1.Clinical characteristics and prognostic factors of young patients with sporadic rectal cancer liver metastasis
Yu GUAN ; Lei YANG ; Shi-Ru JIANG ; Wei-Dong DOU ; Jin-Gui WANG ; Shan-Wen CHEN ; Zhan-Bing LIU ; Ying-Chao WU
Medical Journal of Chinese People's Liberation Army 2024;49(1):23-30
Objective To identify the clinical characteristics and prognostic factors of young patients with sporadic rectal cancer liver metastasis(RCLM).Methods The clinical data of young RCLM patients at 45 years or under(n=40,as younger patient group)in Peking University First Hospital from January 2016 to January 2021 were reviewed,meanwhile,elder RCLM patient group were comprised of 82 patients older than 45-year-old in a 1:2 ratio.Proportions of categorical variables were compared between young patients and old patients.The clinicopathologic parameters were analyzed with univariate and multivariate Cox regression models and Kaplan-Meier method for demonstrating survival differences between the maximum diameter of liver metastasis and local therapy.Results One hundred and twenty-two RCLM patients were identified,the 1-,3-and 5-year survival rates of young patient group were 97.5%,47.5%,15.0%,those of elder patient group were 84.1%,26.8%,9.8%,respectively.The differences in BMI(P=0.008),primary tumor with obstruction and bleeding(P=0.006),synchronous rectal cancer liver metastases(P=0.005),the maximum diameter of liver metastasis>3 cm(P=0.019)were statistically significant between the two groups.And univariate and multivariate analyses showed that age(P=0.003),N stage(P=0.007),local therapy for liver metastases(P=0.047)and the maximum diameter of liver metastasis(P=0.030)were independent risk factors for influencing the prognosis of RCLM patients;curative resection or not of primary tumor(P=0.035)and the maximum diameter of liver metastasis(P=0.041)were independent risk factors for influencing the prognosis of young RCLM patients.Kaplan-Maier curve demonstrated survival differences between the maximum diameter of liver metastasis and local therapy for liver metastasis in RCLM patients(log-rank P=0.000).Conclusions Although with later staging of initial tumor station,young RCLM patients may obtain better survival benefit compared with old patients.Higher degree of lymph node metastasis,local therapy for liver metastases and the maximum diameter of liver metastasis>3 cm indicates poor prognosis in RCLM patients,and without curative resection of primary tumor and maximum diameter of liver metastasis are also considered as the independent poor prognostic factors of young RCLM patients.Local therapy for liver metastases appears to play an important role in the treatment strategy of RCLM patients.
2.Allergy Associated With N-glycans on Glycoprotein Allergens
Yu-Xin ZHANG ; Rui-Jie LIU ; Shao-Xing ZHANG ; Shu-Ying YUAN ; Yan-Wen CHEN ; Yi-Lin YE ; Qian-Ge LIN ; Xin-Rong LU ; Yong-Liang TONG ; Li CHEN ; Gui-Qin SUN
Progress in Biochemistry and Biophysics 2024;51(5):1023-1033
Protein as the allergens could lead to allergy. In addition, a widespread class of allergens were known as glycans of N-glycoprotein. N-glycoprotein contained oligosaccharide linked by covalent bonds with protein. Recently,studies implicated that allergy was associated with glycans of heterologous N-glycoprotein found in food, inhalants, insect toxins, etc. The N-glycan structure of N-glycoprotein allergen has exerted an influence on the binding between allergens and IgE, while the recognition and presentation of allergens by antigen-presenting cells (APCs) were also affected. Some researches showed thatN-glycan structure of allergen was remodeled by N-glycosidase, such as cFase I, gpcXylase, as binding of allergen and IgE partly decreased. Thus, allergic problems caused by N-glycoproteins could potentially be solved by modifying or altering the structure ofN-glycoprotein allergens, addressing the root of the issue. Mechanism of N-glycans associated allergy could also be elaborated through glycosylation enzymes, alterations of host glycosylation. This article hopes to provide a separate insight for glycoimmunology perspective, and an alternative strategy for clinical prevention or therapy of allergic diseases.
3.Clinical trial of pegylated losenatide in the treatment of obese patients with type 2 diabetes mellitus undergoing axial gastrectomy
Jing-Feng GU ; Hai-Xia LIU ; Feng FENG ; Jian ZHANG ; Dong-Yang XING ; Hao-Wen GAO ; Gui-Qi WANG
The Chinese Journal of Clinical Pharmacology 2024;40(3):330-334
Objective To observe the effects of pegylated losenatide injection combined with metformin tablets on serum metabolism,lipid levels and intestinal flora in obese type 2 diabetes mellitus(T2DM)patients after axial gastrectomy.Methods Obese T2DM patients who underwent axial gastrectomy were divided into treatment group and control group by cohort methods.The control group was treated with metformin hydrochloride tablet 0.5 g orally,tid.The treatment group was treated by subcutaneous injection of pegylated losenatide injection 0.2 mg once a week on the basis of control group.Both groups were treated continuously for 3 months.Body mass index(BMI),serum metabolic indexes,blood lipid levels,blood glucose levels,intestinal flora and adverse drug reactions were compared between the two groups.Results In this study,a total of 70 subjects were included in the treatment group,and 50 subjects were included in the control group.After three months of treatment,the BMI indices of the treatment and control groups were(26.35±2.36)and(29.34±3.59)kg·m-2,respectively;the glutathione peroxidase levels were(192.42±13.18)and(134.27±12.86)U;interleukin-6 levels were(6.14±1.78)and(7.65±2.09)μg·L-1;fasting blood glucose levels were(5.36±0.41)and(7.43±0.78)mmol·L-1;total cholesterol levels were(2.55±0.67)and(3.47±0.79)mmol·L-1 for the treatment and control groups,respectively.The levels of Bifidobacteria,Bacteroides,Lactobacilli,Enterobacteria,and Enterococci in the treatment group were(8.79±1.36),(9.62±1.37),(6.74±2.15),(7.98±0.61),and(7.23±1.29)logN·g-1,respectively;in the control group,these levels were(7.98±1.79),(8.13±1.45),(5.71±2.41),(9.21±0.88),and(8.15±1.54)logN·g-1.The differences in the above indicators between the treatment and control groups were statistically significant(all P<0.05).The main adverse drug reactions in the treatment group included nausea,headache,dizziness,elevated blood pressure,and indigestion.In the control group,the main adverse drug reactions were nausea,headache,and indigestion.The total incidence of adverse drug reactions in the treatment and control groups was 8.57%and 6.00%,respectively,with no statistically significant difference(P>0.05).Conclusion Pegylated losenatide injection combined with metformin tablets has a significant effect on axial gastrectomy in obese type 2 diabetes patients.
4.Expressions of CMTM6 and RASAL2 in prostate cancer tissues and their relationship with clinicopathological features and prognosis
Taiyang LIU ; Jie LI ; Yanbing SHEN ; Qi GUI ; Xueqiang HUANG ; Xiuhua WEN
Journal of Modern Urology 2024;29(3):248-252
【Objective】 To investigate the expressions of containing CKLF like MARVEL transmembrane domain gene 6 (CMTM6) and ras protein activator like 2 (RASAL2) in prostate cancer tissues, and to analyze the relationships between the above factors and the clinicopathological characteristics and prognosis of prostate cancer patients. 【Methods】 The prostate cancer tissues and adjacent tissues of 80 prostate cancer patients admitted to Zhumadian City Center Hospital during Feb.2018 and Feb.2020 were collected.Expressions of CMTM6 and RASAL2 were detected with immunohistochemical method.The relationship between the expressions of CMTM6 and RASAL2 and the clinical pathological characteristics of prostate cancer were analyzed.The survival curve was plotted with Kaplan-Meier method.The prognostic factors were analyzed with multivariate Cox regression. 【Results】 The positive expression rate of CMTM6 in prostate cancer tissues was 67.50%, which was obviously higher than 38.75% in adjacent tissues (χ2=13.277, P<0.001).The positive expression rate of RASAL2 in prostate cancer tissues was 47.50%, which was obviously lower than 73.75% in adjacent tissues (χ2=11.546, P=0.001).The expressions of CMTM6 and RASAL2 were not related to patients’ age, tumor size and tissue differentiation (P>0.05), but to TNM staging, Gleason score, lymph node metastasis and preoperative PSA level (P<0.05).Survival curve showed that the 3-year survival rate of positive CMTM6 expression patients was 61.11% (33/54), which was obviously lower than that of negative patients, which was 88.46% (23/26) (χ2=5.940, P=0.015).The 3-year survival rate of positive RASAL2 expression patients was 81.85% (31/38), which was obviously higher than that of negative patients, which was 59.52% (25/42) (χ2=4.887, P=0.027).Cox multivariate regression showed that Gleason score, lymph node metastasis, preoperative PSA level, CMTM6, and RASAL2 were independent influencing factors of prognosis (P<0.05). 【Conclusion】 The positive expression rate of CMTM6 in prostate cancer tissues is significantly higher than that in paracancer tissues, while the positive expression rate of RASAL2 in prostate cancer tissues is significantly lower than that in paracancer tissues. Both CMTM6 and RASAL2 are closely related to the clinical pathological characteristics and prognosis of prostate cancer patients, and may provide reference for the prognosis.
5.Resveratrol protects dopaminergic neurons in a mouse model of Parkinson's disease by regulating the gut-brain axis via inhibiting the TLR4 signaling pathway
Jianjun GUI ; Xiaodong SUN ; Shu WEN ; Xin LIU ; Bingqing QIN ; Ming SANG
Journal of Southern Medical University 2024;44(2):270-279
Objective To investigate the protective effect of resveratrol on intestinal barrier in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced Parkinson's disease(PD)mouse models and its mechanism for regulating TLR4/MyD88/NF-κB signaling to protect dopaminergic neurons.Methods Fifty-two C57BL/6J mice were randomized into control group(n= 12),MPTP group(n=14),MPTP+resveratrol(30 mg/kg)group(n=13),and MPTP+resveratrol(90 mg/kg)group(n=13),and mouse models were established by intraperitoneal MPTP(30 mg/kg)injection for 7 days in the latter 3 groups.Behavioral tests were conducted to evaluate the effect of resveratrol on motor symptoms of the mice.Western blotting was used to detect the expression of TH,α-syn,ZO-1,Claudin-1,TLR4,MyD88,and NF-κB in the brain tissues of the mice.Immunohistochemistry,immunofluorescence,ELISA and transmission electron microscopy were used to verify the effect of resveratrol for suppressing inflammation and protecting the intestinal barrier.Results Compared with those in the normal control group,the mice in MPTP group showed significant changes in motor function,number of dopaminergic neurons,neuroinflammation,levels of LPS and LBP,and expressions of tight junction proteins in the intestinal barrier.Resveratrol treatment significantly improved motor function of the PD mice(P<0.01),increased the number of neurons and TH protein expression(P<0.05),down-regulated the expressions of GFAP,Iba-1,and TLR4,lowered fecal and plasma levels of LPS and LBP(P<0.05),restored the expression levels of ZO-1 and Claudin-1(P<0.01),and down-regulated the expressions of TLR4,MyD88,and NF-κB in the colon tissue(P<0.05).The mice with resveratrol treatment at 30 mg/kg showed normal morphology of the tight junction complex with neatly and tightly arranged intestinal villi.Conclusion Resveratrol repairs the intestinal barrier by inhibiting TLR4/MyD88/NF-κB signaling pathway-mediated inflammatory response,thereby improving motor function and neuropathy in mouse models of MPTP-induced PD.
6.Metabolomic Analysis of Mesenteric Lymph Fluid in Rats After Alcohol Gavage
Yuan ZHANG ; Zi-Ye MENG ; Wen-Bo LI ; Yu-Meng JING ; Gui-Chen LIU ; Zi-Yao HAO ; Xiu XU ; Zhen-Ao ZHAO
Progress in Biochemistry and Biophysics 2024;51(9):2194-2209
ObjectiveThe absorption of substances into blood is mainly dependent on the mesenteric lymphatic pathway and the portal venous pathway. The substances transported via the portal venous pathway can be metabolized by the biotransformation in the liver. On the contrary, the substances in the mesenteric lymph fluid enter the blood circulation without biotransformation and can affect the body directly. Alcohol consumption is strongly linked to global health risk. Previous reports have analyzed the changes of metabolites in plasma, serum, urine, liver and feces after alcohol consumption. Whether alcohol consumption affects the metabolites in lymph fluid is still unknown. Therefore, it is particularly important to explore the changes of substances transported via the mesenteric lymphatic pathway and analyze their harmfulness after alcohol drinking. MethodsIn this study, male Wistar rats were divided into high, medium, and low-dosage alcohol groups (receiving Chinese Baijiu at 56%, 28% and 5.6% ABV, respectively) and water groups. The experiment was conducted by alcohol gavage lasting 10 d, 10 ml·kg-1·d-1. Then mesenteric lymph fluid was collected for non-targeted metabolomic analysis by using liquid chromatography-mass spectrometry (LC-MS) and bioinformatic analysis. Principal component analysis and hierarchical clustering were performed by using Biodeep. Meanwhile, KEGG enrichment analysis of the differential metabolites was also performed by Biodeep. MetaboAnalyst was used to analyze the relationship between the differential metabolites and diseases. ResultsThe metabolites in the mesenteric lymph fluid of the high-dosage alcohol group change the most. Based on the KEGG enrichment analysis, the pathways of differential metabolites between the high-dosage alcohol group and the control group are mainly enriched in the central carbon metabolism in cancer, bile secretion, linoleic acid metabolism, biosynthesis of unsaturated fatty acids, etc. Interestingly, in the biosynthesis of unsaturated fatty acids category, the content of arachidonic acid is increased by 7.25 times, whereas the contents of palmitic acid, oleic acid, stearic acid, arachidic acid and erucic acid all decrease, indicating lipid substances in lymph fluid are absorbed selectively after alcohol intake. It’s worth noting that arachidonic acid is closely related to inflammatory response. Furthermore, the differential metabolites are mainly related with schizophrenia, Alzheimer’s disease and lung cancer. The differential metabolites between the medium-dosage alcohol and the control group were mainly enriched in phenylalanine metabolism, valine, leucine and isoleucine biosynthesis, linoleic acid metabolism and cholesterol metabolism. The differential metabolites are mainly related to schizophrenia, Alzheimer’s disease, lung cancer and Parkinson’s disease. As the dose of alcohol increases, the contents of some metabolites in lymph fluid increase, including cholesterol, L-leucine, fumaric acid and mannitol, and the number of metabolites related to schizophrenia also tends to increase, indicatingthat some metabolites absorbed by the intestine-lymphatic pathway are dose-dependent on alcohol intake. ConclusionAfter alcohol intake, the metabolites transported via the intestinal-lymphatic pathway are significantly changed, especially in the high-dosage group. Some metabolites absorbed via the intestinal-lymphatic pathway are dose-dependent on alcohol intake. Most importantly, alcohol intake may cause inflammatory response and the occurrence of neurological diseases, psychiatric diseases and cancer diseases. High-dosage drinking may aggravate or accelerate the occurrence of related diseases. These results provide new insights into the pathogenesis of alcohol-related diseases based on the intestinal-lymphatic pathway.
7.Predicting the potential suitable areas of Platycodon grandiflorum in China using the optimized Maxent model
Yu-jie ZHANG ; Han-wen YU ; Zhao-huan ZHENG ; Chao JIANG ; Juan LIU ; Liang-ping ZHA ; Xiu-lian CHI ; Shuang-ying GUI
Acta Pharmaceutica Sinica 2024;59(9):2625-2633
italic>Platycodon grandiflorum (Jacq.) A. DC is one of the most commonly used bulk medicinal herbs. It has important value in the fields of medicine, food and cosmetics, and its market demand is increasing year by year, and it has a good development prospect. In this study, based on 403 distribution records and 8 environmental variables, we used Maxent model to predict the potential distribution of
8.Clinical Observation on Shuangye San in the Treatment of Type 2 Diabetes Mellitus Complicated with Non-alcoholic Fatty Liver Disease of Spleen Deficiency and Phlegm Stasis Type
Dao-Cheng ZHOU ; Gui-Ji RUAN ; You-You SHUAI ; Wen-Hua XU ; De-Liang LIU ; Heng-Xia ZHAO ; Hui-Lin LI
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(10):2687-2694
Objective To observe the clinical efficacy of Shuangye San(the prescription mainly composed of Mori Folium and Nelumbinis Folium)in the treatment of type 2 diabetes mellitus(T2DM)complicated with non-alcoholic fatty liver disease(NAFLD)of spleen deficiency and phlegm stasis type.Methods A total of 80 patients with T2DM complicated with NAFLD of spleen deficiency and phlegm stasis type were randomly divided into a treatment group and a control group,with 40 cases in each group.The control group was treated with conventional western medicine for lowering blood glucose and lipid,protecting liver and lowering enzymes.The treatment group was treated with the granules of Shuangye San orally on the basis of treatment for the control group.The course of treatment lasted for three months.The changes of traditional Chinese medicine(TCM)syndrome scores,homeostasis model assessment of insulin resistance(HOMA-IR),fasting insulin(FINS),fasting blood glucose(FBG),2-hour postprandial blood glucose(2hPG),glycosylated hemoglobin(HbA1C),total cholesterol(TC),triglyceride(TG),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),liver function indicators and B-ultrasound grading of fatty liver in the two groups were observed before and after treatment.After treatment,the clinical efficacy and safety of the two groups were evaluated.Results(1)After three months of treatment,the total effective rate of the treatment group was 85.00%(34/40),and that of the control group was 70.00%(28/40).The intergroup comparison(tested by chi-square test)showed that the efficacy of the treatment group was significantly superior to that of the control group(P<0.01).(2)After treatment,the scores of TCM symptoms of obese physique,heaviness and weakness in the limbs,shortness of breath and unwilling to talk,tightness and stabbing pain in the chest,abdominal distension and poor appetite in the two groups were decreased compared with those before treatment(P<0.05),and the decrease of TCM syndrome scores in the treatment group was significantly superior to that in the control group(P<0.05).(3)After treatment,the levels of glucose and lipid metabolism indicators of FINS,HOMA-IR,FBG,2hPG,HbA1C,TC,TG and LDL-C in the two groups were significantly decreased compared with those before treatment(P<0.05),and the level of HDL-C was significantly increased compared with that before treatment(P<0.05).The decrease of FINS,HOMA-IR,FBG,2hPG,HbA1C,TC,TG and LDL-C levels and the increase of HDL-C levels in the treatment group were significantly superior to those in the control group(P<0.05).(4)After treatment,the levels of liver function indicators of alanine aminotransferase(ALT),aspartate aminotransferase(AST)and gamma-glutamyl transpeptidase(GGT)in the two groups were significantly decreased compared with those before treatment(P<0.05),and the decrease of liver function indicators in the treatment group was significantly superior to that in the control group(P<0.05).(5)After treatment,the B-ultrasound grading of fatty liver of the two groups was significantly improved compared with that before treatment(P<0.05),and the improvement of fatty liver B-ultrasound grading in the treatment group was significantly superior to that in the control group,and the difference was statistically significant(P<0.05).(6)During the treatment,there were no adverse reactions such as impairment of liver and kidney function and abnormalities in routine blood,urine and stool test in the two groups.Conclusion Shuangye San exerts certain effect in the treatment of T2DM complicated with NAFLD of spleen deficiency and phlegm stasis type.It can alleviate the clinical symptoms of patients,correct the disorder of glucose and lipid metabolism,and improve liver function and fatty liver B-ultrasound grading.
9.Correlation analysis between eNOS gene single nucleotide polymorphism and systemic lupus erythematosus in Hainan
Xuan ZHANG ; Hui-Tao WU ; Qi ZHANG ; Gui-Ling LIN ; Xi-Yu YIN ; Wen-Lu XU ; Zhe WANG ; Zi-Man HE ; Ying LIU ; Long MI ; Yan-Ping ZHUANG ; Ai-Min GONG
Medical Journal of Chinese People's Liberation Army 2024;49(9):986-991
Objective To investigate the relationship between single nucleotide polymorphisms(SNPs)in the eNOS gene and genetic susceptibility to systemic lupus erythematosus(SLE)in Hainan.Methods Blood samples were collected from SLE patients(SLE group,n=214)and healthy controls(control group,n=214)from January 2020 to December 2022 at the First Affiliated Hospital of Hainan Medical College and Hainan Provincial People's Hospital.The bases of eNOS gene rs3918188,rs1799983 and rs1007311 loci in each group were detected by SNaPshot sequencing technology.Logistic regression was used to analyze the correlation between genotypes,alleles and gene models(dominant model,recessive model,and overdominant model)of the above 3 target loci of the eNOS gene and genetic susceptibility to SLE.Haplotype analysis was conducted using HaploView 4.2 software to investigate the relationship between haploid and genetic susceptibility to SLE at each site.Results The results of logistic regression analysis revealed that the CC genotype and the C allele at rs3918188 locus were risk factors for genetic susceptibility to SLE(CC vs.AA:OR=2.449,P<0.05;C vs.A:OR=2.133,P<0.001).In recessive model at rs3918188 locus,CC genotype carriers had an increased risk of SLE development compared with AA+AC genotype carriers(OR=2.774,P<0.001).In contrast,in overdominant model at this locus,AC genotype carriers had a decreased risk of SLE occurrence compared with AA+CC genotype carriers(OR=0.385,P<0.001).In addition,polymorphisms of rs1799983 and rs1007311 were not associated with susceptibility to SLE in genotype,allele type and the 3 genetic models(P>0.05).Haplotype analysis revealed a strong linkage disequilibrium between the rs1007311 and rs1799983 loci of the eNOS gene,but no significant correlation was found between haplotype and genetic susceptibility to SLE(P>0.05).Conclusion The CC genotype and C allele at rs3918188 locus of eNOS gene may be risk factors for SLE in Hainan,while the risk of SLE occurrence is reduced in carriers of AC genotype under the overdominant model.
10.Morphological classification and molecular identification of Hyalomma asiaticum in parts of Xindi Township,Xinjiang
Xiao-Qing ZAN ; Qiao-Yun REN ; Jin LUO ; Yan-Long WANG ; Pei-Wen DIAO ; Li-Yan CHE ; Jian-Xun LUO ; Hong YIN ; Gui-Quan GUAN ; Guang-Yuan LIU ; Hong-Xi ZHAO
Chinese Journal of Zoonoses 2024;40(4):289-294
The purpose of this study was to identify the tick species native to Xindi Township,Yumin County,Xinjiang,China.Preliminary morphological identification of parasitic ticks collected from animals in the area was conducted with an ultra-depth of field three-dimensional VHX 600 digital stereo microscope.Total DNA of the ticks was extracted,amplified by PCR based on the COI and ITS2 gene loci,and the posi-tive PCR products were sequenced.The sequence were a-ligned with reference sequences from the NCBI database were aligned with the Basic Local Alignment Search Tool.A genet-ic phylogenetic tree was generated with the neighbor-joining method of MEGA 7.0 software to determine the evolutionary biological characteristics of ticks.Morphological identification showed that the ticks collected from Xindi Township of Yu-min County were consistent with the characteristics of Hya-lomma asiaticum.An evolutionary tree based on the COI and ITS2 gene sequences showed that the ticks collected in this study were clustered with known H.asiaticum sequences.The PCR products of COI and ITS2 were sequenced and compared,which confirmed that the collected tick species were H.asiaticum,in agreement with the morphological and molecular biological results.These findings help to clarify the distribution of ticks in Xindi Township of Xinjiang,and provide basic data for the analysis of tick genetic and evolutionary characteristics,as reference for surveillance and control of ticks in the Xinjiang Uygur Autonomous Region.

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