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.

Objective To discuss the clinical application value of super selective renal artery embolization-assisted(SRAE-assisted)laparoscopic partial nephrectomy(LPN).Methods A retrospective analysis of the clinical data of patients with stage T1 renal carcinoma,who received LPN,was conducted.The patients were divided into SRAE group(performing LPN without adopting renal hilum vascular clamping)and VC group(performing LPN with adopting renal hilum vascular clamping).The time spent for operation,amount of intraoperative blood loss,and preoperative and postoperative renal functions were compared between the two groups.According to the warm ischemia time(WIT),the patients of the VC group were subdivided into WIT＜25 min subgroup and WIT≥25 min subgroup,and the preoperative and postoperative renal functions were compared between the two subgroups.Results A total of 59 patients with renal carcinoma were enrolled in this study,including 12 patients in SRAE group and 47 patients in VC group.In VC group,WIT＜25 min subgroup had 33 patients and WIT≥25 min subgroup had 14 patients.In both SRAE group and VC group,no patient was referred to open surgery or total nephrectomy.No patient in SRAE group was referred to traditional LPN.The time spent for operation in SRAE group and VC group was 100.50(73.75,132.50)min and 120.00(90.00,145.00)min respectively,the difference between the two groups was not statistically significant(P＞0.05).The postoperative estimated glomerular filtration rate(eGFR)in SRAE group was 100.56(82.85,106.81),which was remarkably higher than 84.66(70.84,94.85)in VC group(P＜0.05).The postoperative serum creatinine level in VC group was 90.50(77.10,104.90)μmol/L,which was strikingly higher than 72.24(65.97,80.27)μmol/L in SRAE group(P＜0.05).The amount of intraoperative blood loss in SRAE group was 50(50,50)mL,which was lower than 50(50,100)mL in VC group(P＜0.05).In VC group,the postoperative eGFR in WIT≥25 min subgroup was 66.13(47.08,82.50),which was lower than 90.80(77.18,98.78)in WIT＜25 min subgroup(P＜0.05).During the postoperative one-year follow-up,no recurrence was observed in both groups.Conclusion Compared with traditional LPN,SRAE-assisted LPN doesn't need to obstruct the renal hilus during surgery,which can avoid the ischemic impairment of the residual renal function and reduce the amount of intraoperative blood loss,moreover,it doesn't increase the operation time,doesn't increase the incidence of complications such as postoperative bleeding,etc.and doesn't affect the curative efficacy and patient's prognosis.

Objective:To explore the effects of Onodera′s prognostic nutritional index (PNI) on the prognosis of locally advanced oropharyngeal squamous cell carcinoma (LA-OPSCC) after induction chemotherapy followed by sequential chemoradiotherapy.Methods:A retrospective analysis was conducted on the clinical data of 52 LA-OPSCC patients receiving induction chemotherapy followed by sequential chemoradiotherapy in The Affiliated Cancer Hospital of Guizhou Medical University during 2014-2018. The PNI values of all the patients at different treatment phases were statistically analyzed, and the ROC curve was employed to determine the optimal critical value of PNI. The patients in this study were divided into a well-nourished group ( n = 27) and a poorly-nourished group ( n = 25). The Kaplan-Meier method was used for survival analysis. The Cox proportional hazards model was utilized to analyze the relationships between different nutritional status and prognosis. Clinical features and adverse reactions were compared between the two groups. Results:The PNI values decreased significantly after radiotherapy, with an optimal critical value of 42.4. The 5-year overall survival (OS) and progression-free survival (PFS) of the well-nourished group (PNI ≥ 42.4) were 62.6% and 60.9%, respectively, which were significantly higher than those (30.1% and 29.7%) of the poorly-nourished group (PNI < 42.4, χ2 = 11.12, 5.74, P < 0.05). The multivariate analysis showed that PNI was an independent prognostic factor for the OS after radiotherapy ( HR = 2.752, 95% CI: 1.095-6.917, P = 0.031). The LA-OPSCC patients aged over 60 years or those who did not respond to induction chemotherapy accounted for a higher proportion of malnutrition after chemoradiotherapy ( χ2 = 4.89, 5.05, P < 0.05). Conclusions:PNI after radiotherapy can be used as a prognostic factor in the evaluation of LA-OPSCC patients receiving induction chemotherapy followed by sequential chemoradiotherapy. The LA-OPSCC patients aged over 60 years or those who do not respond to induction chemotherapy should receive more nutritional support during the chemoradiotherapy.

Objective:To explore the effect of clinical conventional fractionated dose radiation on the expression levels of immunogenic cell death (ICD) related proteins in patients with nasopharyngeal carcinoma (NPC).Methods:A total of 38 newly-treated NPC patients admitted to the Affiliated Cancer Hospital of Guizhou Medical University from November 2020 to December 2021 were enrolled, all of whom received induction chemotherapy and concurrent chemoradiotherapy, and another 20 healthy volunteers were selected as controls for a prospective study. The contents of ICD related proteins, namely calreticulin (CRT), high mobility group box 1 protein (HMGB-1) and heat shock protein 70 (HSP70) and the proportion of dendritic cell (DC) in the peripheral blood of patients were detected before treatment, after induction chemotherapy and after concurrent chemoradiotherapy, respectively. The correlation between the above indicators, general clinical data and short-term efficacy was analyzed by statistical methods such as t-test and analysis of variance (ANOVA). Results:The levels of HSP70 and HMGB-1 in peripheral blood of NPC patients before treatment were higher than those of healthy controls (both P<0.05). After concurrent chemoradiotherapy, the content of CRT was significantly higher than that before treatment ( P<0.05), whereas the difference before and after induction chemotherapy and the difference before and after concurrent chemoradiotherapy were not significantly correlated with the short-term efficacy of NPC patients. HSP70 level was significantly decreased after concurrent chemoradiotherapy ( P<0.001). There were no significant differences in the content of HMGB-1 after induction chemotherapy and concurrent chemoradiotherapy (both P>0.05). Conclusion:NPC patients receiving TPF regimen (docetaxel+cisplatin+fluorouracil) for induction chemotherapy and sequential cisplatin concurrent chemotherapy may induce ICD in NPC cells, and CRT has potential value in reflecting the clinical efficacy of NPC.

Objective:To explore the clinical significance and prognostic value of fibrinogen (FIB) in the treatment of locally advanced head and neck squamous cell carcinoma with induction chemotherapy combined with radiotherapy.Methods:A retrospective analysis was conducted for the clinical data of 114 patients with locally advanced head and neck squamous cell carcinoma receiving non-surgical treatment in the Department of Head and Neck Oncology, the Affiliated Cancer Hospital of Guizhou Medical University from May 2011 to May 2021. The FIB critical value was determined based on the median FIB level before induction chemotherapy, by which patients were divided into high-FIB and low-FIB groups. The ROC curves were used to determine the optimal cut-off value for other hematologic-related parameters such as neutrophils, lymphocytes, and platelets. Statistical methods were used to analyze the results. The enumeration data were analyzed by Chi-square test or Fisher exact probability method. Survival curves for OS and PFS were plotted by Kalplan-Meier method and tested by Log-rank method. Prognostic factors were evaluated by Cox proportional hazard regression model.Results:There were 59 cases in the high-FIB group (FIB > 3.6 g/L) and 55 cases in the low-FIB group (FIB ≤ 3.6 g/L). The high FIB group had higher neutrophils, platelets, NLR, and PLR ( χ2= 7.84, 12.80, 15.04, 9.14; P<0.05) than the low FIB group. The 3- and 5-year overall survival (OS) rates were significantly longer in the low FIB group than those in the high-FIB group (62.9% vs. 39.6%; 46.9% vs. 25.8%), and progression-free survival (PFS) rates of the low FIB group significantly longer than those of the high-FIB group (63.3% vs. 40.3%; 48.1% vs. 26.2%). The univariate analysis showed that the OS and PFS in patients with locally advanced head and neck squamous cell carcinoma were related to FIB, the application of concurrent chemoradiotherapy, and the efficacy of radiotherapy for lymph nodes. The multivariate analysis showed that FIB, the application of concurrent chemoradiotherapy, and the efficacy of radiotherapy for lymph nodes were independent prognostic factors of the OS [ HR (95% CI): 1.89 (1.08-3.31), 3.76 (1.12-12.65), 2.14 (1.09-4.21), P < 0.05]and PFS HR (95% CI): 1.92 (1.90-3.36), 3.93 (1.01-11.34), 2.15 (1.09-4.22), P < 0.05]of patients with locally advanced head and neck squamous cell carcinoma. Conclusions:Patients with low FIB receive high OS and PFS rates after induction chemotherapy combined with radiotherapy. Therefore, FIB can be used as a prognostic factor in the evaluation of non-surgical treatment of patients with locally advanced head and neck squamous cell carcinoma.

Tumor immunogenic cell death is a type of regulatory cell death, which is driven by stress including chemotherapy drugs, radiotherapy, oncolytic virus, nano carrier drugs and photodynamic force. It can induce specific immune response to tumor death cell antigen. The further study can provide theoretical basis and new ideas for anti-tumor immunity and clinical immunotherapy of tumor.

Objective:To explore the indications of lung transplantation for pulmonary interstitial fibrosis after COVID-19 and the precautionary measures of medical staff during operation.Methods:Lung transplantation was performed for three cases of COVID-19 from February 15, 2020 to March 1, 2020. The course of disease, mechanical ventilation time, extra-corporeal membrane oxygenation (ECMO) support time, surgical procedures and precautionary measures of medical staff during operation were analyzed.Results:The course of disease were 40, 7, 39 days, the mechanical ventilation time 26, 22, 27 days and ECMO support time 16, 7, 14 days. The postoperative pathological results of three cases indicated pulmonary interstitial fibrosis. One case died on the operative day and two survivors stayed currently in rehabilitation. Thirty-nine medical staff had no symptoms of COVID-19 after 14 days of isolation. The detection of 2019-nCoV nucleic acid was negative for both nasal and pharyngeal swabs.Conclusions:Patients with pulmonary interstitial fibrosis after COVID-19 show no improvement after 1 month of active medical treatment. And the 1-month risk of mortality was over 50% and nucleic acid of 2019-nCoV turned negative. Lung transplantation might be considered. The triple precautionary levels of medical staff during operation prevented the transmission of 2019-nCoV.

Objective:To explore abnormal microstructural changes of white matter in patients with white matter lesions(WML) using diffusion tensor imaging(DTI), and to determine the association of such abnormalities of DTI parameters with executive function.Methods:Totally 34 patients with WML were recruited from the department of Neurology, Beijing Tiantan Hospital, Capital Medical University from March 2012 to May 2019.All patients with WML were scored with Hamilton depression scale (HAMD) and Hamilton anxiety scale (HAMA), and assessed with Montreal cognitive assessment (MoCA) and clinical dementia rating(CDR). They were divided into WML-cognitive normal group, WML-vascular cognitive impairment-non dementia group and WML-Dementia group.The Stroop color and word test (SCWT), trail making test-A (TMTA), digit symbol test and verbal fluency test were carried out to evaluate executive function.In addition, the healthy elderly without WML lesions were selected as the control group after they were examined by MRI, and all brains of the subjects went through DTI with Siemens 3.0 T MR.The data were collected and analyzed by voxel based analysis (VBA). The anisotropy and mean diffusion coefficient of DTI in the region of interest (ROI) and other regions in the brain were studied in the four groups, and their correlation with scores of executive function in WML patients was analyzed.Results:(1)In these executive function test, there were significant differences between the patients with cognitive impairment (WML-VAD group, WML-VCIND group) and normal cognition group(WML-CN group, NC group), such as SCWT(B)(65.54±6.24 vs 43.67±0.95, 76.75±2.13 vs 43.67±0. 95, 65.54±6.24 vs 43.66±1.81, 76.75±2.13 vs 43.66±1.81), SCWT(C)(88.58±6.76 vs 61.63±1.31, 96.37±1.47 vs 61 63±1.31, 88.58±6.76 vs 66.31±8.19, 96.37±1.47 vs 66.31±8.19), TMTA(40.47±2.76 vs 30.92±0.47, 44.24±1.43 vs 30.92±0.47, 44.24±1.43 vs 31.99±2.07, 40.47±2.76 vs 31.99±2.07), TMTB(88.66±6.55 vs 80.34±0.61, 96.70±1.72 vs 80.34±0.61, 88.66±6.55 vs 83.10±5.91, 96.70±1.72 vs 83. 10±5.91), Digit Symbol Test(39.25±5.63 vs 47.00±2.55, 31.27±3.93 vs 47.00±2.5, 39.25±5.63 vs 48.86±4.34, 31.27±3.93 vs 48.86±4.34) and Verbal Fluency Test(8.94±1.00 vs 11.71±0.47, 6.64±0.81 vs 11.71±0.47, 8.94±1.00 vs 10.86±0.69, 6.64±0.81 vs 10.86±0.69) scores ( P<0.05); In the patients with cognitive impairment, there were significant differences between WML-VAD group and WML-VCIND group, such as SCWT(B), SCWT(C), TMTA, TMTB, digit symbol test and verbal fluency test scores ( P<0.05); There were significant differences between WML-CN patients and NC group in the scores of SCWT (C), verbal fluency test( P<0.05). (2)FA values in the genu of corpus callosum and the inferior longitudinal fasciculus were negatively correlated with the time of SCWT (B), SCWT (C) and the TMTA( r=-0.436--0.471), but positively correlated with the scores of digit symbol test and verbal fluency test( r=0.428-0.573). MD values in the genu of corpus callosum, the superior/inferior longitudinal fasciculus and the inferior fronto-occipital fasciculus were positively correlated with the time of SCWT (B), SCWT (C) and TMTA( r=0.432~0.609), but negatively correlated with the scores of digit symbol test and verbal fluency test( r=-0.424--0.630, all P<0.003125 after emendation). Conclusion:The executive function of patients with WML-Dementia decreases significantly.The more serious the damage of white matter microstructure, the more serious the damage of executive of function.