1.Single-cell RNA sequencing reveals the process of CA19-9 production and dynamics of the immune microenvironment between CA19-9 (+) and CA19-9 (-) PDAC
Deyu ZHANG ; Fang CUI ; Kailian ZHENG ; Wanshun LI ; Yue LIU ; Chang WU ; Lisi PENG ; Zhenghui YANG ; Qianqian CHEN ; Chuanchao XIA ; Shiyu LI ; Zhendong JIN ; Xiaojiang XU ; Gang JIN ; Zhaoshen LI ; Haojie HUANG
Chinese Medical Journal 2024;137(20):2415-2428
Background::Pancreatic ductal adenocarcinoma (PDAC) is one of the main types of malignant tumor of the digestive system, and patient prognosis is affected by difficulties in early diagnosis, poor treatment response, and a high postoperative recurrence rate. Carbohydrate antigen 19-9 (CA19-9) has been widely used as a biomarker for the diagnosis and postoperative follow-up of PDAC patients. Nevertheless, the production mechanism and potential role of CA19-9 in PDAC progression have not yet been elucidated.Methods::We performed single-cell RNA sequencing on six samples pathologically diagnosed as PDAC (three CA19-9-positive and three CA19-9-negative PDAC samples) and two paracarcinoma samples. We also downloaded and integrated PDAC samples (each from three CA19-9-positive and CA19-9-negative patients) from an online database. The dynamics of the proportion and potential function of each cell type were verified through immunofluorescence. Moreover, we built an in vitro coculture cellular model to confirm the potential function of CA19-9. Results::Three subtypes of cancer cells with a high ability to produce CA19-9 were identified by the markers TOP2A, AQP5, and MUC5AC. CA19-9 production bypass was discovered on antigen-presenting cancer-associated fibroblasts (apCAFs). Importantly, the proportion of immature ficolin-1 positive (FCN1+) macrophages was high in the CA19-9-negative group, and the proportion of mature M2-like macrophages was high in the CA19-9-positive group. High proportions of these two macrophage subtypes were associated with an unfavourable clinical prognosis. Further experiments indicated that CA19-9 could facilitate the transformation of M0 macrophages into M2 macrophages in the tumor microenvironment. Conclusions::Our study described CA19-9 production at single-cell resolution and the dynamics of the immune atlas in CA19-9-positive and CA19-9-negative PDAC. CA19-9 could promote M2 polarization of macrophage in the pancreatic tumor microenvironment.
2.Influencing factors of thyroid volume in children aged 8 - 10 in Yunnan Province
Changyan PENG ; Hesong WU ; Jiaguo LI ; Kailian HUANG ; Yuxi GUO ; Liangjing SHI ; Feng YE ; Haitao ZHANG ; Shujuan LI ; Zhihua ZHAO ; Qianxia GE ; Anwei WANG
Chinese Journal of Endemiology 2024;43(3):225-228
Objective:To analyze the influencing factors of thyroid volume in children aged 8 - 10 in Yunnan Province, and provide scientific basis for improving iodine deficiency disorders monitoring.Methods:From March to July 2020, in 129 counties (cities, districts) under the jurisdiction of Yunnan Province, each county (city, district) was divided into 5 sampling areas based on east, west, south, north, and middle. One township was selected from each area, and 40 non-boarding children aged 8 - 10 from one primary school were selected from each township (age balanced, half male and half female) as survey subjects. One random urine sample and household edible salt samples were collected for urine iodine and salt iodine testing, and physical examination and thyroid volume measurement were conducted for children. The influencing factors of thyroid volume were analyzed using Pearson correlation.Results:A total of 24 934 urine samples were collected from children, with a median urine iodine of 233.2 μg/L. A total of 24 933 household edible salt samples were collected from children, the median salt iodine was 24.17 mg/kg, and the qualified rate of iodized salt was 96.63% (24 003/24 839); A total of 24 937 children were examined of their thyroid gland, with a median thyroid volume of 2.62 ml and a goiter rate of 1.12% (280/24 937). Among them, there were 12 410 boys and 12 527 girls, with thyroid volumes of 2.61 and 2.64 ml, respectively. The thyroid volume of boys was positively correlated with age, height, weight, body mass index, body surface area, and salt iodine ( r = 0.15, 0.21, 0.26, 0.18, 0.25, 0.03, P < 0.001). The thyroid volume of girls was positively correlated with age, height, weight, body mass index, and body surface area ( r = 0.17, 0.26, 0.28, 0.17, 0.27, P < 0.001). Conclusion:Children aged 8 - 10 in Yunnan Province are at an iodine excess level; the age, weight, height, body mass index, and body surface area are influencing factors of thyroid volume.
3.Risk assessment for patients with severe acute pancreatitis complicated by clinically significant bleeding
Kailian ZHENG ; Chenming NI ; Tao LIU ; Yanbo ZENG ; Yikai LI ; Song ZHANG ; Yiqi DU ; Gang JIN
Chinese Journal of Hepatobiliary Surgery 2023;29(4):263-267
Objective:To analyze the risk factors of clinically significant bleeding in patients with severe acute pancreatitis (SAP).Methods:The clinical data of SAP patients who were managed at Changhai Hospital affiliated to Naval Medical University from January 1, 2014 to October 31, 2022 were retrospectively analyzed. Twenty-nine SAP patients with clinically significant bleeding were classified to form the bleeding group. There were 23 males and 6 females, aged (56.25±14.01) years old. Another 116 SAP patients with similar general data but with no clinically significant bleeding during the same hospitalization period were included to form the non-bleeding group based on a ratio of 1∶4. There were 94 males and 22 females, aged (56.14±13.96) years old in this non-bleeding group. The general data, modified CT severity index (MCTSI), bedside index for severity of acute pancreatitis (BISAP) and other clinical data of the two groups were collected to determine the risk factors of bleeding in SAP patients.Results:Of the 29 patients with bleeding, 6 had gastrointestinal bleeding, 14 had intra-abdominal bleeding, and 9 had mixed bleeding sites, 15 were cured and discharged, and 14 died. All the 29 SAP patients with bleeding received treatment using drugs. In addition, 8 patients underwent successful hemostasis using digital subtraction angiography, 3 underwent successful endoscopic hemostasis, 2 underwent successful surgical hemostasis, and 2 underwent successful conservative drug hemostasis. Multivariate logistic regression analysis showed that SAP patients with higher MCTSI ( OR=1.824, 95% CI: 1.187-2.802), longer prothrombin time (PT) ( OR=3.431, 95% CI: 1.470-8.007) and higher BISAP ( OR=2.286, 95% CI: 1.054-4.957) had an increased risk of bleeding (all P<0.05). Conclusion:The prognosis of SAP patients was compromised with bleeding. High MCTSI, prolonged PT, and high BISAP were independent risk factors for bleeding in SAP patients.
4.Iodine nutrition status of children and pregnant women in Yunnan Province in 2020
Qianxia GE ; Anwei WANG ; Liangjing SHI ; Kailian HUANG ; Jiaguo LI ; Haitao ZHANG ; Feng YE ; Hesong WU ; Yuxi GUO ; Lin YANG ; Zhihua ZHAO ; Shujuan LI ; Xu DONG ; Xingqi DONG
Chinese Journal of Endemiology 2022;41(1):49-53
Objective:To understand the contents of edible salt iodine and urinary iodine of children and pregnant women in Yunnan Province, and to evaluate the iodine nutrition status, so as to provide a basis for scientific prevention and treatment of iodine deficiency disorders (IDD).Methods:From November to December 2020, one county (city) was selected from each prefecture (city), two townships (towns and streets) were selected from each county (city) and two villages (neighborhood committees) were selected from each township (town and street) from each of the 16 prefectures (cities) in Yunnan Province as the investigation sites. A total of 20 non-boarding children (male and female balanced) aged 8 - 10 years old were selected from each primary school in each village (neighborhood committee) to collect salt and urine samples. A total of 80 children were investigated in each county (city). A total of 20 pregnant women were selected from each township (town and street) to collect salt and urine samples. A total of 40 pregnant women were investigated in each county (city). All salt samples and urine samples were tested for iodine contents.Results:A total of 2 009 salt samples and 2 041 urine samples (1 375 for children, 666 for pregnant women) were collected from children aged 8 - 10 years old and pregnant women in 16 counties (cities) of Yunnan Province. Among them, the median salt iodine was 26.0 mg/kg, the coverage rate of iodized salt was 100.0% (2 009/2 009), the qualified rate of iodized salt was 98.7% (1 982/2 009), and the consumption rate of qualified iodized salt was 98.7% (1 982/2 009). The difference of salt iodine content in key populations in different counties (cities) was statistically significant ( H = 258.98, P < 0.01). The median urinary iodine of children aged 8 - 10 years old was 188.5 μg/L. There was statistically significant difference in urinary iodine content among children of different ages ( H = 29.45, P < 0.01), but there was no statistically significant difference in urinary iodine content among children of different genders ( H = 1.43, P > 0.05). In addition, the median urinary iodine of pregnant women was 141.9 μg/L, 52.1% (347/666) was < 150 μg/L. There was statistically significant difference in urinary iodine content of pregnant women in different counties (cities, H = 88.32, P < 0.01). Conclusions:The qualified rate of iodized salt, the coverage rate of iodized salt and the consumption rate of qualified iodized salt in key populations of Yunnan Province are more than 90%, and the iodized salt supply is good. Iodine nutrition of children aged 8 - 10 years old is at an appropriate level (100 - 199 μg/L); iodine nutrition of pregnant women is in an state of iodine deficiency ( < 150 μg/L). It is suggested to strengthen IDD monitoring and health education among key populations, improve residents' awareness of disease prevention, and make scientific iodine supplementation.
5.Research progress on the occurrence and prevention of low back pain in naval officers and soldiers
Na ZHAO ; Xiaofei MAO ; Kailian ZHENG ; Yijie ZHANG ; Gang JIN
Chinese Journal of Industrial Hygiene and Occupational Diseases 2020;38(10):794-796
Low back pain (LBP) is a common occupational disease among naval officers and soldiers. This article reviewed the incidence of LBP in naval personnel in different positions in recent years, and analyzed the causes combined with the operating environment and occupational characteristics of personnel in different positions in order to clarify the causes of LBP in naval officers and soldiers in different positions and improve their awareness of the disease. Moreover, this study aims to help naval officers and soldiers to take protective measures in training life to reduce the incidence of LBP.
6.Research progress on the occurrence and prevention of low back pain in naval officers and soldiers
Na ZHAO ; Xiaofei MAO ; Kailian ZHENG ; Yijie ZHANG ; Gang JIN
Chinese Journal of Industrial Hygiene and Occupational Diseases 2020;38(10):794-796
Low back pain (LBP) is a common occupational disease among naval officers and soldiers. This article reviewed the incidence of LBP in naval personnel in different positions in recent years, and analyzed the causes combined with the operating environment and occupational characteristics of personnel in different positions in order to clarify the causes of LBP in naval officers and soldiers in different positions and improve their awareness of the disease. Moreover, this study aims to help naval officers and soldiers to take protective measures in training life to reduce the incidence of LBP.
7.Research on immunophenotype of primary pancreatic cancer
Chunyan QIU ; Kailian ZHENG ; Huojun ZHANG
Chinese Journal of Pancreatology 2019;19(2):91-97
Objective To comprehensively analyse the immunophenotype of primary pancreatic cancer,providing biological clues for treating pancreatic cancer.Methods The genome nap of 177 primary pancreatic cancer patients from the Cancer Genome Atlas (TCGA) database were enrolled.The overall immune infiltration score (IIS),T cell infiltration score (TIS) and antigen presenting machinery (APM) score were quantified for each specimen.By using unsupervised clustering,the patients were divided into immune-high group and immune-low group according to IIS,TIS,and APM scores.The differences on the inffiltration of immune cell subtype,expression of immune checkpoint and immunological function evaluation were compared between two groups.Results In the radiotherapy population,the survival rate of immune-high group was slightly higher than that of immune-low group with no statistical significance.The immune-high group had more infiltrated neutrophils (63.4% vs 36.6%),eosinophils (75.5% vs 24.5%),activated CD4 + memory T lymphocytes (80.7% vs 19.3%),naive CD4 + T lymphocytes (81.2% vs 18.8%) and naive B lymphocytes (59.5% vs 40.5%) compared with immune low group;while the immune-low group had more activated NK cells (67.3% vs 32.7%),regulatory T lymphocytes (68.9% vs 31.1%),T follicular helper (67.7% vs 32.3%),and activated mast cells (62.9% vs 37.1%).Co-stimulatory molecules such as CD28,ICOS,CD40,CD40L,CD27,CD27L,4-1BB,OX40,GITR and co-inhibitory molecules including CTLA-4,PD-L2,PD-1,VISTA,LAG-3,TIGIT,Galectin-9,TIM-3,and IDO-1 were significantly higher expressed in the immune-low group (all P < 0.05).The PC1 value of principal component analysis of chemokine expression levels and the cytolytic activity (CYT) in the immune-high group were significantly higher (all P <0.001).Conclusions Clustering on the three inmune quantification scores could be preliminarily used for immunophenotyping pancreatic cancer.The immune-high group may have synergistic effect with radiation therapy.Treatment with immune checkpoint inhibitor may be effective in immune-low group.
8.Clinical efficacy of pancreaticoduodenectomy using artery first approach and prior portal vein-superior mesenteric vein shunting and reconstruction for complicated pancreatic head tumors
Kailian ZHENG ; Huan WANG ; Chenming NI ; Jing SHEN ; Sijia BAI ; Yijie ZHANG ; Xiangui HU ; Zhuo SHAO ; Shiwei GUO ; Gang JIN
Chinese Journal of Digestive Surgery 2018;17(7):703-710
Objective To investigate the clinical efficacy of pancreaticoduodenectomy using artery first approach and prior portal vein (PV)-superior mesenteric vein (SMV) shunting for complicated pancreatic head tumors.Methods The retrospective cohort study was conducted.The clinicopathological data of 91 patients with pancreatic head cancer who were admitted to the Changhai Hospital of Navy Medical University from February 2011 to December 2016 were collected.Among 91 patients undergoing pancreaticoduodenectomy combined with vascular resection and reconstruction,27 using artery first approach and PV-SMV shunting and reconstruction were allocated into the PD-PVR group,23 using conventional approach were allocated into the PD-CVR group,and 41 receiving pancreaticoduodenectomy with vascular resection were allocated into the PD-SVR group.Observation indicators:(1) comparison of intra-and post-operative situations among groups;(2) comparison of postoperative pathological results among groups;(3) comparison of postoperative survival among groups.Follow-up using outpatient examination and telephone interview was performed to detect postoperative survival up to December 2017.Comparisons among groups of count data were done by the chi-square test or Fisher exact probability.Measurement data with normal distribution were represented as x±s,comparisons among groups were analyzed using the ANOVA,and pairwise comparison was done using the LSD method.Measurement data with skewed distribution were described as M(Q),comparison among groups was analyzed using the Kurskal-Wallis rank sum test,and pairwise comparison was done using the paired comparison with adjusted P value.Ordinal data were compared using the nonparametric test.The survival rate and curve were respectively calculated and drawn by the Kaplan-Meier method,and Log-rank test was used for survival analysis.Results (1) Comparison of intra-and post-operative situations among groups:operation time,time of hepatic inflow occlusion,volume of intraoperative blood loss,cases with intraoperative blood transfusion,length of PV or SMV removal,cases with vascular grafts,grading 1,2,3,4 and 5 of Clavien-Dindo classification of postoperative complications and duration of hospital stay were respectively (274±36)minutes,(22±7)minutes,1 661 mL (110 mL,3 800 mL),20,(5.6±1.4)cm,6,11,1,1,1,1,(20±7)days in the PD-PVR group and (281±41)minutes,(27±5)minutes,1 888 mL (176 mL,4 162 mL),18,(5.4±1.5) cm,3,1,8,2,0,0,(21±7)days in the PD-CVR group and (201± 36)minutes,(16±6)minutes,1052 mL (74 mL,3 926 mL),17,(3.2±2.0) cm,5,15,2,3,1,1,(13± 6)days in the PD-SVR group,with statistically significant differences among groups (F=37.060,34.530,x2=13.771,14.015,F=32.260,x2 =39.309,F =19.880,P<0.05).Patients with postoperative complications were improved by symptomatic and supporting treatment.(2) Comparison of postoperative pathological results among groups:mnaximum tumour dimension was respectively (3.6± 1.3) cm,(4.0± 1.3) cm and (2.6± 1.3) cm in the PD-PVR,PD-CVR and PD-SVR groups,with a statistically significant difference among groups (F =7.845,P<0.05).Cases with high-differentiated,moderate-differentiated and low-differentiated tumors of tumor differentiation,staging Ⅱ A and Ⅱ B of tumor staging,nerve invasion,positive lymph node,positive resection margins in neck of pancreas,bile duct and SMV were respectively 0,13,14,17,10,17,21,0,0,0 in the PD-PVR group and 1,12,10,10,13,15,19,1,0,0 in the PD-CVR group and 1,29,11,17,24,30,29,2,1,1 in the PD-SVR group,with no statistically significant difference among groups (x2 =4.122,3.306,0.902,1.214,P>0.05).(3) Comparisons of postoperative survival among groups:of 91 patients,52 were followed up for 3.0-69.3 months,with a median time of 18.0 months and follow-up rate of 57.1% (52/91),including 16 in the PD-PVR group and 14 in the PD-CVR group and 22 in the PD-SVR group.The median survival time,1-,2-and 3-year overall survival rates in 52 patients were respectively 16.6 months,63.5%,35.7% and 26.8%.The survival time in the PD-PVR,PD-CVR and PD-SVR groups were respectively 12.3 months (3.9-69.3 months),15.0 months (3.0-63.3 months) and 20.0 months (6.0-65.2 months),with a statistically significant difference in survival among groups (x2=6.201,P<0.05),and between PD-PVR and PD-SVR groups (x2 =4.412,P<0.05).There was no statistically significant difference in survival between PD-PVR and PD-CVR groups (x2 =0.001,P>0.05).Conclusion Pancreaticoduodenectomy using artery first approach and PV-SMV shunting and reconstruction for complicated pancreatic head tumors can reduce the time of hepatic inflow occlusion,it also contributes to the risk control of surgery for complicated pancreatic tumors,increases surgical safety and improves patients' prognosis.
9.An investigation on iodine nutritional status of children in Yunnan Province before and after adjustment of iodine content in edible salt
Anwei WANG ; Wenli HUANG ; Feng YE ; Haitao ZHANG ; Yuxi GUO ; Kailian HUANG ; Zhaoxiang LI ; Rongji CAO ; Changyan PENG ; Jiaguo LI ; Hesong WU ; Lin YANG ; Haowei ZHANG
Chinese Journal of Endemiology 2018;37(1):49-53
Objective To understand the situation of iodine deficiency disorders and iodine nutrition of children in Yunnan Province after the implementation of new standard of salt iodine,and provide the basic data for prevention and control of iodine deficiency disorders.Methods Using multistage sampling method,Yunnan provincial evaluations for iodine deficiency disorders elimination were carried out.According to the comparative analysis of 2010 (pre-adjustment) and 2015 (post-adjustment) evaluation results,the changes of the median of salt iodine,the coverage rate of iodized salt,the qualified rate of iodized salt,the rate of qualified iodized salt consumption,goiter rate of school children aged 8-10 and the median of urinary iodine were evaluated.Salt iodine was tested using the "Salt Industry General Test Method for Determination of Iodine" (GB/T 13025.7-1999);thyroid volume examination of children using B-scan ultrasonography,thyroid volume calculation and enlargement judgment using "Diagnostic Criteria for Endemic Goiter" (WS 276-2007);and urinary iodine detection using "Urinary Iodine Arsenic Cerium Catalytic Spectrophotometry" (WS/T 107-2006).Results The medians of salt iodine in 2010 and 2015 were 30.6 and 22.4 mg/kg,respectively,the difference was statistically significant (U =317 503.50,P < 0.01).The coverage rates of iodized salt in 2010 and 2015 were 99.6% (1 681/1 688) and 98.9% (2 592/2 622),the qualified rates of iodized salt were 98.6% (1 657/1 681) and 89.7% (2 325/2 592),and the rates of qualified iodized salt consumption were 98.2% (1 657/1 688) and 88.7% (2 325/2 622),and the differences were statistically significant (x2 =6.42,125.11,130.18,P < 0.01);the rates of children goiter in 2010 and 2015 were 0.8% (25/3 272) and 1.4%(44/3 245),respectively;the medians of urinary iodine of children were 289.0 and 157.3 μg/L,respectively,the difference was statistically significant (U =1 121 669.50,P < 0.01).Conclusion After decreasing of salt iodine level starting from 2012 in Yunnan Province,the children iodine nutrition condition is in a more proper level.
10.Investigation on the status and prevention of drinking-water-borne endemic fluorosis in the disease affected areas in Yunnan Province
Kailian HUANG ; Anwei WANG ; Zhihua ZHAO ; Haitao ZHANG ; Feng YE ; Wenli HUANG
Chinese Journal of Endemiology 2018;37(10):802-806
Objective To investigate the epidemic situation of drinking-water-borne endemic fluorosis in Yunnan Province,to evaluate the effect of prevention and control measures,to find out existing problems,and to guide the development of prevention and control measures in Yunnan Province.Methods All villages in 14 drinking-water-borne endemic fluorosis areas were selected in Yunnan Province in 2015,in which the progress and effectiveness of water-improving and defluoridation projects were investigated.Fluoride content of drinking water was determined by standard test method for drinking water (GB/T 5750.5-2006),and dental fluorosis of all children aged 8 to 12 was examined.Dental fluorosis diagnosis was based on "Diagnostic Criteria for Endemic Skeletal Fluorosis"(WS/T 208-2011).Results In the 143 disease affected villages,the water improvement projects were completed in 138 villages with accomplishment rate 96.50% (138/143),127 water improvement projects were normal operated with the normal operation rate 92.03% (127/138).Totally 126 water improvement projects were tested for fluorine content and 120 of them were qualified with qualified rate 95.24% (120/126).A total of 3 449 children aged 8 to 12 were monitored,the detection rate of dental fluorosis was 4.00% (138/3 449),the dental fluorosis index was 0.08.Totally 11 out of the 14 disease affected counties had met the disease control standards.Conclusion The prevalence of drinking-water-borne endemic fluorosis in Yunnan Province has been under control,but management and monitoring of the water improvement projects still should be strengthened.

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