1.Effect of preoperative immune checkpoint inhibitors on reducing residual lymph node metastases in patients with gastric cancer: a retrospective study
Xinhua CHEN ; Hexin LIN ; Yuehong CHEN ; Xiaodong WANG ; Chaoqun LIU ; Huilin HUANG ; Huayuan LIANG ; Huimin ZHANG ; Fengping LI ; Hao LIU ; Yanfeng HU ; Guoxin LI ; Jun YOU ; Liying ZHAO ; Jiang YU
Chinese Journal of Gastrointestinal Surgery 2024;27(7):694-701
Objective:To investigate the effect of immune checkpoint inhibitors on reducing residual lymph node metastasis in patients with gastric cancer.Methods:The cohort of this retrospective study comprised patients from Nanfang Hospital of Southern Medical University and the First Affiliated Hospital of Xiamen University who had undergone systemic treatment prior to gastrectomy with D2 lymphadenectomy and had achieved Grade 1 primary tumor regression (TRG1) from January 2014 to December 2023. After exclusion of patients who had undergone preoperative radiotherapy, data of 58 patients (Nanfang Hospital: 46; First Affiliated Hospital of Xiamen University: 12) were analyzed. These patients were allocated to preoperative chemotherapy (Chemotherapy group, N=36 cases) and preoperative immunotherapy plus chemotherapy groups (Immunotherapy group, N=22 cases). There were no significant differences between these groups in sex, age, body mass index, diabetes, tumor location, pathological type, Lauren classification, tumor differentiation, pretreatment depth of invasion by primary tumor, pretreatment lymph node stage, pretreatment clinical stage, mismatch repair protein status, number of preoperative treatment cycles, or duration of preoperative treatment (all P>0.05). The primary outcome measure was postoperative lymph node downstaging. Secondary outcomes included postoperative depth of invasion by tumor, number of lymph nodes examined, and factors affecting residual lymph node metastasis status. Results:Lymph node downstaging was achieved significantly more often in the Immunotherapy group than the Chemotherapy group (pN0: 90.9% [20/22] vs. 61.1% [22/36]; pN1: 4.5% [1/22] vs. 36.1% [13/36]; pN2: 4.5% [1/22) vs. 0; pN3: 0 vs. 2.8% [1/36], Z=-2.315, P=0.021). There were no significant difference between the two groups in number of lymph nodes examined (40.5±16.3 vs. 40.8±17.5, t=0.076, P=0.940) or postoperative depth of invasion by primary tumor (pT1a: 50.0% [11/22] vs. 30.6% [11/36]; pT1b: 13.6% [3/22] vs. 19.4% [7/36]; pT2: 13.6% [3/22] vs. 13.9% [5/36]; pT3: 13.6% [3/22] vs. 25.0% [9/36]; pT4a: 9.1% [2/22] vs. 11.1% [4/36], Z=-1.331, P=0.183). Univariate analysis revealed that both preoperative treatment regimens were associated with residual lymph node metastasis status in patients whose primary tumor regression was TRG1 (χ 2=6.070, P=0.014). Multivariate analysis incorporated the following factors: pretreatment depth of invasion by primary tumor, pretreatment lymph node stage, pretreatment clinical stage, number of preoperative treatment cycles, and preoperative treatment duration. We found that a combination of immunotherapy and chemotherapy administered preoperatively was an independent protective factor for reducing residual lymph node metastases in study patients whose primary tumor regression was TRG1 (OR=0.147, 95%CI: 0.026–0.828, P=0.030). Conclusion:Compared with preoperative chemotherapy alone, a combination of preoperative immunotherapy and chemotherapy achieved greater reduction of residual lymph node metastases in the study patients who achieved TRG1 tumor regression in their primary lesions.
2.Effect of preoperative immune checkpoint inhibitors on reducing residual lymph node metastases in patients with gastric cancer: a retrospective study
Xinhua CHEN ; Hexin LIN ; Yuehong CHEN ; Xiaodong WANG ; Chaoqun LIU ; Huilin HUANG ; Huayuan LIANG ; Huimin ZHANG ; Fengping LI ; Hao LIU ; Yanfeng HU ; Guoxin LI ; Jun YOU ; Liying ZHAO ; Jiang YU
Chinese Journal of Gastrointestinal Surgery 2024;27(7):694-701
Objective:To investigate the effect of immune checkpoint inhibitors on reducing residual lymph node metastasis in patients with gastric cancer.Methods:The cohort of this retrospective study comprised patients from Nanfang Hospital of Southern Medical University and the First Affiliated Hospital of Xiamen University who had undergone systemic treatment prior to gastrectomy with D2 lymphadenectomy and had achieved Grade 1 primary tumor regression (TRG1) from January 2014 to December 2023. After exclusion of patients who had undergone preoperative radiotherapy, data of 58 patients (Nanfang Hospital: 46; First Affiliated Hospital of Xiamen University: 12) were analyzed. These patients were allocated to preoperative chemotherapy (Chemotherapy group, N=36 cases) and preoperative immunotherapy plus chemotherapy groups (Immunotherapy group, N=22 cases). There were no significant differences between these groups in sex, age, body mass index, diabetes, tumor location, pathological type, Lauren classification, tumor differentiation, pretreatment depth of invasion by primary tumor, pretreatment lymph node stage, pretreatment clinical stage, mismatch repair protein status, number of preoperative treatment cycles, or duration of preoperative treatment (all P>0.05). The primary outcome measure was postoperative lymph node downstaging. Secondary outcomes included postoperative depth of invasion by tumor, number of lymph nodes examined, and factors affecting residual lymph node metastasis status. Results:Lymph node downstaging was achieved significantly more often in the Immunotherapy group than the Chemotherapy group (pN0: 90.9% [20/22] vs. 61.1% [22/36]; pN1: 4.5% [1/22] vs. 36.1% [13/36]; pN2: 4.5% [1/22) vs. 0; pN3: 0 vs. 2.8% [1/36], Z=-2.315, P=0.021). There were no significant difference between the two groups in number of lymph nodes examined (40.5±16.3 vs. 40.8±17.5, t=0.076, P=0.940) or postoperative depth of invasion by primary tumor (pT1a: 50.0% [11/22] vs. 30.6% [11/36]; pT1b: 13.6% [3/22] vs. 19.4% [7/36]; pT2: 13.6% [3/22] vs. 13.9% [5/36]; pT3: 13.6% [3/22] vs. 25.0% [9/36]; pT4a: 9.1% [2/22] vs. 11.1% [4/36], Z=-1.331, P=0.183). Univariate analysis revealed that both preoperative treatment regimens were associated with residual lymph node metastasis status in patients whose primary tumor regression was TRG1 (χ 2=6.070, P=0.014). Multivariate analysis incorporated the following factors: pretreatment depth of invasion by primary tumor, pretreatment lymph node stage, pretreatment clinical stage, number of preoperative treatment cycles, and preoperative treatment duration. We found that a combination of immunotherapy and chemotherapy administered preoperatively was an independent protective factor for reducing residual lymph node metastases in study patients whose primary tumor regression was TRG1 (OR=0.147, 95%CI: 0.026–0.828, P=0.030). Conclusion:Compared with preoperative chemotherapy alone, a combination of preoperative immunotherapy and chemotherapy achieved greater reduction of residual lymph node metastases in the study patients who achieved TRG1 tumor regression in their primary lesions.
3.Diabetes mellitus promoted lymph node metastasis in gastric cancer: a 15-year single-institution experience
Xinhua CHEN ; Yuehong CHEN ; Tao LI ; Weiqi LIANG ; Huilin HUANG ; Hongtao SU ; Chuyang SUI ; Yanfeng HU ; Hao CHEN ; Tian LIN ; Tao CHEN ; Liying ZHAO ; Hao LIU ; Guoxin LI ; Jiang YU
Chinese Medical Journal 2022;135(8):950-961
Background::Previous studies have revealed that diabetes mellitus (DM) promotes disease progress of gastric cancer (GC). This study aimed to further investigating whether DM advanced lymph nodes (LNs) metastasis in GC.Methods::The clinicopathologic data of GC patients with >15 examined LN (ELN) between October 2004 and December 2019 from a prospectively maintained database were included. The observational outcomes included the number (N3b status) and anatomical distribution (N3 stations) of metastatic LN (MLN).Results::A total of 2142 eligible patients were included in the study between October 2004 and December 2019. N3 stations metastasis (26.8% in DM vs. 19.3% in non-DM, P = 0.026) and N3b status (18.8% in DM vs. 12.8% in non-DM, P = 0.039) were more advanced in the DM group, and multivariate logistic regression analyses confirmed that DM was an independent factor of developing N3 stations metastasis (odds ratio [OR] = 1.771, P= 0.011) and N3b status (OR= 1.752, P= 0.028). Also, multivariate analyses determined DM was independently associated with more MLN (β = 1.424, P = 0.047). The preponderance of N3 stations metastasis (DM vs. non-DM, T1-2: 2.2% vs. 4.9%, T3: 29.0% vs. 20.3%, T4a: 38.9% vs. 25.8%, T4b: 50.0% vs. 36.6%; ELN16-29: 8.6% vs. 10.4%, ELN30-44: 27.9% vs. 20.5%, ELN ≥ 45: 37.7% vs. 25.3%), N3b status (DM vs. non-DM, T1-2: 0% vs. 1.7%, T3: 16.1% vs. 5.1%, T4a: 27.8% vs. 19.1%, T4b: 44.0% vs. 28.0%; ELN16-29: 8.6% vs. 7.9%, ELN30-44: 18.0% vs. 11.8%, ELN ≥ 45: 26.4% vs. 17.3%), and the number of MLN (DM vs. non-DM, T1-2: 0.4 vs. 1.1, T3: 8.6 vs. 5.2, T4a: 9.7 vs. 8.6, T4b: 17.0 vs. 12.8; ELN16-29: 3.6 vs. 4.6, ELN30-44: 5.8 vs. 5.5, ELN ≥ 45: 12.0 vs. 7.7) of DM group increased with the advancement of primary tumor depth stage and raising of ELN. Conclusions::DM was an independent risk factor for promoting LN metastasis. The preponderance of LN involvement in the DM group was aggravated with the advancement of tumor depth.
4.Effects and Mechanism of Qiwei Qinggan Powder on Hepatic Fibrosis Based on Proteomics
Jie LIANG ; MENGGENSILIMU ; Yuxin YAN ; Rong JIN ; Xiaomei BAO ; Lijie MA ; NARISU ; Xiaoli SU ; Minqi XIE ; Yuehong MA
China Pharmacy 2020;31(11):1294-1302
OBJECTIVE:To investigate the anti- hepatic fibrosis (HF)effects of Qiwei qinggan powder and explore its possible mechanism. METHODS :Male Wistar rats were randomly divided into blank group ,HF model group ,Qiwei qinggan powder low-dose,medium-dose and high-dose groups [ 135,270,405 mg/(kg·d),by total amount of crude drugs] ,with 12 rats in each group. Except for blank group ,other groups were given 50% CCl4-peanut oil solution intragastrically (2 mL/kg,twice a week ,for consecutive 8 weeks) to induce HF model. At same time , blank group and model group were given constant volume of 0.5% CMC-Na solution intragastrically ;administration groups were given relevant medicine intragastrically ,once a day ,for consecutive 8 weeks. General situation of rats were observedand liver morphology was observed after last administration and hepatic indexes were detected. The contents of liverfunction indexes (ALT,AST,ALP,HYP)in serum and the expression of α-SMA in hepatic tissue were determined , and HE and Masson staining were performed to observe the histopathology. Using the difference multiple of expression quantity as the index ,TMT technology was used to screen the differentially expressed protein in medicine group (combining the liver tissue samples of Qiwei qinggan powder groups )and HF model group. Uniprot-GOA database and KAAS ,KEGG mapper online tools were used to analyze GO and KEGG pathway enrichment. RESULTS :The rats in the blank group were in good health ;the liver was bright red and smooth ,the liver lobules were intact ,no degeneration and necrosis ,inflammatory cell infiltration or fibrous tissue proliferation was found. Compared with blank group ,the rats in HF model group had poor diet ,depressed spirit ,disordered and lusterless fur ;the liver was dark red or yellow with rough surface ,hard texture ,inflammatory cell infiltration ,fiber tissue destruction ,bridge connection and so on ;the hepatic index ,the contents of liver function indexes and the expression of α-SMA were increased significantly (P<0.05). Compared with HF model group ,above symptoms of rats were improved to different extent in different dose groups of Qiwei qinggan powder ;hepatic index in Qiwei qinggan powder low-dose group ,the content of ALP in high-dose group ,the contents of ALT,AST and HYP and the expression of α-SMA in different dose groups were decreased significantly (P<0.05). A total of 42 differentially expressed proteins related to HF were screened ,of which 15 were up-regulated and 27 were down-regulated in expression,including fatty acid binding protein 4(FABP4),cholesterol 7α-hydroxylase(CYP7A1). The results of enrichment analysis showed that the differentially expressed proteins were mainly enriched in extracellular space ,blood particles and other cell parts,involving the molecular functions of oxidoreductase activity and fatty acid binding ,the biological processes of the regulation of heterotypic cell adhesion ,protein activation cascade ,as well as retinol metabolism ,arachidonic acid metabolism ,PPAR and other signal pathway. CONCLUSIONS :Qiwei qinggan powder can reduce the hepatic index ,ALT,AST,ALP and HYP contents in serum ,down-regulate the expression of α-SMA,improve the degree of inflammation and fibrosis of liver tissue ,and have a certain protective effect on rats. The anti-HF mechanism of it involves multiple targets and signal pathways ,such as FABP 4, CYP7A1 and PPAR.
5.Change of Serum Angiopoietin-like Protein 2 and Its Significance in Patients with Arteriosclerotic Occlusion.
Yue LIANG ; Hao NIE ; Hualiang REN ; Fangda LI ; Cui TIAN ; Huihua LI ; Yuehong ZHENG
Acta Academiae Medicinae Sinicae 2017;39(2):188-195
Objective To investigated the changes of angiopoietin-like protein 2(Angptl2) in patients with arteriosclerotic occlusion (ASO). Methods A total of 140 subjects including 75 ASO patients (ASO group) and 65 healthy subjects (control group) were enrolled in this study. Angptl2 and adiponectin were evaluated by using enzyme-linked immunosorbent assay. Biochemical data and high sensitive C reactive protein were measured and recorded as well. Results Compared to the control group,the ASO group presented with significantly higher level of plasma Angptl2 [(13.55±9.17) μg/L vs. (9.04±4.79) μg/L,P=0.010]. Plasma Angptl2 level of critical limb ischemia subjects was significantly higher than that of intermittent claudication subjects [(17.01±10.20)μg/L vs. (10.53±6.97) μg/L,P=0.003]. The best diagnostic cutoff value of Angptl2 was 13.67 μg/L,with a sensitivity of 60.34% and a specificity of 81.25%. In addition,type 2 diabetes mellitus patients with ASO exhibited significantly higher serum Angptl2 levels [(18.67±9.84)μg/L] than those without ASO [(13.01±3.47) μg/L] (P=0.021). In ASO group,serum Angptl2 levels were negatively correlated with ankle brachial index (r=-0.244,P=0.035). Conclusion The plasma level of Angptl2 increases in ASO patients. Its level is remarkably increased when the disease progressions to critical limb ischemia. Angptl2 can be a potential biological marker of disease progression.
6.Research on Traditional Chinese Medicine Healthy Life-style Guiding Principles Based on Delphi Indagate
Xinyan CHEN ; Meifang LIU ; Yuehong LAI ; Jia'en LIANG ; Hai LI ; Ziyi YE ; Jiancheng TAN ; Jiawen ZHANG ; Yupeng FAN ; Yanzhao LIN
World Science and Technology-Modernization of Traditional Chinese Medicine 2017;19(9):1560-1566
Through the expert questionnaire (Delphi Indagate) to form Traditional Chinese Medicine (TCM) Healthy Lifestyle Guiding Principles.We conducted two rounds of surveys of TCM experts in the field of preventive health care on the basis of previous literature research.This study was aimed to form the framework in order to entry to the TCM Healthy Life-style Guiding Principles.The results showed that the positive coefficient of experts in two rounds of investigation were 84.31% and 100%,respectively.The authoritative decree were both more than 0.7.The expert opinion score mean median was 9.21 and 9.085.Median mean values were 7.965 and 7.925.The median scores of full marks were higher than 65.12% and 66.67%.The minimum coefficients of variation were 0.11 and 0.10.It was concluded that in the investigation and study,the enthusiasm of the experts,professional standards and credibility were high.Expert opinion is more concentrated.Expert opinion is well coordinated and gradually converges through two rounds of surveys.Through the Delphi indagate,the basic framework and items of TCM guiding principles of healthy lifestyle were established,which laid the foundation for further standardizing the guiding principles of TCM in healthy lifestyle.
7.Lumbar interbody fusion with porous biphasic calcium phosphate enhanced by recombinant human bone morphogenetic protein-2/silk fibroin sustained-release microsphere in a sheep model
Hailong LIU ; Liang CHEN ; Yong GU ; Chunzeng WANG ; Yuehong LIU
Chinese Journal of Tissue Engineering Research 2017;21(26):4178-4184
BACKGROUND: The authors have studied the porosity, pore size, mechanical strength, in vitro biological activity,ectopic osteogenic activity of porous biphasic calcium phosphate enhanced by recombinant bone morphogenetic protein-2/silk fibroin sustained-release microsphere (BCP/rBMP-2/SF). However, further investigation on the osteogenic ability of the composite bone graft material is warranted based on a reliable animal model, which will provide experimental data for the clinical application of the composite material in the spinal fusion.OBJECTIVE: To investigate the osteogenic efficacy of BCP/rBMP-2/SF in a sheep lumbar interbody fusion model.METHODS: Sixteen healthy adult sheep were divided into two groups randomly. All sheep were operated on the left extraperitoneal approach and intervertebral discs of L1/2, L3/4, and L5/6 were exposed respectively. Three of the following four materials were randomly implanted into the L1/2, L3/4, and L5/6 of each animal: autologous iliac, BCP/rhBMP-2/SF,BCP/rhBMP-2 or BCP/SF.RESULTS AND CONCLUSION: The group of BCP/SF/rhBMP-2 achieved a similar fusion rate compared with the group of autologous iliac at 12 and 24 weeks after operation, and they were significantly better than the other two groups. These findings indicate that the novel new artificial bone, BCP/rhBMP-2/SF, can obtain similar lumbar fusion results compared with the autologous iliac. It is expected to be applied to clinical practice in the future by further improving its properties.
8."One of the Series of ""Life Dignity"": What is ""Human Dignity"""
Xinqing ZHANG ; Yuehong HAN ; Yongfu CAO ; Miao HE ; Fuling WANG ; Li LIANG
Chinese Medical Ethics 2017;30(2):151-157
9.Genetic analysis and prenatal diagnosis for patients with non-syndromic hearing impairment
Yuehong LIANG ; Chenchun REN ; Wenjing WANG ; Haixia ZHANG ; Weiwei YANG ; Deming LI ; Yuexiang ZHANG
Tianjin Medical Journal 2017;45(9):953-957
Objective To explore the genetic pathogen of patients with non-syndromic hearing impairment and to provide prenatal diagnosis for the families of hereditary deafness. Methods Mutation screening of GJB2, SLC26A4, GJB3 and mitochondrial 12 S rRNA genes was performed in 208 patients with non-syndromic hearing impairment by gene chip. Then direct sequencing was used in 41 patients who were found one mutation of GJB2 or SLC26A4 gene. And prenatal diagnosis was carried out in two families by direct sequencing. Results Eighty-six patients (41.35%) were found at least one mutation by gene chip. Among them, 40 patients were found to carry two mutations and 46 patients were found to carry one mutation. The most frequent mutation was 235delC, which was found in 46 patients. And 12 cases were found the second mutation through direct sequencing. A total of 52 (25.00%) patients were detected two mutations. Prenatal diagnosis showed that one fetus carried compound mutations of 299-300delAT and 235delC, and another one carried heterozygous mutation of IVS7-2A>G. Conclusion Patients with non-syndromic hearing impairment can be accurately diagnosed by gene chip and Sanger sequencing. The prenatal diagnosis is primary means for high-risk fetuses.
10.Outcomes of pregnancy among women with alpha-thalassemia minor: A retrospective study of Pingguo county in Guangxi Zhuang Autonomous Region
Ting PANG ; Xuefeng GUO ; Yuehong ZHOU ; Xiaoqiang QIU ; Shu LI ; Zerui LIANG ; Xiaoling QIN ; Kehua LI ; Xiaoyun ZENG
Chinese Journal of Epidemiology 2017;38(12):1620-1623
Objective To investigate the association between the value of α-thalassemia minor and the outcomes in pregnant women.Methods A total of 445 pregnant women with α-thalassemia minor were selected as thalassemia group in the Pingguo County Maternal and Child Health Hospital of Guangxi from January 2011 to December 2015,with ratio of 1 ∶ 4 healthy pregnant women was randomly recruited as non-thalassemia group.Clinical characteristics and pregnancy outcomes of the two groups were retrospectively analyzed using methods including t test,x2 test,and logistic regression model and ROC curve.Results There were no significant differences noticed in factors as age,BMI,gestational age and educational level of the two groups.Hemoglobin of the thalassemia group was significantly lower than that of the non-thalassemia group (P<0.001).Differences on parity,ethnicities or occupation were statistically significant.Results from univariate analysis showed that the proportions of low birth weight,small for date infant and 1 min Apgar score <7 were higher in the thalassemia group,but the ratio of adverse pregnancy outcomes was comparable on parameters as preterm birth,stillbirth,macrosomia.Findings from the unconditional logistic regression showed that pregnancy complicated with α-thalassemia minor appeared a risk for both newboms with low birth weight (aOR=2.29,95%CI:1.32-3.95) and small for date infant (aOR=2.11,95% CI:1.16-3.84).The ROC curve showed that α-thalassemia minor combined with multiple indicators presented a certain predictive value on neonatal birth weight.Conclusion Pregnancy complicated with α-thalassemia minor was likely to increase the risk of birth weight loss in newborns,suggesting that prenatal care for pregnant women with thalassemia be strengthened,in order to reduce the incidence of adverse pregnancy outcomes.

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