1.Fufang Kangjiaolv Capsules Treat Anxiety in Rat Model of Chronic Restraint Stress via Microbiota-gut-brain Axis
Wenxin FAN ; Tingyue JIANG ; Yu WANG ; Ge ZHANG ; Yifan LU ; Mengmeng LIU ; Jiayuan LI ; Renzhi MA ; Jinli SHI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(4):95-107
ObjectiveTo observe the intervention effect of Fufang Kangjiaolv capsules on anxiety-like behaviors in the rat model of chronic restraint stress (CRS) and explore the mechanism underlying the anti-anxiety effect via the microbiota-gut-brain axis. MethodsRats were assigned into blank, model, positive drug (diazepam, 1 mg·kg-1), and low-, medium-, and high-dose (0.75, 1.5, 3 g·kg-1, respectively) Fufang Kangjiaolv capsules groups. After 14 days of administration, the elevated plus maze test, open field test, light and dark box test, and marble burying test were performed. Hematoxylin-eosin staining was employed to observe the pathological changes in the hippocampus and colon of rats, and Nissl staining was conducted to observe the damage of hippocampal neurons. The gut microbiota was analyzed by 16S rRNA gene sequencing. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was employed to determine the mRNA levels of zonula occludens-1 (ZO-1) and occludin in the colon of rats. The levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) in the colon, serum, and hippocampus were determined by enzyme-linked immunosorbent assay. Western blot was employed to determine the protein levels of ZO-1, occludin, nuclear factor-κB p65 (NF-κB p65) in the colon tissue and NF-κB p65 and brain-derived neurotrophic factor (BDNF) in the hippocampal tissue. ResultsCompared with the blank group, the model group showed reductions in the time and frequency ratio of rats entering the elevated plus maze, the time and frequency of rats entering the central area of the open field, the time of entering the open box, the times of passing through the light and dark box, and the number of unburied beads (P<0.05, P<0.01). Compared with the model group, Fufang Kangjiaolv capsules ameliorated the anxiety of the model rats to varying degrees, and the high-dose group had the best effect, with increases in the proportions of time and frequency of rats entering the open arm in the elevated plus maze (P<0.05), the number of rats entering the central area in the open field (P<0.05), the time of entering the open box, the times of passing through the light and dark boxes, and the number of unburied beads (P<0.01). Moreover, the high-dose group showed alleviated pathological damage of hippocampal neurons and colon. The results of 16S rRNA gene sequencing showed that the model group had increased relative abundance of Firmicutes, Deferribacterota, Romboutsia, and Phascolarctobacterium, while it had decreased relative abundance of Bavcteroidota and Lactobacillus. The drug administration groups showed increased relative abundance of Bavcteroidota, Bacteroides, norank f norank o Clostridia UCG-014, and Blautia and decreased relative abundance of Firmicutes and Deferribacterota. Compared with the blank group, the model group showed down-regulated protein and mRNA levels of ZO-1 and occludin in the colon (P<0.01), elevated levels of TNF-α, IL-6, and IL-β in the colon, serum, and hippocampus (P<0.01), up-regulated protein level of NF-κB p65 in the colon and hippocampus (P<0.01), and down-regulated protein level of BDNF in the hippocampus (P<0.05). Compared with the model group, high-dose Fufang Kangjiaolv capsules up-regulated the mRNA levels of ZO-1 and occludin in the colon (P<0.01), lowered the levels of TNF-α, IL-6, and IL-β in the colon, serum, and hippocampus (P<0.01), up-regulated the protein levels of ZO-1 (P<0.01) and occludin (P<0.05) in the colon, down-regulated the protein level of NF-κB p65 in the colon and hippocampus (P<0.05), and up-regulated the protein level of BDNF in the hippocampus. ConclusionFufang Kangjiaolv capsules can reduce the anxiety-like behaviors in the rat model of CRS by regulating the gut microbiota disturbance, up-regulating the expression of tight junction proteins in the colon, repairing intestinal mucosal mechanical barrier, and down-regulating NF-κB/BDNF signaling pathway, thereby reducing peripheral and central inflammation. This study proves the hypothesis that Fufang Kangjiaolv capsules play an anti-anxiety role via the microbiota-gut-brain axis, providing a new idea for further research.
2.Observations of lower limb lymphatic reflux and para-uterine lymphatic reflux by injecting indocya-nine green
Jinli ZHAO ; Guangxin LIU ; He YU
Journal of Xinxiang Medical College 2024;41(3):262-265
Objective To observe the differences between the lymphatic reflux in the lower extremities and near the uterus by interphalangeal and cervical injection of indocyanine green(ICG).Methods A total of 50 patients with early-stage endometrial cancer or cervical cancer admitted to Zhoukou Central Hospital from June 2019 to November 2022 were selected as the research subjects.According to the ICG injection site during the surgery,patients were divided into the interphalangeal injection group(n=20)and the cervical injection group(n=30).The patients in the two groups were injected with ICG at the toes or cervix uteri,respectively.The lower limb lymphatic reflux pathway in the pelvic cavity and the para-uterine lymphatic reflux pathway were observed under fluorescence laparoscopy,and the differences between the two groups were analyzed.Results Among the patients with the interphalangeal injection of ICG(20 patients,40 sides),the lower limb lymphatic reflux was developed on 33 sides of 18 patients but not developed on both sides of 2 patients.Among the 18 patients,26 sides showed the lower limb lymphatic reflux through deep inguinal lymph nodes,circumflex iliac lymph nodes,external iliac lymph nodes,and common iliac lymph nodes;5 sides showed the lower limb lymphatic reflux to deep inguinal lymph nodes,circumflex iliac lymph nodes,obturator lymph nodes,internal iliac lymph nodes,and common iliac lymph nodes;and 2 sides showed the lower limb lymphatic reflux to deep inguinal lymph nodes,obturator lymph nodes,internal iliac lymph nodes,and common iliac lymph nodes.Among the patients with the cervical injection of ICG(30 patients,60 sides),pelvic lymph nodes were developed on 55 sides of 29 patients but not developed bilaterally in 1 patient.In the 29 patients,2 sides showed para-uterine lymphatic reflux to obturator lymph nodes,circumflex iliac lymph nodes,external iliac lymph nodes,and common iliac lymph nodes,in which circumflex iliac lymph nodes were non-sentinel lymph nodes;40 sides showed para-uterine lymphatic reflux to medial iliac lymph nodes(or obturator lymph nodes)and common iliac lymph nodes along the superior paracervical lymphatic reflux pathway;and 13 sides showed para-uterine lymphatic reflux to the internal iliac or presacral lymph nodes along the inferior paracervical lymphatic reflux pathway.The shared pathway of lower limb lymphatic reflux and para-uterine lymphatic reflux was upward reflux from obturator,external iliac and common iliac lymph nodes.The circumflex iliac lymph node developing rates in the interphalangeal and cervical injection groups were 93.94%(31/33)and 3.63%(2/55),respectively.The interphalangeal injection group had a significantly higher circumflex iliac lymph node developing rate than the cervical injection group(P<0.05).Conclusion The application of ICG under fluorescence laparoscopy intuitively observed the lower limb lymphatic reflux and the para-uetine lymphatic reflux pathway.The difference between the two is that the lower limb lymphatic reflux flows through the circumflex iliac lymph nodes at the distal end of the external iliac lymph nodes,while cervical cancer and endometrial cancer rarely transfer there.
3.Study on epidemiological prevalence and serological marker characteristics of hepatitis E infection
Chengrong BIAN ; Xin LIU ; Ruirui HAN ; Lili ZHAO ; Yeli HE ; Lihua YANG ; Weiwei LI ; Lijuan SONG ; Yingwei SONG ; Yongli LI ; Aixia LIU ; Jinli LOU ; Bo′an LI
Chinese Journal of Laboratory Medicine 2024;47(3):245-251
Objective:This study aims to explore the prevalence of hepatitis E virus (HEV) infection in patients and the screening value of serological indicators for HEV infection patients.Methods:Retrospective analysis was conducted on 97 440 cases of anti-HEV IgM and IgG simultaneously tested in two Beijing hospitals from January 1, 2018 to August 31, 2023. Among them, there were 61 005 males and 36 435 females, with an average age of 51.65±13.05 years old. According to the positivity of anti HEV specific antibodies, they were divided into anti-HEV IgM positive group (3 588 cases), anti-HEV IgG positive group (18 083 cases), and anti-HEV antibody negative group (78 892 cases). Results of HEV RNA, liver function, AFP, PIVKA-Ⅱ and PT were collected, and their basic clinical information were recorded. The prevalence of HEV infection in patients, as well as the relationship between the positivity of anti-HEV specific antibodies and the patient′s age group, HEV RNA, and clinical characteristics were analyzed.Results:Among 97 440 patients who tested anti-HEV IgM and IgG simultaneously, the positivity rate of anti-HEV IgM was 3.68% (3 588/97 440), and was 18.56% for anti-HEV IgG (18 083/97 440). The overall positivity rates of anti-HEV IgM in two Beijing hospitals from 2018 to 2023 were 2.51%, 2.53%, 3.02%, 4.59%, 5.72%, and 4.26% ( χ2=1 401.73, P<0.001), while the positivity rates of anti-HEV IgG were 12.56%, 12.32%, 12.85%, 22.65%, 27.42%, and 26.66% ( χ2=1 058.29, P<0.001). These rates showed a gradual increase until 2023 when a decline was observed. The positivity rates of anti-HEV IgM (2.28%, 3.60%, 4.47%) ( χ2=89.62, P<0.001) and IgG (4.71%, 17.86%, 25.94%) ( χ2=2 017.32, P<0.001) increased with age in patients who aged 1-30, >30-60, and over 60 years old. The age and ALB values of patients in the anti-HEV IgM positive group were lower than the IgG-positive group, while the proportion of males, TBIL, ALT, AFP and PT values were higher than the IgG-positive group, and the differences were statistically significance ( P<0.05). Furthermore, patients in both the anti-HEV IgM and IgG positive groups had higher age, male proportion, TBIL, ALT, AFP, PIVKA-Ⅱ, and PT values than the anti-HEV negative group. Additionally, both groups had lower ALB values than the anti-HEV negative group, all of which were statistically significant ( P<0.05). 2 162 HEV infected patients were grouped based on HEV RNA positivity. The proportion of anti-HEV IgM single positive, IgG single positive, IgM+IgG double positive, and antibody negative patients in the HEV RNA positive group were 5.42% (18/332), 3.62% (12/332), 90.36% (300/332), and 0.60% (2/332), respectively. Among them, the proportion of anti-HEV IgM+IgG double positive patients in the HEV RNA positive group was higher than that in the HEV RNA negative group ( χ2=302.87, P<0.001), while the proportion of anti-HEV IgG single positive ( χ2=174.36, P<0.001) and anti-HEV antibody negative patients ( χ2=59.28, P<0.001) were lower than that in the HEV RNA negative group, both of which were statistically significant ( P<0.001). In addition, the positive rates of HEV RNA in anti-HEV IgM positive, IgG positive, and antibody negative patients were 29.23% (318/1 088), 17.59% (312/1 774), and 0.65% (2/306), respectively. Conclusion:The HEV infection rate among patients declined in 2023. HEV infection is age-related, with older individuals being more susceptible. Abnormal liver function and jaundice were commonly observed during HEV infection. It is crucial to note that the absence of anti-HEV specific antibodies cannot rule out HEV infection; therefore, additional testing for HEV RNA and/or HEV Ag is necessary for accurate diagnosis.
4.Molecular docking analysis on screening of novel antibacterial targets and their drugs of Staphylococcus aureus based on pan-genomics and subtractive proteomics techniques
Jinli TAN ; Dan HUANG ; Jingyang LIAO ; Liuchong ZHU ; Wenbin LIU
Journal of Jilin University(Medicine Edition) 2024;50(4):970-977
Objective:To use pan-genomics and subtractive proteomics techniques to screen the new antibacterial targets from the Staphylococcus aureus genome,and to lay the foundation for the development of anti-Staphylococcus aureus drugs.Methods:The genome sequencing data of 50 strains with sequencing level Complete were collected by searching the whole genome sequencing data in the National Center for Biotechnology Information(NCBI)Database with Staphylococcus aureus as the keyword;BPGA tool was used to conduct the pan-genomics analysis on the genomic data to obtain the core genes of Staphylococcus aureus;subtractive proteomics technique was used to screen the potential antibacterial targets from the core genes.These potential antibacterial targets were used as the receptors;LibDock software was used to screen the potential anti-Staphylococcus aureus drugs from the US Food and Drug Administration(FDA)-approved drug library;molecular docking technology was used to analyze the binding abilities of the drugs and targets.Results:There were 14 379 gene families in the 50 Staphylococcus aureus genomes,of which 1 620 were the core genes.The subtractive proteomics analysis results showed that tyrosine autokinase 1335 was the potential anti-Staphylococcus aureus target.LibDock software screened out nine compounds,including balofloxacin,tenofovir disoproxil fumarate,and adefovir,that may exert anti-Staphylococcus aureus effects on this target protein.The molecular docking results showed there was good binding abilities between the targets and the compounds.Conclusion:Tyrosine autokinase may be the potential target for antii-Staphylococcus aureus.
5.The regulation between risk loci single nucleotide polymorphism rs9268832 and susceptibility gene human leukocyte antigen DRB1 in systemic lupus erythematosus
Jinli LIU ; Tengfei XU ; Quanzhen LI
Chinese Journal of Rheumatology 2024;28(10):733-737
Objective:To study the regulatory relationship between the loci single nucleotide polymorphism(SNP) rs9268832 and susceptibility gene human leukocyte antigen(HLA) DRB1 in systemic lupus erythematosus (SLE), and to enhance the understanding of genetic susceptibility to SLE.Methods:①A total of 223 out-and inpatients with SLE and 2 223 healthy controls were collected from Weihai Municipal Hospital from September 2017 to September 2019, and the SNP sites that might significantly associated with SLE were screened by genome-wide association study. ②Sequencing technology was used to genotype 100 out and -in patients with SLE and 100 healthy controls in Weihai Municipal Hospital from December 2019 to December 2020, the levels of anti-nuclear antibody and anti-double-stranded DNA antibody were detected by indirecte immunofluorescence and chemiluminescence immunoassay. Real-time quantitative PCR was used to determine HLA-DRB1 mRNA expression in peripheral blood mononuclear cells and B lymphocytes of 100 patients with SLE. ③One-way analysis of variance was used in this study, and SNK- q test or Tamhane′s T2 test were used for comparison between groups. Results:①A number of SNPs associated with SLE were identified by genome-wide association studies. Rs9268832, located in the HLA-DR region of susceptibility genes, was significantly associated with antinuclear antibodies. ②Of the 100 SLE patients, 41 had TT genotype of rs9268832, 32 had CT genotype, and 27 had CC genotype. In the 100 normal subjects, 10 had TT genotype of rs9268832, 59 had CT genotype, and 31 had CC genotype. The distribution frequency of T allele in SLE patients is higher than in normal people( χ2=27.58, P=0.020). ③Indirecy immunofluorescence and Chen iluminescence results showed that compared with CC genotype [antinuclear antibody (23.5±1.2)U/ml, anti-double-stranded DNA antibody (16.6±0.9)U/ml], CT genotype [antinuclear antibody (40.2±2.5)U/ml, anti-double-stranded DNA antibody (36.2±1.8)U/ml] were increased ( q=5.35, P=0.004; q=4.23, P=0.002), TT genotype [antinuclear antibody (56.3±3.1)U/ml, anti-double-stranded DNA antibody (52.5±2.9)U/ml] were increased ( q=8.21, P<0.001; q=7.59, P<0.001). PCR results showed that : compared with CC genotype [monocyte (402±8)×10 3, lymphocyte (462±7)×10 3], CT genotype [monocyte (572±11)×10 3, lymphocyte (470±8)×10 3] increased HLA-DRB1 mRNA expression ( q=1.11, P=0.030; q=1.03, P=0.040), TT genotype [monocytes (1 052±16)×10 3, lymphocytes (856±6)] increased HLA-DRB1 mRNA expression ( q=4.27, P=0.007; q=3.05, P=0.010). Conclusion:The T allele of SNP rs9268832 may be a risk locus for SLE, and there may be a regulatory relationship between different genotypes and the expression of susceptibility gene HLA-DRB1.
6.Clinical application value of rapid arterial spin labeling imaging in brain glioma
Yanling ZHANG ; Murong XU ; Xiaolu XU ; Jinli DING ; Yunyun DUAN ; Yaou LIU ; Yuhua JIANG ; Zhizheng ZHUO
Chinese Journal of Radiology 2024;58(5):529-533
Objective:To investigate the feasibility and clinical diagnostic value of rapid arterial spin labeling (ASL) imaging in brain glioma.Methods:Patients with glioma admitted to Beijing Tiantan Hospital, Capital Medical University from May 2021 to December 2022 were prospectively enrolled. All patients received MR rapid ASL (scan time: 1 min) and conventional ASL (scan time: 4 min 30 s), where the cerebral blood flow (CBF) perfusion maps were obtained. The qualitative analysis of CBF signal intensity and quantitative analysis of average CBF values from both tumor solid and edema regions were conducted by two radiologists independently. Kappa test and intraclass correlation coefficient ( ICC) were used to analyze the consistency of qualitative and quantitative results, respectively. Results:A total of 30 patients with brain glioma were included. The 2 physicians used rapid ASL to determine low perfusion, isoperfusion, and hyperperfusion in the tumor area in 1, 6, 23 cases and 0, 5, and 25 cases, respectively; and used conventional ASL to determine low perfusion, isoperfusion, and hyperperfusion in the tumor area in 0, 9, and 21 cases, respectively. The results of qualitative analysis of rapid ASL and conventional ASL were highly consistent within and between groups ( Kappa was 0.830 and 0.850 respectively). The results of quantitative analysis of rapid ASL and conventional ASL were highly consistent within and between groups ( ICC 0.940—0.994). Conclusion:Rapid ASL with shorter scanning time could be applied in assessing tissue perfusion in brain glioma and contribute to the clinical diagnosis of gliomas.
7.The best evidence summary of wound procedural pain management in patients with chronic wounds
Yuan ZHANG ; Jinli GUO ; Hong LIU ; Caixia GUO ; Xiang LIU
Chinese Journal of Nursing 2024;59(14):1761-1768
Objective To search,evaluate and integrate the best evidence of wound procedural pain management in patients with chronic wounds,and to provide evidence-based references for clinical practice.Methods Following the"6S"evidence model,we systematically searched relevant literature of wound procedural pain management in patients with chronic wounds,including clinical practice guidelines,clinical decisions,expert consensuses,evidence summaries,recommended practice and systematic reviews,with the search period from the datebase establishment to December 2022.The quality evaluation,extraction and integration for evidence were conducted independently by 2 researchers,respectively.Results A total of 17 articles were involved,including 2 guidelines,1 expert consensus,3 clinical decisions,6 evidence summaries,2 recommended practice,3 systematic reviews.34 pieces of best evidence were synthesized into 9 categories,including general principles,pain assessment and documentation,replacement and selection of the wound dressing,wound cleaning,wound debridement,negative pressure wound therapy,drug intervention strategies,non-drug intervention strategies,education and training.Conclusion The best evidence of wound procedural pain management in patients with chronic wounds in this study is scientific and practical.Medical staff can select and apply the best evidence based on clinical situation and patient willingness to reduce wound procedural pain.
8.Research progress on the relationship between time in range and cardiovascular complications in patients with diabetes mellitus
Zhitong LI ; Weili LIU ; Haiyao CHANG ; Jinli RU
Chinese Journal of General Practitioners 2024;23(9):985-990
Time in range (TIR) refers to the time or percentage of time within 24 h that glucose levels are in the target range; or the time that blood glucose levels are higher and lower the target range. TIR is a core parameter of continuous glucose monitoring (CGM) and an important indicator for the evaluation of blood glucose in treatment of diabetic patients. Recent studies have confirmed that TIR is closely related to cardiovascular complications of diabetes, and it may become a key indicator for predicting the risk of cardiovascular complications in the future. This article reviews the research progress on the relationship between TIR and cardiovascular complications in diabetic patients, and discusses the value of TIR in the integrated management of diabetes and cardiovascular diseases.
9.Advances in organoids of the digestive system.
Hongyuan LIU ; Ruofan WANG ; Xulong LI ; Zhengyang WU ; Jinli SUN ; Weiyi LU ; Xianli WANG
Chinese Journal of Biotechnology 2023;39(4):1332-1350
Organoid is a newly developed cellular there-dimensional culture system in recent years. Organoids have a three-dimensional structure, which is similar to that of the real organs. Together with the characteristics of self-renewal and reproduction of tissue origin, organoids can better simulate the function of real organs. Organoids provide a new platform for the study of organogenesis, regeneration, disease pathogenesis, and drug screening. The digestive system is an essential part of the human body and performs important functions. To date, organoid models of various digestive organs have been successfully established. This review summarizes the latest research progress of organoids of taste buds, esophagi, stomachs, livers and intestines, and prospects future application of organoids.
Humans
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Liver
10.Association of different components and combinations of metabolic syndrome with hyperuricemia in community residents
Huimin LEI ; Yan LIU ; Pengna PING ; Jinli RU ; Jinxiu ZHANG
Chinese Journal of General Practitioners 2023;22(8):796-802
Objective:To explore the relationship between different components of metabolic syndrome (MS) and their combinations with hyperuricemia (HUA) in community residents.Methods:A cross-sectional survey was conducted from March to November 2020 among 10% residents aged 18 and above selected by cluster sampling method from Nanzhai Community of Taiyuan City. According to serum uric acid levels, the selected individuals were divided into HUA group and non HUA group. The general clinical data of the selected subjects was collected, and routine physical examination and laboratory tests were performed. The serum uric acid levels were detected in fasting blood samples. The association of 5 components (hypertension, hyperglycemia, abdominal obesity, hypertriglyceridemia (TG), and low high-density lipoprotein cholesterol (HDL-C)) of MS and their combinations with HUA was analyzed by multivariate logistic regression model.Results:A total of 2 167 community residents were included in the survey, there were 385 cases of HUA with the age of (49.1±15.8) years old, and 297 males (77.1%); 1 782 subjects without HUA and with the age of (48.2±16.2) years old, and 695 males (39.0%). Compared with the non HUA group, the HUA group had a higher proportion of males, smoking, alcohol consumption, and gout attacks, higher abdominal circumference and body mass index (all P<0.05). The proportion of hypertension, hypertriglyceridemia, and abdominal obesity of MS patients in the HUA group was higher, while the proportion of low HDL-C syndrome was lower (all P<0.05). However, there was no significant difference in the proportion of hyperglycemia between the two groups ( P>0.05). After adjusting for smoking, drinking alcohol, taking antihypertensive and hypoglycemic drugs, multivariate logistic regression analysis showed that except for hyperglycemia, all other components of MS were independently associated with HUA. low HDL-C was negatively associated with HUA ( OR=0.408, 95% CI: 0.231-0.721, P=0.002), and high TG was strongly associated with HUA ( OR=1.834, 95% CI: 1.339-2.513, P<0.001). Multivariate logistic regression analysis also showed that 9 out of 31 combinations of MS components were associated with HUA (all P<0.05), and abdominal obesity+hypertriglyceridemia had the strongest association with HUA ( OR=4.379, 95% CI: 2.184-8.780, P<0.001). Conclusion:Except hyperglycemia, all components of MS and their combinations are significantly associated with HUA, the association between hyper-TG and HUA is the strongest one.

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