1.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.
2.Honey-processed Hedysari Radix in treatment of spleen-Qi deficiency rats based on metabonomics of the cecum contents
Yu-Jing SUN ; Qin-Jie SONG ; Yan-Jun WANG ; Tian-Tian BIAN ; Yu-Gui ZHANG ; Xian-Wei LI ; Guo-Feng LI ; Yue-Feng LI
The Chinese Journal of Clinical Pharmacology 2024;40(4):584-588
Objective To find potential biomarkers and analyzing metabolic pathways of the treatment by honey-processed Hedysari Radix,the cecal contents of rats with spleen-Qi deficiency were used as samples for analysis.Methods Sixty male SD rats were randomly divided into blank,model,experimental and control groups.The rats in other groups except the control group were carried out by using the three-factor compound modeling method of bitter-cold diarrhea,excessive exertion and hunger and satiety disorders.Experimental group was given 12.60 g·kg-1 honey-processed Hedysari Radix;control group was given 0.63 g·kg-1 lactobacillus bifidum triplex tabletsa;control and model groups received with equal volume of distilled water for a total of 15 days.Measure body weight,anal temperature,immune organ index of rats.Ultra-pressure liquid chromatography-quadrupole-exactive-mass spectrometry technology was used to measure the levels of endogenous metabolites in cecum contents.Orthogonal partial least squares discriminant analysis and database"Kyoto Encyclopedia of Genes and Genomes"were used to identify potential differential metabolites and possible metabolic pathways.Results After the intervention,the average body weight of the experimental,control,model and blank groups was(216.87±7.85),(210.96±9.03),(159.47±5.18)and(293.51±22.98)g;anal temperature was(36.14±0.48),(35.40±0.64),(34.50±0.78)and(36.61±0.34)℃;the thymus indexes were(1.19±0.20),(1.24±0.25),(0.47±0.15)and(1.31±0.21)mg·g-1;the spleen indexes were(1.95±0.33),(2.18±0.28),(1.61±0.27)and(2.29±0.24)mg·g-1.Compared with the model group,the above indexes of the experimental group and the control group were significantly increased(all P<0.01).A total of 14 potential biomarkers of Honey-processed Hedysari Radix in treating spleen-Qi deficiency syndrome were screened out in this study,which mainly involved amino acid metabolism such as tryptophan and glutamate,riboflavin metabolism and adenosine 5'-monophosphate-activated protein kinase metabolism.Conclusion Honey-processed Hedysari Radix can further protect the intestinal mucosal barrier and reduce the intestinal inflammatory response by improving the metabolic level of cecum contents in rats with spleen-Qi deficiency in cecum contents,thus exerting the effect of strengthening the spleen and tonifying the Qi.
3.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.
4.Correlation of CD200-CD200R axis and diseases and its research progress
Han XU ; Yu-xin BI ; Gui-xia LI ; Jian LI ; Liu-li WANG ; Rui-jia HAO ; Xue-min ZHENG ; Rui-jing HUANG ; Jin HAN ; Fei LI ; Gen-bei WANG
Acta Pharmaceutica Sinica 2024;59(4):822-830
CD200 and its receptor CD200R constitute an endogenous inhibitory signal. The binding of CD200 and CD200R can regulate the immune response to pathogenic stimuli, which has received much attention in recent years. It has been found that CD200-CD200R is involved in the regulation of many kinds of pathological inflammation, including autoimmune diseases, cardiac cerebrovascular disease, infection and tumor. This paper reviews the protein structure, distribution, expression, biological function of CD200-CD200R and the correlation with diseases, and analyses the current status and development ideas of CD200-CD200R as drug targets. It aims to provide theoretical support for new drug research and development based on this target.
5.Correlation analysis of miR-4500,NGF expressions with preoperative magnetic resonance signs in breast cancer
Fan YANG ; Jing CHEN ; Bin ZHENG ; Jiao-Jiao LI ; Li ZHANG ; Gui-Feng BIAN ; Ya-Jing BIAN ; Xiao-Yan LANG
Journal of Regional Anatomy and Operative Surgery 2024;33(1):47-50
Objective To analyze the correlations of the expressions of miR-4500 and nerve growth factor(NGF)in breast cancer patients with preoperative magnetic resonance(MR)signs.Methods A total of 105 patients with breast cancer admitted to our hospital were selected,the mRNA expression levels of miR-4500 and NGF in breast cancer tissues and adjacent tissues of patients were detected by qRT-PCR,and the positive expression rates of NGF in breast cancer tissues and adjacent tissues were determined by immunohistochemistry method.The correlations of the expressions of miR-4500 and NGF in breast cancer tissues with clinicopathological features and MR signs of patients were analyzed.The targeting relationship between miR-4500 and NGF was predicted by the bioinformatics website,and the correla-tion between the expressions of the two was analyzed.Results Compared with the adjacent tissues,the expression level of miR-4500 in breast cancer tissue decreased(P<0.05),while the level of NGF mRNA and the positive expression rate of NGF increased(P<0.05).There was no significant difference in age,pathological type,tumor classification,parenchymal background,apparent diffusion coefficient or enhancement curve among different expressions of miR-4500 and NGF(P>0.05).The histological grade,lymph node metastasis,tumor diameter,tumor morphology,ring-like enhancement,and peritu-moral brain edema were related to the expressions of miR-4500 and NGF(P<0.05).The bioinformatics website prediction showed that miR-4500 and NGF had binding sites,and the expressions of miR-4500 and NGF mRNA in breast cancer tissues were negatively correlated(r=-0.576,P<0.05).Conclusion The expression of miR-4500 in breast cancer tissue is low,and the expression of NGF is high,which are correlated with the preoperative MR signs in patients,providing a molecu-lar basis for MR signs.
6. The neuroprotective effects of Herba siegesbeckiae extract on cerebral ischemia/reperfusion in rats
Hui-Ling WU ; Qing-Qing WU ; Jing-Quan CHEN ; Bin-Bin ZHOU ; Zheng-Shuang YU ; Ze-Lin YANG ; Wen-Fang LAI ; Gui-Zhu HONG
Chinese Pharmacological Bulletin 2024;40(1):70-75
Aim To study the neuroprotective effects of Herba siegesbeckiae extract on cerebral ischemia/ reperfusion rats and its mechanism. Methods Sixty SD rats were randomly divided into model group, low, middle and high dose groups of Herba siegesbeckiae, and Sham operation group, and the drug was given continuously for seven days. The degree of neurologic impairment was evaluated by mNSS, and the infarct volume was measured by MRI. The number of Nissl-posi- tive cells was detected by Nissl staining, and the apop- tosis was accessed by Tunel staining. Furthermore, the expression of Bax, Bcl-2 and NeuN was observed by Western blot, and the expression of NeuN was detected by immunofluorescence staining. The expression of IL- 1β, TNF-α and IL-6 mRNA was performed by RT- qPCR. Results The mNSS score and the volume of ischemic cerebral infarction in the model group were significantly increased, and Herba siegesbeckiae extract treatment significantly decreased the mNSS score and infarct volume (P<0.05, P<0.01). Herba siegesbeckiae extract could increase the number of Nissl-pos- itive cells and the expression of NeuN (P<0.01), and reduce the number of Tunel-positive cells (P<0.01). Western blot showed that Herba siegesbeckiae extract inhibited the expression of Bax, increased Bcl-2 and NeuN in ischemic brain tissue (P<0.01). RT-qPCR showed that Herba siegesbeckiae extract inhibited the expression of IL-1 β, TNF-α and IL-6 mRNA in the is-chemic brain tissue (P<0.01). Conclusions Herba siegesbeckiae extract can reduce the cerebral infarction volume, improve the neurological function damage, inhibit the apoptosis of nerve cells and the expression of inflammatory factors and promote the expression of NeuN, there by exerting protective effects on MCAO rats.
7.Development of a national health standard:Guideline for pediatric transfusion
Rong HUANG ; Qingnan HE ; Mingyan HEI ; Minghua YANG ; Xiaofan ZHU ; Jun LU ; Xiaojun XU ; Tian-Ming YUAN ; Rong ZHANG ; Xu WANG ; Jinping LIU ; Jing WANG ; Zhili SHAO ; Mingyi ZHAO ; Jia GUO ; Xiny-In WU ; Jiarui CHEN ; Qirong CHEN ; Rong GUI ; Yongjian GUO
Chinese Journal of Blood Transfusion 2024;37(7):839-844
Children and adults differ significantly in physiology,biochemistry and immune function,which leads to sig-nificant differences in blood transfusion strategies between children and adults.To guide the clinical transfusion practice of pediatric patients and improve the prognosis of children,the National Health Commission organized the formulation and re-lease of the health industry standard Guideline for Pediatric Transfusion(WS/T 795-2022).This paper will briefly introduce some concepts that help understand of the Standard and the preparation process of the Standard,and explain and interpret the preparation of the"scope","general provisions"and"factors to consider"of the Standard,hoping to contribute to the understanding and implementation of the Standard.
8.IgG4-related hepatic inflammatory pseudotumor complicated with hepatic tissue infection:a case report and literature review
Si-Min LIAO ; Gui LUO ; Jing-Yu JIN ; Qian-Qian ZHAO ; Jian ZHU ; Jiang-Lin ZHANG ; Zheng ZHAO
Medical Journal of Chinese People's Liberation Army 2024;49(7):783-789
Objective To report the clinical and imaging characteristics of a case with the clinical manifestation of multiple lung and liver nodules,diagnosed as IgG4-related hepatic inflammatory pseudotumor(HIPT)complicated by hepatic tissue-infection,and review the literature in order to facilitate clinical diagnosis and differential identification of IgG4-related HIPT.Methods A retrospective analysis was conducted on the medical records of a patient with IgG4-related disease(IgG4-RD)characterized by multiple lung and liver nodules.A literature review was performed by searching Chinese and English databases to summarize the clinical and imaging characteristics of IgG4-related HIPT and hepatic tissue infection.Results The case involved a 64-year-old female admitted to the Rheumatology and Immunology Department of the First Medical Center of Chinese PLA General Hospital due to"poor appetite and fatigue for over a year,and dry cough for four months".She presented with multiple nodules in the lungs and liver,without involvement of the eyelids,salivary glands,submandibular glands,or pancreas.Laboratory test results revealed elevated serum IgG4 levels at 14.1 g/L and C-reactive protein(CRP)at 82.1 mg/L.Pulmonary CT scans indicated multiple solid nodules in both lungs with clear boundaries.Abdominal contrast-enhanced MRI revealed a nodule in liver segment S7 with a pseudocapsule around it,clear boundaries,and uniform enhancement;another nodule in liver segment S5 with blurred boundaries and ring enhancement.The final diagnosis of the liver nodules was confirmed by pathological and metagenomic sequencing to be an IgG4-related HIPT in segment S7 and hepatic tissue infection in segment S5.After a full course of anti-infection and treatment with methylprednisolone and leflunomide,follow-up imaging showed near-complete resolution of the lung and liver nodules.Literatures were searched in China National Knowledge Infrastructure(CNKI),Wanfang,and PubMed databases(up to September 2023),and no case of IgG4-RD complicated with both liver involvement and infection was found.A total of 26 cases of IgG4-RD involving the liver have been reported so far,predominantly in males(92.3%),with an average age of 51 years.Most patients presented with abnormal liver function as the initial symptom,with normal blood inflammatory markers.Imaging typically shows a single nodule in 88.5%of cases,with clear boundaries and uniform enhancement,as well as ring enhancement.Concurrent involvement of the pancreas and biliary tract is common.Pathology is the gold standard for confirming the disease.Conclusions This case reports coexistence of IgG4-related HIPT and infection within multiple hepatic nodules.In the diagnosis and treatment of patients with IgG4-RD presenting with multiple hepatic nodules,if the imaging characteristics of the nodules are inconsistent,it is necessary to consider the possibility of the underlying disease coexisting with other conditions,which can be easily misdiagnosed.Actively obtaining pathological tissue is crucial for aiding in the definitive diagnosis.
9.A case of new mutation of NIPBL gene found by prenatal diagnosis
Tingting GUO ; Ziyin CHANG ; Huan LOU ; Xinmeng YANG ; Jing GUI ; Xiaofeng YANG
Chinese Journal of Clinical Laboratory Science 2024;42(9):702-706
Objective To analyze the genetic etiology of a fetus with growth restriction,short long bones,small head circumference and enhanced kidney echoes,and explore the clinical significance of nonsense mutations in the NIPBL gene.Methods The clinical data of the fetus and his/her parents were collected.The variation sites of the NIPBL gene were verified by the chromosome karyotype a-nalysis of amniotic fluid,copy number variation detection in the human genome(CNV-seq),whole exome sequencing(WES)and Sanger sequencing.The databases such as China National Knowledge Infrastructure(CNKI),Wanfang Data,Wanfang Medical,and Pubmed were searched to further analyze the relationship between clinical symptoms and gene mutation sites in the fetus.Results The sequencing results showed that there was c.4555A>T heterozygous mutation in exon 21 of the NIPBL gene in the fetus,and that the same mutation was not detected in his/her parents.The above variation had not been included in databases such as Human Exon Data-base(ExAC),1000 genomes(1000G)and Genome Aggregation Database(gnomAD),and were comprehensively judged as harmful variation.Conclusion The detection of the nonsense variation,c.4555A>T(p.Lys1519?),in the NIPBL gene may provide experi-mental evidence for the prenatal diagnosis and fertility in this family.
10.Investigation of oxidised low-density lipoprotein as a risk assessment indicator in patients with type 2 dia-betes mellitus combined with pulmonary tuberculosis
Jing GUI ; Feng WANG ; Hui YANG ; Yumao CAI ; Chuangyue HONG
The Journal of Practical Medicine 2024;40(14):1995-2002
Objective to explore the risk assessment potential of oxLDL in patients with T2DM combined with PTB.Methods A prospective study was conducted,which included 60 cases of simple hyperlipidemia,100 cases of PTB,100 cases of T2DM,and 100 cases of T2DM combined with PTB.These patients visited the outpatient department of our center from June 2022 to June 2023.The PTB group,T2DM group,and T2DM combined with PTB group were further divided into subgroups based on normal blood lipids(40 cases)and hyperlipidemia(60 cases),totaling 360 cases in the case group.Additionally,a control group consisting of 60 healthy individuals was included.The age range for inclusion in the study was between 35 to70 years old.Venous blood samples were collected from each group to detect HbA1c,INS,FSG,CHOL,TG,HDL,LDL,ApoA I and Apo B.OxLDL levels were measured using the ELISA method.Differences in levels between groups were compared.Multivariate logistic regression analysis was applied to assess the association between oxLDL levels and PTB as well as T2DM combined with PTB.Results There were no statistically significant differences in BMI,blood sugar,blood lipids,and insulin resis-tance between the T2DM hyperlipidemia subgroup and the T2DM combined with PTB hyperlipidemia subgroup.The oxLDL level in the T2DM hypertipidemia subgroup was more than double that of the control group,while the oxLDL level in the subgroup with normal blood lipids was significantly higher than that of the control group.Moreover,both the T2DM combined with PTB hyperlipidemia subgroup and simple hyperlipidemia group exhibited significantly elevated levels of oxLDL compared to the control group;however,there were no statistically significant differences when compared to the PTB hyperlipidemia subgroup.Correlation analysis revealed a significant positive linear corre-lation between TG and LDL with oxLDL in both the T2DM hyperlipidemia subgroup and the T2DM combined with PTB hyperlipidemia subgroup(R=0.352,P<0.05).Additionally,CHOL and LDL levels in the PTB hyperlipid-emia subgroup also showed a significant positive correlation with oxLDL(R=0.441,P<0.05).Multivariate logistic regression analysis indicated that having oxLDL levels more than double that of the control group was an independent risk factor for both PTB and T2DM combined with PTB(P<0.05).Conclusion The significantly elevated levels of oxLDL may serve as a potential risk factor for the comorbidity of T2DM and PTB.It is recommended to consider oxLDL levels exceeding twice those of the control group as a clinically meaningful pathological threshold for further assessment.

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