Object To study on the structure of sapogenins from pod of Gleditsia sinensis Lam Methods Pod of G. sinensis was extracted with solvents and the constituents in the extraction isolated, after hydrolised completely, with the aid of flash chromatography to obtain 2 gledgenins Results The structures of the 2 gledgenins were proved to be 3 hydroxy 12 oleanen 28 oic acid and 3, 16 dihydroxy 12 oleanen 28 oic acid respectively as shown by IR, NMR, MS and crystallographic data The structures were further verified by acylation, methylation and followed by reaction with 3, 5 dinitro benzoyl chloride Conclusion New crystalline derivatives were obtained to provide further evidence of their structures

Objective To observe the protective effect of dexmedetomidine(Dex)at different doses com-bined with ulinastatin in lung resection patients with one lung ventilation. Methods 80 patients having undergone unilateral lung resection were divided into four groups randomly:control group(C group)and groups Dex 1-3,20 cases in each group.One lung ventilation(OLV)was used in all the groups during operation.The patients in groups Dex 1-3 were treated with 0.5,1.0,2.0 μg/kg combined with ulinastatin,and the C group with amount of normal sa-line instead.The comparisons were done among the four groups in terms of SOD,L-6,IL-10,serum malondialde-hyde(MDA)concentration at 5 min after endotracheal intubation(T0),30 min(T1),60 min(T2),120 min (T3)as well as the levels of FVC,FEVl and FEVl/FVC at 24 h,48 h and 72 h after surgery. Results In the groups C and Dex 1,SOD decreased at T1-4 and IL-6,MDA and IL-10 at T2-4 rose.SOD decreased at T2-4 in groups Dex 2-3 and MDA,IL-6 and IL-10 rose.Compared with group C,the levels of SOD and IL-10 at T2-4 in groups Dex 1-2 and at T1-4 in group Dex 3 rose. In groups Dex 1-3,postoperative FVC,FEVl and FEVl/FVC rose.Compared with group Dex 1 or 2 respectively,SOD and IL-10 at T2-4 in group Dex 3 significantly rose,but MDA and IL-6 significantly declined;FVC,FEVl and FEVl/FVC significantly rose 48 h and 72 h after surgery (P<0.05). Conclusion Dex combined with ulinastatin has a protective effect for patients with one lung ventila-tion after lung resection,with the best-suggested dose of 1.0 μg/kg.

Objective:To investigate the value of immune inflammatory index in predic-ting the therapeutic efficacy of neoadjuvant chemoradiotherapy for esophageal squamous cell carci-noma (ESCC).Methods:The retrospective case-control study was conducted. The clinicopatholo-gical data of 163 patients with ESCC who were admitted to Zhongshan Hospital of Fudan University from December 2015 to December 2020 were collected. There were 135 males and 28 females, aged (62±8)years. All 163 patients underwent neoadjuvant chemoradiotherapy and radical resection for ESCC. Observation indicators: (1) relationship between immune inflammatory index and clinical characteristic in patients; (2) relationship between immune inflammatory index and efficacy of neoadjuvant chemoradiotherapy in patients; (3) influencing factor analysis for pathologic complete response and good response of tumor regression grade after neoadjuvant chemoradiotherapy; (4) efficiency of immune inflammatory index in predicting efficacy of neoadjuvant chemoradiotherapy. Measurement data with normal distribution were represented as Mean± SD. Count data were described as absolute numbers, and comparison between groups was conducted using chi-square test. Comparison of ordinal data was conducted using the rank sum test. The receiver operating characteristic (ROC) curve was used to determine the optimal cut-off value. Univariate and multi-variate analyses were conducted using the Logistic regression model. The area under the curve (AUC) of ROC curve was used to evaluate the efficiency of predictive model. Results:(1) Relationship between immune inflammatory index and clinical characteristic in patients. ① Optimal cut-off value of systemic immune-inflammation index (SII), neutrophil-lymphocyte ratio (NLR), platelet-lympho-cyte ratio (PLR). Results of ROC curve analysis showed that the AUC of SII, NLR, PLR in predicting efficacy of neoadjuvant chemoradiotherapy for patients with ESCC was 0.70(95% confidence interval as 0.61?0.77), 0.78(95% confidence interval as 0.69?0.84), 0.79(95% confidence interval as 0.70?0.85), respectively, with the maximum value of Youden index and the optimal cut-off value as 0.25, 0.32, 0.52 and 446×10 9/L, 2.09, 138. ② Relationship between SII, NLR, PLR and clinical charac-teristic in patients. According to the optimal cut-off value of SII, NLR, PLR, all 163 patients were divided into cases with SII <446×10 9/L as 99, cases with SII ≥446×10 9/L as 64, cases with NLR <2.09 as 107, cases with NLR ≥2.09 as 56, cases with PLR<138 as 88, cases with PLR ≥138 as 75, respectively. There was a significant difference in clinical N staging of tumor in patients with SII <446×10 9/L and SII ≥446×10 9/L ( P<0.05). There were significant differences in clinical N staging and clinical TNM staging of tumor in patients with NLR<2.09 and NLR≥2.09 ( P<0.05). (2) Relationship between immune inflammatory index and efficacy of neoadjuvant chemoradiotherapy in patients. Of 163 patients undergoing neoadjuvant chemoradiotherapy, there were 54 cases with pathologic complete response and 109 cases without pathologic complete response, 94 cases with good response of tumor regression grade and 69 cases with poor response of tumor regression grade. Of the 54 patients with pathologic complete response, cases with SII <446×10 9/L and SII ≥446×10 9/L, cases with NLR <2.09 and NLR ≥2.09, cases with PLR <138 and PLR ≥138 before neoadjuvant chemoradiotherapy were 42 and 12, 47 and 7, 48 and 6, respectively. The above indicators were 57 and 52, 60 and 49, 40 and 69 in the 109 cases without pathologic complete response. There were significant differences in the above indicators between patients with pathologic complete response and without pathologic complete response ( χ2=9.83, 16.39, 39.60, P<0.05). Of the 94 cases with good response of tumor regression grade, cases with SII <446×10 9/L and SII ≥446×10 9/L, cases with NLR <2.09 and NLR ≥2.09, cases with PLR <138 and PLR ≥138 before neoadjuvant chemoradiotherapy were 59 and 35, 78 and 16, 56 and 38, respectively. The above indicators were 40 and 29, 29 and 40, 32 and 37 in the 69 cases with poor response of tumor regression grade. There was no significant difference in the SII and PLR ( χ2=0.38, 2.79, P>0.05) and there was a significant difference in the NLR ( χ2=29.59, P<0.05) between patients with good response of tumor regression grade and poor response of tumor regre-ssion grade. (3) Influencing factor analysis for pathologic complete response and good response of tumor regression grade after neoadjuvant chemoradiotherapy. Results of multivariate analysis showed that PLR <138 before neoadjuvant chemoradiotherapy was an independent protective factor for pathologic complete response in ESCC patients undergoing neoadjuvant chemoradiotherapy ( odds ratio=1.98, 95% confidence interval as 1.56?2.51, P<0.05) and NLR <2.09 before neoadjuvant chemo-radiotherapy was an independent protective factor for good response of tumor regression grade ( odds ratio=2.50, 95% confidence interval as 1.40?4.46, P<0.05). (4) Efficiency of immune inflam-matory index in predicting efficacy of neoadjuvant chemoradio-therapy. The AUC of PLR <138 before neoadjuvant chemoradiotherapy in predicting pathologic complete response of ESCC patients undergoing neoadjuvant chemoradiotherapy was 0.79(95% confidence interval as 0.64?0.87, P<0.05), with the sensitivity, specificity and Youden index as 0.89, 0.63 and 0.52, respectively. The AUC of NLR <2.09 before neoadjuvant chemoradiotherapy in predic-ting good response of tumor regression grade of ESCC patients undergoing neoadjuvant chemoradio-therapy was 0.76 (95% confidence interval as 0.64?0.81, P<0.05), with the sensitivity, specificity and Youden index as 0.83, 0.58 and 0.41, respectively. Conclusion:The PLR<138 and NLR <2.09 before neoadjuvant chemoradiotherapy are independent protective factors for the pathologic complete response and good response of tumor regression grade, respectively, of ESCC patients undergoing neoadjuvant chemoradiotherapy, and both of them can predict the curative effect of neoadjuvant chemoradiotherapy well.

Background::Heterotaxy (HTX) is a thoracoabdominal organ anomaly syndrome and commonly accompanied by congenital heart disease (CHD). The aim of this study was to analyze rare copy number variations (CNVs) in a HTX/CHD cohort and to examine the potential mechanisms contributing to HTX/CHD.Methods::Chromosome microarray analysis was used to identify rare CNVs in a cohort of 120 unrelated HTX/CHD patients, and available samples from parents were used to confirm the inheritance pattern. Potential candidate genes in CNVs region were prioritized via the DECIPHER database, and PNPLA4 was identified as the leading candidate gene. To validate, we generated PNPLA4-overexpressing human induced pluripotent stem cell lines as well as pnpla4-overexpressing zebrafish model, followed by a series of transcriptomic, biochemical and cellular analyses. Results::Seventeen rare CNVs were identified in 15 of the 120 HTX/CHD patients (12.5%). Xp22.31 duplication was one of the inherited CNVs identified in this HTX/CHD cohort, and PNPLA4 in the Xp22.31 was a candidate gene associated with HTX/CHD. PNPLA4 is expressed in the lateral plate mesoderm, which is known to be critical for left/right embryonic patterning as well as cardiomyocyte differentiation, and in the neural crest cell lineage. Through a series of in vivo and in vitro analyses at the molecular and cellular levels, we revealed that the biological function of PNPLA4 is importantly involved in the primary cilia formation and function via its regulation of energy metabolism and mitochondria-mediated ATP production. Conclusions::Our findings demonstrated a significant association between CNVs and HTX/CHD. Our data strongly suggested that an increased genetic dose of PNPLA4 due to Xp22.31 duplication is a disease-causing risk factor for HTX/CHD.