ObjectiveTo screen and evaluate the antidepressant compounds of Curcumae Rhizoma， and explore its mechanism of regulating the nuclear factor erythroid 2-related factor 2（Nrf2）/glutathione（GSH） peroxidase 4（GPX4）/GSH pathway from an antioxidant perspective. MethodsThe antioxidant activities in vitro of 11 characteristic components from Curcumae Rhizoma， including curcumol， curgerenone， curdione， curzerene， curcumenol， curcumenone， dehydrocurdione， isocurcumenol， furanodienone， furanodiene and zederone， were detected using 1，1-diphenyl-2-picrylhydrazyl（DPPH） and 2，2'-azinobis-（3-ethylbenzothiazoline-6-sulphonic acid） diammonium salt（ABTS） radical scavenging assays. The depression in Drosophila melanogaster was induced by chronic unpredictable mild stress（CUMS）， and W1118 wild-type male D. melanogaster were randomly divided into blank group， model group， curcumol group， curgerenone group， curdione group， curzerene group， curcumenol group，curcumenone group， dehydrocurdione group， isocurcumenol group， furanodienone group， furanodiene group， zederone group and fluoxetine group（10 μmol·L^-1）. The treatment groups received a dose of 0.1 g·L^-1 of 11 characteristic components from Curcumae Rhizoma， while the blank and model groups were administered equivalent volumes of solvent. The sucrose preference test， climbing test and forced swimming test were used to evaluate the behavioral indicators of depression in D. melanogaster. Liquid chromatography-mass spectrometry（LC-MS） was used to detect the levels of 5-hydroxytryptamine（5-HT） and dopamine（DA） in the brain of D. melanogaster， and the entropy weight method was used to comprehensively evaluate neurobehavioral and neurotransmitter indicators， resulting in the identification of the antidepressant active components of Curcumae Rhizoma. In addition， a mouse depression model was established by CUMS， and C57BL/6J mice were randomly divided into blank group， model group， low and high dose groups of curzerene（0.5， 1 mg·kg^-1）， and fluoxetine group（10 mg·kg^-1） to confirm the antidepressant effect of the optimal active ingredient by behavioral analysis. Flow cytometry was used to detect the content of reactive oxygen species（ROS） in the hippocampus of mice from each group. Enzyme-linked immunosorbent assay was used to detect the contents of adenosine triphosphate（ATP）， superoxide dismutase（SOD）， catalase（CAT） and GSH. Transmission electron microscope（TEM） was used to observe the effect of curzerene on the ultrastructure of mitochondria in hippocampal tissue. Western blot was performed to determine the level of Nrf2 protein， and Nrf2 inhibitor（ML385） was used to verify the relationship between the antidepressant effect of curzerene and regulation of Nrf2. Real time fluorescence quantitative polymerase chain reaction（Real-time PCR） was employed to detect the effect of curzerene on the mRNA expression level of GPX. ResultsIn vitro antioxidant experiments showed that curzerene and curgerenone exhibited the most significant ability to scavenge free radicals， and comprehensive evaluation results of entropy weight method indicated that curzerene stood out as the most promising active component. Compared with the blank group， the model group exhibited a significant decrease in sucrose preference coefficient and the number of times entering the open field center（P<0.01）， as well as a significant increase in immobility time in the forced swimming and tail suspension tests（P<0.01）， and the ROS content in hippocampus significantly elevated（P<0.01）， while the ATP content significantly reduced（P<0.01）. In the hippocampal neurons of the model group， mitochondrial cristae were disordered， with vacuolation of the inner membrane and severe damage. Nrf2 protein expression level in the model group was significantly decreased（P<0.05）， and the antioxidant enzymes SOD， CAT and GSH contents were also significantly reduced（P<0.05， P<0.01）， and the gene expression levels of GPX1， GPX4 and GPX7 were significantly decreased（P<0.01）. Compared with the model group， the high-dose group of curzerene showed a significant increase in the sucrose preference coefficient and the number of times entering the open field center（P<0.05）， as well as a significant decrease in immobility time in the forced swimming and tail suspension tests（P<0.05， P<0.01）. The ROS content in the hippocampus of the high-dose group of curzerene was significantly reduced（P<0.01）， while the ATP content was significantly increased（P<0.05）. The neuronal mitochondrial damage in the hippocampus of the high-dose group of curzerene was alleviated， and the expression level of Nrf2 protein was significantly increased（P<0.05）. The Nrf2 inhibitor ML385 reversed the improvement of curzerene on depressive behaviors in CUMS mice. The GSH content in the hippocampal neurons of the high-dose group of curzerene was significantly increased（P<0.01）， while there were no significant differences in SOD and CAT contents. The expression level of GPX4 gene in the hippocampal neurons of the high-dose group of curzerene was significantly increased（P<0.05）， while there were no significant differences in other GPX genes. ConclusionCurzerene is the best component with antidepressant activity in Curcumae Rhizoma. It may improve mitochondrial dysfunction to exert its antidepressant effect by regulating Nrf2 and its downstream GPX4/GSH pathway rather than CAT or SOD pathways.

Objective : To investigate the molecular mechanism of Toll⁃like receptor 4 ( TLR4)/Ras homologue A (RhoA) signaling pathway involved in regulating the effect of septic serum on vascular endothelial cell permeability before and after continuous hemofiltration. Methods : The serum of 5 patients with sepsis before and after continuous hemofiltration treatment was collected , and the levels of inflammatory cytokines in serum before and after hemofiltration were detected. Human umbilical vein endothelial cells (HUVEC) were treated with serum before and after continuous hemofiltration for 24 hours. The expression of VE⁃cadherin , F ⁃actin , TLR4 and RhoA in vascular endothelial cells were detected by Western blot. A TLR4 low expression cell line was constructed to detect the effect of TLR4 low expression on the expression of VE⁃cadherin , F ⁃actin and RhoA and the permeability of endothelial cells. Results : After continuous blood treatment , the serum levels of TLR4 , RhoA , interleukin⁃1 (IL⁃1) , interleukin⁃6 (IL⁃6) and tumor necrosis factor⁃α (TNF⁃α ) significantly decreased. The expression levels of VE⁃cadherin , F ⁃actin , TLR4 and RhoA in the serum intervention group after continuous hemofiltration treatment significantly decreased , and the cell permeability significantly decreased. Low expression of TLR4 significantly promoted the expression of VE⁃cadherin and F ⁃actin , and inhibited the expression of RhoA protein. Conclusion TLR4/RhoA signaling pathway is involved in the regulation of changes in vascular endothelial cell permeability induced by septic serum after continuous hemofiltration treatment.

Objective:To investigate the application value of domestic robotic surgical system in radical resection of hilar cholangiocarcinoma (hCCA).Methods:The retrospective and descriptive study was constructed. The clinicopathological data of a 66-year-old male patient with hCCA who was admitted to the Second Hospital of Shandong University in November 2022 were collected. Radical resection of hCCA was performed using the Toumai? laparoscopic surgical robot system. Observation indicators: (1) intraoperative conditions; (2) postoperative conditions; (3) follow-up. Count data were represented as absolute numbers and (or) percentages.Results:(1) Intraoperative conditions. The patient underwent radical resection of hCCA successfully using robotic surgical system, including tumor resection, lymph node dissection, and gastrointestinal reconstruc-tion. The operation time and volume of intraoperative blood loss were 400 minutes and 100 mL, respectively, and no intraoperative blood transfusion was required. (2) Postoperative conditions. The patient began ambulation on postoperative day 1 and began taking liquid food on postoperative day 4. Liver function examination and abdominal computed tomograph (CT) on postoperative day 5 showed a decrease in serum bilirubin, no biliary or intestinal leakage, and no edema or necrosis at the anastomotic site. The abdominal pre-anastomotic and post-anastomotic drainage tubes were removed on the 7th and 9th day after the surgery respectively, and the patient was discharged on the 10th day after surgery. Results of postoperative pathological examination showed moderately to poorly differentiated adenocarcinoma of the bile duct. Immunostaining was positive for CK7 and CK19. The Ki-67 proliferation index was 35%. The proximal and distal resection margin of bile duct were negative. The tumor diameter was 30 mm. Perineural invasion was positive. The surgical specimen margin was negative. Two lymph nodes were identified containing tumor cells positive for malignancy. No tumor cell metastasis was detected in the No.8, No.12 or gastric lesser curvature lymph nodes submitted for pathological examination. (3) Follow-up. The patient was followed up at postoperative 1-, 3-, 5-month after discharge. During follow-up period, results of liver function examination and abdominal CT showed liver function restore to normal levels, no complication such as biliary fistula, intestinal fistula, gastroparesis or tumor metastasis.Conclusion:The Domestic Toumai ? laparoscopic surgical robot system can be applied to radical resection of hCCA.

ObjectiveTo determine whether HBV DNA polymerase is associated with T-cell failure and thus mediates the immune escape of HBV-related hepatocellular carcinoma （HCC） tumor cells， and to investigate the specific molecular mechanisms. MethodsLiver cancer cell lines Huh7 and HepG2 stably transfected with HBV DNA polymerase expression plasmid with Flag （Flag-HBV-P） and intercellular adhesion molecule-1 （ICAM1） were co-cultured with Jurkat cells， and MTT assay， qRT-PCR， and ELISA were used to measure Jurkat cell proliferation， activation （CD69 expression）， and secretion of the cytokine IFN-γ. RNA-seq was used to screen for differentially expressed immune-associated molecules between stably transfected cell lines and control cells， and mRNA half-life and protein half-life assays were used to determine the specific levels of the immune-associated molecules that were affected by HBV DNA polymerase. Related websites were used to predict the transcription factors that may bind to the promoter region of this immune-associated molecule， Western blot was used to verify the effect of transcription factors on the immune-associated molecule， and rescue experiment was used to determine whether HBV DNA polymerase affects the expression level of the immune-associated molecule through this transcription factor. The independent-samples t test was used for comparison between two groups. ResultsThe experimental group had significant reductions in Jurkat cell proliferation， activation， and cytokine secretion compared with the control group （all P<0.01）. Compared with the control group， the experimental group （Huh7 and HepG2 cell lines） had significant reductions in the mRNA and protein expression levels of ICAM1 （all P<0.01）. Website prediction identified the ICAM1 promoter and preliminarily highlighted NFKB1， RELA， and STAT3. Compared with the control group， the experimental group （Huh7 and HepG2 cell lines） had a significant reduction in the protein expression level of p65 （all P<0.01）. After p65 overexpression， there was a significant increase in the protein expression level of ICAM1， and after the expression of p65 was reduced， there was a significant reduction in the protein expression level of ICAM1 （all P<0.01）. In the rescue experiment， there was no significant difference in the protein expression level of ICAM1 between the control group and the experimental group after p65 overexpression （all P>0.05）. After the overexpression of ICAM1， there were no significant differences in the proliferation， activation， and cytokine secretion of Jurkat cells between the control group and the experimental group （Huh7 and HepG2 cell lines） （all P>0.05）. ConclusionHBV DNA polymerase downregulates the level of ICAM1 to mediate HCC immune escape by inhibiting the expression of p65 in NF-κB.

Triple-negative breast cancer (TNBC) is a nasty disease with extremely high malignancy and poor prognosis. Annexin A3 (ANXA3) is a potential prognosis biomarker, displaying an excellent correlation of ANXA3 overexpression with patients' poor prognosis. Silencing the expression of ANXA3 effectively inhibits the proliferation and metastasis of TNBC, suggesting that ANXA3 can be a promising therapeutic target to treat TNBC. Herein, we report a first-in-class ANXA3-targeted small molecule (R)-SL18, which demonstrated excellent anti-proliferative and anti-invasive activities to TNBC cells. (R)-SL18 directly bound to ANXA3 and increased its ubiquitination, thereby inducing ANXA3 degradation with moderate family selectivity. Importantly, (R)-SL18 showed a safe and effective therapeutic potency in a high ANXA3-expressing TNBC patient-derived xenograft model. Furthermore, (R)-SL18 could reduce the β-catenin level, and accordingly inhibit the Wnt/β-catenin signaling pathway in TNBC cells. Collectively, our data suggested that targeting degradation of ANXA3 by (R)-SL18 possesses the potential to treat TNBC.

Objective:To explore the clinical efficacy and adverse reactions of albumin-bound paclitaxel (Nab-P) and conventional paclitaxel combined with cisplatin and concurrent radiotherapy for the treatment of patients with locally advanced esophageal squamous cell carcinoma.Methods:Forty-nine patients with locally advanced esophageal squamous cell carcinoma admitted to the First People's Hospital of Suqian from November 2016 to May 2020 were included. Of the 49 patients, 23 cases were treated with Nab-P combined with cisplatin and concurrent radiotherapy (NP group), 26 cases were treated with conventional paclitaxel combined with cisplatin and concurrent radiotherapy (TP group). All patients received 2 cycles of chemotherapy. The curative efficacy was evaluated one month after the end of radiotherapy, and the curative effect and adverse reactions of the two treatment regimens were compared.Results:The objective remission rate in NP group was 78.3% (18/23), and the disease control rate was 100.0% (23/23). The objective response rate in TP group was 61.5% (16/26), and the disease control rate was 92.3% (24/26). The objective response rate and disease control rate in NP group were higher than those in TP group, but the differences were not statistically significant (both P > 0.05). The common adverse reactions were mainly hair loss, loss of appetite, bone marrow suppression, radiation esophagitis, radiation pneumonia, malaise and myalgia. The incidence rate of grade 3-4 acute bone marrow suppression in NP group (8.7%, 2/23) was lower than that in TP group (38.5%, 10/26), and the difference was statistically significant ( χ2 = 4.35, P = 0.037). The incidence rate of myalgia in NP group (26.1%, 6/23) was lower than that in TP group (61.5%, 16/26), and the difference was statistically significant ( χ2 = 4.85, P = 0.028). Conclusions:Nab-P combined with cisplatin and concurrent radiotherapy has good efficacy in the treatment of patients with locally advanced esophageal squamous cell carcinoma, and the incidence rate of adverse reactions is lower than that of conventional paclitaxel combined with cisplatin and concurrent radiotherapy, so that the regimen is safe.

Objective:To compare the effect of three-dimensional CT angiography (CTA) and color Doppler ultrasound (CDU) in reconstruction of soft tissue defects after oral cancer surgery with anterolateral thigh flap (ALTF).Methods:Patients who underwent reconstruction of postoperative defects with ALTF in Department of Oral and Maxillofacial Surgery, the Affiliated Stomatological Hospital of Southwest Medical University from January 2013 to January 2020 were retrospectively reviewed. According to the imaging method used for examining perforating artery, all patients were divided into two groups. In group A, CTA and three-dimensional vascular reconstruction were used to locate the lateral femoral circumflex artery and its perforating vessels, and the individualized ALTF was designed. In group B, the lateral circumflex femoral artery and its perforating vessels were located by CDU. The clinical features, operation time, flap survival rate, postoperative complication rate, image quality of angiography, difference of superficial skin points of perforating vessels before and during operation, and diameter of perforators were compared between the two groups. The measurement data were expressed by Mean±SD, and the differences between the two groups were compared by independent sample t-test; paired sample t-test was used to compare the intra-group differences; patients’ clinical features and other enumeration data were expressed in the number of cases (%), and analyzed by chi-square test; reliability analysis was adopted for the image quality score of two doctors at different times, taking Cronbach’s α value; correlations between body mass index (BMI) and flap survival rate were tested by Pearson correlation, whereas the correlation between flap survival rate and underlying diseases, drug combination, bad smoking and drinking habits, and surgical complications were tested by Spearman correlation, which were all performed using SPSS version 20.0 at significance level P<0.05. Results:A total of 50 patients with oral cancer were collected, 25 patients in each group. There were no significant differences between the two groups in clinical features such as sex distribution, age, TNM stage, BMI, underlying diseases, drug combination, bad smoking and drinking habits, tumor location and so on ( P>0.05). The mean operation time of group A was significantly shorter than that of group B[(67.64±5.94) min vs. (70.88±4.88) min, P<0.05]. All flaps in group A survived; one case in group B had complete flap necrosis. There was no significant difference in flap survival rate between the two groups(100% vs. 96%, P>0.05). One case in group A and two cases in group B had complications such as effusion of donor site wound, and there was no significant difference ( P>0.05). Compared with the image quality of the two groups, the angiographic quality score of group A was significantly higher than that of group B, the difference was statistically significant [(3.08±0.64) scores vs. (2.56±0.65) scores, P<0.05]. In group A, the distance difference between the position of the skin superficial point of perforator vessel positioned before operation and during operation was significantly shorter than that in group B, and the difference was statistically significant [(1.32±0.50) mm vs. (1.75±0.84) mm, P<0.05]. In group A, the diameter of perforating artery measured by imaging before operation was (1.68±0.17) mm, which had no significant difference with the actual value[(1.70±0.18) mm] ( P>0.05); whereas, in group B, the diameter of perforating artery measured by imaging before operation was (1.77±0.14) mm. The actual measured value during operation was (1.66±0.15) mm, the difference was statistically significant ( P<0.05). A significant correlation emerged between surgical complications and flap survival rate ( r=0.57, P<0.001), however, there were no significant correlations between BMI, combined with basic diseases, combined medication, bad smoking and drinking habits and flap survival ( P>0.05). Conclusions:Compared with CDU, CTA combined with three-dimensional vascular reconstruction is a feasible and reliable method for preoperative evaluation, flap design. The flap preparation time is shorter. Therefore, it is a good method of preoperative vascular localization.

Objective:To compare the effect of three-dimensional CT angiography (CTA) and color Doppler ultrasound (CDU) in reconstruction of soft tissue defects after oral cancer surgery with anterolateral thigh flap (ALTF).Methods:Patients who underwent reconstruction of postoperative defects with ALTF in Department of Oral and Maxillofacial Surgery, the Affiliated Stomatological Hospital of Southwest Medical University from January 2013 to January 2020 were retrospectively reviewed. According to the imaging method used for examining perforating artery, all patients were divided into two groups. In group A, CTA and three-dimensional vascular reconstruction were used to locate the lateral femoral circumflex artery and its perforating vessels, and the individualized ALTF was designed. In group B, the lateral circumflex femoral artery and its perforating vessels were located by CDU. The clinical features, operation time, flap survival rate, postoperative complication rate, image quality of angiography, difference of superficial skin points of perforating vessels before and during operation, and diameter of perforators were compared between the two groups. The measurement data were expressed by Mean±SD, and the differences between the two groups were compared by independent sample t-test; paired sample t-test was used to compare the intra-group differences; patients’ clinical features and other enumeration data were expressed in the number of cases (%), and analyzed by chi-square test; reliability analysis was adopted for the image quality score of two doctors at different times, taking Cronbach’s α value; correlations between body mass index (BMI) and flap survival rate were tested by Pearson correlation, whereas the correlation between flap survival rate and underlying diseases, drug combination, bad smoking and drinking habits, and surgical complications were tested by Spearman correlation, which were all performed using SPSS version 20.0 at significance level P<0.05. Results:A total of 50 patients with oral cancer were collected, 25 patients in each group. There were no significant differences between the two groups in clinical features such as sex distribution, age, TNM stage, BMI, underlying diseases, drug combination, bad smoking and drinking habits, tumor location and so on ( P>0.05). The mean operation time of group A was significantly shorter than that of group B[(67.64±5.94) min vs. (70.88±4.88) min, P<0.05]. All flaps in group A survived; one case in group B had complete flap necrosis. There was no significant difference in flap survival rate between the two groups(100% vs. 96%, P>0.05). One case in group A and two cases in group B had complications such as effusion of donor site wound, and there was no significant difference ( P>0.05). Compared with the image quality of the two groups, the angiographic quality score of group A was significantly higher than that of group B, the difference was statistically significant [(3.08±0.64) scores vs. (2.56±0.65) scores, P<0.05]. In group A, the distance difference between the position of the skin superficial point of perforator vessel positioned before operation and during operation was significantly shorter than that in group B, and the difference was statistically significant [(1.32±0.50) mm vs. (1.75±0.84) mm, P<0.05]. In group A, the diameter of perforating artery measured by imaging before operation was (1.68±0.17) mm, which had no significant difference with the actual value[(1.70±0.18) mm] ( P>0.05); whereas, in group B, the diameter of perforating artery measured by imaging before operation was (1.77±0.14) mm. The actual measured value during operation was (1.66±0.15) mm, the difference was statistically significant ( P<0.05). A significant correlation emerged between surgical complications and flap survival rate ( r=0.57, P<0.001), however, there were no significant correlations between BMI, combined with basic diseases, combined medication, bad smoking and drinking habits and flap survival ( P>0.05). Conclusions:Compared with CDU, CTA combined with three-dimensional vascular reconstruction is a feasible and reliable method for preoperative evaluation, flap design. The flap preparation time is shorter. Therefore, it is a good method of preoperative vascular localization.

Objective:To observe the effect of breastfeeding on the incidence of retinopathy of prematurity (ROP).Methods:A retrospective clinical study. From June 2017 to December 2019, 1256 eyes of 628 premature infants who were born in Ningbo Women and Children's Hospital and were screened for ROP were included in the study. Among them, there were in 325 males (650 eyes) and 303 females (606 eyes). According to the feeding situation, premature infants were divided into breastfeeding (research) group and formula feeding (control) group, with 390 cases of 780 eyes and 238 cases of 476 eyes, respectively. The changes in the retina of the fundus of the two groups of premature infants during the observation period were compared. The qualitative data comparison between groups was performed by the χ2 test; the quantitative data comparison was performed by the two independent sample t test. Results:The sex ratio of premature infants in the study group and control group ( χ2=0.217), birth weight ( t=0.728), gestational age at birth ( t=0.351), Apgar score at birth ( t=0.816), oxygen inhalation time ( t=0.427), were compared with the length of stay in the neonatal intensive care unit ( t=1.580), the difference was not statistically significant ( P>0.05). Among the 390 cases in the study group, 108 cases (27.7%, 108/390) and 282 cases (72.3%, 282/390) were with or without ROP, respectively; in the 238 cases in the control group, 86 (36.1%, 86/238) were with ROP, 152 (63.9%, 152/238) cases were without ROP. There was a statistically significant difference in the incidence of ROP between the two groups ( χ2=4.934, P=0.026). Among the 108 cases of ROP in the study group, 50 (12.8%, 50/108), 35 (9.0%, 35/108), 23 (5.9%, 23/108) cases were in stage 1, 2 and 3, respectively. Among the 86 ROP cases in the control group, stages 1, 2 and 3 were 25 (10.5%, 25/86), 40 (16.8%, 40/86), and 21 (8.8%, 21/86), respectively. In the comparison of ROP staging between the two groups, the difference in stage 1 was not statistically significant ( χ2=0.754, P>0.05), and the difference in stage 2 and above was statistically significant ( χ2=11.400, P<0.05). Conclusion:Breastfeeding may reduce the incidence and severity of ROP.

Objective:To explore the risk factors of acute renal injury (AKI) in exertional heat radiation disease (EHS) .Methods:In november 2019, the clinical data of 69 EHS patients admitted from July 2015 to September 2019 were reviewed. The general data, laboratory indexes, Glasgow score (GCS) at admission, 24-hour acute physiology and chronic health score Ⅱ (APACHE Ⅱ) , exposure time rate and physical labor intensity were collected. According to the occurrence of AKI, the patients were divided into AKI group and non-AKI group, 31 and 38 in each group. The differences of general data and laboratory indexes between the two groups were compared, and the t and Mann-Whitney U test were used to compare the two groups. The enumeration data are expressed by examples and constituent ratio (%) . Independent sample χ 2 test is used for inter-group comparison, and multiple test is used for multi-sample comparison. The correlation was analyzed by linear regression. Risk factors were analyzed by Logistic regression analysis. Results:At discharge, 31 of 69 EHS patients developed AKI. Compared with the non-AKI group, the heart rate, white blood cell count, lactic acid, D-dimer and myoglobin were higher; MAP, platelet count and PH were lower in the AKI group. The difference was statistically significant ( P<0.05) . APACHE Ⅱ score, core temperature, time to drop to 38.5 ℃, contact time rate, platelet count, pH, lactic acid, D-dimer and myoglobin were all correlated with creatinine ( r=0.57, 0.42, 0.80, 0.78, 0.57, 0.43, 0.51, 0.55, 0.79) . APACHE Ⅱ score, time to drop to 38.5C, Lac and MYO are the risk factors of AKI in EHS patients. Multivariate Logistic regression analysis showed that the time required to drop to 38.5C was an independent risk factor for the occurrence of AKI. Conclusion:AKI is a serious complication of EHS. EHS complicated with AKI, should be identified early and effective intervention measures should be taken.