[Clinical analysis of 10 patients with Fabry disease].

We aimed to analyze the clinical data of 10 patients (6 male and 4 female) with Fabry disease (FD). The mean age of the patients was (28.80±9.27) years. Seven patients had classical FD and three had delayed onset FD. Among the 10 patients, six had skin involvement and cutaneous angiokeratoma; five had hypohidrosis or anhidrosis; nine had intermittent neuralgia; and three had supraorbital ridge protrusion, forehead bulge, and lip thickening. Five patients had proteinuria, including one with chronic kidney disease stage 3 and one with chronic kidney disease stage 5. Cardiac involvement occurred in three patients, two had myocardial hypertrophy and one had valvular insufficiency. The activity of galactosidase decreased in seven patients (2.80-1.55 µmol·L-1·h-1). Plasma deacetyl-GL-3 was elevated in all 10 patients(3.12-120.00 ng/ml). Three patients underwent renal biopsy, wherein two cases of focal segmental glomerulosclerosis and one of mesangial proliferative glomerulonephritis was found. A large number of myeloid and zebra bodies were found in the podocytes in three patients, including a small number of myeloid and zebra bodies in the renal tubular epithelial cells in one patient with occasional zebra bodies in the renal interstitium. Nine patients had GLA gene mutations. One patient was c.102T>A, a de novo mutation. Four patients were treated with agalsidase α injection (0.2 mg/kg, intravenous infusion every 2 weeks), and their prognosis was good. FD has various clinical manifestations and multi-system involvement, which requires multidisciplinary cooperation. Detection of galactosidase activity, plasma globotriaosylsphingosine, and GLA gene mutation can help for accurate diagnosis.

[Efficacy and outcomes of shunt surgery for secondary hydrocephalus].

Records of secondary hydrocephalus patients undergoing shunt surgery in the Department of Neurosurgery of Peking Union Medical College Hospital from September 2012 to April 2022 and their clinical characteristics and outcomes were retrospectively reviewed and analyzed. Among 121 patients who received first time shunt placement, the most common causes of secondary hydrocephalus were brain hemorrhage (55, 45.5%) and trauma (35, 28.9%). Cognition decline (106, 87.6%), abnormal gait (50, 41.3%) and incontinence (40, 33.1%) were the most prevalent manifestations. Postoperative central nervous system infection (4, 3.3%), shunt obstruction (3, 2.5%) and subdural hematoma/effusion (4, 3.3%) were the most frequent neurological complications. Overall incidence of postoperative complications was 9% (11 cases) in the current cohort. And 50.5% (54/107) of the patients receiving shunting achieved a Glasgow outcome scale (GOS) score of at least 4. Shunt surgery is preferred for secondary hydrocephalus, especially for secondary normal pressure hydrocephalus. Moreover, it is recommended to complete cranioplasty in staged operation or one-stage operation for the patients with decompressive craniectomy.

[Clinical characteristics of 6 children with idiopathic interstitial pneumonia].

Objective: To analyze the clinical characteristics and prognosis of 6 children with idiopathic interstitial pneumonia (IIP). Methods: This retrospective study analyzed the clinical manifestations, examinations, treatment and prognosis of 6 children with IIP who were hospitalized in Children's Hospital of Nanjing Medical University from January 2015 to March 2020. Results: Of the 6 children, 2 were males and 4 were females, aged 4.8 to10.6 years. All children had a subacute onset, and presented with cough, shortness of breath and cyanosis. The lung high-resolution CT (HRCT) showed diffuse patchiness in bilateral lung fields in all the children and reticular pattern in 2 cases. Pulmonary function test found moderate to severe mixed defect in 5 children. Lung biopsy was performed in 4 children. All of the 6 children were treated with systemic glucocorticoids, of whom 2 cases had additional inhaled glucocorticoids. Four children were finally diagnosed as cryptogenic organizing pneumonia (COP), whose lung HRCT return to normal in 1-11 months. Two children were finally diagnosed as nonspecific interstitial pneumonia (NSIP), and had long-term residual fibrosis on lung HRCT. The 6 children were followed up for 1 year to 6 years and 5 months after discontinuation of systemic glucocorticoids, and all had no recurrence. Conclusions: The clinical characteristics of IIP in children are subacute onset presented with cough, shortness of breath, cyanosis and diffuse patchiness in bilateral lungs on HRCT. The common subtypes of IIP in children are COP and NSIP. Systemic glucocorticoid is effective for IIP in children and there is a good prognosis overall.

[The necessity and importance of standardized management of acromegaly: from the perspective of development of expert consensuses and clinical guidelines].

Acromegaly is a rare disease, and multidisciplinary collaboration is essential for its diagnosis, treatment, and follow-up.In recent years, a series of novel findings have been echieved in clinical studies on acromegaly.Therefore, the China Pituitary Adenoma Specialist council has convened Chinese specialists in neurosurgery, endocrinology, radiology, and radiotherapy to release the Chinese Consensus for the Diagnosis and Treatment of Acromegaly (2021), which aims to promote the standardized and individualized management of acromegaly.Looking back to the past, the consensuses and guidelines have played vital roles in establishing the widely recognized biochemical remission criteria, promoting new drugs and novel therapeutic strategies which are of significance for standardized treatment, and emphasizing the need to focus on the systemic complications of acromegaly and the long-term quality of life. In this editorial, we briefly reviewed the expert consensuses and clinical guidelines on acromegaly at home and abroad, and discussed their important roles in promoting standardized disease management from three aspects including biochemical remission standards, medical treatment, and the diagnosis and treatment of systemic complications.

[Updated key points of Chinese Consensus for the Diagnosis and Treatment of Acromegaly (2021 edition)].

Led by the China Pituitary Adenoma Specialist Council, the Chinese Consensus for the Diagnosis and Treatment of Acromegaly (2021 Edition) is developed combined with the research progress of pituitary growth hormone (GH)-secreting adenoma both at home and abroad, evidence-based evidence of the diagnosis and treatment of acromegaly, and China's national conditions. Based on the guideline for acromegaly (2013 Edition), the new version of consensus emphasizes the importance of multidisciplinary team (MDT) and individual therapy. The criteria for control of acromegaly is discussed. Pathological criteria for the diagnosis of pituitary GH-secreting adenoma is updated. New developments in surgery, drug and radiotherapy are introduced. Meanwhile, the diagnosis and treatment of acromegaly patients concurrent with other particular scenarios, including pregnancy and refractory pituitary GH-secreting adenoma is suggested. This article aims to describe the updated key points of the new version of the consensus, and thus facilitate the clinical implementation of standardized diagnosis and treatment for acromegaly patients.

[Performance of Knosp grade for cavernous sinus invasion of Cushing's disease].

Objective: To review the outcomes in patients with Cushing's disease (CD) after transsphenoidal surgery (TSS) and to assess the performance of Knosp grade for cavernous sinus invasion (CSI). Methods: Medical records were reviewed for patients with CD undergoing TSS from 1978 to 2017 at Peking Union Medical College Hospital. Based on whether CSI was observed during surgery, the sensitivity and specificity of Knosp grade for CSI were evaluated. Results: There were 1 061 records of CD reviewed, 83 (7.82%) of which were invasive tumors evaluated by surgery, and 44 (53.0%) of these remained in endocrinological remission at the last follow-up. The sensitivity of Knosp grade for CSI was 47.0%, and the specificity was 91.1%; besides, the positive predictive value was 31.0%, and the negative predictive value was 95.3%. Conclusions: Initial TSS for CD with invasive adenomas is of relatively low remission rate. Knosp grade 0-2 for non-invasive tumors is reliable, while it is doubtful whether or not Knosp grade 3-4 indicates invasive tumor.

Research on mechanism of PCS in damaging vascular endothelial cells and promoting formation of atherosclerosis via TLR4/TREM-1.

OBJECTIVE: The study aimed to explore the effects of p-cresyl sulfate (PCS) of damaging vascular endothelial cells and promoting the formation of atherosclerosis in mice. MATERIALS AND METHODS: The apolipoprotein E (ApoE)-/- mice were fed normally and with a high-fat diet; the ApoE-/- mice fed with high-fat diet were divided into two groups and treated with blank control and PCS, respectively. The aortic arch in each group was taken and underwent the oil red O staining, and the serum PCS content in each group was detected. The basic components of plaque were observed, including foam cells, lipid deposition, and cholesterol crystal. Moreover, human umbilical vein endothelial cells were cultured and divided into control group, PCS treatment group (PCS), PCS treatment with TLR4 overexpression group (PCS+TLR4+), and PCS treatment with TLR4 knock-out group (PCS+TLR4-). The degree of endothelial cell damage was detected using a cluster of differentiation CD42b-/CD31+ endothelial microparticles (EMPs), and expressions of Toll-like receptor 4 (TLR4), triggering receptor expressed on myeloid cells-1 (TREM-1), phosphorylated-endothelial nitric oxide synthase (p-eNOS), and tumor necrosis factor-α (TNF-α) in cells were detected via Polymerase Chain Reaction (PCR) and Western blotting. RESULTS: The serum PCS concentration in high-fat ApoE-/- mice was increased, and the aortic arch sections of ApoE-/- mice treated with PCS displayed the evident atherosclerotic plaques. Experimental results of human umbilical vein endothelial cells showed that the activity of human umbilical vein endothelial cells treated with PCS declined, the expression levels of TLR4, TREM-1, and TNF-α were increased, while that of p-eNOS was decreased. After the TLR4 knockout, the above effects of PCS were reversed. CONCLUSIONS: PCS damages vascular endothelial cells through TRL4/TREM-1, thereby accelerating the formation of atherosclerosis.

[The localization diagnosis of patients with adrenocorticotropic hormone-dependent Cushing's syndrome in adolescence].

Objective: To elucidate the clinical characteristics and localization diagnosis of patients with adrenocorticotropic hormone (ACTH)-dependent Cushing's syndrome (CS) in adolescence. Methods: The clinical data, laboratory examination and localization diagnosis from 35 patients aged less than 18 years old with adolescent CS who were treated at Peking Union Medical College Hospital between January 1990 and March 2012 were analyzed. Results: There were 29 cases of Cushing's disease (CD) and 6 cases of ectopic ACTH syndrome (EAS). Compared to patients with EAS, those with CD were older at diagnosis[(15.2±2.7) vs (12.8±4.4) years], and had longer disease course[(1.9±1.5) vs (0.7±0.3) years]and higher serum potassium[(3.8±0.6) vs (2.5±0.7) mmol/L], however the plasma ACTH level[(15.4±14.9) vs (42.5±22.7) pmol/L]was lower (all P<0.05). If the cut-off of the ratio of 24-hour urine free cortisol (24 h UFC) after low-dose dexamethasone suppression test (LDDST) to before LDDST was 0.65, the sensibility to diagnose CD was 70.8%, and the specificity was 100%. If the cut-off of the 24 h UFC ratio after high-dose dexamethasone suppression test (HDDST) to before HDDST was 0.54, the sensibility to diagnose CD was 91.7%, and the specificity was 100%. If the cut-off of the plasma ACTH ratio of inferior petrosal vein[bilateral inferior petrosal sinus sampling (BIPSS)]to peripheral vein was 2, only 6 CD patients (6/8) met it. Conclusion: The study suggested that HDDST was more meaningful in the localization diagnosis of patients with ACTH-dependent CS in adolescence.

[The diagnosis and treatment of systemic lupus erythematosus complicated with hydrocephalus].

Objective: To investigate the pathogenesis and management of the hydrocephalus in patients with systemic lupus erythematosus (SLE). Methods: Eight cases of hospitalized lupus patients with hydrocephalus in Peking Union Medical College Hospital from Jan 1990 to Mar 2017 were analyzed retrospectively.We collected the patients' medical records including medical history, CT and/or MRI images and analysis of cerebrospinal fluid via lumbar puncture in order to investigate the pathogenesis of the hydrocephalus in patients with SLE and summarize treatment experience. Results: All the 8 patients with SLE complicated with hydrocephalus were treated with steroids or immunosuppressive agents, and 5 cases were diagnosed with the central nervous system infection. Three cases received ventriculoperitoneal shunt, 5 cases received treatment of medicine.They all were followed up for 2-12 months, of which 3 cases were markedly effective, 1 case effective and 4 cases dead. Conclusion: The pathogenesis of lupus combined with hydrocephalus may have a certain relationship with the central infection, should take effective anti-infection treatment.We recommend cerebrospinal fluid shunt surgery intervention.

[Cost-effectiveness analysis of octreotide long acting release and lanreotide slow release for the treatment of postoperative patients with active acromegaly in China].

Objective: To evaluate the cost-effectiveness of octreotide long acting release (LAR) vs lanreotide slow release (SR) for the treatment of postoperative acromegalic patients with elevated levels of growth hormone (GH) and insulin-like growth factor 1 (IGF-1) in China. Methods: A decision tree model was constructed and the treatment impact was projected for one year in Chinese setting. The clinical efficacy measure used was the percentage of patients achieving normalization (control) of either IGF-1 or GH levels. Efficacy of octreotide LAR and lanreotide SR, incidence of comorbidities, impact of acromegaly on health-related quality of life, and drug-related side effects data were obtained from literature. The cost of medication was collected through a chart review from five hospitals in five cities of China. Clinical experts from these hospitals were requested to complete a questionnaire to document the utilization of medical resources, costs of comorbidities, side effects as well as cost of administration. One-way sensitivity analysis was performed to evaluate the robustness of the results. Results: Compared to lanreotied SR group, the percentage of patients achieving normalization of IGF-1 and GH levels of octreotide LAR group were 10% and 9% higher, respectively. When either IGF-1 or GH control were used as the efficacy measure, patients in the octreotide LAR group exhibit less comorbidities and need less continued treatment with a second operation and radiotherapy than those in lanreotide SR group. When IGF-1 was used as efficacy measure, octreotide LAR not only achieved better efficacy but resulted in overall cost-saving, with a total cost savings of ï¿¥ 3 792 per patient for one year, which demonstrated that octreotide LAR was a dominant cost-saving strategy. When GH control was used as the efficacy measure, octreotide LAR achieved a better overall clinical efficacy with a slightly higher total costs (ï¿¥ 4 121 higher per patient per year). Sensitivity analysis didn't change the conclusion that octreotide LAR remains dominant over lanreotide SR, indicating the robustness of this model. Conclusion: Octreotide LAR achieved better overall biochemical control compared with lanreotide SR which result in less comorbidity rate, second operation and radiotherapy as well as related costs.

Analysis of bromocriptine treatment in pregnant pituitary prolactinoma patients.

OBJECTIVE: To investigate the therapeutic effects and duration of bromocriptine treatment during pregnancy in patients with pituitary prolactinoma. MATERIALS AND METHODS: A retrospective analysis of the clinical data of 230 female pituitary prolactinoma patients at the Beijing Union Medical College Hospital neurosurgery clinic from January 2001 to May 2014 was conducted. When confirmed pregnant, patients in the control group immediately stopped taking bromocriptine, but patients in the treatment group continued to take the same dose of bromocriptine. RESULTS: The embryos stop rate in the control group was 16.7%, significantly higher than the rate in the natural population (p < 0.05), while the rate in the treatment group (0.9%) not statistically different from that of the natural population (p > 0.05). There was no significant difference in the embryonic malformation rate between the two study groups compared to the normal pregnancy group (p > 0.05). CONCLUSION: Pregnant pituitary prolactinoma patients should not stop bromocriptine treatment, but should instead continue with the same dose for four months. For patients with macroadenoma, bromocriptine should be taken during the entire pregnancy. Blood prolactin, progesterone, human chorionic gonadotropin (hCG), and visual dysfunction should be monitored every two weeks during treatment. Patients should be treated with progesterone and hCG if the blood levels become too low. If regular monitoring shows that prolactin has increased too fast and/or visual dysfunction worsened, the dose of bromocriptine should be in- creased. The authors have found that bromocriptine treatment during pregnancy significantly reduces the embryo stop rate without in- creasing the embryo deformity rate; therefore, bromocriptine treatment is safe and necessary during pregnancy of pituitary prolactinoma patients.

[Surgical treatment of pituitary adenomas in childhood and adolescence].

Objective: To investigate the clinical characteristics and treatment of pituitary adenomas of childhood and adolescence. Methods: Thisarticle was a retrospective study of 140 pituitary adenomas of childhood and adolescence that was admitted into Peking Union Medical College Hospital from December 1987 to December 2014, whose clinical manifestations, hormone secretions, images, pathological types, surgical complications and follow-ups were studied. Results: A total of 58 (41.4%) males and 82 females (58.6%) were included, whose mean age was 12.5 years old (age range from 7 to 18). As for the type of tumors, ACTH adenoma, PRL adenoma, GH adenoma, non-functional adenoma and multiple-secreting adenoma accounted for 35.7%, 25.7%, 12.2%, 25.7% and 0.7%, respectively. Microadenoma accounted for 33.6% of total patients, while macroadenoma and giant adenoma accounted for 60.0% and 6.4% respectively. 19.3% of adenomas in our study wereinvasive. Transsphenoidal approach surgery was commonly used and accounted for 97.9% of cases in our study, 2 of which used intraoperative navigation assistance. Total resection was achieved in 93.6% of patients, and the rest achieved subtotal resection. 108 (77.1%) patients got full term follow-up until 1 year after surgery, and tumor recurred in 14 patients (13.0%). Conclusions: ACTH-secreting adenoma is the most common pituitary adenoma in childhood and adolescence which need surgical treatment. Transsphenoidal approach surgery is the most commonly used surgical procedure. The recurrence rate is about 13%, and the patients need regular examination of pituitary hormones and image study to confirm the recurrence.

[Effect of Notch1, 2, 3 genes silencing on Notch and nuclear factor-κB signaling pathway of macrophages derived from patients with coronary artery disease].

Objective: To investigate the effects of Notch1, 2, 3 genes silencing by siRNA on Notch signaling pathway (Delta-like 4(DLL4), Jagged 1(JAG1)) and nuclear factor-κB (NF-κB) signaling pathway (IκBα, P52) of macrophages derived from patients with coronary artery disease (CAD), thus to explore the potential genetic treatment perspectives for CAD. Methods: Peripheral blood mononuclear cells of CAD patients were isolated by density gradient centrifugation and transformed by phorbol-12-myristate-13-acetate (PMA) to macrophages. Macrophages were then transfected with Notch1-small interference RNA (siRNA, Notch1-siRNA group), Notch2-siRNA (Notch2-siRNA group), Notch3-siRNA (Notch3-siRNA group), negative control siRNA (NC group) and none siRNA (control group) respectively. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis were applied to assess the mRNA and protein expression levels of DLL4, JAG1, IκBα and p52, respectively. Electrophoretic mobility shift assay (EMSA) was used to observe the NF-κB DNA binding activity. Subcellular distributions of NF-κB/p52 were detected through immunofluorescence. Results: (1) The mRNA and protein expressions of DLL4, JAG1 and p52 in Notch1-siRNA group, Notch2-siRNA group and Notch3-siRNA group were significantly downregulated, while the mRNA and protein expression of IκBα was significantly upregulated compared with NC group and control group(P<0.05 or 0.01). The mRNA and protein expressions of DLL4, JAG1 and p52 in Notch1-siRNA group were significantly downregulated, while the mRNA and protein expression of IκBα was significantly upregulated compared with Notch2-siRNA group and Notch3-siRNA group(P<0.05 or 0.01). The mRNA and protein expressions of DLL4, JAG1, IκBα and p52 were similar between NC group and control group (all P>0.05). (2) The binding activity of NF-κB DNA was significantly lower in Notch1-siRNA group (613±57), Notch2-siRNA group (1 169±85) and Notch3-siRNA group (1 454±90) compared with control group (2 643±115) and NC group (2 407±100) (all P<0.01), which was also significantly lower in Notch1-siRNA group compared to Notch2-siRNA group and Notch3-siRNA group (P<0.01); was significantly lower in Notch2-siRNA group compared with Notch3-siRNA group (P<0.01) and was similar between control group and NC group (P>0.05). (3) The fluorescence intensity of NF-κB/p52 was significantly lower both in the nucleus and cytoplasm in Notch1-siRNA group, Notch2-siRNA group and Notch3-siRNA group compared with NC group and control group (all P<0.01), and the decrease was more obviously in the nucleus than in cytoplasm in Notch1-siRNA group, Notch2-siRNA group and Notch3-siRNA group (P<0.05 or 0.01). The fluorescence intensity of NF-κB/p52 was similar between control group and NC group (P>0.05). Conclusion: There is a positive regulation between Notch and NF-κB pathway in macrophages derived from CAD patients, the regulation power on NF-κB signaling pathway of Notch1 is stronger than that of Notch2 and Notch 3.

[Use early morning serum cortisollevel to evaluate the effect of Cushing's disease after transsphenoidal surgery].

OBJECTIVE: To predict the therapeutic effect of Cushing's disease after transsphenoidal surgery by using morning serum cortisol level. METHODS: The clinical data of 275 cases that had transsphenoidal surgery in Peking Union Medical College Hospital from 2010 to 2014 were analyzed retrospectively.Early morning serum cortisol level less than 140 nmol/L 3 days postoperation was usedto predict endocrinological remission. And long-term efficacy was evaluated by follow-up. RESULTS: Of the 275 patients, there were 49 males and 226 females; average age was 36.5 years old.Remission wasconfirmed in 201 cases, the remission rate was 73.1%, and 8 cases recurrent duringfollow-up.There were 17 macroadenomas, theremission rate was 47.1%; 258 microadenomas and MRI negative adenomas, the remission rate was 74.8%.And 43 recurrent cases had reoperations; the remission rate was 46.5%. CONCLUSION: Early morningserum cortisol 3 days post operation can evaluate the effectof transsphenoidal surgery, but even if the level of cortisol is less than 140 nmol/L, there is still tumor recurrence.Patients should be follow-up for a lifetime.