Using simple and easy water quality parameters to predict trihalomethane occurrence in tap water.

Monitoring of disinfection by-products (DBPs) in water supply system is important to ensure safety of drinking water. Yet it is a laborious job. Developing predictive DBPs models using simple and easy parameters is a promising way. Yet current models could not be well applied into practice because of the improper dataset (e.g. not from real tap water) they used or involving the parameters that are difficult to measure or require expensive instruments. In this study, four simple and easy water quality parameters (temperature, pH, UVA254 and Cl2) were used to predict trihalomethane (THMs) occurrence in tap water. Linear/log linear regression models (LRM) and radial basis function artificial neural network (RBF ANN) were adopted to develop the THMs models. 64 observations from tap water samples were used to develop and test models. Results showed that only one or two parameters entered LRMs, and their prediction ability was very limited (testing datasets: N25 = 46-69%, rp = 0.334-0.459). Different from LRM, the prediction accuracy of RBF ANNs developed with pH, temperature, UVA254 and Cl2 can be improved continuously by tweaking the maximum number of neuron (MN) and Gaussian function spread (S) until it reached best. The optimum RBF ANNs of T-THMs, TCM and BDCM were obtained when setting MN = 20, S = 100, 100.1 and 60, respectively, where the N25 and rp values for testing datasets reached 85-92% and 0.813-0.886, respectively. Accurate predictions of THMs by RBF ANNs with these four simple and easy parameters paved an economic and convenient way for THMs monitoring in real water supply system.

Insulinoma misdiagnosed as epilepsy in 44 Chinese patients.

OBJECTIVE: Insulinoma is a rare pancreatic neuroendocrine tumor that can spontaneously produce excess endogenous insulin, resulting in recurrent and serious hypoglycemia. Patients with insulinoma always have intermittent neuroglycopenia, which has been frequently reported as being misdiagnosed as epilepsy. In this report, we analyzed the clinical data of patients with confirmed insulinoma who had ever been misdiagnosed to have epilepsy. METHODS: The retrospective review was performed on 266 patients with confirmed insulinoma at the First Medical Center of Chinese PLA General Hospital between January 2000 and July 2020. RESULTS: 1. The diagnosis of insulinoma was confirmed in 266 patients. Forty-four patients [male/female=1/1.8, aged (41.25±12.30) years old] were misdiagnosed to have epilepsy, with a misdiagnosis rate of 16.5%. 2. Thirty-eight patients presented with consciousness disorder. Eleven patients presented with palpitation, sweating, and anxiety. Five patients presented with convulsion and 6 patients presented with abnormal behavior and delirium. 3. Twenty-two patients underwent EEG examination. EEG showed spike wave or spike-slow complex wave in 5 patients, decreased α wave and increased slow wave in θ and δ band in 7 patients, and was normal in 10 patients. 4. Thirty-five patients were incorrectly prescribed with AEDs and 22 patients were even misdiagnosed to have refractory epilepsy. 5. All these 44 patients underwent successful surgery, and hypoglycemia symptoms were relieved after insulinoma resection. CONCLUSION: Patients with insulinoma sometimes share common clinical characteristics with epilepsy. To patients with epilepsy or suspected epilepsy, especially with poor response to ADEs, hypoglycemia caused by insulinoma should be emphasized in the differential diagnosis.

Clinical Characteristics and Management of Functional Pancreatic Neuroendocrine Neoplasms: A Single Institution 20-Year Experience with 286 Patients.

BACKGROUND: Functional pancreatic neuroendocrine neoplasms (PanNENs) are very rare disorders but have complex spectrum, including insulinoma, gastrinoma, glucagonoma, somatostatinoma, and VIPoma. Patients with PanNENs usually present with characteristic symptoms caused by corresponding hormone hypersecretion. It has always been challenging in dealing with such rare but complicated disorders. In this report, we analyzed the clinical characteristics of functional PanNENs in a large cohort of Chinese patients and summarized our clinical experience in diagnosis and treatment. METHODS: The retrospective analysis was performed in patients with a definite diagnosis of functional PanNENs hospitalized in Chinese PLA General Hospital between 2000 and 2020. The clinical characteristics, surgical information, and pathological findings were extracted from their medical records and were analyzed. RESULTS: Totally, 286 patients (gender: male 103 and female 183; age: 45.55 ± 15.23 years old) were diagnosed with definite functional PanNENs. The most frequent functional PanNENs were insulinoma (266/286) followed by glucagonoma (10/286), somatostatinoma (3/286), adrenocorticotropic hormone- (ACTH-) producing tumor (3/286), gastrinoma (2/286), and VIPoma (2/286). Nine patients were diagnosed with multiple endocrine neoplasia type 1 (MEN1) in which all the associated functional PanNENs were insulinomas. The duration from symptoms' onset to confirmed diagnosis was 3.67 ± 4.28 years. Two hundred and eighty patients with tumor localized in pancreatic or with limited metastasis underwent surgery. The symptoms associated with hormonal oversecretion were improved significantly after surgery. Five patients with unresectable metastases or tumor recurrence after surgery were administrated with systemic chemotherapy or other targeted therapies. With these various therapies, the symptoms were also partially relieved. According to findings in pathological and immunochemical examination, all the functional PanNENs were categorized into NEN-G1 (41.95%), NEN-G2 (54.90%), NEN-G3 (3.15%), and NEC-G3 (0%). CONCLUSION: Patients with suspected functional PanNENs should have a systematic endocrine examination at diagnosis. Multidisciplinary collaborations are essential for precise diagnosis and tumor localization. A successful surgery or other targeted therapies can improve the prognosis of patients with such rare but complex disorders.

Melatonin alleviates progression of uterine endometrial cancer by suppressing estrogen/ubiquitin C/SDHB-mediated succinate accumulation.

Succinate is an important intermediate of the tricarboxylic acid cycle. Recently discovered roles of succinate demonstrate its involvement in immunity and cancer biology; however, the precise underlying mechanisms of its involvement in these additional roles remain to be determined. In the present study, succinate dehydrogenase (SDH) B was decreased in uterine endometrial cancer cells (UECC) under negative regulation of estrogen. This decrease was the result of lower expression levels of ubiquitin C (UBC), which was associated with the activation of peroxisome proliferator-activated receptor gamma and specificity protein 1. The decreased levels of SDHB resulted in the accumulation of succinate in UECC, and thus, a decrease in the production of fumaric acid. Succinate downregulated voltage-gated potassium channel subfamily Q member 1 (KCNQ1) levels by activating serum/glucocorticoid regulated kinase 1 and promoted the growth of UECC in vitro and in vivo. Treatment with melatonin restricted estrogen/UBC/SDHB-induced succinate accumulation and upregulated expression of KCNQ1 and reduced the succinate-mediated growth of UECC in vitro and in vivo. Furthermore, overexpression of melatonin receptor 1B amplified the inhibitory effects of melatonin on succinate-mediated UECC growth. Together, the data in the present study suggest that melatonin suppresses UECC progression by inhibiting estrogen/UBC/SDHB-induced succinate accumulation. The present study provides a scientific basis for potential therapeutic strategies and targets in UEC, particularly for patients with abnormally low levels of SDHB.

The expression of IMP3 in 366 cases with ovarian carcinoma of high grade serous, endometrioid and clear cell subtypes.

The clear cell (CCC), high grade serous (HGSC) and endometrioid (EC) ovarian carcinomas share overlapping histological features. The oncogene IMP3 is implicated in CCC with an elusive utility in differential diagnosis. We collected 366 cases with ovarian primary carcinomas to detect IMP3, Napsin-A and HNF-1ß by immunochemistry. In 351 cases, the positive expression rate of IMP3 in CCC was significantly higher than that either in EC or HGSC (p < 0.01). The sensitivity of IMP3 in CCC was higher than Napsin-A but lower than HNF-1ß (p < 0.01). The specificity of IMP3 in CCC was lower than Napsin-A but higher than HNF-1ß (p < 0.01). The composite markers Napsin-A+/IMP3+ and the IMP3+/HNF-1ß+/Napsin-A+ offered the highest odds ratio (p < 0.001), the highest specificity, the highest positive predictive value and the highest positive likelihood ratio. The ROC analysis showed that the combination of Napsin-A, HNF-1ß and IMP3 offered the biggest AUC compared with either the singular marker performances or the other binary combinations (p < 0.001). In 15 cases of EC mixed with CCC, IMP3 showed a better discrimination value than the other two markers. Consequently, adding IMP3 to the diagnostic panel might provide some help with the pathological diagnosis of ovarian CCC.

IMP3 is upregulated in primary ovarian mucinous carcinoma and promotes tumor progression.

OBJECTIVE: Primary ovarian mucinous tumors progress from benign adenoma to borderline tumors to invasive mucinous carcinoma. A proper differential diagnosis is crucial to discriminate malignancies at the early stages of disease. However, few biomarkers are clinically available. We designed this study to analyze the clinical application of the oncogene IMP3 in monitoring early malignancies in ovarian primary mucinous tumors. METHODS: We collected 250 samples of ovarian primary mucinous tumors along with the corresponding clinicopathological information between 2009 and 2015 at the Gynecology and Obstetrics Hospital of Fudan University and performed immunochemical assays. Statistical analysis of the correlation between expression of IMP3 and clinic-pathological parameters as well as the survivals of these patients was carried out. Finally, wound-healing and transwell assays were performed in SKOV3 and CAOV3 cells. RESULTS: The expression rate and intensity of IMP3 were much higher in invasive carcinoma than those in benign adenoma and classic borderline adenoma (P<0.05). The expression rate and intensity of IMP3 were also higher in cases with mucinous intraepithelial carcinoma than those in cases with classic borderline tumors (P<0.05). Among the malignant cases, the expression rate and intensity of IMP3 increased with advancing FIGO staging (P<0.05). The expression rate and intensity of IMP3 were much higher in cases with involved fallopian tubes, uterine and omentum than those in cases without the involvement of these tissues (P<0.05). The expression rate and intensity of IMP3 were much higher in cases with lymph node metastasis than those in cases without lymph node metastasis (P<0.05). Elevated expression of IMP3 significantly deteriorated the disease-free survival (DFS) and overall survival (OS) of mucinous carcinoma (P<0.05). IMP3 was an independent risk factor of DFS but not OS. Further in vitro experiments indicated that IMP3 promoted the proliferation, motility and invasive potential of ovarian tumor cells. CONCLUSIONS: IMP3 is highly expressed in ovarian mucinous tumors and is positively correlated with malignancy. IMP3 could be used in the differential diagnosis of ovarian mucinous tumors and might be applicable in monitoring tumor initiation and progression.

Clinicopathological study of 24 cases of ovarian cellular fibromas / 中国肿瘤临床

Objective:To investigate the clinical and pathological characteristics of ovarian cellular fibromas.Methods:The sample con-sisted of 24 cases of ovarian cellular fibromas from February 2008 to March 2017 in the Obstetrics and Gynecology Hospital of Fudan University.Clinical histories were retrieved,and pathological slides were reviewed.Results:The age of the patients ranged from 17 to 70 years old,with a mean age of 46.5 years.Clinical symptoms included ovarian masses,abdominal pain,or pleuroperitoneal fluid.Se-rum CA125 notably increased in two patients.Of the 24 cases,13 and 10 occurred in the right and left ovaries,respectively,and one case occurred bilaterally.Tumor cells were densely cellular in all cases and were mitotically active in three cases(5-7/10 high power fields).A minor component of sex cord elements(<10% area of the tumor)was present in three cases,and luteinized cells were ob-served in four cases.None of the cases manifested recurrence during follow-up ranging from 1 month to 109 months.Conclusion:Ovarian cellular fibromas are pure ovarian stromal tumors that may manifest mitotic activity, sex cord elements, and luteinization. Some patients present with pleuroperitoneal fluid and increased CA125.Thus,the pathological features of cellular fibromas must be mastered to avoid misdiagnosis for other benign or malignant tumors and improper treatment.

Clinicopathological study of 24 cases of ovarian cellular fibromas / 中国肿瘤临床

Objective:To investigate the clinical and pathological characteristics of ovarian cellular fibromas.Methods:The sample con-sisted of 24 cases of ovarian cellular fibromas from February 2008 to March 2017 in the Obstetrics and Gynecology Hospital of Fudan University.Clinical histories were retrieved,and pathological slides were reviewed.Results:The age of the patients ranged from 17 to 70 years old,with a mean age of 46.5 years.Clinical symptoms included ovarian masses,abdominal pain,or pleuroperitoneal fluid.Se-rum CA125 notably increased in two patients.Of the 24 cases,13 and 10 occurred in the right and left ovaries,respectively,and one case occurred bilaterally.Tumor cells were densely cellular in all cases and were mitotically active in three cases(5-7/10 high power fields).A minor component of sex cord elements(<10% area of the tumor)was present in three cases,and luteinized cells were ob-served in four cases.None of the cases manifested recurrence during follow-up ranging from 1 month to 109 months.Conclusion:Ovarian cellular fibromas are pure ovarian stromal tumors that may manifest mitotic activity, sex cord elements, and luteinization. Some patients present with pleuroperitoneal fluid and increased CA125.Thus,the pathological features of cellular fibromas must be mastered to avoid misdiagnosis for other benign or malignant tumors and improper treatment.

Malignant insulinoma: Report of 6 patients and literature review.

OBJECTIVE: Patients with malignant insulinoma always present with symptoms of severe hypoglycemia and have poor life expectancy. In addition, inoperable metastatic malignant insulinomas are very difficult to manage. The aim of this report is to present our successful experiences in diagnosis and treatment of this disease in 6 patients. PATIENTS/METHODS: Six patients (male 2, female 4) with malignant insulinomas were admitted into our hospital. Their clinical histories, including clinical presentations, endocrine evaluations, radiological images, pathological examination and treatments, were reviewed. RESULTS: The diagnosis of malignant insulinoma combined with liver metastases was confirmed in all patients by endocrine evaluation and radiological images. Patients 1-3 underwent surgical management. The primary and metastasized tumors were completely resected. After successful surgery, no hypoglycemia recurred. Patients 4-6 did not undergo surgery because of systemic disease and poor health. Instead, they were administrated with diazoxide 50 mg Three Times a Day (TID), with final doses up to 200-300 mg TID. These 3 patients had good responses to diazoxide administration. After treatment, the frequency and severity of hypoglycemia were improved significantly. All 6 patients had better life quality than previously expected. CONCLUSION: Combination of surgical and medical approaches can improve life quality and prolong survival of patients with malignant insulinomas.

Factors that influence persistence or recurrence of high-grade squamous intraepithelial lesion with positive margins after the loop electrosurgical excision procedure: a retrospective study.

BACKGROUND: In 5-20 % of patients with cervical high-grade squamous intraepithelial lesion (HSIL), a positive margin after the loop electrosurgical excision procedure (LEEP) is associated with persistence/recurrence, but the prognostic value of other clinico-pathological factors is less clear. METHODS: Among 4336 patients with HSIL who underwent an initial LEEP, 275 (6 %) had HSIL-positive margins, 37 of whom were lost to follow-up. We evaluated the remaining 238 patients. Persistence/recurrence was defined as histopathological HSIL during follow-up. RESULTS: The age of the patients ranged from 21 to 69 years (median: 40). The median follow-up period was 25 months (range: 6-43). Of the 238 patients, 211 (88.7 %) patients remained free of persistence/recurrence, while 27 (11.3 %) experienced persistence/recurrence. According to a univariate analysis, age (P = 0.03) and maximum specimen diameter (P = 0.043) were associated with persistence/recurrence, but number/location of involved margin sections and the pathology of the endocervical curettage were not (P > 0.10). The relative risk of the subjects (greater than or equal to 35 years ages) was 4.6 times of the subject less than 35 years, the difference was statistically significant (14 % vs. 3 %, P < 0.05). A multivariate analysis indicated that an age of 35 years or older was the only independent risk factor (OR 4.97, 95 % CI 1.14-21.62, P = 0.03). CONCLUSION: In patients with HSIL and HSIL-involved margins after an initial LEEP, age is a strong independent predictor of persistence/recurrence. Follow-up with screening cytology and/or biopsy may be considered in younger patients, whereas a secondary LEEP/hysterectomy may be considered in older patients.

[Ovarian clear cell carcinoma derived from endometriotic cyst: a clinicopathological analysis of 54 cases].

OBJECTIVE: To clarify the clinicopathological features of ovarian clear cell carcinoma derived from endometriotic cyst (EC-OCCC). METHODS: Totally 54 cases of EC-OCCC were recruited in the current retrospective study. The relation between ages, clinical symptoms and signs, surgical and pathological stages, serum CA125, findings of ultrasound, treatments and the sites of tumors, macro- and micro-features and expression of immunostainings were analyzed. RESULTS: (1) Clinical features: the ages of patients were (50±6) years old (range 31-62 years old). Pelvic mass was the major complaint of 50 patients (93% , 50/54). Forty-five cases belonged to International federation of Gynecology and Obstetrics (FIGO) stage I, 4 cases were stage II and another 5 cases were stage III. Serum CA125 was elevated in 21 cases (54%, 21/39) before therapy. Doppler ultrasound showed 46 cases (85%, 46/54) had solid masses in pelvis. (2) Pathological findings: 52 cases (96%, 52/54) had their tumor unilaterally, and 2 cases (4%, 2/54) occurred bilaterally. The maximal diameters of endometriotic cyst (EC) ranged from 1.5 to 23.0 cm and maximal diameters of ovarian clear cell carcinoma (OCCC) components were from 0.5 to 12.0 cm. Fifty-one cases (94%, 51/54) had their tumor within EC, which showed focally irregular protrudings, grey-white papillae or solid nodules attached to the cyst wall. Three cases (6%, 3/54) appeared as irregular thickened wall of the cysts, ranged from 1.5 to 6.0 cm in the maximal length, with the microscopic features of EC and OCCC and the transitional areas between the 2 morphologies. All cases expressed cytokeratin (CK) 7 and pan-CK AE1/AE3, 17 cases (33%, 17/51) expressed ER and 5 cases (10%, 5/51) expressed PR. TP53 showed mutational phenotype in 19 cases (36%, 19/53). Sixteen cases (30%, 16/54) combined with uterine adenomyosis and 25 cases (46%, 25/54) with endometriosis at other sites. (3) Survival survey: during the period of 39.1 months follow-up, 3 cases relapsed and 2 cases died. (4) There was a significant difference of serum CA125 between patients of early-and advanced-stages (P=0.049). There were no differences identified in ages, diameters of EC and OCCC, the expression level of ER, PR and TP53, the co-existence of adenomyosis and endometrosis, as well as ultrasonic findings (P>0.05). CONCLUSION: EC-OCCC could be recognized in early stage by symptoms and ultrasound due to accompanied endometriotic cysts, resulting in relatively good prognosis.

Acquired generalized lipodystrophy in a young lean Chinese girl. Case Report.

Lipodystrophies is a really rare group of diseases characterized by altered body fat amount and/or repartition and serious insulin resistance.We reported a lean Chinese girl with acquired generalized lipodystrophy, who had a long history of poorly controlled diabetes mellitus (DM) despite with extremely high dose insulin (6 u/kg/d) therapy, combined with severe hypertriglyceridemia and acanthosis nigricans. The differential diagnosis of Lipodystrophies should be considered in lean patients presenting with early onset DM, combined with serious insulin resistance.