[Persistent and serious hyperkalemia after surgery of primary aldosteronism: A case report].

Hyperkalemia was one of the complications after primary aldosteronism surgery. Hyperkalemia after primary aldosteronism surgery was uncommon in clinical practice, especially persistent and serious hyperkalemia was rare. This complication was not attached great importance in clinical work. A case about persistent and serious hyperkalemia after primary aldosteronism adrenal adenoma surgery was reported and the patient was followed-up for fourteen months in this study. This patient had a laparoscopic adrenalectomy due to primary aldosteronism. Hyperkalemia was detected one month after surgery of this patient, the highest level of plasma potassium was 7.0 mmol/L. The patient felt skin itchy, nausea, palpitation. Plasma aldosterone concentration fell to 2.12 ng/dL post-operation from 35.69 ng/dL pre-operation, zona glomerulosa insufficiency was confirmed by hormonal tests in this patient after surgery. And levels of 24 hours urinary potassium excretion declined. Decrease of aldosterone levels after surgery might be the cause of hyperkalemia. Hyperkalemia lasted for 14 months after surgery and kalemia-lowering drugs were needed. A systemic search with "primary aldosteronism", "hyperkalemia", "surgical treatment" was performed in PubMed and Wanfang Database for articles published between January 2009 and December 2019. Literature review indicated that the incidence of hyperkalemia after primary aldosteronism surgery was 6% to 29%. Most of them was mild to moderator hyperkalemia (plasma potassium 5.5 to 6.0 mmol/L) and transient. 19% to 33% in hyperkalemia patients was persistent hyperkalemia. Previous studies in the levels of plasma potassium reached the level as high as 7 mmol/L in our case were rare. Whether hypoaldosteronemia was the cause of hyperkalemia was not consistent in the published studies. Risk factors of hyperkalemia after primary aldosteronism surgery included kidney dysfunction, old age, long duration of hypertention. This paper aimed to improve doctors' aweareness of hyperkalemia complication after primary aldosteronism surgery. Plasma potassium should be monitored closely after primary aldosteronism surgery, especially in the patients with risk factors. Some patients could have persistent and serious hyperkalemia, and need medicine treatment.

[Clinical value of captopril test in noninvasive diagnosis of aldosterone-producing adenoma].

OBJECTIVE: To analyze the clinical characteristics of aldosterone-producing adenoma (APA) subtypes in primary aldosteronism (PA) and the application value of captopril challenge test (CCT) in adenomas. And to find out the clinically specific non-invasive index for identifying APA subtypes from PA. METHODS: The clinical data of hospitalized patients with hypertension were retrospectively collected. All the patients were conducted with the CCT and 90 patients with PA were confirmed. Among them, 34 patients were confirmed to have APA by surgery. The clinical indicators of the two groups of patients including plasma aldosterone concentration (PAC), aldosterone inhibition rate (%), and aldosterone to renin ratio (ARR) before and after the CCT were compared, the receiver operating characteristic (ROC) curves for the relevant indicators before and after the CCT drawn, and the areas under the curve (AUC) compared. The ROC curves were used to analyze the efficiency of the different CCT diagnostic criteria for diagnosing APA. RESULTS: Compared with the PA group, the duration of hypertension was shorter, the incidence of hypokalemia was higher, and the average serum potassium level was lower when APA was diagnosed. There were no significant differences in blood pressure level, gender, serum sodium and body mass index between the two groups. Compared with PA population, APA group had higher PAC and ARR whether before or after the CCT, but lower plasma renin concentration (PRC). In APA patients, the mean degree of PAC declined after CCT was approximately 5.7%, but 5% with that of PA. As for diagnosing, ARR before or after CCT had diagnostic value for APA, in which the ARR cut-off point was 7.12, which yielded a sensitivity and specificity of 35.85% and 77.78%. The cut-off point of ARR after CCT was 4.23, with a sensitivity of 71.43% and specificity of 62.22%. For the diagnosis, the ARR before and after CCT were of no significant difference. However, the diagnostic specificity of ARR>7.12 combined with hypokalemia was up to 80%. CONCLUSION: ARR before or after CCT have clinical value for the diagnosis of APA from PA, when combined with hypokalemia yielded high specificity.

[Analysis of diagnosis and treatment of 100 patients with Hürthle cell adenoma].

OBJECTIVE: To summarize and analyze the clinical data and prognosis of the patients with Hürthle cell tumor (HCT) in order to raise the clinicians' awareness of the disease. METHODS: The clinical data on patients with histopathologically proven HCT, without other thyroid carcinomas, were collected retrospectively in Peking University First Hospital from January 2001 to February 2017. All the patients underwent surgery due to thyroid nodules. The follow-up information was also collected. RESULTS: A total of 100 patients were enrolled in the current study. All of them were diagnosed with Hürthle cell adenoma (HCA). There were 77 females and 23 males, with the male-to-female ratio of 1 : 3.3. The average age of these patients was (52±14) years at the time of operation. Fifty-one patients were found their thyroid nodules accidentally by ultrasonography during their health check-ups. 69.4% of the 49 symptomatic patients presented with painless cervical nodules. 83.0% HCA patients were combined with multinodular goiters (MNGs). 88.4% (76/86) patients were euthyroid and 53.8% (21/39) had increasing thyroglobulin levels. The mean longest diameter of HCAs was (3.2±1.5) cm (range: 0.9-7.3 cm) on ultrasonography. There were a series of sonographic features of HCA, such as larger, solidity, hypoecho, a smooth outline, intranodular vascularization, perinodular vascularization, absence of calcification in nodules and absence of enlarged cervical lymph nodes. Compared with the histological diagnosis, the diagnostic accuracy by frozen section (FS) during operation was 97.4%. Twenty-nine patients were followed up with an average period of (49.2±22.1) months and none of them had local recurrence or cervical lymph node metastasis. Six patients accepted thyroid hormone replacement treatment and one had thyrotoxicosis due to over-dose. CONCLUSION: HCA is more common in women. It is often found accidentally by ultrasonography during their health check-ups or presented with painless cervical nodules. It is combined with MNG frequently. HCA exhibits numerous sonographic features but not unique. FS during operation is a reliable method to identify HCA with high diagnostic accuracy. Patients with thyroid hormone administration should be monitored for thyroid function after thyroid surgery.

[Clinical characteristics of primary aldosteronism with concurrent adrenal Cushing's syndrome].

Objective: To analyze and summarize the clinical characteristics of primary aldosteronism (PA) with concurrent adrenal Cushing's syndrome (ACS). Methods: The clinical, imaging and pathological data of 87 patients with PA admitted to Peking University First Hospital from January 1st, 2013 to December 31th, 2016 were reviewed. There were 45 males (51.7%) and 42 females (48.3%) with an average age of (52.7±10.5) years (range: 15-70 years). According to whether they were diagnosed with ACS, the patients were divided into PA with concurrent ACS group (n=11) and pure PA group (n=55). The clinical characteristics of PA with concurrent ACS were summarized. Results: Ten of the eleven patients in PA with concurrent ACS group were diagnosed with subclinical ACS. Compared with these in pure PA group, the patients in PA with concurrent ACS group were older [(55.6±9.1) years vs (48.4±10.2) years, P=0.033], with larger diameters of adrenal tumors [(2.3±1.6) cm vs (1.4±0.6) cm, P=0.015], higher serum cortisol levels in the circadian rhythm [158 (92, 217) nmol/L vs 71 (43, 128) nmol/L at 0∶00, P=0.004], lower plasma adrenocorticotropic hormone (ACTH) levels in the circadian rhythm [0.80 (<0.22, 1.45) pmol/L vs 4.40 (2.58, 5.93) pmol/L at 8∶00, P<0.001; 0.25 (<0.22, 0.91) pmol/L vs 2.03 (0.74, 3.69) pmol/L at 16∶00, P<0.001;<0.22 (<0.22, 0.44) pmol/L vs 1.27 (<0.22, 2.66) pmol/L at 0∶00, P<0.001], and higher serum cortisol levels after 1 mg overnight dexamethasone suppression test [95 (73, 142) nmol/L vs 30 (22, 41) nmol/L, P<0.001]. Unilateral adrenalectomy was performed in 31 patients, of whom 3 patients in PA with concurrent ACS group (3/8) and 3 patients in pure PA group (3/23) presented with adrenal insufficiency and received glucocorticoid replacement therapy after adrenalectomy. Conclusions: PA with concurrent ACS is not rare in PA patients, which are mainly complicated with subclinical ACS and easily misdiagnosed. It is recommended that elderly PA patients with large adrenal tumors should be screened for ACS by means of cortisol and ACTH circadian rhythm and 1 mg overnight dexamethasone suppression test. Postoperative adrenal insufficiency is prone to occur in those patients, who should be followed up closely after adrenalectomy, and receive glucocorticoid replacement therapy in time.

[Clinical profile of pheochromocytoma and paraganglioma with normal plasma free metanephrines].

OBJECTIVE: Plasma free metanephrines (MNs) have been widely used as an initial test for pheochromocytoma and paraganglioma (PPGL). PPGL without MNs elevation has been reported on rare occasions. The objective of this study was to analyze the clinical profile of sporadic PPGL patients with normal MNs. METHODS: In the study, 104 patients with sporadic PPGL diagnosed by histopathology in Peking University First Hospital from March 2015 to January 2020 were enrolled. All the patients had plasma MNs result, of whom, eight (7.69%) were with normal MNs. The reasons for their medical visits, clinical manifestations, the levels of plasma free MNs, 3-methoxytyramine (3-MT), catecholamines and chromogranin A (CgA), and the imaging findings were documented. Their preoperative diagnosis, perioperative medical management, and intraoperative blood pressure were analyzed. All the data mentioned above were compared with the MNs elevated group. The postoperative follow-up for MNs normal patients were applied. RESULTS: For the eight PPGL patients with normal plasma MNs, the most common clinical symptoms were sweating (3/8), abdominal and back pain (3/8), headache (2/8), palpitations (2/8), and fatigue (2/8). There were no significant differences in plasma free 3-MT and catecholamines' diagnostic positive rate between the MNs normal group and MNs elevated group, but the rate for plasma CgA was significantly decreased in the MNs normal group (2/5 vs. 41/43, P=0.005). No significant difference was found for the incidence of typical findings by enhanced CT between the two groups. In these eight MNs normal patients, six were diagnosed with PPGL by the previous history of PPGL, typical symptoms and CT findings, or elevation of 3-MT, CgA levels or positive results of PET-CT; two patients were misdiagnosed as nonfunctioning adenoma or primary aldosteronism. All these MNs normal patients underwent preoperative management with alpha adrenergic receptor blockers, of whom, one had an average intraoperative arterial pressure < 60 mmHg during surgery. The median follow-up time for the eight patients was 1.5 (0.5－4.5) years. No evidence of new tumors was found on the enhanced CT scans. Two MNs normal patients' plasma 3-MT and (or) CgA decreased to normal. CONCLUSION: For patients with adrenal or retroperitoneal tumors, typical symptoms or a previous history of PPGL, normal plasma MNs is not a sufficient exclusion for PPGL. Plasma 3-MT, catecholamine, CgA results and the imaging findings are helpful for the diagnosis of PPGL. We recommend patients with suspected MNs normal PPGL take alpha adrenergic receptor blockers as preoperative blockade, but should avoid overdose. Postoperative follow-up for patients with normal MNs should focus on the positive biochemical markers before surgery.

[The expression and significance of chromobox protein homolog 2 in breast cancer].

Objective: To study the relationship between the expression of Chromobox protein homolog (CBX) mRNA and the clinicopathological prognosis of breast cancer, and to investigate the possibility of Chromobox protein homolog 2 as a therapeutic target for breast cancer. Methods: First, we analyzed the mRNA expression of 8 CBX family genes by METABRIC database, and investigated the relationship between the expression of CBX2 mRNA and the clinicopathological parameters of breast cancer. Then we explored its relationship with prognosis. CBX2 siRNA was used to treat breast cancer cell lines with high expression of CBX2(SUM159 and SUM1315). The effects of knockdown of CBX20 on mRNA and protein expression and cell proliferation were observed. Results: According to the analysis of METABRIC database, among the 8 CBX genes, the most obvious increase in mRNA expression was CBX2, and 22.47% (445/1 980) of the patients showed high mRNA expression. The high expression of CBX2 was closely related to tumor histological grade and the molecular type of breast cancer (P<0.001). Compared with the low-expression group of CBX2 mRNA, the proportion of HER2 breast cancer (28.1% vs 7.5%) and Basal-like (44.5% vs 8.5%) in the high-expression group were both higher. Patients with high CBX2 expression had significantly shorter disease-free survival (DFS) and overall survival (OS). The knockdown of CBX2 by siRNA inhibited the proliferation of breast cancer cells. Conclusion: CBX2 is closely related to the prognosis of breast cancer and may be a target for breast cancer treatment.

[Preoperative evaluation of sentinel lymph node biopsy using contrast-enhanced ultrasonography in early breast cancer patients and the involved disturbing factors].

Objective: To explore the preoperative evaluation of sentinel lymph node (SLN) biopsy using contrast-enhanced ultrasonography (CEUS) in early breast cancer patients and the involved disturbing factors. Methods: Eighty-three female early breast cancer patients who underwent concurrent surgery in the Affiliated Cancer Hospital of Zhengzhou University between January 2017 and May 2018 were enrolled. CEUS was used to seek SLN and determine lymph node metastasis after signature of preoperative informed consent. Rapid pathological examination was used to determine whether metastasis existed in SLN. The sensitivity, specificity, accuracy, the differences between CEUS and pathological results, and the involved disturbing factors were evaluated. Results: A total of 212 SLNs were detected by CEUS and SLN biopsy with an average of 2.6 SLNs detected per patient, including 39 SLNs with cancer metastasis (18.4%) and 173 SLNs without cancer metastasis (81.6%). Among the 83 patients, 29 patients were predicted SLN-positive preoperatively utilizing CEUS (including 21 cases with SLN pathological metastasis and 8 cases with non-metastasis), 54 patients were predicted SLN-negative (including 5 cases with SLN pathological metastasis and 49 cases with non-metastasis). The preoperative evaluation of SLN utilizing CEUS were performed with a sensitivity of 80.8% (21/26), specificity of 86.0% (49/57), positive predictive value of 72.4% (21/29), and negative predictive value of 90.7% (49/54), positive likelihood ratio of 5.75, negative likelihood ratio of 0.22, and the accuracy of 84.3% (70/83), respectively. The area under the ROC curve (AUC) was 0.834 (95% CI: 0.736-0.906). The primary tumor mean size of SLN-negative group predicted preoperatively utilizing CEUS was (1.78±0.14) cm, and that of the SLN positive group was (2.64±0.19) cm. The difference between the two groups was (0.86±0.24) cm with statistical significance (P=0.000 6). The SLN mean size of SLN-negative group (141 SLNs) was (1.41±0.05) cm and that of SLN-positive group (71 SLNs) was (1.69±0.07) cm. The difference between the two groups was (0.28±0.09) cm with statistical significance (P=0.002 8). Conclusions: Preoperative CEUS possesses the predictive value for SLN metastasis in early breast cancer. The predicted results may be influenced by the primary tumor size and the SLN size.

[A retrospective analysis of 12 cases of primary thyroid lymphoma].

OBJECTIVE: To discuss the clinical characteristics and diagnostic and therapeutic considerations of primary thyroid lymphoma (PTL) by reviewing PTL cases. METHODS: In the study, 12 cases of PTL diagnosed and treated in Peking University First Hospital between January 1995 and September 2015 were identified. The clinical characteristics, management experiences and prognosis of these cases were reviewed retrospectively. RESULTS: A total of 12 PTL patients (four males and eight females) were collected, with an average age of 63 years (42 to 81 years) at the time of diagnosis. The average time to clarify diagnosis was 5 months (0.5 to 24 months). Eleven patients presented with a rapidly growing neck mass and visited surgical department, except one complained of coughing and suffocated. Seven patients were hypothyroid, and four were euthyroid at the time of diagnosis. In sonography of 11 cases, nine showed bilateral nodules, with an average diameter of 3.87 cm. Pathologic diagnosis of non-Hodgkin's lymphoma was confirmed in all the 12 cases by means of partial thyroidectomy (four) or core needle biopsy (eight). The pathological subtypes were diffuse large B cell lymphoma in nine patients, mucosa-associated lymphoid tissue lymphoma (MALToma) in two, and small B cell lymphoma in the other one patient. Five patients were concomitant with Hashimoto's thyroiditis. Eleven patients received chemotherapy. Only one patient did not have any further treatment after operation due to an inertia type of tumor. The median overall survival time was 24 months (1-117 months), three patients died. Among the patients who survived, seven completed chemotherapy without disease progression, one MALToma case did not receive chemotherapy after thyroidectomy but was still alive with PTL, and one patient just finished his second course of chemotherapy. CONCLUSION: The diagnosis of PTL should be considered when dealing with rapidly growing goiters in elder female Hashimoto's thyroiditis patients whose B ultrasound indicates hypoechogenicity in thyroid nodules or parenchyma, especially with lymphadenopathy and tracheal compressions. Timely use of coreneedle biopsy on suspicious cases can avoid unnecessary surgical trauma, and chemotherapy is the main treatment.

[Effect of overexpression of apoptosis-stimulating protein 2 of p53 on activation and apoptosis of hepatic stellate cells induced by transforming growth factor-ß1 and its mechanism].

Objective: To study the effect of apoptosis-stimulating protein 2 of p53 (ASPP2) on the activation and apoptosis of hepatic stellate cells induced by transforming growth factor-ß1 (TGF - ß1), and to explore the role of autophagy in this process. Methods: Mouse hepatic stellate cells were primarily isolated and cultured with green fluorescent protein (GFP) expressing empty vector adenovirus (Ad-GFP) and ASPP2 expressing adenovirus (Ad-ASPP2) for 12 h by transfection kit, and then treated with TGF-ß1 (10ng/ml) for 24 h. The experiments were grouped as follows: control group: green fluorescent protein (GFP) expressing empty vector adeno (Ad-GFP); experimental group 1: transfected with Ad-GFP and added with TGF-ß1; experimental group 2: transfected with Ad-ASPP2 and induced by TGF-ß1. Western blot and quantitative fluorescence PCR were used to detect the expression of ASPP2, α-smooth muscle actin (SMA). At the same time, autophagy was determined by microtubule-associated protein 1 light chain 3-ß (LC3). Autophagy and apoptosis of MHSc were observed by immunocytochemistry and RNA interference (RNAi). Multiple pairwise-comparisons between the mean of groups was performed by one-way ANOVA. Results: The relative expression of α-SMA mRNA in mHSC of TGF-ß1 + Ad-GFP group (16.83 ± 2.41) was significantly higher than Ad-GFP group (3.62 ± 0.56) (P < 0.05), while the relative expression of α-SMA mRNA (4.22 ± 0.48) in TGF-ß1 + Ad-GFP group was significantly lower than TGF-ß1 + Ad-GFP group (P < 0.05). The expression of α-SMA protein in each group was consistent with mRNA expression. The proportion of mHSC autophagy in TGF-ß1 + Ad-GFP group (80%) was significantly higher than Ad-GFP group (35%); however, there was no statistically significant difference between the two groups. The proportion of mHSC autophagy in TGF-ß1 + Ad-ASPP2 group was 42%, which was significantly lower than TGF-ß1 + Ad-GFP group, but the apoptotic rate was significantly increased. Cells were simultaneously treated with autophagy inhibitors 3-MA and TGF-ß1. The level of autophagy was not statistically significantly different from that of TGF-ß1 + Ad-ASPP2 group, but the apoptotic rate was increased. In addition, the RNAi group added with ASPP2 had increased autophagy (LC3-II/LC3-I) than control RNAi group, and the rate of apoptosis was significantly decreased. Conclusion: Overexpression of ASPP2 can alleviate the activation of mHSC and promote the apoptosis of HSC by inhibiting autophagy, so as to alleviate liver fibrosis.

CalliSpheres® drug-eluting beads (DEB) transarterial chemoembolization (TACE) is equally efficient and safe in liver cancer patients with different times of previous conventional TACE treatments: a result from CTILC study.

PURPOSE: To assess the efficacy and safety of drug-eluting beads transarterial chemoembolization (DEB-TACE) in liver cancer patients with different times of previous conventional transarterial chemoembolization (cTACE) treatments. METHODS: 367 liver cancer patients about to receive DEB-TACE treatment were enrolled in this prospective cohort study. All patients were divided into no previous cTACE group (NPC group), 1-2 times previous cTACE group (PC group) and triple or above previous cTACE group (TPC group) according to the times of previous cTACE treatments. RESULTS: There was no difference in complete response (CR) (P = 0.671) and objective response rate (ORR) (P = 0.062) among three groups. Additionally, no difference in overall survival (OS) among groups (P = 0.899) was found. As to liver function, most liver function indexes were deteriorative at 1 week after DEB-TACE operation, but returned to baseline at 1-3 months after DEB-TACE operation in all three groups, while percentage of abnormal total bile acid (TBA) patients was higher in TPC group than NPC and PC groups at 1-3 month post-DEB-TACE (P = 0.018). As for safety profiles, the incidence of pain during DEB-TACE operation was lower in TPC group compared to NPC and PC groups (P = 0.005), while no difference of other adverse events was found during and 1 month post-DEB-TACE treatment among three groups. CONCLUSION: DEB-TACE treatment was equally efficient and tolerated in liver cancer patients with different times of previous cTACE treatments.

[Clinical characteristics of silent pheochromocytoma].

Objective: To summarize the clinical characteristics of silent paraganglioma. Methods: A total of 247 pheochromocytoma cases in Peking University First Hospital between January 1993 and December 2015 were analyzed retrospectively.The cases were divided into two groups according to whether they had hypertension: non-silent group (193 cases) and silent group (53 cases), then the clinical characteristics between the groups were compared, and the clinical features of silent pheochromocytoma were reviewed. Results: There were 53 silent pheochromocytoma cases in this study, which accounted for 21.5% (53/247), and imaging was the main way to find the tumor. Forty-one in 53 cases (77.4%) located in adrenal gland, in which 31 cases (75.6%) were benign and 2.3-8.0 cm in diameter, while 10 cases (24.4%) were malignant and 3.5-12.0 cm in diameter. Twelve in 53 cases (22.6%) located in extra-adrenal tissue, in which 4 cases were benign and 2.0-5.5 cm in diameter, while 8 cases were malignant and 5.0-10.5 cm in diameter. With the tumor diameter increased, the malignant rate increased: 1 in 8 cases in diameter<3 cm, 2 in 12 cases in diameter 3-5 cm, 15 in 33 cases in diameter>5 cm were malignant. There was no significant difference in age, sex, tumor location, benign or malignant rate between the two groups (all P>0.05). Compared with the non-silent group, the proportion of tumor size≥5 cm in silent group was significantly higher (62.3% vs 45.9%, P=0.034), and the incidence of hyperglycemia and the concentrations of norepinephrine and epinephrine were lower (all P<0.05) in silent group.Misdiagnosis was common in silent group, and up to 35.8% (19/53) had not been diagnosed correctly before operation. Twenty-one in 53 (39.6%) silent pheochromocytoma cases occured severe intra-operative blood pressure fluctuation. Conclusions: Silent pheochromocytoma was not uncommon and imaging was the main way to find it. The tumor size was always big and misdiagnosis was common, especially extra-adrenal tumors. Therefore, regardless of the adrenal or extra-adrenal tumors, especially in diameter>3.0 cm but with normal blood pressure, the possibility of silent pheochromocytoma should be considered. In order to reduce misdiagnosis and intra-operative blood pressure fluctuations, preoperative diagnosis and preparation, as well as intra-operative monitoring should be fully made.

[Germline gene testing of the RET, VHL, SDHD and SDHB genes in patients with pheochromocytoma/paraganglioma].

OBJECTIVE: To analyze the germline variations of genes RET, VHL, SDHD and SDHB in patients with pheochromocytoma and/or paraganglioma and to evaluate variations of these genes in Chinese patients. METHODS: Patients who were treated in Peking University First Hospital from September 2012 to March 2014 and diagnosed with pheochromocytoma and/or paraganglioma by pathologists were included in this study. Twelve patients were included in total, of whom 11 had pheochromocytoma, and 1 had paraganglioma. Deoxyribonucleic acid (DNA) was extracted from the leukocytes of peripheral blood of the patients. The exons 10, 11, 13-16 of the RET gene, and all exons of VHL, SDHB and SDHD genes and their nearby introns (±20 bp) were amplified with polymerase chain reactions, and the products were sent to a biotechnology company for sequencing. The sequencing results were compared with wildtype sequences of these genes to identify variations. One of the patients was diagnosed with multiple endocrine neoplasia type 2A. A family analysis was performed in his kindred, and his family members received genetic tests for the related variations. RESULTS: Three patients were found to have germline gene variations. A c.136C>T (p.R46X) variation of the SDHB gene was found in a patient with malignant pheochromocytoma. A c.1901G>A (C634Y) variation, as well as c.2071G>A (p.G691S) and c.2712C>G (p.S904S) variations of the RET gene were found in a patient with multiple endocrine neoplasia type 2A. After a family analysis, five family members of this patient were found to have the same variations. c.2071G>A (p.G691S) and c.2712C>G (p.S904S) variations of the RET gene were also found in a clinical sporadic patient without evidence of malignancy. A patient with congenital single ventricle malformation and pheochromocytoma was included in this study, and no variation with clinical significance was found in the four genes of this patient. CONCLUSION: 25% (3/12) patients with pheochromocytoma or paraganglioma were found to have missense or nonsense germline gene variations in this study, including the c.136C>T (p.R46X) variation of the SDHB gene, the c.1901G>A (C634Y) variation of the RET gene, and c.2071G>A (p.G691S) and c.2712C>G (p.S904S) variations of the RET gene. The former two variations have already been confirmed to be pathogenic. The existence of these variations in Chinese patients with pheochromocytoma and/or paraganglioma was validated in this study, which supports the conclusion that genetic testing is necessary to be generally performed in patients with pheochromocytoma and/or paraganglioma.

[Screening results and influencing factors of upper gastrointestinal carcinoma and precancerous lesions in Feicheng City].

Objective: To clarify the situation of the detection of upper gastrointestinal cancer and precancerous lesions in the Feicheng city and discuss the possible influencing factors. Methods: A cluster sampling method was used to determine the participants. A unified questionnaire was used to investigate the basic information including history of alcohol intake, smoking and chinese tea, as well as other eating habits, medical history of digestive tract and cancer. Endoscopy was used to to screen the patients with upper gastrointestinal cancer and precancerous lesions. Influential factors were explored by non-conditional logistic regression model. Results: 911 of 7 291participants were positive, and the total detection rate was 12.49%. The total positive detection rate of male and female was 17.94% and 8.71%, respectively (P<0.001). Multivariate logistic regression analysis showed that the sex (OR=0.527, 95%CI: 0.440-0.631), age (OR=2.037, 95%CI: 1.849-2.245), smoking (OR=1.240, 95%CI: 1.014-1.516) and alcohol consumption (OR=1.232, 95%CI: 1.012-1.500) , meat and protein intake (OR=0.794, 95%CI: 0.638-0.987) and drink tea (OR=1.233, 95%CI: 1.056-1.440) may be influencing factors of the total detection rate of upper gastrointestinal cancer and precancerosis. Conclusions: In Feicheng city, intake of meat and protein is the protective factor of the upper gastrointestinal cancer and precancerous lesions. Men, aged, smoking, drinking and tea will increase the risk of upper gastrointestinal cancer and precancerous lesions.

[Analysis of clinical characteristics of paraganglioma in 42 patients].

Objective: To summarize the clinical characteristics of paraganglioma. Methods: A total of 215 pheochromocytoma/ paraganglioma cases in Peking University First Hospital between January 1996 and December 2014 were retrospectively analyzed. The patients were divided into two groups according to the tumor position: pheochromacytoma group (173 patients) and paraganglioma group (42 patients). Then the clinical characteristics between the groups were compared. Results: There were 42 paraganglioma cases in the study, accounting for 19.5%. The most common position was retroperitoneum (66.7%, 28/42), followed by bladder (19.0%, 8/42), para-aorta (11.9%, 5/42) and pelvic cavity (2.4%, 1/42). Sixty-nine percent (29/42) of patients had different degree of hypertension, while up to 31.0% (13/42) was silent type. There was no statistical difference between the two groups in severity of hypertension, age, gender, duration, abnormal glucose metabolism, and the incidence of hypokalemia( all P>0.05). Adrenaline level was higher in pheochromocytoma group (13.4% vs 9.5%, P=0.004), while noradrenaline level was higher in paraganglioma group (80.8% vs 59.2%, P=0.001). Malignancy (21.4% vs 4.6%, P<0.001) and bigger tumor size [(6.67±3.24)cm vs (5.55±2.76)cm, P=0.024] was more common in paraganglioma group. The maximum tumor volume was 18.0 cm×18.0 cm×10.5 cm vs 14.0 cm×13.0 cm×7.0 cm, while the minimum was 1.8 cm×1.3 cm×1.3 cm vs 1.2 cm×1.0 cm×1.0 cm. There was no significant difference in the pathological manifestations between the two groups. In the study, 11.9% (5/42) of patients in paraganglioma group was misdiagnosed or indefinite at the early diagnosis. Conclusion: Compared with pheochromocytoma, paraganglioma has the characteristics of widely distribution, more various clinical performance, more silent type and higher malignant rate. It is critical to put emphasis on its early diagnosis and treatment.

Continuous blood purification in children with severe sepsis.

This study aims to analyse the clinical effects of continuous blood purification (CBP) in children with severe sepsis to form a basis for CBP application in this context. One hundred and twenty children with severe sepsis treated in Binzhou People’s Hospital, Shandong, China, from June 2013 to June 2014 were divided into two groups, a treatment and a control group, depending on parental preference. The control group was treated conventionally, and the treatment group underwent CBP in addition to conventional therapy. Cardiovascular and respiratory parameters were measured on admission and after 72 h. This study also assayed interleukin (IL)-8 and tumour necrosis factor (TNF)-α levels, and monitored clinical outcomes and prognosis. The cardiovascular and respiratory parameters of the treatment group improved to a significantly greater extent than did those of the control group (all P less than 0.05). After treatment, the levels of IL-8, IL-6, IL-10, and TNF-α declined in both groups, but more so in the treatment group (all P<0.05). The white blood cell count and C-reactive protein level fell more in the treatment than control group, with statistical significance (both P less than 0.05). CBP remarkably improved the cardiovascular and respiratory functions of children with severe sepsis, probably by eliminating factors mediating inflammation.

[Efficacy and safety of IA regimen containing different doses of idarubicin in de-novo acute myeloid leukemia for adult patients].

Objective: To investigate the efficacy and safety of IA regimen which contains idarubicin (IDA) 8 mg/m(2), 10 mg/m(2) or 12 mg/m(2) as induction chemotherapy for adult patients with de-novo acute myeloid leukemia (AML) . Methods: A total of 1 215 newly diagnosed adult AML patients, ranging from May 2011 to March 2015 in the First Affiliated Hospital of Soochow University and other 36 clinical blood centers in China were enrolled in the multicenter, single-blind, non-randomized, clinical controlled study. To compare the response rate of complete remission (CR) , adverse events between different dose idarubicin combined with cytarabine (100 mg/m(2)) as induction chemotherapy in newly diagnosed patients of adult AML. Results: Of 1 207 evaluable AML patients were assigned to this analysis of CR rate. The CR rates of IDA 8 mg/m(2) group, IDA 10 mg/m(2) group and IDA 12 mg/m(2) group were 73.6% (215/292) , 84.1% (662/787) and 86.7% (111/128) , respectively (P<0.001) . After adjusted for age, blast ratio of bone marrow, FAB classification and risk stratification, the odds ratios (95% CI) of IDA 10 mg/m(2) group and IDA 12 mg/m(2) group were 0.49 (0.34-0.70) and 0.36 (0.18-0.71) , as compared with the IDA 8 mg/m(2) group (P<0.001, P=0.003) . In the intermediate and favorable groups, CR rates was 76.5% (163/213) , 86.9% (506/582) and 86.1% (68/79) in different doses of IDA (P=0.007) . Interestingly, IA regimen with IDA 10 mg/m(2) was the only beneficial factor affecting CR in this group after adjusted for age, blast ratio of bone marrow and FAB classification[OR=0.47 (95% CI 0.31-0.71) , P<0.001]. CR rates in adverse group was 50.0% (18/36) , 60.6% (43/71) and 81.8% (18/22) respectively (P=0.089) . However, the odds ratios (95% CI) of IDA 12 mg/m(2) when compared with the IDA 8 mg/m(2) was 0.22 (0.06-0.80) , after adjusted for age, blast ratio of bone marrow and FAB classification. The median time (days) of neutrophil count less than 0.5×10(9)/L in IDA 8 mg/m(2) group, IDA 10 mg/m(2) group and IDA 12 mg/m(2) group were 14 (11-18) , 15 (11-20) and 18 (14-22) , respectively (P=0.012) and of platelet count lower than 20×10(9)/L were 14 (7-17) , 15 (11-20) and 17 (15-21) , respectively (P=0.001) . The incidences of lung infection in the three groups were 9.8%, 13.5% and 25.2%, respectively (P<0.001) . Conclusions: For young adult patients (aged 18-60 years) with AML in China, intensifying induction therapy with idarubicin 10 mg/m(2) is clinically superior to IDA 8 mg/m(2) and IDA 12 mg/m(2) in favorable intermediate AML subgroup. However, idarubicin 12 mg/m(2) is more suitable to adverse AML subgroup.

Rehmannia glutinosa oligosaccharide induces differentiation of bone marrow mesenchymal stem cells into cardiomyocyte-like cells.

The aim of this study was to observe the effect of Rehmannia glutinosa oligosaccharide (RGO) on differentiation of bone marrow mesenchymal stem cells (MSCs) into cardiomyocyte-like cells . Rat MSCs were isolated, treated, and grouped as follows: RGO treatment group, 5-azacytidine (5-aza) treatment group, RGO + 5-aza treatment group, and control group. Following a four-week induction period, cardiac troponin I (cTnI) levels in MSCs were quantified by chemiluminescence, and the levels of myocardial enzymes creatine kinase (CK) and creatine kinase isoenzyme-MB (CK-MB) were measured using a dry chemistry analyzer. The cTnI- and connexin 43 (Cx43)-positive MSC population was identified by immunofluorescence, and expression levels of cTnI and Cx43 were analyzed by western blots. Following induction, cTnI, CK, and CK-MB levels were significantly higher in the RGO + 5-aza group as compared with the RGO and 5-aza groups (P < 0.05). In addition, fluorescence intensity of cTnI and Cx43 was higher in the RGO + 5-aza group as compared with the RGO and 5-aza groups. No cTnI- or Cx43-positive cells were detected in the control group. Western blot analysis further confirmed that cTnI and Cx43 were not expressed in the control group, while cTnI and Cx43 was higher in the RGO + 5-aza group than in the RGO and 5-aza groups. These results suggest that MSCs can be induced by RGO to differentiate into cardiomyocyte-like cells in vitro, and that RGO in combination with 5-aza enhance differentiation of MSCs.

[Eccrine angiomatous hamartoma: a clinicalopathologic analysis of 4 cases].

OBJECTIVE: To investigate the clinical and histopathologic features, diagnosis and differential diagnosis of eccrine angiomatous hamartoma(EAH). METHODS: Four cases of eccrine angiomatous hamartoma were studied by light microscopy and immunohistochemical staining along with review of the literature. RESULTS: There were 3 male and 1 female patients at diagnosis in age of 4 months, 3.5 years, 5.5 years and 14.0 years, respectively. Tumor sites included the left little finger (1 case), right index finger (1 case), lower back (1 case) and knee (1 case). Clinically, most cases presented as a solitary, flesh or reddish papule, plaque or nodule with size of 0.4-6.0 cm in diameter. The skin lesions in 3 cases enlarged commensurate with the growth of the patients, and local hyperhidrosis in one case. Histologically, EAH was characterized by proliferation of well-differentiated eccrine secretory and ductal elements closely associated with thin-walled angiomatous channels in the middle or deep dermis and subcutaneous tissue. By immunohistochemistry, the vascular components were positive for CD31, CD34 and factor Ⅷ related antigen while the eccrine glands were positive for S-100 protein, CEA, EMA, CAM5.2 and GCDFP15. Local surgical resection was performed in 4 cases and follow-up data (0.5 to 4.5 years) showed no recurrence. CONCLUSION: EAH is a rare, benign cutaneous hamartoma. Combination of clinical manifestations, histological changes and immunohistochemical findings is useful for the diagnosis and differential diagnosis.