Comparison of coagulation function between adrenocorticotropic hormone independent Cushing syndrome and nonfunctional adrenal adenoma and its influence factors / 北京大学学报(医学版)

OBJECTIVE@#To investigate the coagulation function indicators and identify influence factors of hypercoagulability in patients with adrenocorticotropic hormone (ACTH) independent Cushing syndrome (CS).@*METHODS@#In our retrospective study, the electronic medical records system of Peking University First Hospital was searched for the patients diagnosed with ACTH independent CS on discharge from January 2014 to June 2019. Nonfunctional adrenal adenoma patients were chosen as control group and matched 1 ∶1 by body mass index (BMI), gender, and discharge date. Clinical features and coagulation function indicators were compared between the two groups.@*RESULTS@#In the study, 171 patients were included in each group. Compared with control group, activated partial thromboplastin time (APTT), and prothrombin time (PT) in ACTH independent CS group were significantly lower [(29.22±3.39) s vs. (31.86±3.63) s, P < 0.001; (29.22±3.39) s vs. (31.86±3.63) s, P < 0.001], and both D-dimer and fibrin degradation products (FDP) levels were significantly higher (P < 0.05). Percentage of APTT levels under the lower limit of reference range in the CS patients was significantly higher than that in nonfunctional group (21.6% vs. 3.5%, P < 0.001). Percentage of D-dimer levels over the upper limit of reference range in the CS patients was significantly higher than that in nonfunctional group (13.5% vs. 6.6%, P=0.041). There were three patients with deep venous thrombosis and one patient with pulmonary embolism in CS group, however none was in control group. The area under curve (AUC) of serum cortisol rhythm (8:00, 16:00 and 24:00) levels was negatively associated with the levels of PT (r=-0.315, P < 0.001) and APTT (r=-0.410, P < 0.001), and positively associated with FDP (r=0.303, P < 0.001) and D-dimer levels (r=0.258, P < 0.001). There were no differences in coagulation function indicators among different histopathologic subgroups (adrenocortical adenoma, adrenocortical hyperplasia, oncocytic adenoma, adrenocortical carcinoma). With Logistic regression analysis, the AUC of cortisol and glycosylated hemoglobin A1c (HbA1c) levels were independent risk factors for hypercoagulability in the ACTH independent CS patients (P < 0.05).@*CONCLUSION@#ACTH independent CS patients were more likely in hypercoagulable state compared with nonfunctional adrenal adenoma, especially in ACTH independent CS patients with higher levels of cortisol AUC and HbA1c. These patients should be paid attention to for the hypercoagulability and thrombosis risk.

Evaluation of p16/Ki-67 double-stained immunohistochemistry in diagnosis of human papilloma virus-positive oropharyngeal squamous cell carcinoma / 中华口腔医学杂志

Objective: To explore the diagnostic value of p16/Ki-67 double-stained immunohistochemistry in the diagnosis of human papilloma virus (HPV)-positive oropharyngeal squamous cell carcinoma(opscc) and find out the optimal index to improve the accuracy of HPV detection. Methods: A total of 153 cases, from May 2014 to May 2020, diagnosed OPSCC in Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, were selected. This cohort included 130 males and 23 females, aged (58.6±10.0) years old. HPV RNA in situ hybridization was chosen as the gold standard to detect their HPV status. p16 immunohistochemistry and p16/Ki-67 double-stained immunohistochemistry were performed on all cases, and the p16/Ki-67 double positive index including 20%, 40%, and 60% were used as the thresholds to compare their sensitivity, specificity, and positive prediction value (PPV), negative prediction value (NPV) and prognosis prediction ability. Results: Among the 153 patients with OPSCC, 114 were HPV-negative and 39 were HPV-positive, and the HPV infection rate of OPSCC patients was 25.5% (39/153). Only 58.1% (36/62) of single p16 positive cases were HPV-positive, and the prognosis of patients could not be distinguished using p16 immunohistochemistry only. Using p16/Ki-67 double staining, the accuracy of HPV positive diagnosis has been improved. The HPV diagnostic ability was the highest when the p16/Ki-67 double positive index was 40% (sensitivity=86.8%, specificity=94.8%, PPV=84.6%, NPV=95.6%, area under the curve=0.897), which could distinguish the prognosis of patients (P=0.012). Conclusions: The p16/Ki-67 double-stained immunohistochemistry can improve the accuracy of HPV positive diagnosis rate and diagnosis of HPV-positive oropharyngeal cancer is the most accurate when the double-positive index is 40% as the threshold to judge HPV status and could serve as better surrogate marker for HPV detection.

Epidemiological Survey of Hemoglobinopathies Based on Next-Generation Sequencing Platform in Hunan Province, China / 生物医学与环境科学（英文）

OBJECTIVE@#This study was aimed at investigating the carrier rate of, and molecular variation in, α- and β-globin gene mutations in Hunan Province.@*METHODS@#We recruited 25,946 individuals attending premarital screening from 42 districts and counties in all 14 cities of Hunan Province. Hematological screening was performed, and molecular parameters were assessed.@*RESULTS@#The overall carrier rate of thalassemia was 7.1%, including 4.83% for α-thalassemia, 2.15% for β-thalassemia, and 0.12% for both α- and β-thalassemia. The highest carrier rate of thalassemia was in Yongzhou (14.57%). The most abundant genotype of α-thalassemia and β-thalassemia was -α 3.7/αα (50.23%) and β IVS-II-654/β N (28.23%), respectively. Four α-globin mutations [CD108 (ACC>AAC), CAP +29 (G>C), Hb Agrinio and Hb Cervantes] and six β-globin mutations [CAP +8 (C>T), IVS-II-848 (C>T), -56 (G>C), beta nt-77 (G>C), codon 20/21 (-TGGA) and Hb Knossos] had not previously been identified in China. Furthermore, this study provides the first report of the carrier rates of abnormal hemoglobin variants and α-globin triplication in Hunan Province, which were 0.49% and 1.99%, respectively.@*CONCLUSION@#Our study demonstrates the high complexity and diversity of thalassemia gene mutations in the Hunan population. The results should facilitate genetic counselling and the prevention of severe thalassemia in this region.

In vitro screening of natural compounds with antitumor activity by trypsin / 生理学报

In order to investigate the feasibility of in vitro screening the antitumor activity of natural compounds by trypsin, porcine trypsin was used to for screening test, which is marked by inhibition of enzyme activity. Four compounds, namely daidzin, genistin, matrine and oxymatrine, were selected as test subjects. The natural antitumor drug camptothecin was used as the control. The inhibitory effect was detected by two experimental methods: direct detection of trypsin activity inhibition and hydrolysis of bovine serum albumin by trypsin. The results showed the inhibitory effects of the four natural compounds on trypsin, and the inhibition rates of the four natural compounds were significantly different. The enzyme activity assay showed that the inhibitory effect of matrine was better than that of oxymatrine, indicating that trypsin had a good screening resolution. The inhibitory effect was significantly increased with the increased ratio of sample to trypsin, suggesting the structure-activity correlation and dose-effect correlation of the screening methods. Altogether, the experimental method of screening antitumor activity of natural compounds by trypsin has good application values. Since porcine trypsin is similar to human trypsin in terms of molecular structure and performance, it is more applicable for screening of antitumor efficacy of natural pharmacodynamic compounds.

Persistent and serious hyperkalemia after surgery of primary aldosteronism: A case report / 北京大学学报(医学版)

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.

Lobeglitazone, A Peroxisome Proliferator-Activated Receptor-Gamma Agonist, Inhibits Papillary Thyroid Cancer Cell Migration and Invasion by Suppressing p38 MAPK Signaling Pathway

Background@#Peroxisome proliferator-activated receptor-gamma (PPAR-γ) ligands have been widely shown to correlate with epithelial-mesenchymal transition (EMT) and cancer progression. Lobeglitazone (LGZ) is a novel ligand of PPAR-γ; and its role in EMT and metastasis in papillary thyroid carcinoma (PTC) is poorly understood. We aimed to investigate the role of LGZ in metastatic behavior of PTC cells. @*Methods@#Half maximal inhibitory concentration (IC50) values of LGZ in BRAF-mutated PTC cell lines (BCPAP and K1) were determined using MTT assay. Rosiglitazone (RGZ), the PPAR-γ ligand was used as a positive control. The protein expression of PPAR-γ, cell-surface proteins (E-cadherin, N-cadherin), cytoskeletal protein (Vimentin), transcription factor (Snail), p38 mitogenactivated protein kinase (MAPK), extracellular signal-regulated kinase (ERK) 1/2 pathway, and matrix metalloproteinase (MMP)-2 expression were measured using Western blotting. Changes in E-cadherin expression were also determined using immunocytochemistry. Cell migration and invasion were analyzed using wound healing and Matrigel invasion assays. @*Results@#Treatment with LGZ or RGZ significantly inhibited transforming growth factor-beta1 (TGF-β1)-induced EMT-associated processes such as fibroblast-like morphological changes, EMT-related protein expression, and increased cell migration and invasion in BCPAP and K1 cells. LGZ restored TGF-β1-induced loss of E-cadherin, as observed using immunocytochemistry. Furthermore, LGZ and RGZ suppressed TGF-β1-induced MMP-2 expression and phosphorylation of p38 MAPK, but not ERK1/2. Although there was no change in PPAR-γ expression after treatment with LGZ or RGZ, the effect of downstream processes mediated by LGZ was hampered by GW9662, a PPAR-γ antagonist. @*Conclusion@#LGZ inhibits TGF-β1-induced EMT, migration, and invasion through the p38 MAPK signaling pathway in a PPAR-γ-dependent manner in PTC cells.

Clinical value of captopril test in noninvasive diagnosis of aldosterone-producing adenoma / 北京大学学报(医学版)

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.

Effect of hydroxysafflor yellow A on COX-2/PGD2/DPs pathway in cortex of mice with cerebral ischemia-reperfusion injury / 中国药理学通报

Aim To observe the effect of hydroxysafflor yellow A (HSYA) on the COX-2/PGD/DPs pathway in the cortex of mice with cerebral ischemia-reperfusion injury. Methods C57BL/6 male mice were randomly divided into sham group, model group and HSYA group. Right middle cerebral artery occlusion/reperfusion model was established in mice by intraluminal suture method. HYSA (20 mg • kg"1) was injected into the tail vein for five consecutive days before the operation. The sham group and the model group were given the same volume of normal saline. The neurological function score and cerebral infarct volume were measured 24 hours after operation. The histopathological changes of mouse cortex were observed by HE staining. The protein and mRNA expression of COX-2, DP, and DP2 were detected by Western blot and qRT- PCR respectively. The levels of TNF-a, IL-1 (3 and PGD2 were detected by ELISA. Results Compared with sham group, the scores of neurological function, infarct volume, the expression of COX-2, DP, and DP2 protein and mRNA, and the contents of TNF-a, IL-1 (3 and PGD2 in the cortex of model group significantly increased. Compared with model group, the scores of neurological function and the infarct volume significantly decreased in HSYA-treated group, and the damage of cortical cells in ischemic area was significantly improved. The expressions of COX-2, DP, and DP2mRNA and protein were significantly down-regula- ted, and the levels of inflammatory factors such as TNF-a, IL-1 p and PGD2 were markedly down-regula- ted. Conclusions HSYA inhibits the activation of COX-2/PGD2/DPs pathway in mouse brain tissues, which may be involved in the protective mechanism of HSYA in cerebral ischemia-reperfusion injury.

ZNRF2 attenuates PC12 cell injury caused by oxygen-glucose deprivation and reoxygenation through inhibiting autophagy / 中国药理学通报

Aim To study the protective effect of ZN-RF2 on OGD/R-induced injury and the autophagy-related mechanism in PC12 cells. Methods PC12 cells were cultured in vitro and divided into normal group and OGD/R group. qRT-PCR and Western blot were used to measure the mRNA and protein expressions of ZNRF2. To explore the effect of ZNRF2 on OGD/R-induced injury in PC12 cells, cells were grouped into normal group, OGD/R group, LV-ZNRF2 group, LV-NC group, siR-ZNRF2 group and siNC group. Cell viability was detected by MTT assay, cell apoptosis was measured by flow cytometry and the expressions of autophagy-related proteins LC3II, p62, Beclin-l were accessed by Western blot. Results Compared with normal group, the cell viability decreased in OGD/R group, the cell apoptosis increased markedly, and the expressions of ZNRF2 mRNA and protein were downregulated significantly. Simultaneously, the proteins expressions of LC3II and Beclin-1 increased, and the expression of p62 protein decreased in OGD/R group. Compared with OGD/R group, the cell viability was enhanced, the cell apoptosis and autophagy were decreased in LV-ZNRF2 group. In contrast, the cell viability decreased and the cell apoptosis and autophagy were aggravated after transfecting siR-ZNRF2. Conclusions ZNRF2 protects PCI2 cells from the injury caused by OGD/R and its mechanism may be related to the inhibition of autophagy.

Research progress of the mechanism and treatment of macrophage in spinal cord injury repair / 上海交通大学学报（医学版）

Self-repair has been initiated after spinal cord injury (SCI). Unlike wound healing, the self-regeneration of spinal cord is incomplete and insufficient. Many studies show that there are a lot of cells and factors active in self-repair of SCI. Inflammatory is a hard problem for us to face in SCI. Over-inflammatory will cause secondary damage to the spinal cord and the capacity of self-repair. In the inflammatory environment, Many kinds of research evidence prove that macrophage pays a vital role in the over inflammatory with damaging the self-repair of SCI. Thus, targeting macrophage in spinal cord injury will hopefully become a method in SCI repair. This review clarifies the function and mechanism of macrophage in SCI repair and the new targeting macrophage methods in recovering the self-repair capacity of SCI.

Diagnostic value of multi-slice spiral CT perfusion imaging combined with serum CYFRA21-1, CEA and NSE for peripheral non-small cell lung cancer / 解放军医学杂志

Objective To investigate the diagnostic value of multi-slice spiral CT (MSCT) perfusion imaging combined with serum cytokeratin 19 fragment antigen 21-1 (CYFRA21-1), carcinoembryonic antigen (CEA) and neuron specific enolase (NSE) for peripheral non-small cell lung cancer (NSCLC). Methods Based on diagnosis, 109 patients with suspected peripheral NSCLC admitted from Aug. 2017 to Aug. 2019 in the Xinxiang Central Hospital were divided into peripheral NSCLC group (n=65) and benign pulmonary nodule group (n=44). Another 56 healthy subjects undergone physical examination during the same period were selected as control group. The parameters of MSCT perfusion imaging and serum levels of CYFRA21-1, CEA and NSE in the 3 groups were compared. The receiver operating curve (ROC) was used to analyze the diagnostic value of MSCT perfusion imaging combined with serous levels of CYFRA21-1, CEA and NSE for peripheral NSCLC. Results The blood volume (BV) was larger in peripheral NSCLC group than those in benign pulmonary nodule group and control group [(10.76±1.26) ml/100 mg vs. (4.01±0.59) ml/100 mg and (2.32±0.42) ml/100 mg]; the same was for surface permeability (PS) [(42.56±5.60) ml/ (100 mg·min) vs. (16.13±1.88) ml/(100 mg·min) and (8.49±0.91) ml/(100 mg·min)]; and for the mean transit time (MTT) of contrast medium [(20.14±3.67) s vs. (12.85±1.49) s and (7.21±0.95) s]. All the BV, PS and contrast medium MTT were higher (larger) in benign pulmonary nodule group than those in control group (P<0.05). The serum level of CYFRA21-1 was higher in peripheral NSCLC group than that in benign pulmonary nodule group and control group [(8.94±1.67) ng/ml vs. (4.73±0.51) ng/ ml and (1.93±0.26) ng/ml]; the same was for the CEA level [(27.91±3.25) ng/ml vs. (7.88±0.92) ng/ml and (2.06±0.47) ng/ml]; and for the NSE level [(19.53±2.16) ng/ml vs. (15.02±1.74) ng/ml and (11.96±1.22) ng/ml]. All the serum levels of CYFRA21-1, CEA and NSE were higher in benign pulmonary nodule group than those in control group (P<0.05). The ROC results showed that the diagnosis of peripheral NSCLC alone and combined with MSCT perfusion imaging, serum levels of CYFRA21-1, CEA and NSE were 0.802, 0.794, 0.698, 0.712 and 0.841, respectively. The diagnostic value of combined detection of the four methods was higher than that of individual detection. Conclusion MSCT perfusion imaging combined with serum levels of CYFRA21-1, CEA and NSE have high diagnostic value for peripheral NSCLC.

Analysis of diagnosis and treatment of 100 patients with Hürthle cell adenoma / 北京大学学报(医学版)

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 profile of pheochromocytoma and paraganglioma with normal plasma free metanephrines / 北京大学学报(医学版)

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.

Feng-liao-chang-wei-kang is synergistic with 5-fluorouracil in inhibiting proliferation of colorectal cancer

Objective: To explore the effect of Feng-liao-chang-wei-kang (FLCWK) on acute and chronic gastroenteritis, synergistic effect on the growth inhibitory effect with 5-fluorouracil (5-FU) on colorectal cancer and its underlying mechanisms. Methods: In the in vitro study, HT-29 cells were divided into 5-FU alone, FLCWK alone and coadministration groups. The MTT assay was used to analyze the proliferation of HT-29 cells at 24 h. Flow cytometry was used to observe the apoptosis, cycle of colorectal cancer HT-29 cells at 24 h. In the in vivo experiment, The subcutaneous transplantation tumor model of colorectal cancer HT-29-Luc was established with nude mice. All mice were randomly divided into 5-FU alone, FLCWK alone and coadministration groups according to body weight. During administration, the Interactive Video Information System small animal live imaging system was used to monitor the growth of subcutaneous transplantation in nude mice. The model of colitis-associated colorectal cancer (CACC) was established with BALB/c mice. BALB/c mice were randomly divided into the normal control group, the model control group, and the FLCWK group. At the end of the administration, the pathological status was detected by HE staining. Cell apoptosis of tumor tissue tumor and colon tissues were observed by TUNEL staining and TUNEL green fluorescence. The protein expression of Caspase 3, p-STAT3, Bcl-2, Bax and P-gp in tumor tissues tumor and colon tissues were tested by using immunohistochemical assay. Results: FLCWK and 5-FU coadministration suppressed HT-29 cell viability and induced S phase arrest and apoptosis compared to treatment with 5-FU alone. Furthermore, compared to treatment with 5-FU alone, coadministration of FLCWK and 5-FU obviously reduced tumor volume and weight and induced apoptosis through decreasing p-STAT3 and P-gp and increasing Caspase 3 protein expression in a murine xenograft tumor model. Moreover, the result revealed decreased number and size of tumors following FLCWK protective administration, downregulated p-STAT3 and Bcl-2 levels and upregulated Bax and Caspase 3 expression in mice with CACC. Conclusions: FLCWK has synergistic effects with 5-FU on colorectal cancer by suppressing the STAT3 pathway and downregulating P-gp expression. Furthermore, FLCWK administration suppresses CACC tumorigenesis by inhibiting the STAT3 pathway.

Prevalence of urogenital tract infections with Ureaplasma urealyticum or HPV among men of reproductive age and the associated factors / 中华男科学杂志

Objective@#To investigate the prevalence of urogenital tract infections with Ureaplasma urealyticum (UU) and human papilloma virus (HPV) in males of reproductive age and the associated factors.@*METHODS@#Using the multi-stage cluster sampling method and a structured questionnaire, we conducted an investigation among 18－50 years old males in Songjiang District, Shanghai, from August 2016 to July 2018. We collected secretory specimens from the urogenital tract of the subjects and detected the infections of UU and HPV by laboratory examination.@*RESULTS@#Among the 621 males included in this study, 279 (44.93%) were found infected with UU, 18 (2.90%) with HPV, and 15 (2.42%) with both UU and HPV. Univariate analysis showed that smokers had a higher rate of UU infection (50.54% ［140/277］) than non-smokers (40.41 ［139/344］), and those with senior high school or secondary technical school education had a higher rate of HPV infection (4.84% ［12/248］) than others (1.61% ［6/373］). Binary stepwise logistic regression analysis revealed a higher risk of UU infection in the subjects with junior high school or lower education than in others (OR = 0.61, 95% CI: 0.39－0.96) as well as in smokers than in non-smokers (OR = 1.46, 95% CI: 1.01－2.01).@*CONCLUSIONS@#The prevalence of UU infection is high, while that of HPV is low among men of reproductive age in Songjiang, Shanghai. The screening of UU infection should be enhanced among men of reproductive age, especially among smokers and those with lower education.

Thyroid function of twin-pregnant women in early pregnancy / 中华医学杂志(英文版)

BACKGROUND@#Serum human chorionic gonadotrophin (hCG) is higher in twin than that in singleton pregnancies. As hCG stimulates the thyroid to produce more free thyroxine (FT4), which may lead to decreased thyroid-stimulating hormone (TSH) levels, the reference ranges of thyroid-related indicators may differ between singleton and twin pregnancies in the first trimester. This study aimed to establish reference ranges for thyroid-related indicators in early twin pregnancies and to compare them with singleton pregnancies.@*METHODS@#Data of 820 twin-pregnant women were extracted from the established database of all pregnant women who delivered at Peking University First Hospital from October 2013 to May 2018; 160 who met National Academy of Clinical Biochemistry criteria were included to establish TSH and FT4 reference ranges. We screened 480 (3:1 paired) women with singleton pregnancies from the same database as controls. The Mann-Whitney test for TSH and FT4 levels was applied for comparisons between singleton and twin pregnancies.@*RESULTS@#First-trimester reference ranges (4-12 gestational weeks) for twin pregnancies were: TSH 0.69 (0.01-3.35) mIU/L and FT4 16.38 (12.45-23.34) pmol/L. Median TSH was significantly lower at 7 to 12 gestational weeks than that at 4 to 6 gestational weeks (0.62 vs. 0.96 mIU/L, Z = -1.964, P = 0.049); FT4 was not significantly different between the two groups. Compared to singleton pregnancies, median TSH was significantly lower (0.69 vs. 1.27 mIU/L, Z = -6.538, P = 0.000), and FT4 was significantly higher (16.38 vs. 14.85 pmol/L, Z = -7.399, P = 0.000) in twin pregnancies in the first trimester.@*CONCLUSIONS@#Specific reference ranges for thyroid-related indicators for twin pregnancies are needed to avoid a misdiagnosis of thyroid dysfunction. Moreover, establishment of separate reference ranges for 4 to 6 and 7 to 12 gestational weeks in twin pregnancies may be considered.

Thyroid function of twin-pregnant women in early pregnancy / 中华医学杂志(英文版)

Background@#Serum human chorionic gonadotrophin (hCG) is higher in twin than that in singleton pregnancies. As hCG stimulates the thyroid to produce more free thyroxine (FT4), which may lead to decreased thyroid-stimulating hormone (TSH) levels, the reference ranges of thyroid-related indicators may differ between singleton and twin pregnancies in the first trimester. This study aimed to establish reference ranges for thyroid-related indicators in early twin pregnancies and to compare them with singleton pregnancies.@*Methods@#Data of 820 twin-pregnant women were extracted from the established database of all pregnant women who delivered at Peking University First Hospital from October 2013 to May 2018; 160 who met National Academy of Clinical Biochemistry criteria were included to establish TSH and FT4 reference ranges. We screened 480 (3:1 paired) women with singleton pregnancies from the same database as controls. The Mann-Whitney test for TSH and FT4 levels was applied for comparisons between singleton and twin pregnancies.@*Results@#First-trimester reference ranges (4–12 gestational weeks) for twin pregnancies were: TSH 0.69 (0.01–3.35) mIU/L and FT4 16.38 (12.45–23.34) pmol/L. Median TSH was significantly lower at 7 to 12 gestational weeks than that at 4 to 6 gestational weeks (0.62 vs. 0.96 mIU/L, Z = -1.964, P = 0.049); FT4 was not significantly different between the two groups. Compared to singleton pregnancies, median TSH was significantly lower (0.69 vs. 1.27 mIU/L, Z = -6.538, P = 0.000), and FT4 was significantly higher (16.38 vs. 14.85 pmol/L, Z = -7.399, P = 0.000) in twin pregnancies in the first trimester.@*Conclusions@#Specific reference ranges for thyroid-related indicators for twin pregnancies are needed to avoid a misdiagnosis of thyroid dysfunction. Moreover, establishment of separate reference ranges for 4 to 6 and 7 to 12 gestational weeks in twin pregnancies may be considered.

Therapeutic effect of single Chinese medicine Bidens pilosa grain on hyperlipidemia and its influence on serum levels of MMP‐9 and TIMP‐1 / 心血管康复医学杂志

Objective :To explore therapeutic effect of single Chinese medicine Bidens pilosa grain on hyperlipidemia and its influence on serum levels of matrix metalloproteinase‐9 (MMP‐9) and tissue inhibitor of metalloproteinases‐1 (TIMP‐1).Methods :A total of 186 hyperlipidemia patients treated in our hospital from Jan 2014 to Jun 2017 were randomly divid‐ed into Bidens pilosa group (n＝94 ,received Bidens pilosa grain based on routine treatment ) and Xuezhikang group (n＝92 ,received Xuezhikang based on routine treatment ).Both groups were treated for two months .Serum levels of total cho‐lesterol (TC) , triglyceride (TG ) ,low density lipoprptein cholesterol (LDL‐ C) , high density lipoprptein cholesterol (HDL‐C) ,MMP‐9 and TIMP‐1 before and after treatment ,and total effective rate were observed and compared between two groups.Results :Compared with before treatment ,after treatment ,there were significant reductions in serum levels of TC ,TG ,LDL‐C and MMP‐9 [ Bidens pilosa group : (24.46 ± 4.92) μg／L vs.(20.53 ± 2.69) μg／L ,Xuezhikang group :(23.40 ± 2.57) μg／L vs.(19.98 ± 2.02) μg／L] ,and significant rise in serum levels of HDL‐C [ Bidens pilosa group :(1.28 ± 0.45) mmol／L vs.(1.54 ± 0.52) mmol／L , Xuezhikang group : (1.28 ± 0.45) mmol／L vs.(1.55 ± 0.52) mmol／L] and TIMP‐1 [ Bidens pilosa group : (4.67 ± 1.26) μg／L vs.(6.02 ± 2.24) μg／L ,Xuezhikang group :(4.63 ± 1.30) μg／L vs.(6.01 ± 2.31) μg／L] in two groups , P＝0.001 all.After treatment ,there were no significant difference in serum levels of TC ,TG ,LDL‐C ,HDL‐C ,MMP‐9 and TIMP‐1 and total effective rate between two groups , P＞0.05 all.Conclusion :Bidens pilosa can significantly improve serum lipid level ,reduce serum level of MMP‐9 and increase serum level of TIMP‐1 in hyperlipidemia patients .It＇s no significant difference compared with Xuezhikang .

Approach to creating early diabetic peripheral neuropathy rat model / 北京大学学报(医学版)

OBJECTIVE@#To create the early diabetic peripheral neuropathy (DPN) rat model.@*METHODS@#After one-week adaption, 26 male Sprague-Dawley (SD) rats were divided into two groups, the control group (n=6) and the model group (n=20). High-sucrose/high-fat diet (D12451, 35% of energy from carbohydrate, 45% of energy from fat) was given to the model group for six weeks to induce insulin resistance, meanwhile normal diet was given to the control group. Afterwards, streptozocin (STZ) buffer solution (35 mg/kg bodyweight) was injected into abdomen of the model group to induce specific pancreatic injury, meanwhile an equal amount of buffer solution was given to the control group. Then 48 h later, type 2 diabetes mellitus (T2DM) was supposed to be successfully induced according to the random blood glucose more than 16.7 mmol/L in the model group. Then the basic features of the T2DM rats were evaluated, including body weight, fasting blood glucose (FBG), glucose tolerance (oral glucose tolerance test, OGTT), and insulin tolerance (intraperitoneal insulin tolerance test, IPITT). Subsequently, withdrawal thermal latency (WTL) was measured regularly to determine when the early DPN occurred. Once confirmed, sciatic nerve conduction velocity (NCV) of all the rats was conducted.@*RESULTS@#The T2DM rats were successfully induced in the model group through high-sucrose/high-fat diet for six weeks along with STZ intraperitoneal injection (35 mg/kg bodyweight). When compared to the control group, the T2DM rats had higher FBG (P<0.001), and the glucose tolerance and insulin tolerance were both damaged (P<0.001 in OGTT, P=0.002 in IPITT). It was on the 17th day when the T2DM rats became much more sensitive to heat stimulus compared to the control group (P=0.004). Meanwhile, the sciatic NCV was conducted. There was no significant difference between the early DPN group and the control group (P=0.196).@*CONCLUSION@#High-sucrose/high-fat diet for six weeks along with STZ intraperitoneal injection (35 mg/kg bodyweight) could successfully induce T2DM rat model, manifested by a certain extent of insulin resistance and deficiency of insulin secretion. It was about 17 days later when the early DPN emerged. In the early DPN, small fiber neuropathy came out earlier than large fiber neuropathy.

Effect of Tongxinluo Treated Conditioned Medium of Cardiac Microvascular Endothelial Cells on Rats' Embryo Cardiomyocyte Apoptosis / 中国循环杂志

Objective: To explore the effect of impaired cardiac microvascular endothelial cells on rat's embryo cardiomyocyte apoptosis and the impact of Tongxinluo in such process. Methods: 3 kinds conditioned medium of cardiac microvascular endothelial cells were prepared. ① normal rat's cardiac microvascular endothelial cell (RCMECs) conditioned medium, ②homocysteine induced impaired RCMECs conditioned medium and ③ Tongxinluo treated RCMECs conditioned medium. Rat's embryo H9c2 cardiomyocytes were divided into 4 groups:① Control group, cells were cultured in DMEM without serum, ② N-CM group, cells were cultured in RCMECs conditioned medium, ③ H-CM group, cells were cultured in homocysteine induced impaired RCMECs conditioned medium and ④ T-CM group, cells were cultured in Tongxinluo treated RCMECs conditioned medium. Cell mitochondrial membrane potential (MMP) was detected by JC-1 agent, ROS level was examined by flow cytometry, cardiomyocytes apoptosis was measured by live cell imaging system, expression levels of cytochrome C (Cyt-C), cysteinyl aspartate specific proteinase-3 (Caspase-3), Bcl-2 associated X protein (Bax) and B-cell leukemia/lymphoma 2 protein (Bcl-2) were detected by Western blot analysis. Results: MMP, expression levels of ROS, Cyt-C and cardiomyocyte apoptosis were similar between Control group and N-CM group, P>0.05. Compared with N-CM group, H-CM group had decreased MMP, increased ROS and cardiomyocyte apoptosis, up-regulated expressions of Cyt-C, Caspase-3 and Bax, all P<0.01. Compared with H-CM group, T-CM group had increased MMP, decreased ROS and cardiomyocyte apoptosis, down regulated expressions of Cyt-C, Caspase-3 and Bax, all P<0.05; while up-regulated expression of Bcl-2, P<0.01. Conclusion: Conditioned medium of impaired cardiac microvascular endothelial cells may induce cardiomyocyte apoptosis and such process could be inhibited by Tongxinluo.