[Retrospective clinicopathological analysis of pulmonary light chain deposition disease secondary to Sjögren's syndrome].

Objective: To analyze of the clinical, imaging, and pathological features of pulmonary light chain deposition disease(PLCDD) secondary to Sjögren's syndrome(SS), and to improve the understanding of the disease. Methods: We retrospectively analyzed the clinical data of 23 PLCDD cases diagnosed by pathology in Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College from 2009 to 2023, a total of 11 cases of PLCDD secondary to SS(SS-PLCDD) were selected, the median age was 51 years old(range:36~74),10 female and 1 male, the clinical, imaging, and pathological features were summarized. Results: All 11 cases showed bilateral multiple pulmonary nodules on HRCT with 10 cases accompanied by cysts, 6 cases with vessels in the cystic wall or crossing the cysts. Microscopically, all 11 cases showed amorphous eosinophilic material with negative Congo red staining deposited in the lung, vascular involvement was common, with variable lymphocyte, plasma cell infiltration and multinucleated giant cell reaction, cysts formation was observed in 6 cases,1 case combined with pulmonary lymphoma. No extrapulmonary involvement in all 11 cases. Ten patients were treated with glucocorticoid and (or) immunosuppressants, 1 patient changed to bortezomib-dexamethasone chemotherapy after 1 year, with a mean follow-up of 50 months, 5 cases were stable on clinical and (or) HRCT findings, 2 cases showed remission on HRCT, 2 cases progressed on HRCT. Conclusions: SS-PLCDD affects predominantly middle-aged females with lesions confined to the lung; HRCT showed bilateral multiple nodules and thin-walled cysts. Pulmonary pathology presented as non-amyloid material with negative Congo red staining and interstitial changes associated with SS. The overall prognosis was good, but caution is advised regarding the underlying lymphoma.

[A multicenter study on the accuracy of PAX1/JAM3 dual genes methylation testing for screening cervical cancer].

Objective: To explore the value of cervical cytologic DNA methylation for screening cervical cancer. Methods: This study was a prospective multicenter study conducted from May to October 2022 in Peking Union Medical College Hospital, Zhejiang Provincial People's Hospital, and the Second Affiliated Hospital of Zhejiang University School of Medicine. Women who accepted opportunistic cervical cancer screening in gynecological outpatient clinics were subjected to liquid-based thin-layer cytology testing (TCT), high-risk human papillomavirus (hrHPV) DNA testing and PAX1/JAM3 dual-genes methylation testing (PAX1m/JAM3m). Colposcopy evaluation and biopsy were offered to women according to current guidelines. The accuracies of various testing methods and their combinations were compared based on histological diagnosis. Results: A total of 1 184 samples diagnosed by histopathology were included in this study, consisting of 541 cases (45.7%) of benign cervical tissue or chronic cervicitis, 273 (23.1%) of cervical intraepithelial neoplasia (CIN) 1, 168 (14.2%) of CIN2, 140 (11.8%) of CIN3, and 62 (5.2%) of cervical cancer. The sensitivity and specificity of PAX1m/JAM3m testing for detecting CIN2 or more severe lesions (CIN2+) were 74.1% and 95.9%, respectively. The sensitivity and specificity of PAX1m/JAM3m testing for detecting CIN3+were 87.6% and 86.8%, respectively. Receiver operating characteristic curve analysis showed that, for detecting CIN3+, the area under curve of PAX1m/JAM3m testing (0.872, 95%CI: 0.847-0.897) was significantly superior to TCT testing (0.580, 95%CI: 0.551-0.610) or hrHPV testing (0.503, 95%CI: 0.479-0.515) (all P values<0.05). Conclusions: The PAX1m/JAM3m test in cervical exfoliated cells has excellent accuracy for the diagnosis of both CIN2+and CIN3+, which is superior to traditional screening protocols and screening strategies.

[The role of DNA methylation in the screening of endometrial cancer in postmenopausal women].

Objective: To explore the application value of cervical exfoliated cell DNA methylation (CDO1m and CELF4m) combined with or without transvaginal sonography (TVS) for screening endometrial cancer in postmenopausal women. Methods: A total of 143 postmenopausal women who underwent hysteroscopy for suspected endometrial lesions in the Department of Obstetrics and Gynecology of Peking Union Medical College Hospital from May 2020 to October 2021 were enrolled in this study. The cervical exfoliated cells were collected for gene methylation before hysteroscopy. Clinical information, tumor biomarkers, and endometrial thickness of TVS were also collected. With endometrial histopathology as the gold standard, multivariate unconditional logistic regression was applied to analyze the risk factors of endometrial cancer. The role of gene methylation with or without TVS were specifically explored. Results: The 143 patients were divided into an endometrial cancer group (n=56) and a control group (n=87), aged (59.27±6.45) and (61.07±8.26) years, respectively (P=0.051). Multivariate logistic regression analysis showed that, CA125≥35 U/ml, postmenopausal bleeding, endometrial thickness≥5 mm, CDO1m ΔCt≤8.4, and CELF4m ΔCt≤8.8 were the risk factors for endometrial cancer, with OR (95%CI) of 33.23 (2.51-1 335.28), 8.41(1.81-39.05), 14.45 (2.35-88.84), 17.34 (3.34-89.98), and 44.01 (6.79-285.25), respectively (all P values<0.05). The sensitivity and specificity of dual-gene methylation (CDO1 or CELF4) in the screening of endometrial carcinoma were both higher than others factors, reaching 87.5% (95%CI: 75.9%-94.8%) and 90.8% (95%CI: 82.7%-95.9%), respectively. TVS combined with DNA methylation detection further improved the sensitivity to 100.0% (95%CI: 93.6%-100.0%), but could not improve the specificity (59.8%, 95%CI: 48.8%-70.1%). Conclusions: In postmenopausal women with suspected endometrial lesions, the accuracy of cervical cytology DNA methylation is better than other noninvasive clinical indicators for the screening of endometrial cancer. DNA methylation combined with TVS can further improve the sensitivity of screening.

[The Chinese guidelines for the diagnosis and treatment of pancreatic neuroendocrine neoplasms (2020)].

Pancreatic neuroendocrine neoplasms (pNENs) are highly heterogeneous, and the management of pNENs patients can be intractable. To address this challenge, an expert committee was established on behalf of the Group of Pancreatic Surgery, Chinese Society of Surgery, Chinese Medical Association, which consisted of surgical oncologists, gastroenterologists, medical oncologists, endocrinologists, radiologists, pathologists, and nuclear medicine specialists. By reviewing the important issues regarding the diagnosis and treatment of pNENs, the committee concluded evidence-based statements and recommendations in this article, in order to further improve the management of pNENs patients in China.

[Analysis of microsatellite instability in endometroid carcinoma with deficient mismatch repair].

Objective: To analyze the microsatellite instability (MSI) status in endometrioid endometrial carcinoma (EEC) with deficient mismatch repair (dMMR) and to explore the concordance between MSI next generation sequencing (NGS)/PCR and MMR immunohistochemistry (IHC) results. Methods: Sixty dMMR EEC cases by IHC from November 2017 to February 2019 were selected in the Department of Pathology, Peking Union Medical College Hospital. Two pathologists reviewed the IHC results. The MSI status and the germline/somatic mutational status of MMR genes were analyzed by NGS. MLH1 promoter methylation status was determined by methylation-specific PCR (MSP) in cases with MLH1 protein deficiency. In cases with discrepant results between MMR IHC and MSI NGS, the MSI status was detected again by PCR, and the reasons for the discrepancy were discussed with gene mutation and MLH1 promoter methylation results. Results: Among 60 dMMR EEC specimens, 3 samples were re-assigned as proficient mismatch repair (pMMR) after pathological review, and identified as MSS by NGS. Another 3 dMMR cases showed MSI-uncertainty (MSI-U) by NGS due to insufficient tumor content. In the remaining 54 cases, the concordance between MMR IHC and MSI NGS was 87% (47/54). The seven discrepant cases was further analyzed: in 5 discrepant cases with MLH1/PMS2 protein loss, one case did not have enough samples for detection, one case was MSI-H, and the remaining three cases were MSS by PCR. All these 5 cases with MLH1/PMS2 protein loss showed the MLH1 promoter hypermethylation, two of which also had a somatic mutation in the MSH2 gene. The two discrepant cases with MSH6 protein loss were both MSS by PCR, one of which was considered to have Lynch syndrome with germline mutation in MSH6 gene. Conclusions: Although the overwhelming majority of dMMR EEC cases by IHC shows MSI-H by NGS/PCR, there are uncommon discrepant dMMR EEC cases with MSS. They are mostly found in cases with MLH1/PMS2 protein loss caused by MLH1 promoter hypermethylation and rarely related to Lynch syndrome. Both MMR IHC and MSI NGS/PCR tests have their advantages and disadvantages, complimentary to each other.

[Clinical analysis of 30 cases of traumatic aortic injury].

Objective: To examine the clinical treatment methods and short- and mid-term results of traumatic aortic injury (TAI). Methods: The clinical data of 30 patients suffering from TAI who were admitted to Department of Cardiothoracic Surgery, General Hospital of Eastern Theater Command from January 2010 to December 2018 were summarized and analyzed retrospectively. All patients were diagnosed as TAI by aortic CT angiography. There were 20 males and 10 females, aging (46.4±15.2) years (range: 17 to 76 years). One patient was diagnosed as extensive intramural hematoma (IMH). The other 29 cases had aortic intimal injury, and the primary intimal tear of all these patients was located in the isthmus of descending aorta. There were 2 cases of ulcer-like changes combined with IMH, and 27 cases of traumatic aortic dissection (TAD) including 23 cases of localized TAD and 4 cases of extensive TAD. Endovascular repair, artificial vascular replacement or conservative treatment were performed according to the patient's specific condition. The patients were followed up in outpatient or by telephone. The clinical data of all the patients of the in-hospital treatment and during follow-up period was analyzed retrospectively. Results: One patient with IMH was treated conservatively. Surgical intervention was performed in 29 cases with intimal injury, of which 14 cases underwent emergency surgery on the day of admission or the next day, and 15 cases underwent elective surgery. Twenty-seven cases underwent thoracic endovascular aortic repair (TEVAR), and 2 cases underwent artificial vascular replacement. Nine cases suffered combined operations in early or late stage. All patients were cured and discharged with in-hospital stay of (13.2±5.4) days (range: 7 to 30 days). There was no in-hospital death. Two patients underwent tracheotomy, and the rest had no serious complications. Up to the last follow-up in June 2019, 4 patients were lost to follow-up, and the remaining 26 patients were followed up for (50.6±34.1) months (range: 6 to 112 months) and survived healthily without new aortic events. Conclusions: Most of TAD cases are ascribed to Stanford type B aortic dissection, and a satisfactory short-term and mid-term result can be achieved by emergency TEVAR in most patients. Some patients can achieve good long-term results by open surgery with artificial vascular replacement.

[Clinicopathological features and prognosis of synchronous bilateral breast cancers].

Objective: To study the clinicopathologic characteristics and relevant factors affecting prognosis of patients with synchronous bilateral breast cancer. Methods: The clinical data, pathologic characteristics and immunohistochemical expression characteristics of 151 patients with synchronous bilateral breast cancers diagnosed in Peking Union Medical College Hospital from 2008 to 2018 were collected and analyzed. The factors affecting the prognosis were analyzed by Log rank test, Kaplan-Meier survival analysis, Cox regression and other methods. Results: Synchronous bilateral breast cancer cases accounted for 1.2% (151/12 239) of all breast cancer patients in the same period, and 14.6% (22/151) had a family history. The patients' age range was 22-88 years, mainly female, with a mean survival of 42.5 months. There were 106 patients with synchronous bilateral invasive breast cancers, 6 patients with synchronous bilateral breast cancer in situ, and 39 patients with unilateral invasive breast cancer and unilateral breast cancer in situ. In synchronous bilateral invasive breast cancers, the histological type was mainly non-specific type (84.9%, 180/212), the histological grade was mainly Grade 2 (60.8%,129/212), the TNM stage was mainly stage Ⅰ (50.5%, 107/212), the tumor size was mainly T1 (68.9%, 146/212), and the regional lymph node was mainly N0 (61.8%, 131/212). The molecular subtypes were mainly Luminal A-like (38.1%, 75/197) and Luminal B-like (43.7%, 86/197); ER (78.2%, 154/197) and PR (72.1%,142/197)were mainly positive, and HER2 was mainly negative (91.9%, 181/197). There were 85 (80.2%) patients and 75 (70.8%) patients with the same histological type and histological grade on both sides, respectively. The concordance of tumor size T stage and the regional lymph nodes N stage were 58.5% (62/106) and 55.7% (59/106), respectively. The concordance of molecular subtype was 54.9% (50/91), and the concordance of ER, PR, HER2 and Ki-67 were 83.5% (76/91), 76.9% (70/91), 89.0% (81/91) and 59.3% (54/91), respectively. The expression of ER and PR in synchronous bilateral invasive breast cancer was significantly correlated with prognosis (P<0.05). Conclusions: Among patients with synchronous bilateral breast cancers, bilateral invasive breast cancer is the most common, the prognosis is the worst, and the pathologic characteristics of bilateral breast cancer tend to be consistent. The expression of ER and PR in synchronous bilateral invasive breast cancer is significantly correlated with prognosis, that is, best for bilateral ER-positive patients, worst for bilateral ER-negative patients, and intermediate for unilateral ER-positive patients, thus suggesting the importance of ER and PR detection in synchronous bilateral invasive breast cancers.

[Correlation analysis between Dx-pH monitoring and proton pump inhibitor test in the diagnosis of laryngopharyngeal reflux disease].

Objective: The consistency of 24-hour oropharyngeal Dx-pH monitoring and proton pump inhibitor(PPI) test in the diagnosis of laryngopharyngeal reflux disease (LPRD) was investigated. Methods: Sixty patients with laryngopharyngeal reflux (LPR) related symptoms who had never received PPI treatment were assessed by reflux symptom index (RSI) and reflux finding score (RFS) between October 2017 and October 2018, including 28 males and 38 females, aged from 16 to 72 years, with a medium age of 38 years. Prior to treatment, all patients were evaluated with 24 hours oropharyngeal Dx-pH monitoring(Restech). After empiric therapy with PPI twice-daily for 8 weeks, the efficacy was evaluated according to posttreatment RSI score.The data was analysed with Kruskal-Wallis test, Student Newman Keuls test and consistency check. Results: (1)Among all 60 patients,13 patients (21.7%) had pathologic Ryan score and all resulted responsive to PPI;27 patients (45.0%) with a negative Ryan score were unresponsive to PPI; 20 patients (33.3%) despite a negative Ryan score resulted responsive to PPI therapy. Considering responsiveness to PPI therapy as the gold standard for the diagnosis of LPRD, the sensitivity, specificity, positive predictive value and negative predictive value of Ryan score were 39.4%, 100%, 100% and 57.4% respectively. The Kappa value was 0.369 (P<0.01). (2)Among 34 patients (56.7%) with positive Dx-pH results (24-hour oropharyngeal acid reflux events≥ 3 times), 29 patients were positive and 5 patients were negative in PPI test. Among 26 patients with negative Dx-pH results (24-hour oropharyngeal acid reflux events<3 times), 4 patients were positive and 22 patients were negative in PPI test. Considering responsiveness to PPI therapy as the gold standard for the diagnosis of LPRD, the sensitivity, specificity, positive predictive value and negative predictive value of 24-hour oropharyngeal acid reflux events were 87.9%, 81.5%, 85.3% and 84.6% respectively. The Kappa value was 0.696(P<0.01). Conclusions: There is a positive correlation between 24-hour oropharyngeal Dx-pH monitoring positive results (24-hour oropharyngeal acid reflux events≥3 times) and PPI test in the diagnosis of LPRD. The 24-hour oropharyngeal Dx-pH monitoring can be a promising tool for the diagnosis of suspected LPRD patients, and more sensitive and accurate Dx-pH diagnostic index will be required in the clinic.

Expression of T follicular helper lymphocytes with different subsets and analysis of serum IL-6, IL-17, TGF-ß and MMP-3 contents in patients with rheumatoid arthritis.

OBJECTIVE: To investigate the expression levels of T follicular helper (Tfh) with different subsets in patients with rheumatoid arthritis (RA) and their serum interleukin-6 (IL-6), interleukin-17 (IL-17), transforming growth factor-ß (TGF-ß) and matrix metalloproteinase 3 (MMP-3) contents. PATIENTS AND METHODS: The medical records of 45 RA patients in the Department of Rheumatology and Immunology in the First Affiliated Hospital of Chengdu Medical College from January 2016 to April 2018 were retrospectively analyzed. They were divided into the RA high activity group (24 cases, group A) (DAS28 score ≥ 5.0) and RA low activity group (21 cases, group B) (3.2 < DAS28 score < 5.0). At the same time, 20 healthy subjects were selected as a control group. Flow cytometry was used to detect the expression levels of Tfh1, Tfh2 and Tfh17, enzyme-linked immunosorbent assay to detect serum IL-6, IL-17, IL-21 and MMP-3 concentrations. The correlation of Tfh cells with IL-6, IL-17, IL-21 and MMP-3 was analyzed. RESULTS: Those of peripheral blood mononuclear cell (PBMC) Tfh2 and Tfh17 cells were significantly higher in group A than those in group B (p < 0.05). Compared with the control group, the concentrations of serum IL-6, IL-17 and MMP-3 significantly increased (p < 0.001), but that of serum TGF-ß markedly decreased in group A and group B (p < 0.01). The concentrations of serum IL-6, IL-17 and MMP-3 were remarkably higher in group A than those in group B (p < 0.001), but that of serum TGF-ß was significantly lower in group A than that in group B (p < 0.001). The expression level of PBMC Tfh2 cells, PBMC Tfh17 cells was positively correlated with serum IL-6, IL-17 and MMP-3. The expression levels of Tfh2 and Tfh17 cells are positively correlated with serum IL-6, IL-17 and MMP-3 concentrations, negatively correlated with serum TGF-ß concentration. CONCLUSIONS: Tfh2 and Tfh17 are expected to be new targets for immunotherapy in RA patients.

Krebs von den Lungen-6 associated with chest high-resolution CT score in evaluation severity of patients with interstitial lung disease.

AIMS: The purpose of this prospective, single-center study was to measure the value of Krebs von den Lungen-6 (KL-6), a kind of transmembrane mucoprotein, in diagnosing interstitial lung disease (ILD) and in assessing the severity of ILD. METHODS: We enrolled 184 patients and 30 healthy controls. Ninety-eight patients were diagnosed with ILD, 47 with pneumonia, 19 with non-small cell lung cancer without ILD (NSCLC/non-ILD) and 20 with other lung diseases. Serum KL-6 levels, CT scores of high-resolution computerised tomography (HRCT) and pulmonary function in ILD patients were assessed. RESULTS: The mean value of serum KL-6 in patients with ILD, pneumonia, NSCLC/non-ILD, other lung diseases and healthy controls were 1000.67±882.73U/ml, 234.11±91.02U/ml, 269.95±149.23U/ml, 234.85±83.51U/ml and 189.03±55.50U/ml, respectively. Serum KL-6 levels of patients with ILD were significantly higher than that of other groups (P<0.000). The level of serum KL-6 in patients with pneumonia, NSCLC/non-ILD and other lung diseases was also statistically higher than healthy controls (P<0.05). When the cut-off value was 312U/ml, the sensitivity and specificity of KL-6 for the diagnosis of ILD was 84.7% and 85.3% respectively (AUC: 0.936, 95% CI: 0.906-0.965). The serum KL-6 levels in patients with ILD were significantly positively correlated with the CT scores (r=0.539, P=0.000) and negatively correlated with DLCO (r=-0.513, P=0.000). CONCLUSION: Serum KL-6 might be useful in the diagnosis of ILD, especially in the hard-to-diagnose cases, with high sensitivity and specificity. Furthermore, KL-6 might be a valuable marker for evaluation of ILD severity.

Study on sildenafil combined with inhalational nitric oxide therapy on the curative effects and serum levels of HIF-1α, ET-1, and calcium in neonatal pulmonary hypertension.

OBJECTIVE: To explore the effect of sildenafil combined with inhalational nitric oxide (NO) therapy on the curative effects and serum levels of hypoxia-inducible factor (HIF)-1α, endothelin-1 (ET-1), and calcium in persistent pulmonary hypertension of the newborn (PPHN). PATIENTS AND METHODS: Eighty-six patients with neonatal pulmonary hypertension treated in Xuzhou Children's Hospital from March 2015 to February 2016 were randomly divided into the observation group and control group, treated with sildenafil and sildenafil combined with inhalational NO, respectively. The clinical efficacy of newborns in the two groups was compared. Fraction of inspiration O2 (FiO2), Oxygen Index (OI), blood oxygen partial pressure (PaO2), blood oxygen saturation (SpO2), and pulmonary arterial pressure of newborns in the two groups were compared before treatment and 2 h, 12 h, and 24 h after treatment. The serum levels of HIF-1α, ET-1, and calcium of patients in the two groups were compared before treatment and 3, 5, 7 days after treatment. RESULTS: The total effective rate of the observation group (95.34%) was significantly higher than that of the control group (74.41%) (p<0.05). After treatment, FiO2, OI, and pulmonary arterial pressure of patients in the two groups decreased, and the decrease in the observation group was significantly lower than in the control group (p<0.05). After treatment, PaO2 and SpO2 of patients in the observation group were higher than those of the control group. The levels of HIF-1α and ET-1 of patients in the two groups decreased and were significantly lower in the observation group compared with the control group. The levels of calcium of patients in the two groups increased and were significantly higher in the observation group than the control group (p<0.05). CONCLUSIONS: Sildenafil combined with inhalational NO therapy for neonatal pulmonary hypertension can quickly improve oxygenation, effectively reduce pulmonary arterial hypertension, and is worthy of clinical application.

[Clinicopathologic features of gastric adenocarcinoma based on the revised Lauren's classification].

Objective: To compare the clinicopathologic features and prognosis of the subtypes in a consecutive series of gastric cancers (GC) patients basing on the revised Lauren's classification so as to better understand the biological behavior of GC. Methods: The surgically resected GC from Peking Union Medical College Hospital during 2003-2005 were reviewed for patients' age, gender, tumor size, location, Borrman classification, depth of invasion, lymph node metastasis, vascular invasion, and tumor growth pattern (Ming classification). Results: One hundred and sixty-six GC cases were enrolled and classified into four groups: intestinal GC (30, 18.1%), diffuse GC (56, 33.7%), solid GC (9, 5.4%), and mixed GC (71, 42.8%). Intestinal GC patients were older[ (63.2±11.3) years], with a male predominance, and were more frequently found in the antrum. Intestinal GC was the most common subtype for early GC, and tend to develop liver metastases. Diffuse GC patients were youngest [(52.2±12.7) years], with no gender difference, and were usually found in the antrum. Microscopically, diffuse GC were more likely infiltrative (51/56, 91.1%), and tended to metastasize by lymphatic pathway. Solid GC were usually large[ (6.4±2.2) cm], with a male predominance, and the most frequent site was the body/fundus. Solid GC were more likely to show expansile growth pattern with greater depth of invasion (8 of 9 cases were T3/4), but lower rate of lymphatic metastasis. Mixed GC also showed a male predominance, usually found in the antrum, and showed an infiltrative growth pattern (49/71, 69.0%). Though there was fewer T3/4 than solid and diffuse GC, mixed GC were more likely to show lymph nodes, vascular metastases and liver metastases (13/71, 18.3%). TNM staging, lymph nodes metastasis, lymphovascular invasion and revised Lauren's classification were four independent prognostic factors on multivariate analysis(P<0.05). The survival of patients with mixed GC were significantly worse than patients with other histological types. Conclusion: Revised Lauren's classification for GC has four distinct subgroups and can be used as independent prognostic factors.

Study on the correlation of changes of IGF-1, GH, and NGB levels and NBNA score in neonates with hypoxic ischemic encephalopathy.

OBJECTIVE: The aim of this work was to investigate the correlation between dynamic changes of serum insulin-like growth factor 1 (IGF-1), growth hormone (GH), neuroglobin (NGB), and neonatal behavioral neurological assessment (NBNA) scores in different periods in neonates with hypoxic ischemic encephalopathy (HIE). PATIENTS AND METHODS: Sixty HIE patients in the Neonatal Department of our hospital were selected. They were divided into the mild group (35 cases), moderate group (19 cases), and severe group (six cases) according to the diagnostic criteria. During the same period, 18 neonatal patients born at term in our hospital were chosen as the control group. Data were analyzed by SPSS19.0 statistical software (SPSS Inc., Chicago, IL, USA). The dynamic changes of IGF-1, GH, and NGB in different periods, as well as NBNA scores in HIE patients and in the control group, were analyzed. Furthermore, we analyzed the degree of correlation of IGF-1, GH, and NGB in different periods as well as NBNA scores in HIE patients and in the control group. RESULTS: 1- IGF-1 levels between the three groups of HIE patients and control group had significant differences (p<0.05); 2- Comparing GH levels between the HIE experimental groups and control group, there was no statistical significance; 3-Comparing serum NGB levels between the three HIE experimental groups and control group, there were significant differences (p<0.05); 4- Comparing NBNA scores of the three groups of HIE patients and control group, there was a significant difference between the mild group and control group; 5- Serum IGF-1 and NBNA scores were positively correlated in the acute and recovery phase, while NGB level and NBNA scores were negatively correlated in the acute and recovery phase (p<0.05), which had statistical significance. CONCLUSIONS: In neonatal HIE, serum IGF-1, GH, and NGB levels change. IGF-1 and NGB levels correlate with the prognosis of HIE.

[Clinical and immunohistopathologic study of phosphaturic mesenchymal tumor].

Objective: To study the clinicopathological characteristics and immunohistochemical phenotype of phosphaturic mesenchymal tumor (PMT) . Methods: The clinicopathological data and immunohistochemical profiles were obtained retrospectively from 206 patients diagnosed with PMT at Peking Union Medical College Hospital (PUMCH) during July 2008 to September 2017, with a review of literature. Results: The mean age of PMT patients was 42 years (range 13 to 70 years), with a male to female ratio of 1.1∶1.0. All patients presented with different degree of bone pain, muscle weakness, shorten of stature, thoracic deformity and pathological fractures, with hypophosphatemia and high serum ALP. Phosphatemia returned to normal within 1 week after operation in all cases underwent complete tumor resection. The duration of osteomalacia before resection (documented in 197 cases) ranged from 20 days to 40 years (average 5.7 years). The average blood phosphorus concentration raised from 0.49 mmol/L to 0.92 mmol/L before and after tumor resection (P<0.01), with 147 cases (84.0%, 147/175) returned to normal range within 2 weeks. The rate or blood phosphorus concentration recovery in 15 days after operation was 79.6% in average, displayed significant differences between patients with complete resection and those with partial resection (85.4% vs. 21.1%, P<0.01). PMT lesions mainly involved lower extremities (55.8%), followed by head and neck (29.1%). In immunohistochemical study, all cases were positive for vimentin (100.0%), while most cases were positive for NSE (96.3%), CD56 (94.2%), FGF23(88.4%), CD68 (88.3%), D2-40 (70.9%), CD34 (23.1%), SMA (55.5%), bcl-2 (59.8%) and CD99 (47.1%). The Ki-67 positive index of tumor varied from less than 2% (51.4%), 3% to 10% (41.3%) to >10% (7.2%). Conclusions: PMT mainly occurs in lower limbs or head and neck, with unique clinical characteristics and blood biochemical indexes. The tumor expresses a variety of immunohistochemical markers, indicating the potential of multi-directional differentiation. Clinical profile, blood biochemistry testing and immunohistochemical phenotype is helpful for diagnosis of PMT.

[Primary carcinoid of ovary: a clinicopathologic analysis of 17 cases].

Objective: To study the clinicopathologic feature, diagnostic strategy and prognostic significance of primary carcinoid of the ovary (PCOTO). Methods: A series of 17 patients previously diagnosed as PCOTO at Department of Pathology, Peking Union Medical College Hospital during the period from 2002 to 2017 were evaluated with clinical data analysis, histopathology and immunohistochemistry, and the patients were followed up and the relevant literatures were reviewed. Results: The age of patients ranged from 24 to 64 years (mean, 42 years). Fourteen patients were found a pelvic mass for a health check-up, and only 3 patients presented with pain in the lower abdomen. The left ovary was involved initially in ten patients, and the right in seven. The major axis of the tumor ranged from 2 to 14 cm. The surface of these tumors was smooth. Seven of the tumors were solid-cystic, 6 were cystic and 4 were solid. Under light microscope, 6 cases were diagnosed as strumal carcinoid, 4 cases were insular carcinoid, 4 cases were trabecular carcinoid, 3 cases were insular and trabecular mixed type carcinoid and 1 case was mucinous carcinoid. The mitotic figures were no more than 1/10 HPF.There were 11 cases complicated with other ovarian tumors, including 10 cases with teratoma, and 1 case with mucinous cystic adenoma. The paraffin-embedded tissues of all cases showed immunoreactivity for NSE and Syn, and the positive propotion of CgA was 10/17. TTF1 was positive in thyroid follicles and negative in strumal carcinoid. The positive index of Ki-67 was no more than 2%. Follow-up of 13 to 188 months showed 16 patients without recurrence and 1 patients were loss to follow-up. Conclusions: PCOTO is very rare. Most of the patients are found with a mass during health check-up in unilateral ovary and without obvious clinical symptoms. Histologically, the tumor always exists with other ovarian tumors, including teratoma and mucinous cystic adenoma, with relatively good prognosis.

Correlation between dual-energy spectral CT imaging parameters and pathological grades of non-small cell lung cancer.

AIM: To investigate the correlation between pathological grades of non-small cell lung cancers (NSCLCs) and quantitative parameters generated in dual-energy spectral computed tomography (CT). MATERIALS AND METHODS: Fifty-three patients with NSCLCs who underwent preoperative dual-energy spectral CT imaging and surgical resection were evaluated retrospectively. These patients were divided into a low-grade group and a high-grade group based on their histopathological differentiation. In the arterial phase (AP) and venous phase (VP), iodine concentration (IC) in cancers was measured in iodine-based material decomposition images, and normalised to the IC in the aorta to calculate the normalised iodine concentration (NIC), the spectral CT curve was generated from the monochromatic images to calculate the slope of the spectral curve (λHU). Differences in quantitative parameters (NIC and λHU) were compared using the two-sample t-test. The correlations between spectral CT parameters and tumour grades were evaluated using the Spearman rank correlation analysis. Receiver operating characteristic (ROC) curves were generated to calculate their diagnostic efficacies. RESULTS: The NIC and λHU in the low-grade NSCLC group were significantly higher than those in the high-grade NSCLC group both in AP and VP (all p<0.001). There was a significant negative correlation between spectral CT parameters and pathological grades by the Spearman rank correlation (all p<0.001). ROC analysis indicated that λHU in VP provided the best diagnostic performance in distinguishing high-grade cancers from low-grade cancers (area under the ROC curve [AUC], 0.914; sensitivity, 85.7%; specificity, 84.4%). CONCLUSION: The quantitative parameters in dual-energy spectral CT imaging provide useful information to differentiate the pathological grades of NSCLCs.

Cardiotoxicity evaluation of nine alkaloids from Rhizoma Coptis.

PURPOSE: Alkaloids derived from Rhizoma Coptis (RC) has been widely applied to clinical treatments in China. However, the toxicity of RC and the alkaloids from RC remained controversial. The research is designed to clarify the cardiotoxic compounds found in RC. METHODS: In this study, the real-time cellular analysis cardio system and the high-content analysis were applied to monitor the function of cardiomyocytes (CMs) in the treatment of nine alkaloids in RC. Luciferase-coupled adenosine triphosphate (ATP) assay was used to detect cell viability. RESULTS: The results showed that berberine, palmatine, berbamine, and oxyberberine were cardiotoxic, which resulted in arrhythmia and cardiac arrest on CMs in a time- and dose-dependent manner. Meanwhile, berbamine and oxyberberine caused shrinkage and detachment on CMs at 10 µM. Cytotoxicity was induced by these two compounds with decline in cell index and ATP depletion. Cardiotoxicity or cytotoxicity was not observed in the other five alkaloids within 10 µM. CONCLUSION: For the first time, the cardiotoxicity of the nine alkaloids was evaluated to clarify the cardiotoxic components in RC. Furthermore, the experimental evidences were provided to support the safety of drug application.