1.Porphyromonas gingivalis promotes the occurrence of esophageal squamous cell carcinoma via an inflammatory microenvironment
Haijun XU ; Yijun QI ; Dangrou WU ; Qiwei LIU ; Pan CHEN ; Mengxiang LI ; Yelin JIAO ; Haojie RUAN ; Zhitao LI ; Shegan GAO
Chinese Journal of Oncology 2024;46(8):746-754
Objective:To investigate the role of an inflammatory microenvironment induced by Porphyromonasgingivalis ( P. gingivalis) in the occurrence of esophageal squamous cell carcinoma (ESCC) in mice. Methods:A total of 180 C57BL/6 mice were randomly divided into 6 groups, i.e. control group, P. gingivalis group, 4NQO group, 4NQO + P. gingivalis group, 4NQO + P. gingivalis + celecoxib group, and 4NQO + P. gingivalis + antibiotic cocktail (ABC, including metronidazole, neomycin, ampicillin, and vancomycin) group, with 30 mice in each group, using the random number table. All mice were normalized by treatment with ABC in drinking water for 2 weeks. In the following 2 weeks, the mice in the control group and the P. gingivalis group were given drinking water, while the other 4 groups were treated with 30 μg/ml 4NQO in the drinking water. In weeks 11-12, the mice in the P. gingivalis group, the 4NQO + P. gingivalis group, the 4NQO + P. gingivalis + celecoxib group, and the 4NQO + P. gingivalis + ABC group were subjected to ligation of the second molar in oral cavity followed by oral P. gingivalis infection thrice weekly for 24 weeks in weeks 11-34. In weeks 13-34, the mice in 4NQO + P. gingivalis+celecoxib group and 4NQO + P. gingivalis + ABC group were administered with celecoxib and ABC for 22 weeks, respectively. At the end of 34 weeks, gross and microscopic alterations were examined followed by RT-qPCR and immunohistochemistry to examine the expression profiles of inflammatory- and tumor-molecules in esophagi of mice. Results:At 34 weeks, 4NQO treatment alone did not affect the foci of papillary hyperproliferation, diseased area, and the thickness of the esophageal wall, but significantly enhanced the foci of hyperproliferation (median 1.00, P<0.05) and mild/moderate dysplasia (median 2.00, P<0.01). In addition, the expression levels of IL-6 [8.35(3.45,8.99)], IL-1β [6.90(2.01,9.72)], TNF-α [12.04(3.31,14.08)], c-myc [2.21(1.80,3.04)], pSTAT3, Ki-67, and pH2AX were higher than those in the control group. The pathological changes of the esophageal mucosa were significantly more overt in the 4NQO + P. gingivalis group in terms of the foci of papillary hyperproliferation (median 2.00), diseased area (median 2.51 mm 2), the thickness of the esophageal wall (median 172.52 μm), the foci of hyperproliferation (median 1.00, P<0.05), and mild/moderate dysplasia (median 1.00, P<0.01). In mice of the 4NQO + P. gingivalis group, the expression levels of IL-6 [12.27(5.35,22.08)], IL-1β [13.89(10.04,15.96)], TNF-α [19.56(6.07,20.36)], IFN-γ [11.37(8.23,20.07)], c-myc [2.62(1.51,4.25)], cyclin D1 [4.52(2.68,7.83)], nuclear pSTAT3, COX-2, Ki-67, and pH2AX were significantly increased compared with the mice in the control group. In mice of the 4NQO + P. gingivalis group, the diseased area, invasive malignant foci as well as pSTAT3 and pH2AX expression were significantly blunted by celecoxib. Treatment with ABC markedly reduced the papillary hyperproliferative foci, invasive malignant foci, and pSTAT3 expression but not pH2AX. Conclusions:P. gingivalis promotes the occurrence of esophageal squamous cell carcinoma in mice by inducing an inflammatory microenvironment primed with 4NQO induced DNA damage. Clearance of P. gingivalis with ABC or anti-inflammatory intervention holds promise for prevention of esophageal squamous cell malignant pathogenesis via blockage of IL-6/STAT3 signaling and amelioration of inflammation.
2.Porphyromonas gingivalis promotes the occurrence of esophageal squamous cell carcinoma via an inflammatory microenvironment
Haijun XU ; Yijun QI ; Dangrou WU ; Qiwei LIU ; Pan CHEN ; Mengxiang LI ; Yelin JIAO ; Haojie RUAN ; Zhitao LI ; Shegan GAO
Chinese Journal of Oncology 2024;46(8):746-754
Objective:To investigate the role of an inflammatory microenvironment induced by Porphyromonasgingivalis ( P. gingivalis) in the occurrence of esophageal squamous cell carcinoma (ESCC) in mice. Methods:A total of 180 C57BL/6 mice were randomly divided into 6 groups, i.e. control group, P. gingivalis group, 4NQO group, 4NQO + P. gingivalis group, 4NQO + P. gingivalis + celecoxib group, and 4NQO + P. gingivalis + antibiotic cocktail (ABC, including metronidazole, neomycin, ampicillin, and vancomycin) group, with 30 mice in each group, using the random number table. All mice were normalized by treatment with ABC in drinking water for 2 weeks. In the following 2 weeks, the mice in the control group and the P. gingivalis group were given drinking water, while the other 4 groups were treated with 30 μg/ml 4NQO in the drinking water. In weeks 11-12, the mice in the P. gingivalis group, the 4NQO + P. gingivalis group, the 4NQO + P. gingivalis + celecoxib group, and the 4NQO + P. gingivalis + ABC group were subjected to ligation of the second molar in oral cavity followed by oral P. gingivalis infection thrice weekly for 24 weeks in weeks 11-34. In weeks 13-34, the mice in 4NQO + P. gingivalis+celecoxib group and 4NQO + P. gingivalis + ABC group were administered with celecoxib and ABC for 22 weeks, respectively. At the end of 34 weeks, gross and microscopic alterations were examined followed by RT-qPCR and immunohistochemistry to examine the expression profiles of inflammatory- and tumor-molecules in esophagi of mice. Results:At 34 weeks, 4NQO treatment alone did not affect the foci of papillary hyperproliferation, diseased area, and the thickness of the esophageal wall, but significantly enhanced the foci of hyperproliferation (median 1.00, P<0.05) and mild/moderate dysplasia (median 2.00, P<0.01). In addition, the expression levels of IL-6 [8.35(3.45,8.99)], IL-1β [6.90(2.01,9.72)], TNF-α [12.04(3.31,14.08)], c-myc [2.21(1.80,3.04)], pSTAT3, Ki-67, and pH2AX were higher than those in the control group. The pathological changes of the esophageal mucosa were significantly more overt in the 4NQO + P. gingivalis group in terms of the foci of papillary hyperproliferation (median 2.00), diseased area (median 2.51 mm 2), the thickness of the esophageal wall (median 172.52 μm), the foci of hyperproliferation (median 1.00, P<0.05), and mild/moderate dysplasia (median 1.00, P<0.01). In mice of the 4NQO + P. gingivalis group, the expression levels of IL-6 [12.27(5.35,22.08)], IL-1β [13.89(10.04,15.96)], TNF-α [19.56(6.07,20.36)], IFN-γ [11.37(8.23,20.07)], c-myc [2.62(1.51,4.25)], cyclin D1 [4.52(2.68,7.83)], nuclear pSTAT3, COX-2, Ki-67, and pH2AX were significantly increased compared with the mice in the control group. In mice of the 4NQO + P. gingivalis group, the diseased area, invasive malignant foci as well as pSTAT3 and pH2AX expression were significantly blunted by celecoxib. Treatment with ABC markedly reduced the papillary hyperproliferative foci, invasive malignant foci, and pSTAT3 expression but not pH2AX. Conclusions:P. gingivalis promotes the occurrence of esophageal squamous cell carcinoma in mice by inducing an inflammatory microenvironment primed with 4NQO induced DNA damage. Clearance of P. gingivalis with ABC or anti-inflammatory intervention holds promise for prevention of esophageal squamous cell malignant pathogenesis via blockage of IL-6/STAT3 signaling and amelioration of inflammation.
3.Identification and phylogenetic analysis of two clinical isolates of Chryseobacterium
Yinglin WU ; Dexiang ZHENG ; Gang LI ; Qiwei LI ; Xuan ZHANG ; Kai LAN ; Yinzhen LIU ; Haining XIA ; Wei JIA ; Jianming ZENG ; Cha CHEN ; Bin HUANG
Chinese Journal of Microbiology and Immunology 2023;43(8):589-596
Objective:To analyze the biological characteristics, phylogenic features and clinical significance of SQ219 and SQ220 isolated from clinical sputum and midstream urine specimens.Methods:The culture and biochemical characteristics of the two strains were observed. VITEK2 System, drug sensitivity testing and MALDI-TOF mass spectrometry were used for bacterial identification. Phylogenetic analysis based on 16S rRNA and core genome was performed. The average nucleotide identity (ANI) based on whole genome sequences was calculated.Results:SQ219 and SQ220 were Gram-stain-negative, aerobic, catalase- and oxidase-positive, and non-motile bacteria. Their optimum growth was observed in NaCl-free medium at 30℃ and pH7. Flexirubin-type pigments were produced by SQ220 on Colombia blood agar, but not by SQ219. Both SQ219 and SQ220 were resistant to aztreonam, amikacin, tobramycin and colistin, which was consistent with the drug resistance phenotype of genus Chryseobacterium. The genome sequences of SQ219 and SQ220 were 5.08 Mb and 4.80 Mb in length, and the G+ C contents were 36.72% and 36.36%, respectively. Both strains carried β-lactam resistance gene ( blaCGA). 16S rRNA phylogenetic analysis showed that SQ219 and SQ220 were closely related to Chryseobacterium gambrini DSM18014 T with the similarities of 98.93% and 98.36%, respectively. Core genome phylogenetic analysis revealed that SQ219 and SQ220 were highly homologous to Chryseobacterium gambrini DSM18014 T. However, the ANI values between the two strains and Chryseobacterium gambrini DSM18014 T were 92.49% and 93.27%, respectively, below the threshold for prokaryotic species identification. Conclusions:Based on the phenotypic and phylogenetic data, SQ219 and SQ220 represent a novel species of the genus Chryseobacterium. This study would help promote the understanding of the evolution of Chrysobacterium and provide reference for the identification of new species of Chrysobacterium.
4.Endogenous HMGB1 Modulates Fatty Acid Metabolism of Hypoxic and Nutrient-poor Pancreatic Cancer Cells and Related Mechanism
Jie GAO ; Qiwei WU ; Lian SONG ; Hui SHI ; Ming WANG ; Aihua GONG ; Dongqing WANG ; Haitao ZHU
Cancer Research on Prevention and Treatment 2021;48(7):667-673
Objective To explore the role and mechanism of HMGB1 in the fatty acid metabolism reprogramming and mitochondrial fusion/fission of hypoxic and nutrient-poor pancreatic cancer cells. Methods The correlation between the expression level of HMGB1 in pancreatic cancer tissue and the survival rate of pancreatic cancer patients were analyzed by GEPIA database. CCK-8 assay was used to measure cell proliferation rate, and scratch test and Transwell chamber method were carried out to detect the effects of endogenous HMGB1 on the invasion and migration abilities of human pancreatic cancer cell line Patu8988 after hypoxic and nutrient-poor treatment. Laser confocal microscope was used to observe the changes of mitochondrial morphology of Patu8988 cells. Western blot was used to detect the expression levels of mitochondrial fusion/fission and de novo fatty acid synthesis-related proteins. Results GEPIA database analysis results showed that HMGB1 was highly expressed in pancreatic cancer tissues (
5.Establishment and operating mode of hospice care beds in cancer center of a Class Ⅲ general hospital
Li FANG ; Ligui WU ; Ling YUAN ; Yujie ZHOU ; Weiqin PENG ; Qiwei GENG
Chinese Journal of Modern Nursing 2018;24(31):3737-3740
Objective To explore the establishment and operating mode of hospice care beds in the cancer center of a tertiary general hospital and to evaluate its operating effects preliminarily. Methods Totally 3 hospice care beds were set up in the Cancer Center of Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School in October 2016. The operating mode of hospice care beds in the Class Ⅲgeneral hospital was explored by building a hospice care team, performing professional training, formulating admission and transfer standards, standardizing working processes, refining service contents and quality standards and establishing a community referral system. Totally 49 patients admitted in the hospice care beds from October 2016 to August 2018 were selected. The satisfaction with symptom control and medical services and the degree of psychological pain were compared before and after hospitalization in the hospice care beds. The patients' referral was statically analyzed. Results The satisfaction with symptom control in the 49 patients after hospice care was higher than that before hospice care except for hematemesis and hematochezia, edema and delirium could not be statistically analyzed because the sample size was too small (P<0.05). The overall satisfaction with medical services rose from (2.88±0.99) to (4.96±0.19);psychological pain decreased from (4.37±1.32) to (1.37±0.73);and the sum of daily hospitalization costs dropped from (899.21±128.46) yuan to (355.16±50.73) yuan (t=10.84, 23.60, 11.34;P< 0.01). Conclusions The establishment of hospice care beds in the cancer center of the tertiary general hospital provides a place of hospice care for cancer patients, connects the patients with community resources, and improve the patients' satisfaction with medical services.
6.Impacts of emotion intelligence and gender on the process of emotion regulation
Yan WU ; Jianfeng WANG ; Xin WEN ; Lushi JING ; Qiwei YANG
Chinese Journal of Behavioral Medicine and Brain Science 2017;26(11):1030-1035
Objective To investigate the impacts of emotion intelligence and sex difference on the process of emotion regulation.Methods The reaction time and the strength of emotion regulation were recorded in the emotion perception and emotion regulation task.Results The males with higher EI scores reacted more quickly in emotion perception and were more efficient in positive emotion regulation than those with lower EI scores (reaction time:(1 821±120) ms < (2 320±133)ms,F(1.87)=3.87,P=0.049;strength of emotion regulation:2.11 ± 0.21 > 0.81 ± 0.23;F(1,87) =17.31,P< 0.001),while the females with higher EI scores reacted more slowly in emotion perception and were more efficient in negative emotion regulation than those with lower EI scores (reaction time:(2 250± 110) ms > (1 939± 115) ms,F(1,87) =6.73,P =0.011;strength of emotion regulation:1.60±0.18 > 0.7±0.18;F(1,87)=12.12,P=0.001).Conclusion The results showed that for men,the EI was associated with efficiency in processing emotion and regulating positive emotions,while for women,the EI was associated with efficiency in regulating negative emotions.
7.Effect of serum of patients with obstructive jaundice on myogenic differentiation of human pulmona-ry microvascular endothelial cells
Qiwei CHEN ; Yong YANG ; Bing CHEN ; Yang CHEN ; Sheng LI ; Guilan WANG ; Yulong WU ; Chonghui CHEN ; Baoli ZU ; Bin YI ; Kaizhi LU ; Lin LIAO
Chinese Journal of Anesthesiology 2016;36(9):1146-1149
Objective To evaluate the effects of the serum of patients with obstructive jaundice on myogenic differentiation of human pulmonary microvascular endothelial cells (PMVECs). Methods Hu?man PMVECs were isolated and then subcultured. The cultured PMVECs were incubated with the serum of patients with obstructive jaundice or with the serum of healthy volunteers. At 24, 48 and 72 h of incubation (T1?3), the inverted microscope was used to observe the morphology of primary PMVECs. The expression of muscular proteins ( alpha?smooth muscle actin [α?SMA ] , smooth muscle?mysion heavy chain [ SM?MHC] , capolnin) in PMVECs was detected using Western blot analysis. Results The expression of cal?ponin andα?SMA was negative, and a few SM?MHC proteins were expressed when PMVECs were incubated with the serum of healthy volunteers; the expression of calponin, α?SMA and SM?MHC was positive when PMVECs were incubated with the serum of patients with obstructive jaundice. Compared with the serum of healthy volunteers, the expression of SM?MHC was significantly up?regulated when PMVECs were incubated with the serum of patients with obstructive jaundice (P<0.05). The expression of calponin, α?SMA and SM?MHC was significantly up?regulated at T2,3 compared with that at T1 , and at T3 compared with that at T2 when PMVECs were incubated with the serum of patients with obstructive jaundice ( P<0.05) . Conclusion The serum of patients with obstructive jaundice promotes myogenic differentiation of human PMVECs, which is probably one of the mechanisms underlying intrapulmonary microvascular dilatation.
8.Influence to the curative effect of THA with different methods to reconstruct limb length for Crowe Ⅳ type developmental dysplasia of the hip
Ruijun CONG ; Peiliang FU ; Yuli WU ; Song CHEN ; Bo WANG ; Xiaohua LI ; Qiwei FU ; Yunli ZHU
Chinese Journal of Orthopaedics 2013;(3):214-219
Objective To explore the differences of the joint function and the patient's satisfaction between two different methods to reconstruct limb length for unilateral Crowe Ⅳ developmental dysplasia of the hip (DDH).Methods The clinical controlled study were used.21 cases with unilateral DDH Crowe Ⅳ treated with total hip arthroplasty were divided into 2 groups randomly.The patients in the first group were reconstructed the limb with the compensatory length and those in the second group were did with the real length.The patients were followed up 10 years.Two independent sample t-test was used to compare these two operations.Harris scores and SF-36 scores were used in the test.Survival analysis with Kaplan-Meier method was involved in the survival of the prosthesis and then test with Log-rank test.X-ray films of different period were compared to confirm the prosthetic loosening.Results Seventeen patients were followed up 8-10 years.There were no significant differences both in Harris score and most of the SF-36 scores at the median follow-up of 10 years.The item mental healthy of SF-36 expressed significant difference.Five patients required revision.There were 10 cases suffered with polyethylene wear,6 cases with severe osteoporosis in greater trochanter,and 3 cases with osteolytic reaction.Conclusion There are no significant differences between the two surgical method in the survival rate of prosthesis and the joint function in the median follow up.The satisfaction of the control groups is lower than the trial groups both at the early stage after the operation and the median follow up.The revision rate between the two groups is similar but the reason is different.
9.The applicated analysis of ultrasound-guided percutaneous transhepatic bile duct drainage
Qiwei ZHAO ; Rongpeng WU ; Lianbing GUO ; Yuhua ZHANG ; Fubao YANG ; Liu WANG
Chinese Journal of Primary Medicine and Pharmacy 2013;20(2):208-209
Objective To investigate the clinical operating skills of the ultrasound-guided percutaneous transhepatic bile duct puncture drainage(PTCD),and improve the success rate.Methods 60 cases of tumor-induced obstructive jaundice underwent ultrasound-guided percutaneous transhepatic bile duct puncture drainage were retrospectively analyzed and summarized.Results 60 cases were all punctureed successfully,and the success rate was 100%.A puncture needle patients which was successfully accounted for 88% (53 cases).No obvious puncture complications were found.Conclusion Preoperative fully prepared for surgery the appropriate action can improve the ultrasoundguided percutaneous bile duct through the success rate of bypass,there is helpfal to reduce the puncture complications.
10.Detection and clinical significance of urinary monocyte chemoattractant protein-1 and interleukin-18 in children with primary nephrotic syndrome
Fang WU ; Qiwei FANG ; Jianjun CUI
Journal of Chinese Physician 2013;(5):621-625
Objective To investigate the concentration of monocyte chemoattractant protein-1 (MCP-1) and interleukin-18 (IL-18) in the urinary of children with primary nephrotic syndrome(PNS) at different time points,and to explore their correlation with occurrence,development,progression,and prognosis of PNS.Methods A total of 65 pediatric cases from our hospital was enrolled in this study,and was divided into three groups based on the retrospective the follow-up results including steroid-sensitive NS (SSNS) (n =35),steroid-resistant NS (SRNS) (n =15),and frequent-relapse NS (FRNS) (n =15) groups.Another 20 healthy children served as normal controls.Peripheral blood samples and urine specimen were collected at three time points (without glucocorticoids,treatment after 8 weeks,and treatment after 16 weeks or recurrence).The levels of MCP-1 and IL-18 in the urine were assayed by enzyme-linked immunosorbent assay (ELISA).The levels of blood urea nitrogen,creatinine,and 24-hour urinary protein excretion were assayed by full-automatic biochemical study appliance.Results (1)In SSNS group,the levels of urinary IL-18 before treatment and treated for 8 weeks were higher than the normal control group [before treatment:(160.30 ±27.29) pg/ml; treated for 8 weeks:(157.62 ±26.85) pg/ml; normal control group:(70.88 ± 14.43) pg/ul].However,after treated for 16 weeks,the levels of urinary MCP-1 and IL-18 were markedly decreased compared with that of control group and those before treatment and treated for 8 weeks [treated for 16 weeks:(20.98 ±4.53) pg/ml,and (79.09 ±7.23) pg/ml,P <0.05].(2)In SRNS group,the levels of urinary MCP-1 and IL-18 before treatment were remarkably higher than that of control group and that of SSNS group before treatment[SSNS group before treatment:(76.84 ± 5.58) pg/ml,and (252.37 ± 25.34)pg/ml,P <0.05],but no significant difference was found when it was compared with that treated for 8 weeks [treated for 8 weeks:(72.32 ±4.30) pg/ml,and (243.70 ±35.43) pg/ml,P >0.05] ; However,its level was markedly decreased after treated with immunosuppressants of CTX for 16 weeks when it was compared with those before treatment and treated for 8 weeks[treated for 16 weeks:(34.03 ± 2.56) pg/ ml,and (114.42 ± 21.33)pg/ml,P < 0.05].(3)In FRNS group,the levels of urinary MCP-1 and IL-18 were no remarkable difference between control and SSNS groups [before treatment:(30.43 ± 4.61) pg/ml,and (156.65 ± 34.39)pg/ml; treated for 8 weeks:(29.41 ± 4.76) pg/ml,and (152.21 ± 34.73) pg/ml,P > 0.05],but its level was markedly lower than SRNS group (P < 0.05).When it was recurred,the levels of urinary MCP-1 and IL-18 were significantly increased compared with before treatment and treated for 8 weeks[recurred:(72.92 ±3.01)pg/ml,and (224.33 ±26.07)pg/ml,P <0.05].(4)No correlation was found between the levels of MCP-1 and IL-18 and the levels of blood urea nitrogen and creatinine (P >0.05).Positive correlation was found between the levels of MCP-1 and IL-18 and the 24-hour urinary protein excretion (r =0.706,0.556,P <0.01).There's a correlation between urinary MCP-1 and IL-18 (r =0.811,P < 0.01).Conclusions For children with PNS,the detection of urinary MCP-1 and IL-1 8 contributed to the early prediction of children'sensitivity on glucocorticoid.The elevated levels of urinary MCP-1 and IL-18 in combination with clinical symptoms and proteinuria can be used as an important noninvasive marker to monitor PNS recurrence.

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