Construction of prediction model of celiac lymph node metastasis in thoracic esophageal squamous cell carcinoma and risk subgroup analysis of celiac lymph node metastasis probability / 中华消化外科杂志

Objective:To investigate the influencing factors for celiac lymph node metastasis in thoracic esophageal squamous cell carcinoma (TE-SCC), construct a prediction model of celiac lymph node metastasis in TE-SCC, and stratify the probability of celiac lymph node metastasis.Methods:The retrospective case-control study was conducted. The clinicopathological data of 443 patients with TE-SCC who underwent thoracoscopic and laparoscopic esophagectomy with systematic lymph node dissection in the First Affiliated Hospital of Zhengzhou University between March 2015 and April 2019 were collected. There were 259 males and 184 females, aged from 41 to 81 years, with a median age of 64 years. The nomogram prediction model was constructed based on the results of multivariate analysis of influencing factors for celiac lymph node metastasis in TE-SCC, of which calibration curve and decision curve were drawed. The predictive performance was evaluated using the concordance index. The score for celiac lymph node metastasis in TE-SCC predicted by nomogram model was used for further recursive partitioning analysis, and patients were stratified into risk subgroups using the decision-making tree model. Observation indicators: (1) celiac lymph node metastasis in TE-SCC; (2) analysis of influencing factors for celiac lymph node metastasis in TE-SCC; (3) construction of nomogram prediction model of celiac lymph node metastasis in TE-SCC; (4) construction of decision-making tree model of celiac lymph node metastasis in TE-SCC and risk subgroup analysis of celiac lymph node metastasis probability. Measurement data with skewed distribution were represented as M (range). Count data were represented as absolute numbers and percentages, and comparison between groups was analyzed using the chi-square test. Comparison of ordinal data between groups was analyzed using the nonparametric rank sum test. Multivariate analysis was performed using the Logistic regression model. Based on Logistic regression model multivariate analysis, a new nomogram model was constructed using the RStudio 3.4 software. Results:(1) Celiac lymph node metastasis in TE-SCC: celiac lymph node metastasis was found in 89 of the 443 patients, with a celiac lymph node metastasis rate of 20.09%(89/443). (2) Analysis of influencing factors for celiac lymph node metastasis in TE-SCC. Results of univariate analysis showed that tumor location, tumor length, tumor differentiation degree, pathological T staging, nerve invasion, vessel invasion, and thoracic lymph node metastasis were related factors for celiac lymph node metastasis in TE-SCC ( χ2=12.177, Z=-2.754, -4.218, -4.254, χ2=3.908, 33.025, 30.387, P<0.05). Results of multivariate analysis showed that tumor location, vessel invasion, and thoracic lymph node metastasis were independent influencing factors for celiac lymph node metastasis in TE-SCC ( odds ratio=2.165, 3.442, 2.876, 95% confidence interval: 1.380-3.396, 1.787-6.633, 1.631-5.071, P<0.05). (3) Construction of nomogram prediction model of celiac lymph node metastasis in TE-SCC: based on the factors screened by multivariate analysis, including tumor location, vessel invasion, and thoracic lymph node metastasis, the nomogram prediction model of celiac lymph node metastasis in TE-SCC was established, with the concordance index of 0.846. The calibration curve showed a high consistency between the celiac lymph node metastasis probability estimated by the prediction model and the actual rate of celiac lymph node metastasis. The decision curve showed that the nomogram prediction model of celiac lymph node metastasis in TE-SCC had a good prediction value when the probability threshold was 0.001-0.819.(4) Construction of decision-making tree model of celiac lymph node metastasis in TE-SCC and risk subgroup analysis of celiac lymph node metastasis probability: patients were stratified into six risk subgroups using the decision-making tree model based on the celiac lymph node metastasis probability. The group A included patients with no vessel invasion+negative thoracic lymph node, group B included patients with no vessel invasion+the number of positive thoracic lymph nodes of 1-3, group C included patients with no vessel invasion+the number of positive thoracic lymph nodes of ≥4, group D included patients with vessel invasion+the number of positive thoracic lymph nodes of 0-2+upper or middle thoracic esophageal carcinoma, group E included patients with vessel invasion+the number of positive thoracic lymph nodes of 0-2+lower thoracic esophageal carcinoma, group F included patients with vessel invasion+the number of positive thoracic lymph nodes of ≥3. The group A was low-risk group with the celiac lymph node metastasis probability of 11%, group B and D were intermediate low-risk groups with the celiac lymph node metastasis probability of 27% and 21%, group C and E were the intermediate high-risk groups with the celiac lymph node metastasis probability of 56% and 55%, and group F was high-risk group with the celiac lymph node metastasis probability of 80%. Conclusions:The tumor location, vessel invasion, and thoracic lymph node metastasis are independent influencing factors for celiac lymph node metastasis in TE-SCC. Vessel invasion has the dominant influence on celiac lymph node metastasis, followed by the number of positive thoracic lymph nodes, and then the tumor location. Patients can be stratified into six risk subgroups based on the nomogram prediction model and decision-making tree model of celiac lymph node metastasis in TE-SCC.

Cardiac catheterization and pulmonary vasoreactivity testing in children with idiopathic pulmonary arterial hypertension / 中华儿科杂志

<p><b>OBJECTIVE</b>As an important method of hemodynamic assessment in idiopathic pulmonary arterial hypertension (IPAH), cardiac catheterization combined with pulmonary vasoreactivity testing remains with limited experience in children, and the acute pulmonary vasodilator agents as well as response criteria for vasoreactivity testing remain controversial. The aim of this study was to investigate the clinical importance, agent selection, and responder definition of cardiac catheterization combined with pulmonary vasoreactivity testing in pediatric IPAH.</p><p><b>METHOD</b>The patients admitted to Department of Pediatric Cardiology of Beijing Anzhen Hospital between April 2009 and September 2013 with suspected IPAH, under 18 years of age, with WHO functional class II or III, were enrolled. All the patients were arranged to receive left and right heart catheterization and pulmonary vasoreactivity testing with inhalation of pure oxygen and iloprost (PGI2) respectively. Hemodynamic changes were analyzed, and two criteria, the European Society of Cardiology recommendation criteria (Sitbon criteria) and traditional application criteria (Barst criteria), were used to evaluate the test results.</p><p><b>RESULT</b>Thirty-nine cases of children with suspected IPAH underwent cardiac catheterization. In 4 patients IPAH was excluded; 4 patients developed pulmonary hypertension crisis. The other 31 patients received standard cardiac catheterization and pulmonary vasoreactivity testing. Baseline mean pulmonary artery pressure (mPAP) was (66 ± 16) mmHg (1 mmHg = 0.133 kPa), and pulmonary vascular resistance index (PVRI) (17 ± 8) Wood U · m². After inhalation of pure oxygen, mPAP fell to (59 ± 16) mmHg, and PVRI to (14 ± 8) Wood U · m² (t = 4.88 and 4.56, both P < 0.001) . After inhalation of PGI2, mPAP fell to (49 ± 21) mmHg, and PVRI to (12 ± 9) Wood U · m² (t = 7.04 and 6.33, both P < 0.001). According to the Sitbon criteria, the proportion of pure oxygen responders was 6.5% (3/31) , while PGI2 responders was 35.5%, and the difference was significant (P = 0.004). According to the Barst criteria, the proportion of pure oxygen responders was 16.1% (5/31), while PGI2 responders was 51.6% (16/31), and the difference was significant (χ² = 0.09, P = 0.001).</p><p><b>CONCLUSION</b>For children with IPAH, cardiac catheterization combined with pulmonary vasoreactivity testing has important value in differential diagnosis, severity estimation, and treatment (including the emergency treatment) choices. Pulmonary hypertension crisis is an important complication of cardiac catheterization in pediatric IPAH. Younger age, general anesthesia, crisis history, and poor heart function are important risk factors for pulmonary hypertension crisis. PGI2 is a relatively ideal agent for vasoreactivity testing in children with IPAH, which has more responders than traditionally used pure oxygen.</p><p><b>RESULTS</b>of responders are not completely consistent using different criteria, and comprehensive evaluation should be done according to the goals of treatment in clinical practice.</p>

Effects of total glucosides of paeony on co-cultured osteoclasts and its mechanisms / 中国药理学通报

s:Aim To study the effects of total gluco-sides of paeony ( TGP) on the differentiation of co-cul-tured osteoclasts and the mechanisms of how TGP influ-ences the osteoclasts. Methods The synovial fibro-blasts and monocytes of peripheral blood in adjuvant-induced arthritic rats were separated and co-cultured to induce osteoclasts. The cells were treated with different TGP dosages (5, 50, 500, 5 000 mg·L-1 , and 50 g ·L-1 ) for 48 h. The proliferation, the TRAP activi-ty, and the bone resorption of osteoclasts were ob-served. The levels of IL-1,TNF-α,M-CSF and RANKL in the supernatants of osteoclasts were detected using ELISA. Meanwhile, the expression of ERK, JNK and p38 was detected by real time PCR. Results The ex-periments revealed that 50, 500, 5 000 mg·L-1 TGP inhibited the osteoclast growth, the TRAP activity, and the resorption pit area in a dose-dependent manner. TGP also inhibited the levels of IL-1 , TNF-α, M-CSF and RANKL in the supernatants and the expression of ERK, JNK and p38 in osteoclasts. The appropriate concentrations were 50 mg·L-1 to 5 000 mg·L-1 and had dose-dependent effects within this range. Conclu-sions TGP regulates the differentiation and activity of co-cultured osteoclasts. The effects of TGP are related to its inhibiting the cytokines secretion of synovial fi-broblasts and the activity of MAPK pathways.