[Oncological outcomes of laparoscopic radical trachelectomy for early stage cervical cancer].

Objective: To analyze and summarize the oncological outcomes after laparoscopic radical trachelectomy (LRT) for early stage cervical cancer. Methods: The clinical data and follow-up results of 148 patients with early stage cervical cancer who underwent LRT in Renji Hospital, School of Medicine, Shanghai Jiao Tong University from July 2014 to June 2023 were collected, while tumor outcomes and postoperative pregnancy were analyzed retrospectively. Results: (1) General situation: the median age of 148 patients with LRT was 33 years (range: 19-42 years). Pathological type: 111 cases of squamous cell carcinoma, 36 cases of adenocarcinoma, 1 case of adenosquamous carcinoma. International Federation of Gynecology and Obstetrics (2018) stage: 17 cases of stage Ⅰa1 with lympho-vascular space invasion, 25 cases of stage Ⅰa2, 102 cases of stage Ⅰb1, and 4 cases of stage Ⅰb2. (2) Tumor outcomes: 148 patients were followed up regularly after LRT, and the median follow-up time was 59 months (range: 2-104 months). During the follow-up period, 5 cases of tumor recurred (including 1 death), and the median recurrence time was 10 months (range: 4-33 months). Among them, there were 3 cases of pelvic metastasis, 1 case of distant metastasis, and 1 case of both pelvic and distant metastasis. Both 3-year and 5-year disease-free survival rates of 148 patients were 94.5%, and the 5-year overall survival rate was 98.9%. (3) Postoperative pregnancy: among 148 patients with LRT, 67 patients had pregnancy requirements, followed up for 1 year, and 20 of them were pregnant, with a pregnancy rate of 29.9% (20/67). Among the 20 pregnant patients, 2 cases early abortion, 1 case mid-term abortion, and 17 cases gave birth (including 4 cases of premature birth and 13 cases of full-term birth). Conclusion: Under the condition of strict control of surgical indications, guaranteed surgical scope and tumor-free operation, LRT in patients with early cervical cancer has a good outcome.

[Plurihormonal PIT1-lineage pituitary neuroendocrine tumors: a clinicopathological study].

Objective: To investigate the clinicopathological characteristics of plurihormonal PIT1-lineage pituitary neuroendocrine tumors. Methods: Forty-eight plurihormonal PIT1-lineage tumors were collected between January 2018 and April 2022 from the pathological database of Sanbo Brain Hospital, Capital Medical University. The related clinical and imaging data were retrieved. H&E, immunohistochemical and special stains were performed. Results: Out of the 48 plurihormonal PIT1-lineage tumors included, 13 cases were mature PIT1-lineage tumors and 35 cases were immature PIT1-lineage tumors. There were some obvious clinicopathological differences between the two groups. Clinically, the mature plurihormonal PIT1-lineage tumor mostly had endocrine symptoms due to increased hormone production, while a small number of immature PIT1-lineage tumors had endocrine symptoms accompanied by low-level increased serum pituitary hormone; patients with the immature PIT1-lineage tumors were younger than the mature PIT1-lineage tumors; the immature PIT1-lineage tumors were larger in size and more likely invasive in imaging. Histopathologically, the mature PIT1-lineage tumors were composed of large eosinophilic cells with high proportion of growth hormone expression, while the immature PIT1-lineage tumors consisted of chromophobe cells with a relatively higher expression of prolactin; the mature PIT1-lineage tumors had consistently diffuse cytoplasmic positive staining for keratin, while the immature PIT1-lineage tumors had various expression for keratin; the immature PIT1-lineage tumors showed more mitotic figures and higher Ki-67 proliferation index; in addition, 25.0% (12/48) of PIT1-positive plurihormonal tumors showed abnormal positive staining for gonadotropin hormones. There was no significant difference in the progression-free survival between the two groups (P=0.648) by Kaplan-Meier analysis. Conclusions: Plurihormonal PIT1-lineage tumor belongs to a rare type of PIT1-lineage pituitary neuroendocrine tumors, most of which are of immature lineage. Clinically increased symptoms owing to pituitary hormone secretion, histopathologically increased number of eosinophilic tumor cells with high proportion of growth hormone expression, diffusely cytoplasmic keratin staining and low proliferative activity can help differentiate the mature plurihormonal PIT1-lineage tumors from the immature PIT1-lineage tumors. The immature PIT1-lineage tumors have more complicated clinicopathological characteristics.

A deep-learning model using enhanced chest CT images to predict PD-L1 expression in non-small-cell lung cancer patients.

AIM: To develop a deep-learning model using contrast-enhanced chest computed tomography (CT) images to predict programmed death-ligand 1 (PD-L1) expression in patients with non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: Preoperative enhanced chest CT images and immunohistochemistry results for PD-L1 expression (<1% and ≥1% were defined as negative and positive, respectively) were collected retrospectively from 125 NSCLC patients to train and validate a deep-learning radiomics model (DLRM) for the prediction of PD-L1 expression in tumours. The DLRM was developed by combining the deep-learning signature (DLS) obtained from a convolutional neural network and clinicopathological factors. The indexes of the area under the curve (AUC), integrated discrimination improvement (IDI), and decision curve analysis (DCA) were used to evaluate the efficiency of the DLRM. RESULTS: DLS and tumour stage were identified as independent predictors of PD-L1 expression by the DLRM. The AUCs of the DLRM were 0.804 (95% confidence interval: 0.697-0.911) and 0.804 (95% confidence interval: 0.679-0.929) in the training and validation cohorts, respectively. IDI analysis showed the DLRM had better diagnostic accuracy than DLS (0.0028 [p<0.05]) in the validation cohort. Additionally, DCA revealed that the DLRM had more net benefit than the DLS for clinical utility. CONCLUSION: The proposed DLRM using enhanced chest CT images could function as a non-invasive diagnostic tool to differentiate PD-L1 expression in NSCLC patients.

[Clinicopathological characteristics of H3K27-altered diffuse midline glioma and evaluation of NTRK as its therapeutic target].

Objective: To investigate the clinicopathological characteristics of H3K27-altered diffuse midline glioma (DMG), and to analyze DMG's prognostic factors, and subsequently, to study the possibility of using NTRK as a therapeutic target for DMG. Methods: A total of 232 DMG diagnosed at the Sanbo Brain Hospital, Capital Medical University, Beijing, China from July 2016 to March 2021 were collected. Their clinical, radiological and pathological features, the ratio of MGMT promoter methylation, expression of NTRK, and characteristics of NTRK gene fusion were analyzed. The prognostic values of different factors were also studied, including age, tumor location, histological grade, gene and protein expression of NTRK, and postoperative adjuvant therapy. Results: Among the 232 DMG cases, there were 8 patients with both primary and relapse tumors on the record. Thus, a total of 224 patients were analyzed, including 118 males and 106 females. There were 126 adults (>18 years of age) and 98 children (≤18 years of age). Notably, the most frequent location was thalamus (41/126, 32.5%) in adults, but brainstem (59/96, 60.2%) in children. The lesions showed T1 hypointensity or isointensity, and T2 hyperintensity. However, contrast enhancement patterns of the tumors varied, with many tumors lacking contrast-enhancing. The histological grades included grade 2 (9/224, 4.0%), grade 3 (41/224, 18.3%) and grade 4 (174/224, 77.7%). Two hundred and twenty-four DMGs were diffusely positive for H3K27M and negative for H3K27me3. The ratio of MGMT promoter methylation was low (1/45, 2.2%). One hundred and seventy-seven of the 224 cases (177/224, 79.0%) were positive for NTRK. Fifty cases were analyzed using fluorescence in situ hybridization. Among them, five DMGs (positive rate, 10.0%) were NTRK fusion positive. This study showed that there were no differences between adult and pediatric DMGs in histological grading, expression of NTRK, and NTRK gene fusion. One hundred and fifty-nine patients were included in the follow-up analysis (P>0.05). During the follow-up period, 109/159 patients (69.6%) died of the disease, with a median survival time of 12 months (range 1 to 55 months). Univariate log-rank analysis showed that age, location, surgical procedure and postoperative adjuvant therapy were associated with overall survivals of the DMG patients (P<0.05). Conclusions: The prognosis of DMG is poor overall. There are differences between adult and pediatric DMGs in anatomic location and prognosis, but not in other features. NTRK1 gene fusion is detected in 10.0% of the tumors. It suggests that TRK inhibitor might be a choice for treating DMG.

[Pediatric SMARCB1/INI1-deficient poorly differentiated chordoma of the skull base: report of five cases and review of literature].

Objective: To investigate the clinicopathological characteristics and differential diagnosis of pediatric SMARCB1/INI1-deficient poorly differentiated chordoma (PDC) of the skull base. Methods: Five cases of SMARCB1/INI1-deficient PDC were identified in 139 cases of chordoma diagnosed in Sanbo Brain Institute, Capital Medical University, Beijing, China from March 2017 to March 2021. The clinical and imaging data of the 5 PDCs were collected. H&E and immunohistochemical staining, and DNA methylation array were used, and the relevant literatures were reviewed. Results: All 5 PDCs were located at the clivus. The average age of the patients was 6.4 years, ranging from 3 to 16 years. Three patients were female and two were male. Morphologically, in contrast with classical chordomas, they presented as epithelioid or spindle tumor cells organized in sheets or nests, with necrosis, active mitoses, and infiltration into surrounding tissue. All cases showed positivity of CKpan, EMA, vimentin and brachyury (nuclear stain), and loss of nuclear SMARCB1/INI1 expression. S-100 protein expression was not frequent (2/5). Ki-67 proliferative index was high (20%-50%). All cases had over-expressed p53. It was necessary to differentiate SMARCB1/INI1-dificient PDC from SMARCB1/INI1-dificient tumors occurring at skull base of children or the tumors with epithelial and spindle cell morphological features. The 3 PDCs with DNA methylation testing showed the methylation profiles different from the pediatric atypical teratoid/rhabdoid tumors. They formed an independent methylation profile cluster. The clinical prognosis of the 5 patients was poor, and the overall survival time was 2-17 months. Conclusions: PDC is a special subtype of chordoma, which often affects children and occurs in the clivus. The PDC shares epithelioid or spindle cell morphologic features which are different from the classic chordoma. Besides the typical immunohistochemical profile of chordoma, PDC also has loss of nuclear SMARCB1/INI1 expression and distinct epigenetic characteristics.

[Mid- and long-term results of endovascular aneurysm repair for abdominal aortic aneurysms: a single center's experience for 10 years].

Objective: To examine the mid- and long-term outcomes of endovascular aneurysm repair (EVAR). Methods: This was a retrospective cohort study of 540 patients with abdominal aortic aneurysm who received EVAR at Department of Vascular Surgery, The First Affiliated Hospital, Sun Yat-sen University from January 2009 to December 2018. There were 503 males and 37 females, aged of (69±8) years (range: 44 to 87 years). Clinical data including concomitant disease, aneurysm size and surgical data were collected and patients were followed up after operation. The cumulative survival rate was assessed using the Kaplan-Meier estimator and multivariate Cox regression was used to analyze the independent prognosis factors. Results: The technical success rate was 91.1% (492/540). The perioperative mortality rate was 1.3% (7/540) and the follow-up rate was 91.7% (489/533). The median follow-up time was 45(63) months (range: 1 to 133 months). The all-cause mortality rate was 21.3% (104/489) and the aneurysm-related mortality rate was 6.3% (31/489) during follow-up period. The overall cumulative survival rate of 1-, 3-, 5- and 10-year were 95.1%, 84.0%, 69.5% and 38.6%, respectively, while freedom from aneurysm-related death were 98.4%, 93.3%, 88.4% and 84.4%. During the follow-up period, the complications rate was 9.0% (44/489), and the re-intervention rate was 4.9% (24/489). Cox regression analysis showed that elder age (HR=2.15, 95%CI: 1.41 to 3.26, P<0.01), preoperative aneurysm rupture (HR=2.72, 95%CI: 1.78 to 4.15, P<0.01) and short neck aneurysm (HR=1.97, 95%CI: 1.07 to 3.61, P=0.029) were independent prognosis factors for long-term survival after EVAR. Connclusion: EVAR has low perioperative mortality, high technical success rate, and satisfactory mid-and long-term outcomes.

[Association of single nucleotide polymorphisms of TBX5 gene and environmental exposure index with susceptibility to oral cancer].

Objective: To explore the association of TBX5 polymorphisms and environmental exposure index with susceptibility to oral cancer. Methods: A case-control study was conducted to collect 300 oral cancer patients hospitalized in the Department of Oral and Maxillofacial Surgery, the First Affiliated Hospital of Fujian Medical University from September 2010 to December 2016. A total of 445 non-tumor patients were selected as the control group. Questionnaires were used to collect the information of all subjects and 5 ml peripheral blood was collected to detect single nucleotide polymorphisms (SNPs) of the rs10492336 locus of TBX5 gene. According to the environmental exposure index score, subjects were divided into two groups, low risk group (0-2.31) and high risk group (2.32-11.76). To analyze the association of TBX5 gene rs10492336 SNPs, environmental exposure index and oral cancer and its interactions. Results: The age of all subjects in the case group and control group were (56.19±13.10) years and (54.56±12.48) years old. Compared with CC genotype, the OR (95%CI) values of the co-dominant genetic model AC genotype and the dominant genetic model AC+AA genotype were 0.69 (0.49-0.98) and 0.70 (0.51-0.97), respectively. Compared with the low risk group, the OR (95%CI) risk of oral cancer in the high risk group was 3.72 (2.55-5.43). The results of gene-environment interaction analysis showed that compared with the group with CC genotype and high risk of environmental exposure index, the OR (95%CI) value of oral cancer in the group with AC+AA genotype and low risk of environmental exposure index was 0.18(0.10-0.31). Furthermore there was a multiplicative interaction between rs10492336 SNPs and environmental exposure index (ß=-0.405, P<0.001). Conclusion: This study suggests that the TBX5 gene rs10492336 SNPs and environmental exposure index were associated with oral cancer. And there was a multiplication interaction between rs10492336 SNPs and environmental exposure index.

[Association between the time of neutrophils to the lowest and prognosis of patients with esophageal squamous cell carcinoma treated with non-operative therapy].

Objective: To investigate the association between the time of neutrophils to the lowest and prognosis of patients with esophageal squamous cell carcinoma (ESCC) treated with non-operative therapy. Methods: The clinical data of 325 non-operative treated ESCC patients were collected in this study. The X-title software was applied to establish optimal threshold of neutrophil reduction to the lowest value. According to the optimal threshold, the patients were divided into early group (115 cases) and late group (210 cases). The clinical features and survival time of the two groups were compared, and the factors of prognosis were analyzed by Cox regression model with univariate and multivariate analysis. Results: The X-title software demonstrated the optimal cutoff values for the time of neutrophils to the lowest was 39 days. The median overall survival time was 21.0 months in the early group which was significantly higher than that in the late group (16.0 months). Multivariate Cox regression analysis showed that the treatment methods and the time of neutrophils to the lowest were independent factors for overall survival of patients with ESCC treated by non-surgical therapy. Compared with radiotherapy alone, concurrent chemoradiation could benefit the survival (HR=0.64, P=0.026). The prognosis of patients in the late group of neutrophils to the lowest (HR=1.38, P=0.038) was poor compared with the early group. Furthermore, stratified by treatment methods, the overall survival of two groups showed statistically significant difference only in patients received concurrent chemoradiation. The mortality risk in the late group was higher than that in the early group (HR=3.53, P=0.010). Conclusion: The time of neutrophils to the lowest is an independent prognosis factor for non-operative treated ESCC patients. The prognosis of patients in the early group is better than that in the late group.

MiR-940 regulates angiogenesis after cerebral infarction through VEGF.

OBJECTIVE: The aim of this study was to investigate whether miR-490 was involved in the regulation of angiogenesis after cerebral infarction by regulating vascular endothelial growth factor (VEGF) expression. MATERIALS AND METHODS: Sprague Dawley (SD) rats were used to establish a middle cerebral artery infarction model. Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was used to detect the expression levels of miR-940 in serum and brain tissues at 1, 3, and 7 days after cerebral infarction. Meanwhile, miR-940 expression in brain microvascular endothelial cells (BMECs) after Oxygen-Glucose Deprivation (OGD) for 2, 4, 6 hours was measured by qRT-PCR, respectively. The cells were transfected with miR-940 mimics/inhibitor to achieve miR-940 overexpression or inhibition. Subsequently, the angiogenesis and proliferation ability of the cells was evaluated by 5-ethynyl-2'-deoxyuridine (EDU) assay. Besides, the mRNA and protein expression levels of VEGF after miR-940 transfection were detected by Western blot and qRT-PCR, respectively. Finally, recovery experiment was used to determine whether miR-940 affected angiogenesis and proliferation of BMECs by regulating VEGF expression. RESULTS: The expression level of miR-940 in serum and brain tissues of rats was markedly decreased at 1, 3, and 7 days after cerebral infarction, which was then recovered on the 7th day. After 2, 4, and 6 hours of glucose and oxygen deprivation in BMECs, the expression level of miR-940 was significantly decreased. However, it was evidently recovered after 6 hours. After miR-940 over-expression in BMECs, the angiogenesis and proliferation of BMECs were remarkably inhibited. Conversely, miR-940 inhibitor transfection could significantly promote the formation of luminal cells and the proliferation of BMECs. QRT-PCR results showed that miR-940 overexpression down-regulated the expression level of VEGF, and the same findings were observed at the protein level. Further studies revealed that VEGF could reverse the inhibitory effect of miR-940 on lumen formation and cell proliferation in BMECs. CONCLUSIONS: The expression of miR-940 was downregulated in cerebral infarction. The low expression of miR-940 could promote the angiogenesis ability of cerebral microvascular endothelial cells after cerebral infarction, which might be resulted from the inhibitory effect of miR-940 on VEGF.

Ipriflavone promotes osteogenesis of MSCs derived from osteoporotic rats.

OBJECTIVE: To explore whether Ipriflavone could prevent postmenopausal osteoporosis (PMOP) and improve bone quality via promoting osteogenesis of bone marrow-derived mesenchymal stem cell (MSCs). MATERIALS AND METHODS: MSCs were extracted from rats and identified using flow cytometry. Osteogenic specific genes and adipogenic specific genes in MSCs were detected by quantitative Real-time polymerase chain reaction (qRT-PCR). The effect of Ipriflavone on osteogenesis was detected by CCK-8 (cell counting kit-8) assay, ALP activity detection, alizarin red staining and Western blot, respectively. Furthermore, ovariectomized PMOP rat model was constructed. The effects of Ipriflavone on osteogenesis, BMD and bone biomechanical properties of ovariectomized rats were detected. RESULTS: MSCs derived from ovariectomized rats exerted multiple differentiation potentials. CCK-8 assay indicated that 0.8 µM Ipriflavone were the maximal dose that did not affect MSCs proliferation, which was selected for the following experiments. In vitro researches demonstrated that Ipriflavone remarkably promoted MSCs osteogenesis. In vivo results indicated that BMD, BV/TV, Tb.N and Tb.Th were decreased in ovariectomized rats than those of rats in sham group. Ipriflavone treatment remarkably prevented osteoporosis via promoting MSCs osteogenesis in ovariectomized rats. CONCLUSIONS: Ipriflavone prevents postmenopausal osteoporosis, improves bone quality and protects bone tissue via promoting MSCs osteogenesis.

[A novel prognostic index for oral cancer in Fujian province].

Objective: To explore the survival factors and construct a prognostic index (PI) for oral squamous cell carcinoma (OSCC). Methods: From January 2004 to June 2016, a total of 634 patients with pathologically confirmed OSCC were recruited in a hospital of Fujian. The clinical and follow-up data of all the patients with pathologically confirmed OSCC were collected to identify the factors influencing the prognosis of OSCC. All the patients were randomly divided into two groups: modeling group (modeling dataset, n=318) and validation group (validation dataset, n=316). Randomization was carried out by using computer-generated random numbers. In the modeling dataset, survival rates were calculated using Kaplan-Meier method and compared using the log-rank test. Cox regression model was used to estimate the hazard ratio (HRs) and 95% confidence intervals (CIs) of prognosis factors. An PI for OSCC patients prognostic prediction model was developed based on ß value of each significant variable obtained from the multivariate Cox regression model. Using the tertile analysis, patients were divided into high-risk group, moderate-risk group, and low-risk group according to the PI, the Akaike information criterion (AIC) and Harrell's c-statistic (C index) were used to evaluated the model's predictability. Results: Results from the multivariate Cox regression model indicated that aged ≥55 years (HR=2.22, 95%CI: 1.45-3.39), poor oral hygiene (HR=2.12, 95%CI: 1.27-3.54), first diagnosis of lymph node metastasis (HR=5.78, 95%CI: 3.60-9.27), TNM stage Ⅲ-Ⅳ (stage Ⅰ as reference) (HR=2.43, 95%CI: 1.10-5.37) and poor differentiation (well differentiation as reference) (HR=2.53, 95%CI: 1.60-4.01) were the risk factors influencing the prognosis of OSCC. The PI model had a high predictability in modeling group and validation group (AIC and C index were 1 205.80, 0.700 2 and 1 150.47, 0.737 3). Conclusion: Age, poor oral hygiene, first diagnosis of lymph node metastasis, TNM stage and histological grade were factors associated with the prognosis of OSCC, and the PI model has a certain significance in the clinical treatment of OSCC.

[Experts consensus on the management of the right heart function in critically ill patients].

To establish the experts consensus on the right heart function management in critically ill patients. The panel of consensus was composed of 30 experts in critical care medicine who are all members of Critical Hemodynamic Therapy Collaboration Group (CHTC Group). Each statement was assessed based on the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) principle. Then the Delphi method was adopted by 52 experts to reassess all the statements. (1) Right heart function is prone to be affected in critically illness, which will result in a auto-exaggerated vicious cycle. (2) Right heart function management is a key step of the hemodynamic therapy in critically ill patients. (3) Fluid resuscitation means the process of fluid therapy through rapid adjustment of intravascular volume aiming to improve tissue perfusion. Reversed fluid resuscitation means reducing volume. (4) The right ventricle afterload should be taken into consideration when using stroke volume variation (SVV) or pulse pressure variation (PPV) to assess fluid responsiveness.(5)Volume overload alone could lead to septal displacement and damage the diastolic function of the left ventricle. (6) The Starling curve of the right ventricle is not the same as the one applied to the left ventricle,the judgement of the different states for the right ventricle is the key of volume management. (7) The alteration of right heart function has its own characteristics, volume assessment and adjustment is an important part of the treatment of right ventricular dysfunction (8) Right ventricular enlargement is the prerequisite for increased cardiac output during reversed fluid resuscitation; Nonetheless, right heart enlargement does not mandate reversed fluid resuscitation.(9)Increased pulmonary vascular resistance induced by a variety of factors could affect right heart function by obstructing the blood flow. (10) When pulmonary hypertension was detected in clinical scenario, the differentiation of critical care-related pulmonary hypertension should be a priority. (11) Attention should be paid to the change of right heart function before and after implementation of mechanical ventilation and adjustment of ventilator parameter. (12) The pulmonary arterial pressure should be monitored timingly when dealing with critical care-related pulmonary hypertension accompanied with circulatory failure.(13) The elevation of pulmonary aterial pressure should be taken into account in critical patients with acute right heart dysfunction. (14) Prone position ventilation is an important measure to reduce pulmonary vascular resistance when treating acute respiratory distress syndrome patients accompanied with acute cor pulmonale. (15) Attention should be paid to right ventricle-pulmonary artery coupling during the management of right heart function. (16) Right ventricular diastolic function is more prone to be affected in critically ill patients, the application of critical ultrasound is more conducive to quantitative assessment of right ventricular diastolic function. (17) As one of the parameters to assess the filling pressure of right heart, central venous pressure can be used to assess right heart diastolic function. (18). The early and prominent manifestation of non-focal cardiac tamponade is right ventricular diastolic involvement, the elevated right atrial pressure should be noticed. (19) The effect of increased intrathoracic pressure on right heart diastolic function should be valued. (20) Ttricuspid annular plane systolic excursion (TAPSE) is an important parameter that reflects right ventricular systolic function, and it is recommended as a general indicator of critically ill patient. (21) Circulation management with right heart protection as the core strategy is the key point of the treatment of acute respiratory distress syndrome. (22) Right heart function involvement after cardiac surgery is very common and should be highly valued. (23) Right ventricular dysfunction should not be considered as a routine excuse for maintaining higher central venous pressure. (24) When left ventricular dilation, attention should be paid to the effect of left ventricle on right ventricular diastolic function. (25) The impact of left ventricular function should be excluded when the contractility of the right ventricle is decreased. (26) When the right heart load increases acutely, the shunt between the left and right heart should be monitored. (27) Attention should be paid to the increase of central venous pressure caused by right ventricular dysfunction and its influence on microcirculation blood flow. (28) When the vasoactive drugs was used to reduce the pressure of pulmonary circulation, different effects on pulmonary and systemic circulation should be evaluated. (29) Right atrial pressure is an important factor affecting venous return. Attention should be paid to the influence of the pressure composition of the right atrium on the venous return. (30) Attention should be paid to the role of the right ventricle in the acute pulmonary edema. (31) Monitoring the difference between the mean systemic filling pressure and the right atrial pressure is helpful to determine whether the infusion increases the venous return. (32) Venous return resistance is often considered to be a insignificant factor that affects venous return, but attention should be paid to the effect of the specific pathophysiological status, such as intrathoracic hypertension, intra-abdominal hypertension and so on. Consensus can promote right heart function management in critically ill patients, optimize hemodynamic therapy, and even affect prognosis.

[Risk factors of rupture of internal carotid artery during surgical resection of carotid body tumor].

Objective: To investigate risk factors of rupture of internal carotid artery resection during carotid body tumor resection and to summarize our treatment experience. Methods: During the period from 1991 to 2016, rupture of internal carotid artery occurred in 27 patients (28 tumors) during surgical resection of carotid body tumor in the First Affiliated Hospital of Sun Yat-sen University. Their clinical and follow-up data were retrospectively collected and analyzed. For all patients underwent surgical resection during this period, Logistic regression analysis was used to investigate the risk factors of intraoperative rupture of internal carotid artery. Results: Of these 28 tumors, there were 15 (53.6%) tumors with diameter≥5 cm and 20 (71.4%) Shamblin Ⅲ tumors. Intraoperatively, shunt was applied for 8 (28.6%) cases. Thirteen (46.4%) patients underwent ligation of external carotid artery, while 2 (7.1%) patients accepted resection of cranial nerves. Direct closure/patchplasty, autologous vessels or graft reconstruction was used in 16, 10 and 2 cases, respectively. Postoperatively, stroke occurred in 4(14.3%) cases and cranial nerve deficit in 15 (53.6%) cases. During a median length of 36 (14-125) months, cranial nerve deficit persisted in 5 cases. Follow-up radiologic examination indicated 3 (10.7%) cases of targeted vessel occlusion. However, no new-onset stroke was identified. Among all patients underwent surgical resection of carotid body tumor, female (OR=3.650, P=0.012), age≤25 years old (OR=3.710, P=0.013) and Shamblin Ⅲ tumor (OR=4.631, P=0.008) increase the risks of intraoperative carotid artery rupture. Conclusions: Shamblin Ⅲ tumor is the predictor of rupture of internal carotid artery. Intraoperative, properly increased blood pressure, intraoperative heparinization and use of shunt for those cases without well-compensated cranial collateral arteries are likely to decreasing the incidence of stroke.

Decreased microRNA-146a in CD4+T cells promote ocular inflammation in thyroid-associated ophthalmopathy by targeting NUMB.

OBJECTIVE: The aim of the study was to explore the functional role of miR-146a in CD4+T cells of active thyroid-associated ophthalmopathy (TAO) patients and to identify the possible molecular mechanism for the modulation of miR-146a in TAO. PATIENTS AND METHODS: The experimental group collected six cases of peripheral venous blood of patients with active TAO. The healthy control group collected six cases of normal peripheral venous blood. All specimens excluded other eye diseases and autoimmune diseases, tumors, asthma, chronic inflammation, Human Immunodeficiency Virus (HIV), recent history of trauma, infection, and showed normal thyroid function. All patients with active TAO and age- and sex-matched healthy control subjects in this study. RESULTS: miR-146a is downregulated in active TAO CD4+T cells. NUMB was a target of miR-146a. CONCLUSIONS: We observed that miR-146a expression was downregulated in CD4+T cells during the active stage of patients with TAO. At the same time, it was found that NUMB can be targeted by miR-146a in CD4+T cells in TAO patients. Decreased microRNA-146a in CD4+T cells promotes ocular inflammation in active TAO by targeting NUMB.

Tea consumption and its interactions with tobacco smoking and alcohol drinking on oral cancer in southeast China.

BACKGROUND/OBJECTIVES: Epidemiological results on the association between tea consumption and oral cancer remain controversial. We aimed to evaluate the exact relationship between tea consumption and oral cancer in Chinese population. SUBJECTS/METHODS: A large-scale case-control study was conducted on 586 oral cancer patients and 1024 controls frequency-matched by age and gender. Epidemiological data were collected through face-to-face interviews with a structure questionnaire. Unconditional logistic regression model was used to assess the effect of tea consumption on oral cancer stratified by smoking, alcohol drinking and demographics. Quantity of tea consumed (ml/day) was categorized into five subgroups based on quartiles and then its interactions was evaluated with tobacco smoking and alcohol drinking at each subgroup. RESULTS: Tea consumption showed an inverse association with oral cancer for non-smokers or non-alcohol drinkers (the odds ratios (ORs) were 0.610 (95% confidence interval (CI): 0.425-0.876) and 0.686 (95% CI: 0.503-0.934), respectively). For smokers or alcohol drinkers, decreased risk was only observed in those who consumed >800 ml/day. Furthermore, oolong tea consumption was associated with decreased risk of oral cancer in smokers or alcohol drinkers but not in non-smokers or non-alcohol drinkers. Tea consumption combined with smoking or/and alcohol drinking had a greater risk than tea consumption alone, but the risk was roughly reduced from zero to Q4 (>800 ml/day). Additionally, when stratified by demographics, the protective effect of tea was especially evident in females, urban residents, normal body mass index population (18.5-23.9), farmers, office workers and those aged <60 years. CONCLUSIONS: Tea consumption protects against oral cancer in non-smokers or non-alcohol drinkers, but this effect may be obscured in smokers or alcohol drinkers. Additionally, demographics may modify the association between tea consumption and oral cancer.

[Management of endo-graft infection following endovascular repair of abdominal aortic aneurysm].

OBJECTIVE: To summarize our experience in the management of stent-graft infection after endo-vascular aortic repair (EVAR) of abdominal aortic aneurysm (AAA). METHODS: Data of patients who were diagnosed as endo-graft infection following EVAR and admitted in our center between January 2000 and December 2015 were reviewed. Clinical records including causes of infection, medical history, re-operative procedures, and prognostic data were analysed. RESULTS: A total of 10 male patients, aged 45-72 years (averaged 62.5 years), were enrolled. Two patients received previous EVAR in our center, accounting for 0.23% of all the 885 EVAR procedures we conducted during the same period. The symptoms related to stent infection, including recurrent fever (100%) and persistent back pain (40%), occured 0 to 27 months (averaged 6.9 months) after EVAR procedure. Eight patients were found to have apparent causes (80%), including 1 case with upper respiratory infection and sepsis, 4 cases with aorto-enteric fistula (AEF) and 3 cases with inflammatory AAA. Except one DNR, other 9 patients received re-operation, including 1 procedure of open debridement and drainage, 1 procedure of endo-graft excision and bilateral axillary-femoral bypass, 7 procedures of endograft excision and axillary-bifemoral bypass. During the follow-up period(2-60 months, averaged 24.1 months), 1 patient was lost, 1 patient died from aortic stump rupture (12.5%) and other 7 patients survived. Bypass occlusion was observed in 1 patient (12.5%) without severe limb ischemia. CONCLUSIONS: AEF and inflammatory AAA are two leading causes of endo-graft infection following EVAR in our patients. Graft excision and axillofemoral bypass is an acceptable management for this life-threatening morbidity.

[A retrospective study on the outcomes of the oncology, fertility and pregnancy in patients with early-stage cervical cancer after undergoing the fertility-sparing treatments].

OBJECTIVE: To explore the outcomes of the oncology, the fertility and pregnancy on patients with early-stage cervical cancer after undergoing fertility-sparing treatments, and to investigate its value on clinical treatment. METHODS: A total of 29 patients with cervical cancer (stage Ⅰa2-Ⅰb1) who had undergone the fertility- sparing treatments in Renji Hospital, School of Medicine, Shanghai Jiaotong University from February 2010 to September 2015 were analyzed retrospectively. Surgical procedures included transvaginal cervical cold knife conization (CKC) + laparoscopic pelvic lymphadenectomy (PLD) or total laparoscopic uterine cervix extensive resection (RT; contains PLD); 48 patients with early cervical cancer under going laparoscopic uterine extensive resection (RH; contains PLD) by the same group of physicians in the same period were chosen as the control group. The perioperative related indicators, postoperative specimen examination, pregnancies after surgery and postoperative tumor follow- up results were retrospectively analyzed and compared between the two groups. RESULTS: (1) Among these 29 patients in the study group, 26 cases were underwent the fertility-sparing surgery quick frozen pathological examinations were positive in 3 cases, which underwent total laparoscopic RT eventually. (2) The perioperative related indicators: compared with the study group and the control group, the operation time [(182±21), (147±24) minutes, respectively] has significant difference (t=6.563, P<0.01). There were no significant difference (P> 0.05) in intra-operative blood loss [(102±26), (99±34) ml], postoperative aerofluxus time [(1.3±0.4), (1.1±0.9) days], the average length of hospital stay [(11.2±2.1), (10.6±3.5) days], rate of urine retention [10%(3/29), 10%(5/48)] and rate of postoperative infection [3% (1/29), 2%(1/48)]. (3)Postoperative specimen examination: compared with the study group and the control group, there were no significant difference (P>0.05) innumber of removed lymphatic nodes (23.4±4.1, 22.8±3.9), length of cardinal ligament [(2.9±0.5), (3.0±0.6) cm], lengthof uterosacral ligament [(2.6±0.7), (2.8±0.4) cm], length of removed vaginal [(3.4±0.3), (3.5±0.3) cm]. (4) Pregnancies after surgery and postoperative tumor follow-up results: in the study group, only 14 patients had fertility requirement after treatments. Pregnancies occurred in 5 women (5/14), which included1 case of full-term labor, 1 case of preterm labor, and 3 cases of spontaneous abortion. The Average follow-up time in postoperative patients of the study group and control group was 29.4, and 30.2 months respectively. In follow- up period, compare with study group and the control group, there was no significant difference (χ(2)=0.004, P> 0.05) in the recurrence rate [4% (1/26), 4% (2/48)]. CONCLUSION: Fertility-sparing surgery of early-stage cervical cancer is safe but the outcome of the fertility and pregnancy is still need toimprove.

Time course of activated coagulation time at various sites during continuous haemodiafiltration using nafamostat mesilate.

OBJECTIVE: To determine the adequate site of activated coagulation time (ACT) measurement during continuous haemodiafiltration (CHDF) using nafamostat mesilate. DESIGN: Prospective, consecutive, clinical study. SETTING: An intensive care unit of a general hospital. PATIENTS: Ten patients with acute organ failure including kidney, lung and liver, caused by sepsis after major surgery. INTERVENTIONS: A CHDF circuit with a haemofilter made of polymethylmethacrylate membrane was primed with 50 mg nafamostat in 500 ml saline, and was started at a circuit flow rate of 100 ml/min. Continuous injection of 0.5 mg/kg per h nafamostat, 700 ml/h of dialysis fluid and 1000 ml/h of filtrate fluid was set. MEASUREMENTS AND RESULTS: The circuit pressure at the inlet and outlet of the circuit were monitored, and ACT was measured every 2 h at the site of nafamostat injection, outlet, patient's artery and inlet until 24 h. A value of standard deviation of ACT at each site was regarded as the variation value of ACT. The circuit pressure did not change significantly. The ACT did not change significantly at any measurement site. The variation value of ACT at the inlet of the circuit was significantly lower than that at the site of nafamostat injection. CONCLUSIONS: The ACT value at the inlet of the circuit may be adequate to monitor anticoagulation during CHDF using nafamostat.

Mutational analysis of the GDNF/RET-GDNFR alpha signaling complex in a kindred with vesicoureteral reflux.

Glial cell line-derived neurotrophic factor (GDNF) mediates signaling across the cell membrane by interaction with the RET-GDNFR alpha receptor complex. We identified a family in which one member had medullary thyroid carcinoma (MTC) and four members had vesicoureteral reflux (VUR). Knowledge that mutations in the RET proto-oncogene cause MTC and studies documenting genitourinary abnormalities in RET or GDNF knockout mice led us to examine the GDNF/RET-GDNFR alpha signaling complex in this family. RET and GDNF were excluded as the causative VUR gene by haplotype and sequence analysis. The GDNFR alpha gene was mapped to chromosome 10q25-26 by radiation hybrid techniques and was eliminated as the causative gene by haplotype analysis and sequencing of cDNA from an obligate carrier. Sequencing identified a 15-nucleotide deletion in GDNFR alpha mRNA, which was found to code for a single exon; analysis of several cell types revealed an identical mRNA form, indicating that this variant is a product of alternative RNA processing. We conclude that GDNFR alpha maps to 10q25-26 and that its RNA transcript is alternatively processed. Mutation abnormalities in the GDNF/RET-GDNFR alpha signaling system do not cause VUR in this family.