italic>Salmonella has emerged as a promising tumor-targeting strategy in recent years due to its good tumor targeting ability and certain safety. In order to further optimize its therapeutic effect, scientists have tried to modify Salmonella, including its attenuation and drug loading. This paper summarizes the mechanism and research progress of Salmonella-mediated targeted tumor therapy, and introduces the strategies and related progress of its modification and optimization. At the same time, the advantages, current challenges and future development directions of Salmonella-mediated tumor therapy are summarized.

This study aims to investigate the role of slient mating-type information regulation 2 homolog 1(SIRT1)/tuberous sclerosis complex 2(TSC2)/mammalian target of rapamycin(mTOR) signaling pathways in the Periplaneta americana extract CⅡ-3-induced senescence of human leukemia K562 cells. K562 cells were cultured in vitro and treated with 0(control), 5, 10, 20, 40, 80, and 160 μg·mL~(-1) of P. americana extract CⅡ-3. Cell counting kit-8(CCK-8) and flow cytometry were employed to examine the proliferation and cell cycle of the K562 cells. Senescence-associated β-galactosidase stain kit(SA-β-gal) was used to detect the positive rate of senescent cells. Mitochondrial membrane potential was detected by flow cytometry. The relative mRNA level of telomerase reverse transcriptase(TERT) was determined by fluorescence quantitative PCR. The mRNA and protein levels of SIRT1, TSC2, and mTOR were determined by fluorescence quantitative PCR and Western blot, respectively. The results showed that CⅡ-3 significantly inhibited the proliferation of K562 cells and the treatment with 80 μg·mL~(-1) CⅡ-3 for 72 h had the highest inhibition rate. Therefore, 80 μg·mL~(-1) CⅡ-3 treatment for 72 h was selected as the standard for subsequent experiments. Compared with the control group, CⅡ-3 increased the proportion of cells arrested in G_0/G_1 phase, decreased the proportion of cells in S phase, increased the positive rate of SA-β-Gal staining, elevated the mitochondrial membrane potential and down-regulated the mRNA expression of TERT. Furthermore, the mRNA expression of SIRT1 and TSC2 was down-regulated, while the mRNA expression of mTOR was up-regulated. The protein expression of SIRT1 and p-TSC2 was down-regulated, while the protein expression of p-mTOR was up-regulated. The results indicated that P. americana extract CⅡ-3 induced the senescence of K562 cells via the SIRT1/mTOR signaling pathway.
Humans ; Animals ; Periplaneta ; Sirtuin 1/genetics* ; K562 Cells ; Signal Transduction ; TOR Serine-Threonine Kinases/genetics* ; RNA, Messenger ; Mammals

Objective To investigate the effect of caloric restriction(CR)on myocardial ischemia/reperfusion injury(MI/RI)in mice and its mechanism.Methods C57 mice were randomly divided into normal diet group(AL group,free feeding)and CR group(diet decreased by 10% every 2 weeks)for 8 weeks and monitored for weight changes.Each group was divided into sham operation group and MI/RI group,total 4 groups,AL + Sham group,AL + I/R group,CR + Sham group and CR + I/R group).The left anterior descending coronary artery was ligated for 30 minutes and then reperfused for 24 hours in mice of MI/RI group and mice in Sham group were only threaded but not ligated.The mice were determined for myocardial ischemia and infarct size by Evans blue/TTC staining,observed for the pathology of myocardium by HE staining,determined for the activities of lactate dehydrogenase(LDH),superoxide dismutase(SOD)and the contents of creatine kinase-MB(CK-MB)and malondialdehvde(MDA)in myocardium by the corresponding kits,determined for serum levels of IL-1β and IL-18 by ELISA and detected for the expression of pyroptosis-associated proteins in myocardium by Western blot.Results After 8weeks,the weights of mice in CR group[(24.54 ± 0.41)g]were significantly lower than those in AL group[(31.46 ±0.25)g](t = 14.34,P<0.05).Compared with those in AL + I/R group,the area of myocardial ischemia in CR + I/R group showed no significant difference(t = 0.783 0,P>0.05),while the area of myocardial infarction decreased significantly(t = 7.250,P<0.01);The myocardial arrangement was relatively neat,and the degree of pathological changes was obviously reduced;LDH activity,CK-MB and MDA contents decreased significantly(t = 4.331,2.875 and 5.343 respectively,each P<0.05),while SOD activity increased significantly(t = 4.211,P<0.05);Serum levels of IL-1β and IL-18 decreased significantly(t = 3.375 and 4.266 respectively,each P<0.05);The expression levels of nod-like receptor protein 3(NLRP3),gasdermin D(GSDMD),apoptosis-associated speckle-like protein(ASC)and caspase-1 significantly decreased(t = 3.412,3.420,3.480 and 2.585 respectively,each P<0.05).Conclusion CR alleviated MI/RI in mice,and its mechanism was related to the inhibition of cardiac pyroptosis.

Objective: To investigate the prognoses of advanced (T3-T4) sinonasal malignancies (SNM). Methods: The clinical data of 229 patients with advanced (T3-4) SNM who underwent surgical treatments in the First Affiliated Hospital of Sun Yat-sen University from 2000 to 2018 were retrospectively analyzed, including 162 males and 67 females, aged (46.8±18.5) years old. Among them, 167 cases received endoscopic surgery alone, 30 cases received assisted incision endoscopic surgery, and 32 cases received open surgery. The Kaplan-Meier method was used to estimate the 3-year and 5-year overall survival (OS) and event-free survival (EFS). Univariate and multivariate Cox regression analyses were performed to explore significant prognostic factors. Results: The 3-year and 5-year OS were respectively 69.7% and 64.0%. The median OS time was 43 months. The 3-year and 5-year EFS were respectively 57.8% and 47.4%. The median EFS time was 34 months. The 5-year OS of the patients with epithelial-derived tumors was better than that of the patients with mesenchymal-derived tumors and malignant melanoma (5-year OS was respectively 72.3%, 47.8% and 30.0%, χ²=36.01, P<0.001). Patients with microscopically margin-negative resection (R0 resection) had the best prognosis, followed by macroscopically margin-negative resection (R1 resection), and debulking surgery was the worst (5-year OS was respectively 78.4%, 55.1% and 37.4%, χ²=24.63, P<0.001). There was no significant difference in 5-year OS between the endoscopic surgery group and the open surgery group (65.8% vs. 53.4%, χ²=2.66, P=0.102). Older patients had worse OS (HR=1.02, P=0.011) and EFS (HR=1.01, P=0.027). Patients receiving adjuvant therapy had a lower risk of death (HR=0.62, P=0.038). Patients with a history of nasal radiotherapy had a higher risk of recurrence (HR=2.48, P=0.002) and a higher risk of death (HR=2.03, P=0.020). Conclusion: For patients with advanced SNM, the efficacy of endoscopic surgery can be comparable to that of open surgery when presence of safe surgical margins, and a treatment plan based on transnasal endoscopic surgery as the main comprehensive treatment is recommended.
Male ; Female ; Humans ; Adult ; Middle Aged ; Aged ; Retrospective Studies ; Prognosis ; Combined Modality Therapy ; Melanoma/surgery* ; Endoscopy

Objective: To analyze the clinicopathologic characteristics and prognosis of testicular diffuse large B-cell lymphoma (DLBCL) . Methods: A retrospective analysis was performed on 68 patients with testicular DLBCL admitted to Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine from October 2001 to April 2020. The gene mutation profile was evaluated by targeted sequencing (55 lymphoma-related genes) , and prognostic factors were analyzed. Results: A total of 68 patients were included, of whom 45 (66.2% ) had primary testicular DLBCL and 23 (33.8% ) had secondary testicular DLBCL. The proportion of secondary testicular DLBCL patients with Ann Arbor stage Ⅲ-Ⅳ (P<0.001) , elevated LDH (P<0.001) , ECOG score ≥ 2 points (P=0.005) , and IPI score 3-5 points (P<0.001) is higher than that of primary testicular DLBCL patients. Sixty-two (91% ) patients received rituximab in combination with cyclophosphamide, adriamycin, vincristine, and prednisone (R-CHOP) -based first-line regimen, whereas 54 cases (79% ) underwent orchiectomy prior to chemotherapy. Patients with secondary testicular DLBCL had a lower estimated 5-year progression-free survival (PFS) rate (16.5% vs 68.1% , P<0.001) and 5-year overall survival (OS) rate (63.4% vs 74.9% , P=0.008) than those with primary testicular DLBCL, and their complete remission rate (57% vs 91% , P=0.003) was also lower than that of primary testicular DLBCL. The ECOG scores of ≥2 (PFS: P=0.018; OS: P<0.001) , Ann Arbor stages Ⅲ-Ⅳ (PFS: P<0.001; OS: P=0.018) , increased LDH levels (PFS: P=0.015; OS: P=0.006) , and multiple extra-nodal involvements (PFS: P<0.001; OS: P=0.013) were poor prognostic factors in testicular DLBCL. Targeted sequencing data in 20 patients with testicular DLBCL showed that the mutation frequencies of ≥20% were PIM1 (12 cases, 60% ) , MYD88 (11 cases, 55% ) , CD79B (9 cases, 45% ) , CREBBP (5 cases, 25% ) , KMT2D (5 cases, 25% ) , ATM (4 cases, 20% ) , and BTG2 (4 cases, 20% ) . The frequency of mutations in KMT2D in patients with secondary testicular DLBCL was higher than that in patients with primary testicular DLBCL (66.7% vs 7.1% , P=0.014) and was associated with a lower 5-year PFS rate in patients with testicular DLBCL (P=0.019) . Conclusion: Patients with secondary testicular DLBCL had worse PFS and OS than those with primary testicular DLBCL. The ECOG scores of ≥2, Ann Arbor stages Ⅲ-Ⅳ, increased LDH levels, and multiple extra-nodal involvements were poor prognostic factors in testicular DLBCL. PIM1, MYD88, CD79B, CREBBP, KMT2D, ATM, and BTG2 were commonly mutated genes in testicular DLBCL, and the prognosis of patients with KMT2D mutations was poor.
Male ; Adult ; Humans ; Prognosis ; Retrospective Studies ; Myeloid Differentiation Factor 88 ; China/epidemiology* ; Testicular Neoplasms/drug therapy* ; Cyclophosphamide ; Rituximab/therapeutic use* ; Lymphoma, Large B-Cell, Diffuse/drug therapy* ; Prednisone/therapeutic use* ; Doxorubicin/therapeutic use* ; Vincristine/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Immediate-Early Proteins/therapeutic use* ; Tumor Suppressor Proteins

Objective: To explore the mechanism of Doublecortin-like kinase 1 (DCLK1) in promoting cell migration, invasion and proliferation in pancreatic cancer. Methods: The correlation between DCLK1 and Hippo pathway was analyzed using TCGA and GTEx databases and confirmed by fluorescence staining of pancreatic cancer tissue microarrays. At the cellular level, immunofluorescence staining of cell crawls and western blot assays were performed to clarify whether DCLK1 regulates yes associated protein1 (YAP1), a downstream effector of the Hippo pathway. Reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) was used to analyze the expressions of YAP1 binding transcription factor TEA-DNA binding proteins (TEAD) and downstream malignant behavior-promoting molecules CYR61, EDN1, AREG, and CTGF. Transwell test of the DCLK1-overexpressing cells treated with the Hippo pathway inhibitor Verteporfin was used to examine whether the malignant behavior-promoting ability was blocked. Analysis of changes in the proliferation index of experimental cells used real-time label-free cells. Results: TCGA combined with GTEx data analysis showed that the expressions of DCLK1 and YAP1 molecules in pancreatic cancer tissues were significantly higher than those in adjacent tissues (P<0.05). Moreover, DCLK1was positively correlated with the expressions of many effectors in the Hippo pathway, including LATS1 (r=0.53, P<0.001), LATS2 (r=0.34, P<0.001), MOB1B (r=0.40, P<0.001). In addition, the tissue microarray of pancreatic cancer patients was stained with multicolor fluorescence, indicated that the high expression of DCLK1 in pancreatic cancer patients was accompanied by the up-regulated expression of YAP1. The expression of DCLK1 in pancreatic cancer cell lines was analyzed by the CCLE database. The results showed that the expression of DCLK1 in AsPC-1 and PANC-1 cells was low. Thus, we overexpressed DCLK1 in AsPC-1 and PANC-1 cell lines and found that DCLK1 overexpression in pancreatic cancer cell lines promoted YAP1 expression and accessible to the nucleus. In addition, DCLK1 up-regulated the expression of YAP1 binding transcription factor TEAD and increased the mRNA expression levels of downstream malignant behavior-promoting molecules. Finally, Verteporfin, an inhibitor of the Hippo pathway, could antagonize the cell's malignant behavior-promoting ability mediated by high expression of DCLK1. We found that the number of migrated cells with DCLK1 overexpressing AsPC-1 group was 68.33±7.09, which was significantly higher than 22.00±4.58 of DCLK1 overexpressing cells treated with Verteporfin (P<0.05). Similarly, the migration number of PANC-1 cells overexpressing DCLK1 was 65.66±8.73, which was significantly higher than 37.00±6.00 of the control group and 32.33±9.61 of Hippo pathway inhibitor-treated group (P<0.05). Meanwhile, the number of invasive cells in the DCLK1-overexpressed group was significantly higher than that in the DCLK1 wild-type group cells, while the Verteporfin-treated DCLK1-overexpressed cells showed a significant decrease. In addition, we monitored the cell proliferation index using the real-time cellular analysis (RTCA) assay, and the proliferation index of DCLK1-overexpressed AsPC-1 cells was 0.66±0.04, which was significantly higher than 0.38±0.01 of DCLK1 wild-type AsPC-1 cells (P<0.05) as well as 0.05±0.03 of DCLK1-overexpressed AsPC1 cells treated with Verteporfin (P<0.05). PANC-1 cells showed the same pattern, with a proliferation index of 0.77±0.04 for DCLK1-overexpressed PANC-1 cells, significantly higher than DCLK1-overexpressed PANC1 cells after Verteporfin treatment (0.14±0.05, P<0.05). Conclusion: The expression of DCLK1 is remarkably associated with the Hippo pathway, it promotes the migration, invasion, and proliferation of pancreatic cancer cells by activating the Hippo pathway.
Humans ; Doublecortin-Like Kinases ; Hippo Signaling Pathway ; Verteporfin/pharmacology* ; Cell Line, Tumor ; Protein Serine-Threonine Kinases/metabolism* ; Pancreatic Neoplasms/pathology* ; YAP-Signaling Proteins ; Transcription Factors/metabolism* ; Cell Proliferation/genetics* ; Gene Expression Regulation, Neoplastic ; Tumor Suppressor Proteins/genetics*

BACKGROUND: Patients with atrial fibrillation (AF) and prior stroke history have a high risk of cardiovascular events despite anticoagulation therapy. It is unclear whether catheter ablation (CA) has further benefits in these patients. METHODS: AF patients with a previous history of stroke or systemic embolism (SE) from the prospective Chinese Atrial Fibrillation Registry study between August 2011 and December 2020 were included in the analysis. Patients were matched in a 1:1 ratio to CA or medical treatment (MT) based on propensity score. The primary outcome was a composite of all-cause death or ischemic stroke (IS)/SE. RESULTS: During a total of 4.1 ± 2.3 years of follow-up, the primary outcome occurred in 111 patients in the CA group (3.3 per 100 person-years) and in 229 patients in the MT group (5.7 per 100 person-years). The CA group had a lower risk of the primary outcome compared to the MT group [hazard ratio (HR) = 0.59, 95% CI: 0.47-0.74, P < 0.001]. There was a significant decreasing risk of all-cause mortality (HR = 0.43, 95% CI: 0.31-0.61, P < 0.001), IS/SE (HR = 0.73, 95% CI: 0.54-0.97, P = 0.033), cardiovascular mortality (HR = 0.32, 95% CI: 0.19-0.54, P < 0.001) and AF recurrence (HR = 0.33, 95% CI: 0.30-0.37, P < 0.001) in the CA group compared to that in the MT group. Sensitivity analysis generated consistent results when adjusting for time-dependent usage of anticoagulants. CONCLUSIONS In AF patients with a prior stroke history, CA was associated with a lower combined risk of all-cause death or IS/SE. Further clinical trials are warranted to confirm the benefits of CA in these patients.

A high-precision human metabolic measurement system is designed. The system uses STM32F103 as the main control chip to acquire oxygen, carbon dioxide and flow signals to calculate four quantitative indicators: oxygen consumption(V_O2), carbon dioxide production(V_CO2), respiratory entropy(RQ) and resting energy metabolism(REE), and finally uses an upper computer to display the calculation results.In this paper, the signal acquisition circuit design was carried out for the oxygen sensor, carbon dioxide sensor and flow sensor, and the validity of the device was verified with the American machine MGCDiagnositcs using Bland-Altman analysis method, and the results showed that the four parameters of V_O2,V_CO2, RQ and REE of both devices fell in the agreement interval of more than 95%. The device thus provides accurate metabolic measurements and offers an effective tool for the field of general health and clinical nutrition support in China.
Calorimetry, Indirect ; Carbon Dioxide/metabolism* ; Energy Metabolism ; Humans ; Oxygen ; Oxygen Consumption

The purpose was to discuss the infection status of human parainfluenza virus type 3 (HPIV-3) in children with acute respiratory tract infection(ARTI) in Qingdao, Shandong province, and to analyze the gene characteristics of HPIV-3 hemagglutinin-neuraminidase protein (HN). This study was a cross-sectional study. A total of 1 674 throat swab samples were collected randomly from children with ARTI, in the three hospitals (Qingdao Women and Children's Hospital, West Coast Branch of Affiliated Hospital of Qingdao University, Laoshan Branch of Affiliated Hospital of Qingdao University) from January 2018 to December 2019. Multiplex real-time fluorescence RT-PCR was performed to screen HPIV-3 positive specimens. For HPIV-3 positive specimens, nested PCR was used to amplify the full-length HN gene of HPIV-3. The HN gene was sequenced and compared with the representative strains of HPIV-3 in GenBank, and the phylogenetic tree was established. As results, this study collected 1 674 samples, in which there were 90 HPIV-3 positive samples showed and the detection rate was 5.37%. Among positive specimens, the number of samples from children under 6 years old was 88, accounting for 97.78%. HPIV-3 positive cases were mainly distributed in spring and summer. The full-length sequences of 44 HPIV-3 HN genes were obtained by nested PCR method. Sequence alignment and evolutionary analysis showed that the HPIV-3HN gene belonged to the C3a and C3b branches of C3 genotype, with 30 strains of subtype C3a and 14 strains of subtype C3b. The nucleotide and amino acid homology of the amplified 44 strains of the HPIV-3 HN gene in Qingdao were 97.0%-100.0% and 98.5%-100.0%, respectively. In conclusion, from 2018 to 2019, the C3a and C3b branches of HPIV-3 C3 genotype were circulating prevalent in Qingdao, Shandong province. HN gene variation rate was low, but showed certain regional characteristics in evolution.
Child ; Child, Preschool ; Cross-Sectional Studies ; Female ; Hemagglutinins ; Humans ; Neuraminidase ; Parainfluenza Virus 3, Human/genetics* ; Phylogeny ; Respiratory Tract Infections/epidemiology* ; Viral Proteins

The incidence of adenocarcinoma of esophagogastric junction (AEG) is increasing in recent years. Its diagnosis, lymph node metastasis and digestive tract reconstruction are all different from those of upper gastric cancer. With the development of the concept of function preserving surgery for gastric cancer, the clinical application of laparoscopic proximal gastrectomy in AEG is increasing. In this kind of operation, in addition to ensuring sufficient radical cure of tumor, the short-term smooth recovery and long-term quality of life of patients are also important. The reconstruction of digestive tract after proximal stomach operation is of great significance. According to the author's own practical experience, in clinical work, the author selects different surgical resection scope and digestive tract reconstruction methods according to Siewert classification of AEG. For Siewert Ⅱ AEG, laparoscopic PG is mostly used, and laparoscopic esophageal tubular gastric side-to-side anastomosis or double channel anastomosis is mostly used for digestive tract reconstruction. It is believed that with the emergence of long-term follow-up results and the development of multicenter randomized controlled research, some controversial questions will be better answered. We should pay attention to the individual differences of patients. For different individuals, combined with the operator's experience, on the basis of ensuring the radical cure of tumor, we should adopt appropriate surgical resection scope and digestive tract reconstruction, so as to bring better long-term quality of life for patients.
Adenocarcinoma/surgery* ; Esophageal Neoplasms/surgery* ; Esophagogastric Junction/surgery* ; Gastrectomy/methods* ; Humans ; Laparoscopy ; Quality of Life ; Retrospective Studies ; Stomach Neoplasms/surgery*