1.Advances in research on the application of Lactobacillus and its engineered probiotics to the prevention and treatment of radiation-induced intestinal injury
Xiaoxiao JIA ; Kaihua JI ; Manman ZHANG ; Yingshuang LIU ; Jianguo LI ; Qiang LIU
Chinese Journal of Radiological Medicine and Protection 2025;45(10):1015-1024
Intestinal radiosensitivity makes radiation-induced intestinal injury (RIII) as a common complication among individuals exposed to accidental radiation and patients with abdominal or pelvic malignancies receiving radiotherapy. At present, there are no effective measures for the prevention and treatment of RIII. Developing novel prevention and treatment strategies is of great significance for improving the prognosis and quality of life for both individuals exposed to accidental radiation and cancer patients. Lactobacillus, a Gram-positive bacterium, is widely observed in humans and animals. It exhibits notable probiotic functions, including maintaining gut microbiota homeostasis, preserving intestinal barrier, and modulating immune responses. Substantial studies have demonstrated that Lactobacillus has remarkable protective and therapeutic effects against radiation-induced injury, specifically significantly alleviating RIII. These probiotic functions of Lactobacillus make it have high priority to become the chassis of genetically engineered strains. However, multiple factors influence the construction of a genetically engineered strain, limiting the application of Lactobacillus as a chassis. This review focuses on the probiotic functions of Lactobacillus, highlighting advances in research on Lactobacillus and its engineered probiotics in radiation protection and treatment. Furthermore, it summarizes key factors influencing the construction of genetically engineered strains based on the Lactobacillus chassis. It aims to provide insights for developing genetically engineered strains with radioprotective and therapeutic effects using Lactobacillus as the chassis.
2.Advances in research on the application of Lactobacillus and its engineered probiotics to the prevention and treatment of radiation-induced intestinal injury
Xiaoxiao JIA ; Kaihua JI ; Manman ZHANG ; Yingshuang LIU ; Jianguo LI ; Qiang LIU
Chinese Journal of Radiological Medicine and Protection 2025;45(10):1015-1024
Intestinal radiosensitivity makes radiation-induced intestinal injury (RIII) as a common complication among individuals exposed to accidental radiation and patients with abdominal or pelvic malignancies receiving radiotherapy. At present, there are no effective measures for the prevention and treatment of RIII. Developing novel prevention and treatment strategies is of great significance for improving the prognosis and quality of life for both individuals exposed to accidental radiation and cancer patients. Lactobacillus, a Gram-positive bacterium, is widely observed in humans and animals. It exhibits notable probiotic functions, including maintaining gut microbiota homeostasis, preserving intestinal barrier, and modulating immune responses. Substantial studies have demonstrated that Lactobacillus has remarkable protective and therapeutic effects against radiation-induced injury, specifically significantly alleviating RIII. These probiotic functions of Lactobacillus make it have high priority to become the chassis of genetically engineered strains. However, multiple factors influence the construction of a genetically engineered strain, limiting the application of Lactobacillus as a chassis. This review focuses on the probiotic functions of Lactobacillus, highlighting advances in research on Lactobacillus and its engineered probiotics in radiation protection and treatment. Furthermore, it summarizes key factors influencing the construction of genetically engineered strains based on the Lactobacillus chassis. It aims to provide insights for developing genetically engineered strains with radioprotective and therapeutic effects using Lactobacillus as the chassis.
3.Development and validation of a questionnaire for the management of nutrition and immune-related adverse events in patients with liver cancer who received immunotherapy
Wen WEN ; Yingshuang CHEN ; Chunling LIU ; Liling TONG ; Hua ZHANG
Chinese Journal of Digestion 2024;44(10):693-701
Objective:To develop and verify the validity of a questionnaire on nutrition and immune-related adverse events in patients with liver cancer and received immune therapy. To provide a survey and evaluation tool for targeted health education, improving compliance and quality of life.Methods:Based on the knowledge attitude practice (KAP) theory, the preliminary draft of questionnaire was determined by literature search and 30 patients with liver cancer who received immunotherapy at Haikou People′s Hospital were selected for pre survey. The expert consultation was conducted by associate chief physicians from the department of hepatobiliary surgery and the department of oncology, the nutritionists and specialist nurses from the department of gastroenterology. According to the consultation results, the questionnaire was modified into the test version. It was estimated that the minimum sample size required for structural validity evaluation was 322 cases. Patients with liver cancer who received immunotherapy at Haikou People′s Hospital were recruited by convenience sampling, and the test version questionnaire were filled in. According to random number table method, the patients were divided into 2 groups. Exploratory and confirmatory factors analysis of the questionnaire were conducted respectively. The reliability of the questionnaire was evaluated by Cronbach′s α coefficient, split half reliability and retest reliability. Results:The completion time of the pre-survey questionnairein was (9.57±7.57) min. A total of 407 test questionnaires were distributed, and 400 were recovered, and the recovery rate of test questionnaire was 98.28%.The final questionnaire consisted of 27 items in 3 dimensions (knowledge, attitude, and practice), including 9 items of knowledge dimension, 10 items of attitude dimension and 8 items of practice dimension. Three factors were extracted in exploratory factors analysis with a cumulative variance contribution rate of 65.265%. In validation factor analysis, the chi-square freedom ratio was 3.956, the root mean square error of approximation was 0.086, the root mean square residual was 0.076, the comparative fit index was 0.871, and the incremental fit index was 0.872. The main indicators of the questionnaire fit were all with in the acceptable range. The total Cronbach′s α coefficient, split-half reliability and test-retest reliability of this questionnaire were 0.935, 0.834, 0.933, respectively. Conclusions:The questionnaire has good reliability and validity, and can be used as a preliminary assessment tool to understand the current status of knowledge, attitude, and practice of nutritional and immune-related adverse events in patients with liver cancer who received immunotherapy.
4.Updates of colonoscopy surveillance guidelines after screening and polypectomy, and related research progress
Yunfeng ZHU ; Yingshuang ZHU ; Chengcheng LIU ; Yeting HU ; Kefeng DING
Chinese Journal of Gastrointestinal Surgery 2024;27(1):99-104
With the widespread application of colorectal cancer screening, the surveillance and management of the increasing number of screened population has become a pivotal aspect in preventing and controlling colorectal cancer. In recent years, researches have been conducted on the risk of colorectal cancer incidence and mortality in the population after screening. At the same time, various organizations in Europe and the United States have continuously updated colonoscopy surveillance after screening and polypectomy based on the latest research evidence. In this review, we summarized the current progress of studies on colorectal cancer risk in post-screening colorectal cancer populations and the key points of relevant guideline updates, in order to provide a reference for conducting relevant studies and formulating surveillance guidelines or consensus in China.
5.Epidemiological characteristics of early-onset colorectal cancer: a prospective cohort study from a single center
Tian JIN ; Yingshuang ZHU ; Chengcheng LIU ; Xing XU ; Wei LU ; Qian XIAO ; Kefeng DING ; Shu ZHENG
Chinese Journal of Gastrointestinal Surgery 2024;27(5):457-463
Objective:To explore the differences in distribution of colorectal cancer-related risk factors between patients with early-onset colorectal cancer (EOCRC) and those with late-onset colorectal cancer (LOCRC) in a Chinese cohort, and to provide reference and guidance for the prevention, diagnosis, and treatment of EOCRC.Methods:Using data from the National Colorectal Cancer Cohort study cohort, 5377 patients with newly diagnosed colorectal cancer (CRC) attending the Department of Colorectal Surgery and Oncology of the Second Affiliated Hospital, Zhejiang University School of Medicine from June 2018 to February 2023 were included in the study cohort. Questionnaires capturing epidemiological features, including lifestyle and dietary habits, were administered. The patients were divided into two groups, the cut-off age being 50 years. Those aged ≥50 years were defined as having LOCRC and those aged <50 years as having EOCRC. Wilcoxon (continuous variates) or χ 2 tests (categorical variates) were performed to compare differences in epidemiological features. Results:A total of 3799 people who had completed the questionnaire were included in this study, 491 of whom had EOCRC and 3308 LOCRC. The response rate to the questionnaire was 70.7%. The median ages of patients in the EOCRC and LOCRC groups were 43 and 66 years, respectively. There was a higher proportion of female patients (48.5% [253/491] vs. 35.8% [1184/3308], χ 2=28.8, P<0.001) in the EOCRC than the LOCRC group. Patients with EOCRC and lower body mass index (medium 22.1 kg/m 2 vs. 22.9 kg/m 2, W=744 793, P=0.005) and lower proportion of abdominal obesity (87.2% [428/491] vs. 93.8% [3103/3308], χ 2=38.3, P<0.001). Patients with EORC significantly less commonly reported a history of hypertension (5.9% [29/491] vs. 41.6% [1375/3308], χ 2=231.8, P<0.001), diabetes (1.4% [7/491] vs. 14.4% [476/3308], χ 2=63.6, P<0.001) and cardiovascular and cerebrovascular diseases (0.8% [4/491] vs. 7.3% [241/3308], χ 2=28.6, P<0.001). However, the proportion of patients with a family history of CRC was significantly higher ( P<0.05) in the EOCRC group (10.2% [50/491] vs. 6.9% [227/3 308], χ 2=6.5, P=0.010]. In terms of lifestyle, patients with EOCRC had shorter sleep duration (median: 8.0 hours vs. 8.5 hours, W=578 989, P<0.001), and were less likely to participate in physical exercise (29.5% [145/491] vs. 38.7% [1281/3308] χ 2=15.0, P<0.001) or engage in physical work (65.2% [320/491] vs. 74.1% [2450/3308], χ 2=16.7, P<0.001). Meanwhile, in the EOCRC group a lower percentage of patients were smokers (29.3% [144/491] vs. 42.7% [1411/3308], χ 2=46.9, P<0.001) and they smoked less (median 17.6 pack/year vs. 30.0 pack/year,W=55 850, P<0.001). Fewer patients in the EOCRC group habitually drank alcohol (21.0% [103/491] vs. 38.0% [1257/3308], χ 2=57.5, P<0.001) or tea (17.5% [86/491] vs. 28.7% [948/3308], χ 2=26.2, P<0.001) than in the LOCRC group. Compared with the LOCRC group, patients with EOCRC had a higher frequency of intake of fresh meat, fresh fruit, eggs, and dairy products and a lower frequency of intake of preserved meat and pickled vegetables; these differences are statistically significant (all P<0.05). There was no statistically significant difference in consumption of fresh vegetables or a high-sugar diet between the two groups (both P>0.05). Conclusions:This study highlights disparities in adverse lifestyle and dietary habits between patients in China with EOCRC versus LOCRC.
6.Updates of colonoscopy surveillance guidelines after screening and polypectomy, and related research progress
Yunfeng ZHU ; Yingshuang ZHU ; Chengcheng LIU ; Yeting HU ; Kefeng DING
Chinese Journal of Gastrointestinal Surgery 2024;27(1):99-104
With the widespread application of colorectal cancer screening, the surveillance and management of the increasing number of screened population has become a pivotal aspect in preventing and controlling colorectal cancer. In recent years, researches have been conducted on the risk of colorectal cancer incidence and mortality in the population after screening. At the same time, various organizations in Europe and the United States have continuously updated colonoscopy surveillance after screening and polypectomy based on the latest research evidence. In this review, we summarized the current progress of studies on colorectal cancer risk in post-screening colorectal cancer populations and the key points of relevant guideline updates, in order to provide a reference for conducting relevant studies and formulating surveillance guidelines or consensus in China.
7.Epidemiological characteristics of early-onset colorectal cancer: a prospective cohort study from a single center
Tian JIN ; Yingshuang ZHU ; Chengcheng LIU ; Xing XU ; Wei LU ; Qian XIAO ; Kefeng DING ; Shu ZHENG
Chinese Journal of Gastrointestinal Surgery 2024;27(5):457-463
Objective:To explore the differences in distribution of colorectal cancer-related risk factors between patients with early-onset colorectal cancer (EOCRC) and those with late-onset colorectal cancer (LOCRC) in a Chinese cohort, and to provide reference and guidance for the prevention, diagnosis, and treatment of EOCRC.Methods:Using data from the National Colorectal Cancer Cohort study cohort, 5377 patients with newly diagnosed colorectal cancer (CRC) attending the Department of Colorectal Surgery and Oncology of the Second Affiliated Hospital, Zhejiang University School of Medicine from June 2018 to February 2023 were included in the study cohort. Questionnaires capturing epidemiological features, including lifestyle and dietary habits, were administered. The patients were divided into two groups, the cut-off age being 50 years. Those aged ≥50 years were defined as having LOCRC and those aged <50 years as having EOCRC. Wilcoxon (continuous variates) or χ 2 tests (categorical variates) were performed to compare differences in epidemiological features. Results:A total of 3799 people who had completed the questionnaire were included in this study, 491 of whom had EOCRC and 3308 LOCRC. The response rate to the questionnaire was 70.7%. The median ages of patients in the EOCRC and LOCRC groups were 43 and 66 years, respectively. There was a higher proportion of female patients (48.5% [253/491] vs. 35.8% [1184/3308], χ 2=28.8, P<0.001) in the EOCRC than the LOCRC group. Patients with EOCRC and lower body mass index (medium 22.1 kg/m 2 vs. 22.9 kg/m 2, W=744 793, P=0.005) and lower proportion of abdominal obesity (87.2% [428/491] vs. 93.8% [3103/3308], χ 2=38.3, P<0.001). Patients with EORC significantly less commonly reported a history of hypertension (5.9% [29/491] vs. 41.6% [1375/3308], χ 2=231.8, P<0.001), diabetes (1.4% [7/491] vs. 14.4% [476/3308], χ 2=63.6, P<0.001) and cardiovascular and cerebrovascular diseases (0.8% [4/491] vs. 7.3% [241/3308], χ 2=28.6, P<0.001). However, the proportion of patients with a family history of CRC was significantly higher ( P<0.05) in the EOCRC group (10.2% [50/491] vs. 6.9% [227/3 308], χ 2=6.5, P=0.010]. In terms of lifestyle, patients with EOCRC had shorter sleep duration (median: 8.0 hours vs. 8.5 hours, W=578 989, P<0.001), and were less likely to participate in physical exercise (29.5% [145/491] vs. 38.7% [1281/3308] χ 2=15.0, P<0.001) or engage in physical work (65.2% [320/491] vs. 74.1% [2450/3308], χ 2=16.7, P<0.001). Meanwhile, in the EOCRC group a lower percentage of patients were smokers (29.3% [144/491] vs. 42.7% [1411/3308], χ 2=46.9, P<0.001) and they smoked less (median 17.6 pack/year vs. 30.0 pack/year,W=55 850, P<0.001). Fewer patients in the EOCRC group habitually drank alcohol (21.0% [103/491] vs. 38.0% [1257/3308], χ 2=57.5, P<0.001) or tea (17.5% [86/491] vs. 28.7% [948/3308], χ 2=26.2, P<0.001) than in the LOCRC group. Compared with the LOCRC group, patients with EOCRC had a higher frequency of intake of fresh meat, fresh fruit, eggs, and dairy products and a lower frequency of intake of preserved meat and pickled vegetables; these differences are statistically significant (all P<0.05). There was no statistically significant difference in consumption of fresh vegetables or a high-sugar diet between the two groups (both P>0.05). Conclusions:This study highlights disparities in adverse lifestyle and dietary habits between patients in China with EOCRC versus LOCRC.
8.Development and validation of a questionnaire for the management of nutrition and immune-related adverse events in patients with liver cancer who received immunotherapy
Wen WEN ; Yingshuang CHEN ; Chunling LIU ; Liling TONG ; Hua ZHANG
Chinese Journal of Digestion 2024;44(10):693-701
Objective:To develop and verify the validity of a questionnaire on nutrition and immune-related adverse events in patients with liver cancer and received immune therapy. To provide a survey and evaluation tool for targeted health education, improving compliance and quality of life.Methods:Based on the knowledge attitude practice (KAP) theory, the preliminary draft of questionnaire was determined by literature search and 30 patients with liver cancer who received immunotherapy at Haikou People′s Hospital were selected for pre survey. The expert consultation was conducted by associate chief physicians from the department of hepatobiliary surgery and the department of oncology, the nutritionists and specialist nurses from the department of gastroenterology. According to the consultation results, the questionnaire was modified into the test version. It was estimated that the minimum sample size required for structural validity evaluation was 322 cases. Patients with liver cancer who received immunotherapy at Haikou People′s Hospital were recruited by convenience sampling, and the test version questionnaire were filled in. According to random number table method, the patients were divided into 2 groups. Exploratory and confirmatory factors analysis of the questionnaire were conducted respectively. The reliability of the questionnaire was evaluated by Cronbach′s α coefficient, split half reliability and retest reliability. Results:The completion time of the pre-survey questionnairein was (9.57±7.57) min. A total of 407 test questionnaires were distributed, and 400 were recovered, and the recovery rate of test questionnaire was 98.28%.The final questionnaire consisted of 27 items in 3 dimensions (knowledge, attitude, and practice), including 9 items of knowledge dimension, 10 items of attitude dimension and 8 items of practice dimension. Three factors were extracted in exploratory factors analysis with a cumulative variance contribution rate of 65.265%. In validation factor analysis, the chi-square freedom ratio was 3.956, the root mean square error of approximation was 0.086, the root mean square residual was 0.076, the comparative fit index was 0.871, and the incremental fit index was 0.872. The main indicators of the questionnaire fit were all with in the acceptable range. The total Cronbach′s α coefficient, split-half reliability and test-retest reliability of this questionnaire were 0.935, 0.834, 0.933, respectively. Conclusions:The questionnaire has good reliability and validity, and can be used as a preliminary assessment tool to understand the current status of knowledge, attitude, and practice of nutritional and immune-related adverse events in patients with liver cancer who received immunotherapy.
9.The genetic distribution in Chinese patients with Charcot-Marie-Tooth diseases: a 14-year cohort study
Xiaoxuan LIU ; Aping SUN ; Xiaohui DUAN ; Yingshuang ZHANG ; Dongsheng FAN
Chinese Journal of Neurology 2022;55(5):481-489
Objective:To investigate the genetic distribution of pathogenic genes of Charcot-Marie-Tooth diseases (CMT) in Chinese Han population, and compare the similarity and difference with the data in Peking University Third Hospital in 2013.Methods:Five hundred and twenty families with CMT and related diseases in Peking University Third Hospital and China-Japan Friendship Hospital from January 2007 to March 2021 were collected. After peripheral myelin protein 22 (PMP22) gene duplication and deletion mutations were initially detected by multiple ligation probe amplification, the probands of these families were sequenced by next-generation sequencing (NGS) gene panel or whole exome sequencing, and validated by Sanger sequencing.Results:Among the 520 families, 336 CMT families were genetically confirmed, and the mutation detection rate increased from 48.6% (51/105) in 2013 to 64.6% (336/520) in 2021 (χ 2=9.54, P=0.003). Among them, 139 families had PMP22 gene duplication mutation (139/520, 26.7%), 46 families had gap junction beta-1 (GJB1) gene mutation (46/520, 8.8%), 26 families had mitofusin-2 (MFN2) gene mutation (26/520, 5.0%), 12 families had myelin protein zero (MPZ) gene mutation (12/520, 2.3%), 11 families had PMP22 gene point mutation (11/520, 2.1%), and 10 families had heat shock protein B1 gene mutation (10/520, 1.9%). There were 10 families with ganglioside induced differentiation associated protein 1 (GDAP1) gene mutation (10/520, 1.9%), 8 families with SH3 domain and tetratricopeptide repeats 2 (SH3TC2) gene mutation (8/520, 1.5%), 7 families with immunoglobulin mu DNA binding protein 2 (IGHMBP2) gene mutation (7/520, 1.3%), 6 families with MORC family CW-type zinc finger 2 (MORC2) gene mutation (6/520, 1.2%), 5 families with sorbitol dehydrogenase (SORD) gene mutation (5/520, 1.0%), 16 families with very rare gene mutation (16/520, 3.1%) and 184 families without genetic diagnosis (184/520, 35.4%). Conclusions:Compared with the results in 2013, the 3 most common genes affecting CMT were still PMP22, GJB1 and MFN2 genes, but the proportion difference of patients with MPZ gene mutation gradually decreased with other genes such as SH3TC2 and GDAP1 genes. The proportion of newly discovered CMT genes, such as MORC2 and SORD genes, was similar with IGHMBP2 gene, which should be paid more attention. NGS greatly improved the detection rate of CMT, especially for patients with autosomal recessive-CMT.
10.Interleukin 6 induces osteogenic differentiation and calcification of human umbilical artery smooth muscle cells via trans-signaling pathway
Xinxin GUO ; Lin PAN ; Ying ZHAN ; Yuwei HE ; Dawei WEN ; Yingshuang LIU ; Yidan QU ; Mingshu SUN
Chinese Journal of Rheumatology 2022;26(2):73-78,C2-1
Objective:To explore the trans-membrane signaling mechanism of interleukin-6 (IL-6)-induced osteogenic differentiation and calcification of human umbilical artery smooth muscle cells (HUASMCs).Methods:HUASMCs were primarily cultured in vitro and were stimulated with IL-6, IL-6+solutable IL-6 receptor (sIL-6R), IL-6+sIL-6R+solutable gp130 (sgp130), or vehicle (blank control). Alizarin red and Von Kossa staining were used for detecting cell calcification, Western blot was used to test the protein expression of tissue-nonspecific alkaline phosphatase (TNAP), osteopontin (OPN), bone morphogenetic protein-2 (BMP-2) and Runt related transcription factor 2 (Runx2), and immunofluorescence was used to examine the mIL-6R expression of HUASMCs. The comparison of measurement date between the two groups was conducted by t-test. The comparison of measurement date between multiple groups was conducted by one-way analysis of variance (ANOVA). Results:The intensity severity of calcification stain was IL-6+sIL-6R group >IL-6+sIL-6R+sgp130 group>IL-6 group=blank control. After stimulated for 12 hours, the TNAP expression in blank control, IL-6 group, IL-6+sIL-6R group, IL-6+sIL-6R+sgp130 group were (0.44±0.08), (0.52±0.14), (0.84±0.16) and (0.55±0.10) respectively ( F=290.96, P<0.001). After stimulated for 3 days, the OPN expression in blank control, IL-6 group, IL-6+sIL-6R group, IL-6+sIL-6R+sgp130 group were (0.61±0.84), (0.95±0.16), (1.65±0.24) and (0.99±0.10) respectively ( F=507.72, P<0.001). After stimulated for 12 hours, the BMP-2 expression in blank control, IL-6 group, IL-6+sIL-6R group, IL-6+sIL-6R+sgp130 group were (0.77±0.05), (1.69±0.16), (2.81±0.26) and (0.57±0.12) respectively ( F=959.09, P<0.001). After stimulated for 3 days, the Runx2 expression in blank control, IL-6 group, IL-6+sIL-6R group,IL-6+sIL-6R+sgp130 group were (0.57±0.03) , (0.92±0.10), (1.31±0.13) and (0.66±0.06) respectively ( F=1141.27, P<0.001). Comparing with Jurkat cells (positive control) and CEM cells (negative control), HUASMCs limited expressed mIL-6R. Conclusion:IL-6 may induce HUASMCs osteogenic differentiation and calcification mainly via the sIL-6R-mediated trans-signaling pathway.

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