in Newly Defined Stage 1 Hypertension among Chinese on the Basis of the 2017 ACC/AHA Hypertension Guidelines

In 2017,American College of Cardiology(ACC)/American Heart Association(AHA)et al.jointly released the latest guidelines for adult hypertension,exactly including prevention,diagnosis,assess and treatment,in which blood pressure levels greater than 130/80 mm Hg were defined as hypertension[1].Based on these modified guidelines,the morbidity of hypertension in US increased from 32%to 46%.

Atypical skeletal manifestations of rickets in a familial hypocalciuric hypercalcemia patient

Familial hypocalciuric hypercalcemia （FHH） is caused by inactivating mutations in the calcium-sensing receptor （CaSR） gene. The loss of function of CaSR presents with rickets as the predominant skeletal abnormality in mice, but is rarely reported in humans. Here we report a case of a 16-year-old boy with FHH who presented with skeletal manifestations of rickets. To identify the possible pathogenic mutation, the patient was evaluated clinically, biochemically, and radiographicaUy. The patient and his family members were screened for genetic mutations. Physical examination revealed a pigeon breast deformity and X-ray examinations showed epiphyseal broadening, both of which indicate rickets. Biochemical tests also showed increased parathyroid hormone （PTH）, 1,25-dihydroxyvitamin D, and elevated ionized calcium. Based on these results, a diagnosis of FHH was suspected. Sequence analysis of the patient＇s CaSR gene revealed a new missense mutation （c.2279T 〉 A） in exon 7, leading to the damaging amino change （p.I760N） in the mature CaSR protein, confirming the diagnosis of ~H. Moreover, the skeletal abnormities may be related to but not limited to vitamin D abnormity. Elevated ~H levels and a rapid skeletal growth period in adolescence may have also contributed. Our study revealed that rickets-like features have a tendency to present atypically in FHH patients who have a mild vitamin D deficiency, and that CaSR mutations may have a partial role in the pathogenesis of skeletal deformities.

Physical Activity,Sedentary Behavior,and the Risk of Cardiovascular Disease in Type 2 Diabetes Mellitus Patients:The MIDiab Study

The aim of this study was to explore the associations of moderate-to-vigorous-intensity physical activity(MVPA)time and sedentary(SED)time with a history of cardiovascular disease(CVD)and multifactorial(i.e.,blood pressure(BP),body mass index(BMI),low-density lipoprotein cholesterol(LDL-C),and glycated hemoglobin A1c(HbA1c))control status among type 2 diabetes mellitus(T2DM)patients in China.A cross-sectional analysis of 9152 people with type 2 diabetes from the Multifactorial Intervention on Type 2 Diabetes(MIDiab)study was performed.Patients were grouped according to their self-reported MVPA time(low,<150 min·week−1;moderate,150 to<450 min·week−1;high,≥450 min·week−1)and SED time(low,<4 h·d–1;moderate,4 to<8 h·d–1;high,≥8 h·d–1).Participants who self-reported a history of CVD were identified as having a CVD risk.Odds ratios(ORs)and 95%confidence intervals(CIs)of CVD risk and multifactorial control status associated with MVPA time and SED time were estimated using mixed-effect logistic regression models,adjusting for China’s geographical region characteristics.The participants had a mean±standard deviation(SD)age of(60.87±8.44)years,44.5%were women,and 25.1%had CVD.After adjustment for potential confounding factors,an inverse association between high MVPA time and CVD risk that was independent of SED time was found,whereas this association was not observed in the moderate-MVPA group.A higher MVPA time was more likely to have a positive effect on the control of BMI.Compared with the reference group(i.e.,those with MVPA time≥450 min·week−1 and SED time<4 h·d–1),CVD risk was higher in the low-MVPA group:The OR associated with an SED time<4 h·d–1 was 1.270(95%CI,1.040–1.553)and that associated with an SED time≥8 h·d–1 was 1.499(95%CI,1.149–1.955).We found that a high MVPA time(i.e.,≥450 min·week−1)was associated with lower odds of CVD risk regardless of SED time among patients with T2DM.

Clinical Characteristics of 261 Cases of Hospitalized Patients with Type 1 Diabetes Mellitus

Objective To retrospectively analyze the clinical characteristics of 261 cases of hospitalized patients with type 1 diabetes mellitus(T1DM) in Peking Union Medical College Hospital(PUMCH). Methods Clinical data of 261 cases of hospitalized patients diagnosed with T1DM in the Department of Endocrinology at PUMCH from January 2007 to December 2014 were analyzed retrospectively. All patients were divided into the T1DM antibodies positive group(n=180) and negative group(n=81) according to the results of immunohistochemistry, in which 123 newly diagnosed T1DM patients were divided into the adult onset group(>18 years, n=58) and non-adult onset group(≤18 years, n=65) according to the onset age of T1DM, respectively. The clinical characteristics from different groups were compared. Results In 261 patients, the average age was 26.6±15.4 years, the average disease duration was 49(1-480) months, the positive rate of antibodies to glutamic acid decarboxylase antibody was 58.8%(153/260). The level of 2-hour postprandial C peptide and the positive rate of T1DM antibodies in the non-adult onset group were higher than those in the adult onset group(0.98 vs. 0.52 ng/ml, P=0.002 and 80.4% vs. 62.5%, P=0.048). The age of onset in the T1DM antibodies positive group was smaller than that in the T1DM antibodies negative group(19.7±11.4 vs. 24.7±15.6 years, P=0.04), while the incidence of ketosis in the T1DM antibodies positive group was higher than that in the T1DM antibodies negative group(48.3% vs. 34.2%, P=0.035). With the progress of the disease, the fasting C peptide level of the T1DM antibodies positive group decreased more rapidly. Compared with the single time hospitalized patients, multiplehospitalized patients had a lower incidence of diabetic retinopathy(8.2% vs. 22.4%, P=0.032), a lower hemoglobin A1 c level(8.04%±2.10% vs. 9.56%±2.64%, P<0.001) and fasting blood glucose level(8.7±3.1 vs. 10.9±4.2 mmol/L, P<0.001). Conclusions Compared with the non-adult onset T1DM patients, the islet function of adult onset patients was even worse. In the T1DM antibodies positive patients, the islet β cell function decreased more rapidly, so the antibodies could not only clarify the diagnosis of T1DM and also predict prognosis of the islet β cell function. In the management of T1DM patients, regular hospital revisits contributed to get better glycemic control and reduced the occurrence of diabetic complications.

A Small Solitary Pulmonary Nodule Discovered by ^(18)F-fluorodeoxyglucose Positron Emission Tomography and CT: Rare Infection Instead of Rare Tumor

THE causes of Cushing＇s syndrome are mainly di- vided into adrenocorticotropic hormone （ACTH） dependent and independent. ACTH dependent hypercortisolism represents excess ACTH se-creting by the pituitary or tumor outside the pituitary; and the latter one is also called as ectopic ACTH syndrome. Thorax is the most common location of causative lesions for ectopic ACTH syndrome, and the size of lesion is too small to be detected in some cases.1＇ 2 Cryptococcal pneumonia usually occurs in immunocompromised patients and excess cortisol production can theoretically produce a state of immunodeficiency. Development of cryptococcal pneumonia concomitant with Cushing syndrome （CS） was rare. Here, we report a case of pulmonary nodule in a patient with CS differentiated with ectopic ACTH-producing tumor. Crypto- coccal pneumonia was diagnosed followinglung resection.

Surgical management of pituitary adenoma during pregnancy

BACKGROUND Although conservative treatment is typically recommended for pregnant patients with pituitary adenoma(PA),surgical treatment is occasionally necessary for those with acute symptoms.Currently,surgical interventions utilized among these patients is poorly studied.AIM To evaluate the surgical indications,timing,perioperative precautions and postoperative complications of PAs during pregnancy and to provide comprehensive guidance.METHODS Six patients with PAs who underwent surgical treatment during pregnancy at Peking Union Medical College Hospital between January 1990 and June 2021 were recruited for this study.Another 35 pregnant patients who were profiled in the literature were included in our analysis.RESULTS The 41 enrolled patients had acute symptoms including visual field defects,severe headaches or vision loss that required emergency pituitary surgeries.PA apoplexies were found in 23 patients.The majority of patients(55.9%)underwent surgery in the second trimester of pregnancy.A multidisciplinary team was involved in patient care from the preoperative period through the postpartum period.With the exception of 1 patient who underwent an induced abortion and 1 fetus that died due to a nuchal cord,39 patients delivered successfully.Among them,37 fetuses were healthy until the most recent follow-up.CONCLUSION PA surgery during pregnancy is effective and safe during the second and third trimesters.Pregnant patients requiring emergency PA surgery require multidisciplinary evaluation and healthcare management.

FGF23 and Phosphate Wasting Disorders

A decade ago, only two hormones, parathyroid hormone and 1,25（OH）2D, were widely recognized to direct-ly affect phosphate homeostasis. Since the discovery of fibroblast growth factor 23 （FGF23） in 2000 （1）, our understanding of the mechanisms of phosphate homeostasis and of bone mineralization has grown exponentially. FGF23 is the link between intestine, bone, and kidney together in phosphate regulation. However, we still do not know the complex mechanism of phosphate homeostasis and bone mineralization. The physiological role of FGF23 is to regulate serum phosphate. Secreted mainly by osteocytes and osteo- blasts in the skeleton （2-3）, it modulates kidney handling of phosphate reabsorption and calcitriol produc-tion. Genetic and acquired abnormalities in FGF23 structure and metabolism cause conditions of either hyper-FGF23 or hypo-FGF23. Hyper-FGF23 is related to hypophosphatemia, while hypo-FGF23 is related to hyperphosphatemia. Both hyper-FGF23 and hypo-FGF23 are detrimentalto humans. In this review, we will discuss the vathovhvsiology of FGF23 and hvver-FGF23 related renal vhosvhate wasting disorders （4）.

Fatty Acid Synthase and Hormone-sensitive Lipase Expression in Liver Are Involved in Zinc-α2-glycoprotein-induced Body Fat Loss in Obese Mice

Objective To explore the effects of zinc-0t2-glycoprotein （ZAG） on body weight and body fat in high-fat-diet （HF1））-induced obesity in mice and the possible mechanism. Methods Thirty-six male mice were fed with standard food （SF） （n=9） and HFD （n=27）, respectively. Five weeks later, 9 mice fed with HFD were subjected to ZAG expression plasmid DNA transfection by liposome transfection method, and another 9 mice to negative control plasmid transfection. Two weeks later, serum ZAG level in the mice was assayed by Western blot, and the effects of ZAG over-expression on body weight, body fat, serum biochemical indexes, and adipose tissue of obese mice were evaluated. The mRNA expressions of fatty acid synthase （FAS） and hormone sensitive lipase （HSL） in liver tissue were deterlnined by reverse transcription-polymerase chain reaction. Results Serum ZAG level significantly lowered in simple HFD-fed mice in comparison to SF-fed mice （0.51±0.10 AU vs. 0.75±0.07 AU, P〈0.01）. Further statistical analysis demonstrated that ZAG level was negatively correlated with body weight （r =-0.56, P〈0.001）, epididymal fat mass （r=-0.67, P〈O. 001）, percentage of epididymal fat （r= 0.65, P〈0.001）, and increased weight （r= 0.57, P〈0.001） in simple SF- and HFD fed mice. ZAG over-expression in obese mice reduced body weight and the percentage of epididyreal fat. Furthermore, FAS mRNA expression decreased （P〈0.01） and HSL mRNA expression increased （P〈0.001） in the liver in ZAG over-expressing mice. Conclusions ZAG is closely related to obesity. Serum ZAG level is inversely correlated with body weight and percentage of body fat. The action of ZAG is associated with reduced FAS expression and increased HSL expression in the liver of obese mice.

Secreted Frizzled-Related Protein 5 (SFRP5) in Patients with Obstructive Sleep Apnea

Objective Obstructive sleep apnea (OSA) is closely related to obesity, insulin resistance and inflammation. Secreted frizzled-related protein 5 (SFRP5) is a recently discovered adipokine. It is involved in insulin resistance and inflammation in obesity. This study aimed at evaluating the association between SFRP5and sleeping characteristics as well as biochemical parameters of OSA patients.Methods This was a prospective case control study. Nondiabetic OSA patients and controls were consecutively recruited and divided into three groups: OSA group, apnea–hypopnea Index (AHI)≥5/h; healthy controls with normal body mass index (BMI); obese controls without OSA, and BMI > 24.0 kg/m2. All participants underwent polysomnography (PSG). Plasma SFRP5 was examined using enzyme-linked immunosorbent assay (ELISA). Blood biochemical examinations, including fasting blood glucose (FBG), lipid profile, hypersensitive Creactive protein (hsCRP), were performed early in the morning after PSG. Patients with severe OSA were treated with nasal continuous positive airway pressure (nCPAP), and plasma SFRP5 was repeatedly measured for comparison.Results Sixty-eight subjects were enrolled in the study, including 38 patients of OSA, whose medium AHI was 58.70 /h (36.63, 71.15), 20 obese controls, and 10 healthy controls. The plasma SFRP5 level of OSA patients was not significantly different from that of healthy controls or obese controls. In OSA patients, SFRP5 level correlated positively with triglyceride level (r=0.447, P=0.005) and negatively with LDL-cholesterol level and HDLcholesterol level (r=?0.472 and P=0.003; r=?0.478 and P=0.002; respectively). SFRP5 level was not found correlating with FBG, AHI, or any of nocturnal hypoxia parameters. After overnight nCPAP treatment, plasma SFRP5 levels of OSA patients did not change significantly (t=1.557, P = 0.148) compared to that of pretreatment.Conclusions In nondiabetic OSA patients, plasma SFRP5 is associated with the lipid profile. However,no correlation was observed between SFRP5 and FBG or sleep parameters. The SFRP5 level of OSA patients did not differ from that of non-OSA individuals in our study.