1.Akkermansia muciniphila gavage improves gut-brain interaction disorders in gp120 transgenic mice.
Jiachun LUO ; Sodnomjamts BATZAYA ; Xuefeng GAO ; Jingyu CHEN ; Zhengying YU ; Shasha XIONG ; Hong CAO
Journal of Southern Medical University 2025;45(3):554-565
OBJECTIVES:
To explore the effect of A. muciniphila gavage on intestinal microbiota and gut-brain interaction disorders (DGBIs) in gp120tg transgenic mouse models of HIV-associated neurocognitive disorder (HAND).
METHODS:
Intestinal microbiota was detected by 16S rRNA gene sequencing in 6-, 9-, and 12-month-old wild-type (WT) mice and gp120tg transgenic mice. The 12-month-old WT and transgenic mice were divided into 2 groups for daily treatment with PBS or A.muciniphila gavage (2×108 CFU/mouse) for 6 weeks. After the treatment, immunohistochemistry, ELISA and qPCR were used to detect changes in colonic expression levels of glycosylated mucins, MBP and IL-1β, eosinophil infiltration, serum lipopolysaccharide (LPS) levels, and colonic expressions of occludin, ZO-1, IL-10, TNF-α and INF-γ mRNA. Morris water maze test and immunofluorescence assay were used to assess learning and spatial memory abilities and neuronal damage of the mice.
RESULTS:
Compared with WT mice, the transgenic mice exhibited significantly lowered Simpson's diversity of the intestinal microbiota with reduced abundance of Akkermansia genus, increased serum LPS levels and decreased colonic expression of glycosylated mucin. A.muciniphila gavage obviously ameliorated the reduction of glycosylated mucin in the transgenic mice without causing significant changes in body weight. The 12-month-old gp120tg mice had significantly decreased cdonic expressions of Occludin and ZO-1 with increased eosinophil infiltration and TNF-β, INF-γ and IL-1β levels and obviously lowered IL-10 level; all these changes were significantly mitigated by A.muciniphila gavage, which also improved cognitive impairment and neuronal loss in the hippocampus and cortex of the transgenic mice.
CONCLUSIONS
The gp120tg mice have lower intestinal microbiota richness and diversity than WT mice. The 12-month-old gp120tg mice have significantly reduced Akkermansia abundance with distinct DGBIs-related indexes, and A. muciniphila gavage can reduce intestinal barrier injury, colonic inflammation and eosinophil activation, cognitive impairment and brain neuron injury in these mice.
Animals
;
Mice, Transgenic
;
Gastrointestinal Microbiome
;
Mice
;
Brain
;
HIV Envelope Protein gp120/genetics*
;
Akkermansia
;
Disease Models, Animal
2.Efficacy of vitamin A adjuvant therapy on bronchial asthma in children and its influence on serum transforming growth factor-β1, eosinophils and interleukin-17 levels
Honghong HOU ; Yan SUN ; Jianli PAN ; Zhijuan LUO ; Shasha LI ; Ying LIU
Clinical Medicine of China 2025;41(1):20-26
Objective:To explore the clinical effect of vitamin A in the adjuvant treatment of bronchial asthma in children and its influence on serum transforming growth factor-β1 (TGF-β1), eosinophils (EOS) and interleukin-17 (IL-17) levels.Methods:A prospective study was conducted on 110 children with bronchial asthma who received treatment in Department of Pediatrics, Xi'an Central Hospital from January 2022 to December 2023. Based on the principle of balanced and comparable baseline characteristics between groups, they were randomly divided into a control group and an observation group, with 55 cases in each group, using a random number table method. The control group was treated with routine pediatric bronchial asthma therapy, while the observation group was added with vitamin A adjuvant therapy on the basis of the control group. After 15 days of continuous treatment, the scores of asthma control condition (Childhood-Asthma Control Test (C-ACT), Asthma Control Questionnaire (ACQ)) in the two groups were evaluated. The pulmonary ventilation function (forced expiratory volume in one second (FEV 1), forced expiratory volume in one second/forced vital capacity (FEV 1/FVC), peak expiratory flow (PEF)), serum inflammatory factors (TGF-β1, EOS, IL-17) and immune function indicators (T helper 17 cell (Th17), T helper 2 cell (Th2), regulatory T cell (Treg) ) were compared between groups of children before treatment and after 15 days of treatment. Measurement data with normal or approximate distribution were expressed as xˉ± s, and independent sample t test was used for comparison between groups. Enumeration data were expressed as percentage, and chi-square test was adopted for between-group comparison. Results:After 15 days of treatment, the C-ACT score with (16.20±3.14) points in observation group was higher than (14.80±2.62) points in control group while the ACQ score with (30.30±4.14) points was lower than (34.60±6.23) points in control group, with statistical differences between groups (t values were 2.54 and 4.26; P values were 0.012 and <0.001). The pulmonary ventilation function indicators in observation group and control group after 15 days of treatment (FEV 1: (1.76±0.34) L与(1.54±0.32) L, FEV 1/FVC:(76.89±5.76)%与(70.25±6.42)%, PEF(2.89±0.35) L/s与(2.68±0.39) L/s) were higher than those before treatment (FEV 1:(1.12±0.31) L与(1.20±0.33) L, FEV 1/FVC:(56.96±4.35)%与(58.12±3.48)%, PEF(2.15±0.66) L/s与(2.34±0.56) L/s), and the differences were statistically significant ( t values were 10.32, 5.49, 20.48, 10.43, 7.35, 3.70, respectively; all P<0.001), and the indicators in observation group were higher compared to control group, the differences were statistically significant ( t values were 3.49, 5.71, and 2.97; P values were 0.001, <0.001, and 0.004). After 15 days of treatment, the levels of serum inflammatory factors (TGF-β1:(6.32±1.36) ng/L与(8.75±1.81) ng/L, EOS:(3.56±0.65)%与(4.28±0.82)%, IL-17:(5.53±1.22) ng/L与(6.42±1.51) ng/L) and CD4 + T lymphocyte immune function indicators (Th17:(0.97±0.26) ng/L与(1.23±0.35) ng/L, Th2:(2.32±0.64) ng/L与(3.15±0.52) ng/L, Treg:(5.41±0.76) ng/L与(5.86±0.23) ng/L ) were lower in observation group and control group than those before treatment (TGF-β1: (14.35±2.23)与(15.26±3.05) ng/L, EOS: (6.32±1.33)%与(6.41±1.27)%, IL-17:(8.86±1.68)与(9.03±1.89) ng/L, Th17:(1.82±0.75)与(1.67±0.68) ng/L, Th2:(4.15±1.49)与(3.98±1.28) ng/L, Treg: (7.26±1.35)与(6.92±1.72) ng/L), and the differences were statistically significant ( t values were 22.80, 13.61, 13.83, 10.45, 11.90, 8.08, 7.94, 4.27, 8.37, 4.46, 8.86, 4.58, respectively; all P<0.001). However, the above indicators in the observation group were lower than those in the control group ( t values were 7.96, 5.10, 3.40, 4.42, 7.47, 4.20, and P-values were <0.001, <0.001, 0.001, <0.001, <0.001, and <0.001 respectively). Conclusion:Vitamin A adjuvant therapy is helpful to the control of bronchial asthma, and it can effectively improve the pulmonary function, reduce the inflammatory reaction and enhance the body's immunity.
3.Efficacy of two surgical approaches in patients with CSOM at stationary phase with soft tissue shadow of mastoid mullae
Shasha SUN ; Hongbing YU ; Wugen LUO
Chinese Archives of Otolaryngology-Head and Neck Surgery 2025;32(3):153-157
OBJECTIVE To clarify the hearing improvement and tympanic membrane healing of tympanoplasty in patients with chronic suppurative otitis media in the stationary phase with soft tissue shadow of mastoid bulla on mastoid CT,and to compare its hearing improvement and tympanic membrane healing with that of canal wall up mastoidectomy+tympanoplasty.METHODS A retrospective analysis was conducted on clinical data of inpatient surgical cases diagnosed with chronic suppurative otitis media in the stationary phase with soft tissue shadow of mastoid bulla by preoperative mastoid CT at the Department of Otolaryngology Head and Neck Surgery,the First Affiliated Hospital of Nanchang University between September 2020 and April 2022.Patients were divided into two groups based on the surgical procedure:Group A,tympanoplasty,including 23 cases of type Ⅰ tympanoplasty(A1)and 26 cases of type Ⅱ tympanoplasty with ossicular chain reconstruction(A2);Group B,canal wall up mastoidectomy+tympanoplasty,including 21 cases of canal wall up mastoidectomy with type Ⅰ tympanoplasty(B1)and 20 cases of canal wall up mastoidectomy with type Ⅱ tympanoplasty and ossicular chain reconstruction(B2).Each patient was followed up for one year postoperatively,and at approximately one year after the operation,otoscopy and pure-tone audiometry(PTA)and air-bone gap(ABG)measurements at four frequencies(500,1 000,2 000,and 4 000 Hz)were performed and compared to preoperative values.RESULTS The average PTA at 1 year postoperatively for group A(A1 and A2)and group B(B1 and B2)were(36.35±16.21)dB HL[(31.96±11.78)dB HL,(40.24±18.68)dB HL]and(35.85±12.19)dB HL[(40.24±18.68)dB HL,(39.69±13.69)dB HL],respectively.Compared with preoperative PTA,the difference was statistically significant with P<0.05.The average ABG at 1 year postoperatively for group A and group B were(16.07±6.69)dB HL[(15.16±5.48)dB HL,(16.88±7.63)dB HL]and(15.21±6.40)dB HL[(13.93±5.29)dB HL,(16.56±7.28)dB HL],respectively.Compared with preoperative ABG,the difference was statistically significant with P<0.05.There was no statistically significant difference in postoperative average PTA and ABG between group A and group B.There was no statistically significant difference in effective rate between group A and group B.The results of ear endoscopy at 1 year postoperatively showed that the tympanic membrane healed well in both group A and group B.CONCLUSION There is no significant difference in hearing improvement and tympanic membrane healing between the two surgical procedures of tympanoplasty and canal wall up mastoidectomy+tympanoplasty for patients with CSOM at rest with shadowing of the mastoid sinus on mastoid CT.In clinical work,patients with CSOM at rest who have soft tissue shadow in the mastoid sinus on mastoid CT can opt for simple tympanoplasty.
4.Akkermansia muciniphila gavage improves gut-brain interaction disorders in gp120 transgenic mice
Jiachun LUO ; Batzaya SODNOMJAMTS ; Xuefeng GAO ; Jingyu CHEN ; Zhengying YU ; Shasha XIONG ; Hong CAO
Journal of Southern Medical University 2025;45(3):554-565
Objective To explore the effect of A.muciniphila gavage on intestinal microbiota and gut-brain interaction disorders(DGBIs)in gp120tg transgenic mouse models of HIV-associated neurocognitive disorder(HAND).Methods Intestinal microbiota was detected by 16S rRNA gene sequencing in 6-,9-,and 12-month-old wild-type(WT)mice and gp120tg transgenic mice.The 12-month-old WT and transgenic mice were divided into 2 groups for daily treatment with PBS or A.muciniphila gavage(2×108 CFU/mouse)for 6 weeks.After the treatment,immunohistochemistry,ELISA and qPCR were used to detect changes in colonic expression levels of glycosylated mucins,MBP and IL-1β,eosinophil infiltration,serum lipopolysaccharide(LPS)levels,and colonic expressions of occludin,ZO-1,IL-10,TNF-α and INF-γ mRNA.Morris water maze test and immunofluorescence assay were used to assess learning and spatial memory abilities and neuronal damage of the mice.Results Compared with WT mice,the transgenic mice exhibited significantly lowered Simpson's diversity of the intestinal microbiota with reduced abundance of Akkermansia genus,increased serum LPS levels and decreased colonic expression of glycosylated mucin.A.muciniphila gavage obviously ameliorated the reduction of glycosylated mucin in the transgenic mice without causing significant changes in body weight.The 12-month-old gp120tg mice had significantly decreased cdonic expressions of Occludin and ZO-1 with increased eosinophil infiltration and TNF-β,INF-γ and IL-1β levels and obviously lowered IL-10 level;all these changes were significantly mitigated by A.muciniphila gavage,which also improved cognitive impairment and neuronal loss in the hippocampus and cortex of the transgenic mice.Conclusion The gp120tg mice have lower intestinal microbiota richness and diversity than WT mice.The 12-month-old gp120tg mice have significantly reduced Akkermansia abundance with distinct DGBIs-related indexes,and A.muciniphila gavage can reduce intestinal barrier injury,colonic inflammation and eosinophil activation,cognitive impairment and brain neuron injury in these mice.
5.RNA-binding protein AUF1 regulates expression of metabolism-related genes and plays a potential role in hepatocellular carcinoma
Shasha WU ; Shunmei HUANG ; Qunhua HAN ; Mengyuan JIA ; Suisui LUO ; Lijun ZHU
Chinese Journal of Pathophysiology 2025;41(6):1066-1076
AIM:To investigate the expression of AU-rich element RNA-binding factor 1(AUF1),an RNA-binding protein,in hepatocellular carcinoma(HCC),and to explore its potential role in HCC progression through regula-tion of metabolism-related genes.METHODS:A tissue microarray containing 99 HCC samples and 95 adjacent nontu-morous liver tissues was used to assess AUF1 expression.The associations between AUF1 expression and HCC clinical pa-rameters were analysed using the GEPIA and UALCAN databases.The AUF1 gene was knocked down in human hepato-blastoma HepG2 cells by siRNA,and transcriptomic and TMT quantitative proteomic analyses were performed to identify alterations in metabolism-related genes.RESULTS:The AUF1 expression was significantly elevated in HCC tissues and correlated with a poor prognosis.Knockdown of AUF1 in HepG2 cells resulted in reduced cell viability and increased apop-tosis.Integrative analyses of transcriptomic and proteomic data revealed that AUF1 knockdown in HepG2 cells led to up-regulation of carboxylesterase 3(CES3),fibrinogen gamma chain(FGG)and 4-hydroxy-2-oxoglutarate aldolase 1(HOGA1),and down-regulation of lamin B receptor(LBR),riboflavin kinase(RFK),sterol O-acyltransferase 1(SOAT1)and TWIST neighbor(TWISTNB).Clinical data from GEPIA and UALCAN databases suggested that the expression of these metabolism-related genes in HCC patients exhibited an opposite trend.CONCLUSION:Our findings suggest that AUF1 is highly expressed in HCC,and may contribute to tumor progression and poor prognosis by modulating the expres-sion of a series of metabolism-related genes.
6.Risk factors and construction of a prediction model for severe pain in patients with postherpetic neuralgia
Journal of Clinical Neurology 2025;38(5):374-379
Objective To analyze the risk factors for severe pain in patients with postherpetic neuralgia(PHN),then construct a Nomogram prediction model,and validate it.Methods A total of 480 PHN patients treated in our hospital from December 2023 to December 2024 were selected and divided into a modeling set(n=240)and a validation set(n=240)using a random number table.Two months after the onset of herpes zoster,the patients in the modeling set were further classified into a severe pain group(n=52)and a mild-to-moderate pain group(n=188)based on the degree of pain.The baseline data of the selected patients were analyzed.The predictive value of continuous variables was analyzed using the ROC test.Univariate and Logistic regression analyses were conducted to screen for risk factors for severe pain.The Nomogram prediction model was constructed using R software and tested for goodness of fit.Results Statistically significant differences were observed between the two groups in age,gender,presence of prodromal pain,presence of diabetes,skin lesion area,and initial treatment time(all P<0.05).Logistic regression analysis revealed that gender,presence of prodromal pain,presence of diabetes,skin lesion area,and initial treatment time were independent risk factors for severe pain in PHN patients(all P<0.05).Construct a Nomogram model with predictive indicators as gender,presence of prodromal pain,presence of diabetes,skin lesion area,and initial treatment time to predict the occurrence of severe pain in PHN patients.The Nomogram model demonstrated good predictive ability and accuracy,with a C-index of 0.974(0.957-0.992)and the Hosmer-Lemeshow goodness-of-fit testx2of 3.030(P=0.933).Conclusions Gender,presence of prodromal pain,presence of diabetes,skin lesion area,and initial treatment time are all influencing factors for severe pain in PHN patients.The constructed model exhibits good predictive ability and accuracy.
7.Analysis on the Patient Flow Characteristics and Cost Structure of Intra-provincial Cross-Regional Medical Treatment in Guangdong
Yixiao SONG ; Shengwei LUO ; Shasha PENG ; Yanqing LIU ; Jiaying LIU ; Guochun XIANG
Chinese Health Economics 2025;44(10):47-50
Objective:It analyzes the flow characteristics and spatial distribution patterns of intra-provincial cross-regional medical patients in Guangdong,while comparing hospitalization cost differences between local and non-local care.Methods:Based on 2022-2023 cross-regional medical data from Guangdong,spatial visualization and descriptive analysis were conducted combined with Mann-Whitney U test to compare the cost burden.Results:Cross-Regional patients in Guangdong primarily flow to Guangzhou,accounting for 77.8%of the total intra-provincial cross-regional hospitalizations.Cross-regional medical expenses were significantly higher than the insured locations,with notable differences in mean total hospitalization costs and personal out-of-pocket payment ratios.Conclusion:Refining pre-approval procedures for cross-regional care,enhancing specialized medical departments in under-resourced regions,and strengthening coordination between healthcare insurance systems and primary healthcare strengthening initiatives are needed to promote balanced medical resource allocation and reduce the cost burden on patients.
8.Risk factors and construction of a prediction model for severe pain in patients with postherpetic neuralgia
Journal of Clinical Neurology 2025;38(5):374-379
Objective To analyze the risk factors for severe pain in patients with postherpetic neuralgia(PHN),then construct a Nomogram prediction model,and validate it.Methods A total of 480 PHN patients treated in our hospital from December 2023 to December 2024 were selected and divided into a modeling set(n=240)and a validation set(n=240)using a random number table.Two months after the onset of herpes zoster,the patients in the modeling set were further classified into a severe pain group(n=52)and a mild-to-moderate pain group(n=188)based on the degree of pain.The baseline data of the selected patients were analyzed.The predictive value of continuous variables was analyzed using the ROC test.Univariate and Logistic regression analyses were conducted to screen for risk factors for severe pain.The Nomogram prediction model was constructed using R software and tested for goodness of fit.Results Statistically significant differences were observed between the two groups in age,gender,presence of prodromal pain,presence of diabetes,skin lesion area,and initial treatment time(all P<0.05).Logistic regression analysis revealed that gender,presence of prodromal pain,presence of diabetes,skin lesion area,and initial treatment time were independent risk factors for severe pain in PHN patients(all P<0.05).Construct a Nomogram model with predictive indicators as gender,presence of prodromal pain,presence of diabetes,skin lesion area,and initial treatment time to predict the occurrence of severe pain in PHN patients.The Nomogram model demonstrated good predictive ability and accuracy,with a C-index of 0.974(0.957-0.992)and the Hosmer-Lemeshow goodness-of-fit testx2of 3.030(P=0.933).Conclusions Gender,presence of prodromal pain,presence of diabetes,skin lesion area,and initial treatment time are all influencing factors for severe pain in PHN patients.The constructed model exhibits good predictive ability and accuracy.
9.Analysis on the Patient Flow Characteristics and Cost Structure of Intra-provincial Cross-Regional Medical Treatment in Guangdong
Yixiao SONG ; Shengwei LUO ; Shasha PENG ; Yanqing LIU ; Jiaying LIU ; Guochun XIANG
Chinese Health Economics 2025;44(10):47-50
Objective:It analyzes the flow characteristics and spatial distribution patterns of intra-provincial cross-regional medical patients in Guangdong,while comparing hospitalization cost differences between local and non-local care.Methods:Based on 2022-2023 cross-regional medical data from Guangdong,spatial visualization and descriptive analysis were conducted combined with Mann-Whitney U test to compare the cost burden.Results:Cross-Regional patients in Guangdong primarily flow to Guangzhou,accounting for 77.8%of the total intra-provincial cross-regional hospitalizations.Cross-regional medical expenses were significantly higher than the insured locations,with notable differences in mean total hospitalization costs and personal out-of-pocket payment ratios.Conclusion:Refining pre-approval procedures for cross-regional care,enhancing specialized medical departments in under-resourced regions,and strengthening coordination between healthcare insurance systems and primary healthcare strengthening initiatives are needed to promote balanced medical resource allocation and reduce the cost burden on patients.
10.RNA-binding protein AUF1 regulates expression of metabolism-related genes and plays a potential role in hepatocellular carcinoma
Shasha WU ; Shunmei HUANG ; Qunhua HAN ; Mengyuan JIA ; Suisui LUO ; Lijun ZHU
Chinese Journal of Pathophysiology 2025;41(6):1066-1076
AIM:To investigate the expression of AU-rich element RNA-binding factor 1(AUF1),an RNA-binding protein,in hepatocellular carcinoma(HCC),and to explore its potential role in HCC progression through regula-tion of metabolism-related genes.METHODS:A tissue microarray containing 99 HCC samples and 95 adjacent nontu-morous liver tissues was used to assess AUF1 expression.The associations between AUF1 expression and HCC clinical pa-rameters were analysed using the GEPIA and UALCAN databases.The AUF1 gene was knocked down in human hepato-blastoma HepG2 cells by siRNA,and transcriptomic and TMT quantitative proteomic analyses were performed to identify alterations in metabolism-related genes.RESULTS:The AUF1 expression was significantly elevated in HCC tissues and correlated with a poor prognosis.Knockdown of AUF1 in HepG2 cells resulted in reduced cell viability and increased apop-tosis.Integrative analyses of transcriptomic and proteomic data revealed that AUF1 knockdown in HepG2 cells led to up-regulation of carboxylesterase 3(CES3),fibrinogen gamma chain(FGG)and 4-hydroxy-2-oxoglutarate aldolase 1(HOGA1),and down-regulation of lamin B receptor(LBR),riboflavin kinase(RFK),sterol O-acyltransferase 1(SOAT1)and TWIST neighbor(TWISTNB).Clinical data from GEPIA and UALCAN databases suggested that the expression of these metabolism-related genes in HCC patients exhibited an opposite trend.CONCLUSION:Our findings suggest that AUF1 is highly expressed in HCC,and may contribute to tumor progression and poor prognosis by modulating the expres-sion of a series of metabolism-related genes.

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