Objective To explore the mechanism of curcumin in enhancing gemcitabine sensitivity by regulating pancreatic cancer cells.Methods In order to verify the effect of curcumin on p53 and NF-κB p65 nuclear translocation in pancreatic cancer cell PANC1,the pancreatic cancer PANC1 cells were treated with 0,10,20,30 μmol/L curcumin to obtain the blank group,10 μmol/L curcumin group,20 μmol/L curcumin group and 30 μmol/L curcumin group.The intracellular distribution of NF-κB p65 was determined by immunofluo-rescence staining under fluorescence microscope.The expression level of p53 protein in cells was determined by Western blot.The expression level of p53 mRNA was determined by reverse transcription-real-time fluo-rescence quantitative PCR.The combined use of miRstar and JASPAR softwares predicted to seek microRNA (miRNA) potentially regulated by NF-κB p65 nuclear translocation.The double luciferase reporting assay was used to respectively verify the relationship between miRNA and p53.In order to verify whether curcumin in-fect the sensitivity of PANC1 cell through NF-κB p65/miR-266-5p/p53 axis,the gemcitabine group was ob-tained by 10 μmol/L gemcitabine treating cells,and the curcumin combined gemcitabine group was obtained by 20 μmol/L curcumin and 10 μmol/L gemcitabine treating cells.After the cells were treated with curcumin (20 μmol/L) and gemcitabine (10 μmol/L),oligonucleotides mimic NC and miR-26b-5p mimic were trans-fected into cells,and the mimic NC group and miR-26b-5p group were obtained.pcDNA3.1 no-load plasmid and pcDNA3.1-p53 overexpression plasmid were transfected into cells,respectively,and the pcDNA3.1 group and p53 group were obtained.The cell activity was detected by MTT assay.The cellular apoptosis level was determined by Annexin V/PI double staining.Results Compared with the blank group,the intracellular p53 mRNA and protein expression levels in the various curcumin treated groups (10,20,30 μmol/L curcumin groups) all were increased.Compared with the blank group,the expression level of NF-κB p65 in the nucleus of 20μmol/L curcumin group was decreased.The miRstar and JASPAR prediction software found 8 miRNA that may be regulated by NF-κB p65 nuclear translocation,in which 3 miRNA had potential to target p53 genes,especially miR-26b-5p effect was most significant.The double luciferase report experiment confirmed that miR-26b-5p did interact with p53.Compared with the mimic NC group,the expression levels of p53 mR-NA and protein in the mimic miR-26b-5p group were decreased.Compared with the gemcitabine group,the cell viability in the curcumin combined gemcitabine group was decreased and the apoptosis rate was increased.Compared with the mimic NC group,the cell activity in the mimic miR-26b-5p group was increased and the apoptosis level was decreased.Moreover compared with the pcDNA3.1 group,the cell activity in the pcDNA3.1-p53 group was decreased and the apoptosis level was increased.Conclusion Curcumin reduces the expression of miR-26b-5p gene by inhibiting the nuclear translocation of NF-κB p65 protein,and then increase the p53 gene and protein expression,and enhance the sensitivity of pancreatic cancer cells to gemcitabine by the NF-κB p65/miR-26b-5p/p53 axis.

Sepsis,characterized by inadequate host responses to infection,leads to life-threatening organ dysfunction and is a major cause of mortality among critically ill patients.Among them,immunosuppression plays a crucial role in the development of sepsis.This review elaborates on the pathogenesis and immunological features of sepsis-induced immunosuppression.Then,we analyzed the current situation of immunotherapy for sepsis from the angles of restoring immune stimulation,eliminating inflammatory mediators,and improving immunity.We emphasized the need for a comprehensive analysis of the traits and immunological types of patients with sepsis,generating new approaches to improve the prognosis of sepsis based on immune targets.

Objective:To understand the prevalence of human parechovirus (HPeV) in neonates of Hunan Provincial People’s Hospital, and analyze genetic evolutionary characteristics.Methods:From June to September 2021, fecal samples of inpatient neonates were collected in Hunan Provincial People′s Hospital. TaqMan real-time qPCR and RT-PCR were used for HPeV screening and genotyping. High-throughput sequencing and PCR were used to obtain whole genomes. Phylogenetic analysis was performed after sequencing.Results:A total of 123 fecal samples of neonates were collected, of which 22 were HPeV positive, with 17.89% positive rate. All the strains belonged to the HPeV-1 genotype. One full-length genomic sequence of 7 269 bp were obtained, and provisionally named Hunan/HPeV/2021, which has the highest nucleotide identity with known HPeV-1 genotype, with 86.6%-91.9% nucleotide identity. The nucleotide and amino acid identity of open reading frame (ORF) with known similar sequences were 90.3%-92.6% and 97.3%-98.3%, respectively. The phylogenetic analysis showed that Hunan/HPeV/2021 belongs to the HPeV-1 genotype, which is clustered into the same clade as the popular HPeV-1 strains in China.Conclusions:HPeV has a high prevalence in inpatient neonates of Hunan Provincial People’s Hospital and belong to the HPeV-1 genotype.

Objective:To explore the clinical application value of routine indicators such as blood routine and liver and kidney function in auxiliary diagnosis and prognosis of COVID-19 patients.Methods:SNK-q and other methods were used to retrospectively analyzed the differences of blood routine test, liver and kidney function and other inflammatory indexes of 30 patients with covid-19, 29 patients with other viral pneumonia, 35 patients with influenza A/B and 25 healthy persons from January 28 to February 14, 2020 in Xiangya Hospital of Central South University.Results:The neutrophils count increased gradually in COVID-19 group, influenza A/B group and other types of viral pneumonia group, and the difference between COVID-19 group and other viral pneumonia groups was statistically significant( H=-19.064, P<0.05); The lymphocyte count decreased gradually in the control group, influenza A/B group, other viral pneumonia group and COVID-19 group. In addition, DB, UA and GLU were also different among groups. Subgroup analysis showed that there were statistically significant differences in N( F=9.581, t=-0.152, P<0.05), N%( F=5.723, t=-0.600, P<0.05), NLR( F=4.773, t=-1.161, P<0.05), PCT( F=17.464, t=-1.477, P<0.05)and CRP( F=7.656, t=-1.973, P<0.05) between patients with lung involvement +-++ and patients with lung involvement +++-++++. There were statistically significant differences in NLR( F=63.931, t=-2.815, P<0.01), AST( F=15.704, t=-1.930, P<0.01), ALT( F=35.551, t=-2.199, P<0.01), LDH( F=7.715, t=-2.703, P<0.05) and GLU( F=6.306, t=-5.116, P<0.05) between the light+common subgroup and the heavy+critical subgroup of COVID-19 clinical classification. Correlation analysis showed that clinical stage and imaging credit period were significantly correlated with NLR ( r=0.406 , P=0.026; r=0.397 , P=0.030), ALT ( r=0.403 , P=0.049; r=0.418 , P=0.047), LDH ( r=0.543 , P<0.01; r=0.643 , P<0.01) and GLU( r=0.750 , P<0.01; r=0.471 , P=0.042). A total of 5 principal components were extracted from all the included indicators, and the comprehensive information extraction rate was 82.86%. Indicators of a large load included Ur, PCT and CRP in PC1; ALT, AST and GLU in PC2; N%, L%, L and NLR in PC3. It indicated that the indicators of acute infection, liver function and blood routine had certein warning effect on disease surveillance. The results of ROC curve analysis showed that the combined detection of N+TB+Urea was the best practice to distinguish COVID-19 and other viral pneumonia, while the combined detection of N+L+UA was the most effective solution to make a distinction between COVID-19 and influenza A/B patients. In the aspect of disease evaluation, NL+LDH+GLU+ALT combined detection represent the best diagnostic performance to distinguish the clinical stage of light+common type and heavy+critical type, achieving the AUC (ROC) to 0.904, with the sensitivity 75% and the specificity 100% at the cut-off value of 0.477. Conclusion:In addition to etiology and imaging examination, doctors can also improve the routine laboratory tests such as blood routine test, liver and kidney function to assist diagnosis and disease prediction of patients with respiratory tract infection.

Objective:To investigate the application of local rotation flap with subcutaneous pedicle for breast conservation in central breast cancer.Methods:Retrospective analysis of clinical data of 14 patients with stage Ⅰor Ⅱ central breast cancer was performed. The local rotation flap with subcutaneous pedicle was used for breast conservation in Jiangxi Provincial Breast Specialist Hospital (Nanchang Third Hospital) from January 2017 to December 2018. The postoperative complications were recorded. One year after operation, the aesthetic result, satisfactory and comfort index were evaluated. Two years after operation, local tumor recurrence and metastasis were followed.Results:All patients were women, aged 37-75 years old with the median age as 47. First-stage healing was achieved in 12 patients. Wound infection happened in one case and necrotic in one case. They were all healed after secondary suture. Fourteen patients were followed up for 1 year, the suprasternal notch-nipple length was (22.27±2.38) cm at the operative side, and (23.33±2.22) cm at the healthy side, showing no statistical significance ( t=-1.253, P=0.242). The nipple-midsternal line length was(10.12±0.91) cm at the operative side, and (10.68±1.09) cm at the healthy side, showing no statistical significance ( t=-1.937, P=0.094). The nipple-inframammary fold length was (6.94±0.95) cm at the operative side, and (7.05±1.30) cm at the healthy side, showing no statistical significance ( t=-0.478, P=0.645). The patient’s breast satisfaction was 60.2±11.4 points before operation and 61.7±12.7 points after operation, with no difference between them ( t=-0.330, P=0.744). The overall postoperative comfort index was 62.05±4.40 points, which indicates a moderate comfort state. The physiological comfort index was 6.52±2.05 points, the mental and psychological comfort index was 15.13±2.56 points, the social comfort index was 19.09±1.57 points, and the environmental comfort index was 21.29±2.11 points. There was no local recurrence and no systemic metastasis 2 years after operation. Conclusions:The breast conservation in central breast cancer with local rotation flap with subcutaneous pedicle is less invasive with few complication and satisfactory results in cosmetic appearance. The moderate comfort index and good prognosis can be prospected.

Objective:To explore the clinical application value of routine indicators such as blood routine and liver and kidney function in auxiliary diagnosis and prognosis of COVID-19 patients.Methods:SNK-q and other methods were used to retrospectively analyzed the differences of blood routine test, liver and kidney function and other inflammatory indexes of 30 patients with covid-19, 29 patients with other viral pneumonia, 35 patients with influenza A/B and 25 healthy persons from January 28 to February 14, 2020 in Xiangya Hospital of Central South University.Results:The neutrophils count increased gradually in COVID-19 group, influenza A/B group and other types of viral pneumonia group, and the difference between COVID-19 group and other viral pneumonia groups was statistically significant( H=-19.064, P<0.05); The lymphocyte count decreased gradually in the control group, influenza A/B group, other viral pneumonia group and COVID-19 group. In addition, DB, UA and GLU were also different among groups. Subgroup analysis showed that there were statistically significant differences in N( F=9.581, t=-0.152, P<0.05), N%( F=5.723, t=-0.600, P<0.05), NLR( F=4.773, t=-1.161, P<0.05), PCT( F=17.464, t=-1.477, P<0.05)and CRP( F=7.656, t=-1.973, P<0.05) between patients with lung involvement +-++ and patients with lung involvement +++-++++. There were statistically significant differences in NLR( F=63.931, t=-2.815, P<0.01), AST( F=15.704, t=-1.930, P<0.01), ALT( F=35.551, t=-2.199, P<0.01), LDH( F=7.715, t=-2.703, P<0.05) and GLU( F=6.306, t=-5.116, P<0.05) between the light+common subgroup and the heavy+critical subgroup of COVID-19 clinical classification. Correlation analysis showed that clinical stage and imaging credit period were significantly correlated with NLR ( r=0.406 , P=0.026; r=0.397 , P=0.030), ALT ( r=0.403 , P=0.049; r=0.418 , P=0.047), LDH ( r=0.543 , P<0.01; r=0.643 , P<0.01) and GLU( r=0.750 , P<0.01; r=0.471 , P=0.042). A total of 5 principal components were extracted from all the included indicators, and the comprehensive information extraction rate was 82.86%. Indicators of a large load included Ur, PCT and CRP in PC1; ALT, AST and GLU in PC2; N%, L%, L and NLR in PC3. It indicated that the indicators of acute infection, liver function and blood routine had certein warning effect on disease surveillance. The results of ROC curve analysis showed that the combined detection of N+TB+Urea was the best practice to distinguish COVID-19 and other viral pneumonia, while the combined detection of N+L+UA was the most effective solution to make a distinction between COVID-19 and influenza A/B patients. In the aspect of disease evaluation, NL+LDH+GLU+ALT combined detection represent the best diagnostic performance to distinguish the clinical stage of light+common type and heavy+critical type, achieving the AUC (ROC) to 0.904, with the sensitivity 75% and the specificity 100% at the cut-off value of 0.477. Conclusion:In addition to etiology and imaging examination, doctors can also improve the routine laboratory tests such as blood routine test, liver and kidney function to assist diagnosis and disease prediction of patients with respiratory tract infection.

Objective:To investigate the application of local rotation flap with subcutaneous pedicle for breast conservation in central breast cancer.Methods:Retrospective analysis of clinical data of 14 patients with stage Ⅰor Ⅱ central breast cancer was performed. The local rotation flap with subcutaneous pedicle was used for breast conservation in Jiangxi Provincial Breast Specialist Hospital (Nanchang Third Hospital) from January 2017 to December 2018. The postoperative complications were recorded. One year after operation, the aesthetic result, satisfactory and comfort index were evaluated. Two years after operation, local tumor recurrence and metastasis were followed.Results:All patients were women, aged 37-75 years old with the median age as 47. First-stage healing was achieved in 12 patients. Wound infection happened in one case and necrotic in one case. They were all healed after secondary suture. Fourteen patients were followed up for 1 year, the suprasternal notch-nipple length was (22.27±2.38) cm at the operative side, and (23.33±2.22) cm at the healthy side, showing no statistical significance ( t=-1.253, P=0.242). The nipple-midsternal line length was(10.12±0.91) cm at the operative side, and (10.68±1.09) cm at the healthy side, showing no statistical significance ( t=-1.937, P=0.094). The nipple-inframammary fold length was (6.94±0.95) cm at the operative side, and (7.05±1.30) cm at the healthy side, showing no statistical significance ( t=-0.478, P=0.645). The patient’s breast satisfaction was 60.2±11.4 points before operation and 61.7±12.7 points after operation, with no difference between them ( t=-0.330, P=0.744). The overall postoperative comfort index was 62.05±4.40 points, which indicates a moderate comfort state. The physiological comfort index was 6.52±2.05 points, the mental and psychological comfort index was 15.13±2.56 points, the social comfort index was 19.09±1.57 points, and the environmental comfort index was 21.29±2.11 points. There was no local recurrence and no systemic metastasis 2 years after operation. Conclusions:The breast conservation in central breast cancer with local rotation flap with subcutaneous pedicle is less invasive with few complication and satisfactory results in cosmetic appearance. The moderate comfort index and good prognosis can be prospected.

The clinical application of immune checkpoint inhibitors (ICIs) has significantly improved the prognosis of hepatocellular carcinoma (HCC) patients. With the widespread applica-tion of ICIs in HCC, the management of immune-related adverse events (irAE) gained more and more attention. However, the complicated disease characteristics and various combination therapies in HCC throw out challenges to irAE management. Therefore, the editorial board of the 'Chinese expert consensus on the management of immune-related adverse events of hepatocellular carcinoma treated with immune checkpoint inhibitors (2021 edition)' organizes multidisciplinary experts to discuss and formulate this consensus. The consensus focuses on issues related to HCC irAE manage-ment, and puts forward suggestions, in order to improve standardized and safety clinical medication, so as to maximize the benefits of immunotherapy for patients.

Objective To investigate the predictive value of serum lactate combined with PIRO (Predisposition,Infection,Response and Organ dysfunction) score in the development of multiple organs dysfunction syndrome (MODS) in septic patients and to study procalcitonin (PCT),in order to provide guidelines for clinical care.Methods From April 2015 to July 2016,a total of 752 sepsis patients were enrolled and divided into MODS group (n =488) and non-MODS group (n =264) according to the criteria of MODS.At 28 d after admission,these patients were divided into survival group (n =477) and death group (n =275).PCT and lactate levels in serum were measured,and PIRO score of these patients was calculated.Then the differences in levels of PCT and lactate in serum were compared among patients at different PIRO score categories.ROC was constructed to observe the clinical values of the biomarkers,PIRO score and lactate combined with PIRO score in predicting prognosis.Result PCT,lactate levels in serum and PIRO score were significantly higher in MODS group and death group,showing significant positive correlation.The areas under ROC curves (AUCs) of serum lactate combined with PIRO score for predicting MODS were 0.906,which was significantly higher than that of serum PCT (0.716),serum lactate (0.851) and PIRO score (0.840) alone (all P ＜ 0.05).Serum PCT,serum lactate and PIRO score were the independent predictors of MODS.Conclusions Serum lactate in combination with PIRO score was a valuable indicator in predicting development of MODS in septic patients.

Objective To explore the correlative factors of sudden death in patients suspected with pulmonary thromboembolism (PTE) in emergency room (ER).Methods A retrospective analysis was conducted.The clinical data of 12 patients with sudden death suspected with PTE (sudden death group) in ER of the Air Force General Hospital from January 2011 to June 2014 were analyzed.The non-sudden death group included 35 patients during the same time period who were diagnosed with PTE based on findings of CT pulmonary arteriography (CTPA) and showed no sudden death in ER.Factors,including sex,age,previous operation,tumor,syncope,dyspnea,bilateral or unilateral edema of lower extremity,heart rate (HR),white blood cell count (WBC),D-dimer,arterial partial pressure of oxygen (PaO2),arterial partial pressure of carbon dioxide (PaCO2) and typical clinical manifestation of electrocardiogram (SⅠTⅢQⅢ),were compared between the two groups.The potential predictors of sudden death of PTE were analyzed by logistic regression analysis.Results Young age (years old:51.3±15.5 vs.62.3±14.4),lower PaO2 [mmHg (1 mmHg =0.133 kPa):49.9± 12.3 vs.62.7± 10.2],higher HR (bpm:122.0± 19.5 vs.89.1 ± 18.5) and higher WBC (× 109/L:13.8 ± 6.9 vs.7.2 ± 2.5) were found in sudden death group as compared with those in non-sudden death group (P ＜ 0.05 or P ＜ 0.01).There was no significant differences in D-dimer level and PaCO2 between sudden death group and non-sudden death group [D-dimer (pg/L):986 (891,3 230) vs.2089 (598,3 397),PaCO2 (mmHg):33.0 (28.6,43.4)vs.36.5 (32.9,41.0),both P ＞ 0.05].The syncope,antineoplaston treatment or tumor metastasis within 6 months,operation in previous 4 months,bilateral asymmetrical edema in sudden death group were more than those of the non-sudden death group,and chest pain was less (P ＜ 0.05 or P ＜ 0.01).Difference in gender,dyspnea and typical SⅠTⅢQⅢ in electrocardiogram were not significant between the two groups (all P ＞ 0.05).It was shown by multiple logistic regression analysis that higher HR [odds ratio (OR) =1.124,95％ confidence interval (95％CI) =1.024-1.235,P =0.014] and higher WBC (OR =1.347,95％CI =1.043-1.738,P =0.022) were identified as independent risk factors of sudden death for PTE.Conclusions Gender,dyspnea,typical S Ⅰ TⅢQⅢ in electrocardiogram,PaCO2 and D-dimer seem unrelated to sudden death of patients with PTE.Young age,chest pain,syncope,bilateral asymmetrical edema,antineoplaston treatment or tumor metastasis within 6 months,operation in previous 4 months and low PaO2 were potential predictors of sudden death according to the univariate analysis.Higher WBC and higher HR are independent risk factors of sudden death for PTE patients.