Receptor-interacting protein kinase 1(RIPK1)is a multi-domain serine/threonine protein kinase that causes downstream signal transduction and biological effects by phosphorylating specific proteins.In recent years,with the in-depth study of RIPK1,scholars have found that it is of great significance in autoimmune diseases,neurodegenerative diseases,and a variety of solid tumors and hematological tumors.On the one hand,RIPK1 promotes cell survival and inflammatory responses by activating specific pathways such as nuclear factor-κB(NF-κB)and mitogen-activated protein kinase(MAPK).On the other hand,RIPKl promotes apoptosis by interacting with cysteinyl aspartate specific proteinase-8(caspase-8),or promotes necroptosis by interacting with RIPK3 and mixed lineage kinase domain-like protein(MLKL).As an upstream signal,RIPK1 has different expression levels in patients with different tumors.Its scaffold function and kinase activity can regulate cancer progression,initiate adaptive immunity,inhibit tumor progression,and generate an immunosuppressive tumor microenvironment to promote tumor development.Its dual role has been demonstrated in regulating the occurrence and development of tumors and the body's immune response,and can be used as a new therapeutic target to control cancer progression.This paper starts with the structure of RIPKI to further explore its function in regulating cancer progression and immune response,and to provide new ideas for the development of cancer-targeted drugs.

Objective:To explore the differences in bacterial community structure between proximal colon cancer (PC), distal colon cancer (DC), and rectal cancer (RC), and the values of featured microbiota in differentiating PC with tumor markers.Methods:This case-control study enrolled 85 newly diagnosed colorectal cancer patients, including 22 PC, 15 DC and 48 RC patients, and 8 colorectal adenoma patients from May 2019 to July 2022 at the Department of General Surgery, Anyang Oncology Hospital. The blood and fecal samples were collected before surgery and then subjected to biochemical tests for tumor markers and 16S rDNA tests, respectively. SPSS (27.0.1) was applied to perform the t-test, one-way ANOVA, Mann-Whitney U test, Kruskal-Wallis H test, and Chi-Squared Test. Also, the receiver operating characteristic curve (ROC) was plotted on tumor markers and/or f_Bacteroidaceae with SPSS software .Results:All groups had significant differences in the CA125 ( F=3.543, P<0.05), CA72-4 ( F=3.596, P<0.05), and serum tumor-associated materials (TAM) levels ( F=5.787, P<0.01). In PC group, the levels of CA125 [PC vs RC, (36.84±6.30) kU/L vs (12.73±4.21) kU/L, P<0.01] and CA72-4 [PC vs RC, (45.56±10.86) kU/L vs (3.30±7.63) kU/L, P<0.01] were significantly higher than that of the RC group, while the level of TAM was remarkably elevated in PC group than in RC group [PC vs RC, (124.84±5.19) U/ml vs (102.44±3.63) U/ml, P<0.001] and CRA group [PC vs CRA, (124.84±5.19) U/ml vs (95.39±8.42) U/ml, P<0.01]. The LEfSe analysis showed that the featured microbiota in the PC group included f_Bacteroidaceae, f_Neisseriaceae, f_Clostridiaceae_1, f_Spirochaetaceae, and so on. The largest area under the ROC belonged to the combination of TAM and f_Bacteroidaceae, which reached 0.845 (95% CI 0.747-0.944), with sensitivity being 0.857 and specificity being 0.815. Conclusions:There is heterogeneity in gut microbiota composition among PC, DC, RC, and CRA. The combination of gut microbiota and tumor biomarkers demonstrated good differentiating effects in proximal colon cancers.

The oral cavity of each person is home to hundreds of bacterial species.While taxa for oral diseases have been studied using culture-based characterization as well as amplicon sequencing,metagenomic and genomic information remains scarce compared to the fecal microbiome.Here,using metagenomic shotgun data for 3346 oral metagenomic samples together with 808 published samples,we obtain 56,213 metagenome-assembled genomes(MAGs),and more than 64％of the 3589 species-level genome bins(SGBs)contain no publicly available genomes.The resulting genome collection is representative of samples around the world and contains many genomes from candi-date phyla radiation(CPR)that lack monoculture.Also,it enables the discovery of new taxa such as a genus Candidatus Bgiplasma within the family Acholeplasmataceae.Large-scale metagenomic data from massive samples also allow the assembly of strains from important oral taxa such as Por-phyromonas and Neisseria.The oral microbes encode genes that could potentially metabolize drugs.Apart from these findings,a strongly male-enriched Campylobacter species was identified.Oral sam-ples would be more user-friendly collected than fecal samples and have the potential for disease diagnosis.Thus,these data lay down a genomic framework for future inquiries of the human oral microbiome.

Objective: To evaluate the safety and efficacy of dental floss traction-assisted endoscopic submucosal dissection (DFS-ESD) for rectal neuroendocrine neoplasm (NEN). Methods: A retrospective cohort study was performed. Clinical data of rectal NEN patients undergoing ESD at Endoscopy Center of Zhongshan Hospital, Fudan University from January 2016 to December 2017 were retrospectively analyzed. Inclusion criteria: 1) age of 18 to 80 years old; 2) maximal diameter of lesions <1.5 cm; 3) tumor locating in the submucosa without invasion into the muscularis propria; 4) no enlarged lymph nodes around bowel and in abdominal cavity; 5) ESD requested actively by patients. A total of 37 patients were enrolled, including 23 male and 14 female cases with mean age of (56.0±11.3) years. All the lesions were single tumor of stage T1, and the mean size was 0.8±0.2(0.5-1.2) cm. Postoperative pathology revealed all samples as neuroendocrine tumors (NET). Seventeen patients received DFS-ESD treatment (DFS-ESD group) and 20 patient received conventional ESD treatment (conventional ESD group). In DFS-ESD group, after the mucosa was partly incised along the marker dots, the endoscopy was extracted, and the dental floss was tied to one arm of the metallic clip. When the endoscope was reinserted, the hemoclip was attached onto the incised mucosa; another hemoclip was attached onto normal mucosa opposite to the lesion in the same way. The submucosa was clearly exposed with the traction of dental floss and the resection could proceed. The conventional ESD group received the traditional ESD operation procedure. The operation time, modified operation time (remaining time after excluding the assembly time of dental floss traction in DFS-ESD group), en bloc resection rate, R0 resection rate, morbidity of operative complication, recurrence and metastasis were compared between two groups. Results: The average tumor size was (0.8±0.2) cm in DFS-ESD group and (0.7±0.2) cm in conventional ESD group (t=0.425, P=0.673). According to postoperative pathological grading of rectal neuroendocrine neoplasm, 13 were G1 and 4 were G2 in DFS-ESD group, while 17 cases were G1 and 3 cases were G2 in conventional ESD group without significant difference (P=0.680). There were no significant differences in baseline data between in the two groups (all P>0.05). All the basal resection margins were negative, the en bloc resection rate was 100% and the R0 resection rate was 100%. Pathological results showed tumor tissue close to the burning margin in 5 cases of conventional ESD group and in 2 cases of DFS-ESD group (P=0.416). The operation time was (17.9±6.6) minutes in conventional ESD group and (14.7±3.3) minutes in DFS-ESD group (t=1.776, P=0.084). The modified operation time of DFS-ESD group was (11.9±2.8) minutes, which was significantly shorter than (17.9±6.6) minutes in conventional ESD group (t=3.425, P=0.002). The hospital stay was (2.3±0.6) days and (2.0±0.5) days in conventional ESD group and DFS-ESD group, respectively, without significant difference (t=1.436, P=0.160). No patient was transferred to surgery, and no delayed bleeding or perforation occurred in either group. There was no recurrence or primary tumor-related death, and all the patients recovered well during a follow-up period of 14(1-24) months. Conclusion Dental floss traction-assisted ESD for rectal neuroendocrine neoplasm can simplify operation and ensure negative basal margin.

Objective To explore the clinical features and prognosis of different PML_RARα fusion gene isoforms in acute promyelocytic leukemia (APL). Methods The clinical data of 78 patients initially diagnosed with APL in Fujian Medical University Union Hospital from February 2013 to July 2016 were collected. The clinical features and prognosis of different PML_RARα fusion gene isoforms were analyzed. Results There were 32 females (41%) and 46 males (59%) in 78 patients, with a median age of 40 years old (13-68 years old). The most common PML_RARα fusion gene was L type (48.7%, 38/78), followed by S type (46.2%, 36/78) and V type (5.1%, 4/78). The patients with white blood cell count more than 10×109/L (high_risk) occurred mostly in S type (61.1%, 22/36), compared with V type and L type, and there were statistically different (χ 2 ＝ 7.683, P < 0.05). A total of 78 patients included 8 cases (10.2%) of combined CD34 positive, 17 cases (21.8%) of combined FLT3_ITD mutation, 12 cases (15.4%) of combined DNMT3A mutation and 9 cases (11.5%) of additional chromosomal abnormalities. There were no significant differences in CD34 positive, FLT3_ITD, DNMT3A, and the incidence of additional chromosomal abnormalities among the three different isoforms (P＞0.05). The most common occurrence of retinoic acid syndrome (RAS) during treatment was S type (21/36), while rare for L type and V type (χ2＝ 7.633, P< 0.05). There were no statistical differences in the complete remission (CR) rate and disease_free survival rate among the patients with different PML_RARα isoforms (P＞0.05). Conclusions The clinical characteristics of different PML_RARα fusion gene isoforms are different, including most_common L type, more_common V type and S type in high risk groups; complicated RAS is commonly found in S type during the treatment. And different isoforms have no effect on the CR and DFS rate.

Objective To evaluate the safety and efficacy of dental floss traction?assisted endoscopic submucosal dissection (DFS?ESD) for rectal neuroendocrine neoplasm (NEN). Methods A retrospective cohort study was performed. Clinical data of rectal NEN patients undergoing ESD at Endoscopy Center of Zhongshan Hospital ,Fudan University from January 2016 to December 2017 were retrospectively analyzed. Inclusion criteria: 1) age of 18 to 80 years old; 2) maximal diameter of lesions <1.5 cm; 3) tumor locating in the submucosa without invasion into the muscularis propria; 4) no enlarged lymph nodes around bowel and in abdominal cavity; 5) ESD requested actively by patients. A total of 37 patients were enrolled,including 23 male and 14 female cases with mean age of (56.0±11.3) years. All the lesions were single tumor of stage T1,and the mean size was 0.8±0.2(0.5?1.2) cm. Postoperative pathology revealed all samples as neuroendocrine tumors (NET). Seventeen patients received DFS?ESD treatment (DFS?ESD group) and 20 patient received conventional ESD treatment (conventional ESD group). In DFS?ESD group,after the mucosa was partly incised along the marker dots ,the endoscopy was extracted,and the dental floss was tied to one arm of the metallic clip. When the endoscope was reinserted,the hemoclip was attached onto the incised mucosa; another hemoclip was attached onto normal mucosa opposite to the lesion in the same way. The submucosa was clearly exposed with the traction of dental floss and the resection could proceed. The conventional ESD group received the traditional ESD operation procedure. The operation time,modified operation time (remaining time after excluding the assembly time of dental floss traction in DFS?ESD group),en bloc resection rate,R0 resection rate, morbidity of operative complication,recurrence and metastasis were compared between two groups. Results The average tumor size was (0.8±0.2) cm in DFS?ESD group and (0.7±0.2) cm in conventional ESD group (t=0.425,P=0.673). According to postoperative pathological grading of rectal neuroendocrine neoplasm,13 were G1 and 4 were G2 in DFS?ESD group,while 17 cases were G1 and 3 cases were G2 in conventional ESD group without significant difference (P=0.680). There were no significant differences in baseline data between in the two groups (all P>0.05). All the basal resection margins were negative,the en bloc resection rate was 100% and the R0 resection rate was 100%. Pathological results showed tumor tissue close to the burning margin in 5 cases of conventional ESD group and in 2 cases of DFS?ESD group (P=0.416). The operation time was (17.9±6.6) minutes in conventional ESD group and (14.7±3.3) minutes in DFS?ESD group (t=1.776,P=0.084). The modified operation time of DFS?ESD group was (11.9±2.8) minutes,which was significantly shorter than (17.9±6.6) minutes in conventional ESD group (t=3.425, P=0.002). The hospital stay was (2.3 ± 0.6) days and (2.0 ± 0.5) days in conventional ESD group and DFS?ESD group,respectively,without significant difference (t=1.436,P=0.160). No patient was transferred to surgery,and no delayed bleeding or perforation occurred in either group. There was no recurrence or primary tumor?related death,and all the patients recovered well during a follow?up period of 14(1?24) months. Conclusion Dental floss traction?assisted ESD for rectal neuroendocrine neoplasm can simplify operation and ensure negative basal margin.

Objective To evaluate the safety and efficacy of dental floss traction?assisted endoscopic submucosal dissection (DFS?ESD) for rectal neuroendocrine neoplasm (NEN). Methods A retrospective cohort study was performed. Clinical data of rectal NEN patients undergoing ESD at Endoscopy Center of Zhongshan Hospital ,Fudan University from January 2016 to December 2017 were retrospectively analyzed. Inclusion criteria: 1) age of 18 to 80 years old; 2) maximal diameter of lesions <1.5 cm; 3) tumor locating in the submucosa without invasion into the muscularis propria; 4) no enlarged lymph nodes around bowel and in abdominal cavity; 5) ESD requested actively by patients. A total of 37 patients were enrolled,including 23 male and 14 female cases with mean age of (56.0±11.3) years. All the lesions were single tumor of stage T1,and the mean size was 0.8±0.2(0.5?1.2) cm. Postoperative pathology revealed all samples as neuroendocrine tumors (NET). Seventeen patients received DFS?ESD treatment (DFS?ESD group) and 20 patient received conventional ESD treatment (conventional ESD group). In DFS?ESD group,after the mucosa was partly incised along the marker dots ,the endoscopy was extracted,and the dental floss was tied to one arm of the metallic clip. When the endoscope was reinserted,the hemoclip was attached onto the incised mucosa; another hemoclip was attached onto normal mucosa opposite to the lesion in the same way. The submucosa was clearly exposed with the traction of dental floss and the resection could proceed. The conventional ESD group received the traditional ESD operation procedure. The operation time,modified operation time (remaining time after excluding the assembly time of dental floss traction in DFS?ESD group),en bloc resection rate,R0 resection rate, morbidity of operative complication,recurrence and metastasis were compared between two groups. Results The average tumor size was (0.8±0.2) cm in DFS?ESD group and (0.7±0.2) cm in conventional ESD group (t=0.425,P=0.673). According to postoperative pathological grading of rectal neuroendocrine neoplasm,13 were G1 and 4 were G2 in DFS?ESD group,while 17 cases were G1 and 3 cases were G2 in conventional ESD group without significant difference (P=0.680). There were no significant differences in baseline data between in the two groups (all P>0.05). All the basal resection margins were negative,the en bloc resection rate was 100% and the R0 resection rate was 100%. Pathological results showed tumor tissue close to the burning margin in 5 cases of conventional ESD group and in 2 cases of DFS?ESD group (P=0.416). The operation time was (17.9±6.6) minutes in conventional ESD group and (14.7±3.3) minutes in DFS?ESD group (t=1.776,P=0.084). The modified operation time of DFS?ESD group was (11.9±2.8) minutes,which was significantly shorter than (17.9±6.6) minutes in conventional ESD group (t=3.425, P=0.002). The hospital stay was (2.3 ± 0.6) days and (2.0 ± 0.5) days in conventional ESD group and DFS?ESD group,respectively,without significant difference (t=1.436,P=0.160). No patient was transferred to surgery,and no delayed bleeding or perforation occurred in either group. There was no recurrence or primary tumor?related death,and all the patients recovered well during a follow?up period of 14(1?24) months. Conclusion Dental floss traction?assisted ESD for rectal neuroendocrine neoplasm can simplify operation and ensure negative basal margin.

Objective To evaluate the quality of primary healthcare institutions entrusted to private hospitals as seen by the consumers. Methods The vertical integrated model between Renhe Hospital and Lixian township health center was selected as the case study. Consumer survey data of both November 2016 and September 2017 were collected by using Primary Care Assessment Tool(PCAT) (n=376). Stata 14.0 and Excel 2013 were used for descriptive statistics and multiple linear regression. Results Scoring in such key domains as continuity, comprehensiveness and coordination, and the derivative domains was higher in 2017 than those of 2016. And the differences were significant except for the domain of continuity and coordination (referral). PACT total score in 2017 was 21.28,higher than 19.83 in 2016 and the difference was significant(P<0.01). Conclusions Under the vertical integrated model between Renhe and Lixian, the quality of primary healthcare institutions was improving from 2016 to 2017 from the perspective of consumers. First contact (accessibility), comprehensiveness (services availability) and community orientation of primary healthcare institutions need to be strengthened in the future.

Objective:To investigate the expression of MACC1 in Klatskin tumor and the relationship between the clinicopathological features and prognosis and the expression of MACC1.Methods:Immunohistochemistry staining was employed to assess the expression of MACC1 protein in Klatskin tumor tissues and matched adjacent non-tumor bile duct tissues.Quantitative real-time PCR was performed to examine MACC1 mRNA expression in Klatskin tumor tissues and the adjacent non-tumor bile duct tissues and normal bile duct tissues.The correlation between MACC1 expression and the clinicopathological features and prognosis was analyzed.Results:The positive rate of MACC1 in Klatskin tumor tissues was significantly higher than that in matched adjacent non-tumor bile duct tissues(P＜0.05).MACC1 mRNA expression in carcinoma tissues was significantly higher than that in the non-tumor bile duct tissues and normal bile duct tissues(P＜0.05).MACC1 expression in Klatskin tumor tissues was related to tumor size,recurrence and lymphatic metastasis(P＜0.05).Survival analysis indicated that the 1-year,3-year,5-year survival rate were with significantly differences between the two groups (P＜0.05).Conclusion:MACC1 expression was significantly higher in Klatskin tumor and it was related to the tumor size,recurrence and lymphatic metastasis.It would affect the prognosis of patients.

Objective: On the basis of typical cases, the objective of this study is to assess the service quality of primary healthcare institutions under the vertically integrated model from the perspective of demanding side.Methods: The vertical model between Renhe Hospital and Lixian Township Health Center was selected as the case study.Quantitative data were collected by exit review using Primary health-Care quality service Assessment Tool (PCAT)-Chinese version from the patients seeking services in Lixian.Quantitative data were analyzed by descriptive statistics and multiple linear regression equations while qualitative data were analyzed by thematic framework analysis.Results: Under the vertical model, the PCAT total score was 20.09.The scores on the first diagnosis, continuity of care, and comprehensiveness of care and coordination of care were 6.59, 3.27, 4.58 and 5.62 respectively.The scores on the three dimensional extensions, family-centered, community-oriented, medical culture were 3.07, 1.86 and 2.67 respectively.The difference was significant for the PCAT total score between a number of visits and the length of waiting time for services in Lixian.Conclusions: Under the vertical model, primary healthcare institutions did better in the first diagnosis while weaker in continuity and the three dimensional extensions.With the development of the integration, the primary healthcare institutions need to strengthen the continuity and downward referral in the future.Future researches and follow-up, analysis is needed to track the impact of the vertically integrated model.