1.Exploring on Processing Mechanism of Enhanced "Invigorating Spleen and Stopping Diarrhea" Effect of Soil-fried Atractylodis Macrocephalae Rhizoma Based on "Microscopic Characterization, Chemical Analysis and Pharmacodynamic Evaluation" Trinity
Guoshun SHAN ; Yuyan XIAO ; Chu YUAN ; Xiuai CHEN ; Qimiao ZHAO ; Xiang LIU ; Hao WU ; Ke ZHANG ; Siqi LIU ; Yongduo YU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):182-193
ObjectiveTo analyze the processing mechanism underlying the enhanced effect of invigorating spleen and stopping diarrhea of soil-fried Atractylodis Macrocephalae Rhizoma(AMR) by analyzing the changes of microstructure, chemical composition and anti-ulcerative colitis(UC) activity before and after soil stir-frying. MethodsThe microstructure and elemental composition of AMR before and after soil stir-frying were analyzed by scanning electron microscopy-energy dispersive spectroscopy(SEM-EDS), to investigate the differences in microstructure and the underlying causes. Ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS) coupled with UNIFI 1.9.2 natural product analysis platform were used to analyze and identify the chemical constituents in raw and soil-fried products, and multivariate statistical methods including principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA) were used to explore the differences and sources of chemical constituents between them. A dextran sulfate sodium(DSS)-induced UC mouse model was established. The method of disease activity index(DAI) was used to evaluate the severity of intestinal inflammation. Hematoxylin-eosin(HE) staining was used to observe the pathological changes of colon tissue, enzyme-linked immunosorbent assay(ELISA) was used to detect the levels of inflammatory factors, Real-time quantitative polymerase chain reaction(Real-time PCR) and Western blot were used to analyze the expressions of key genes and proteins involved in the intestinal mucosal barrier. The 16S rRNA sequencing was used to evaluate the diversity of intestinal flora, headspace gas chromatography-mass spectrometry(HS-GC-MS) was used to explore the levels of short-chain fatty acids(SCFAs) in feces. Base on the above findings, this paper investigated the effects of raw and soil-fried AMR on the biological, chemical, mechanical and immune barriers of model animals, and the differences in pharmacological effects and underlying mechanisms from the perspective of regulating the intestinal mucosal barrier in UC mice. ResultsSEM observation revealed numerous hearth soil particles on the surface of soil-fried AMR, accompanied by bubble-like bulges. At the same time, there were many cracks and folds on the surface of the hearth soil. EDS analysis revealed that the contents of Si, Al, Mg and Ca in soil-fried AMR were significantly higher than those of raw products, and these elements constituted the primary components of hearth soil. UPLC-Q-TOF-MS combined with database comparison was used to identify the chemical constituents of raw and soil-fried AMR. In positive ion mode, a total of 132 components were identified, primarily comprising three categories of terpenoids, polyphenols and amino acids. In negative ion mode, a total of 40 components were identified, primarily polyphenolic and glycoside compounds. Among them, the contents of sesquiterpenes and polyphenolic acids were changed significantly before and after processing. Soil-fried AMR could reduce the DAI score of UC mice, alleviate the shortening of colon length, reduce the levels of pro-inflammatory factors such as interleukin(IL)-17, IL-18, γ-interferon(IFN-γ) and tumor necrosis factor(TNF)-α in serum, increase the levels of anti-inflammatory factors such as secretory immunoglobulin A(sIgA), IL-10, IL-4 and transforming growth factor-β(TGF-β) in serum, increase the expressions of key genes and proteins of intestinal mucosal barrier such as tight junction protein-1(ZO-1), Occludin, Claudin-1 and mucin 2(MUC2) in colonic mucosa, and improve the disorders of intestinal flora diversity and the levels of SCFAs(P<0.05, P<0.01). The raw and stir-fried products of AMR also exhibited the aforementioned effects, but they were weaker than the soil-fried products. Additionally, the auxiliary material hearth soil also had a certain pharmacodynamic effect. ConclusionSoil-fried AMR can enhance the protective effect on intestinal mucosal barrier in UC mice. These changes or heating-induced alterations in the microscopic structure and chemical composition of AMR may be attributed to the dual effects of adsorption of hearth soil.
2.Change trend of compound obesity among different occupational groups in nine provinces of China from 1993 to 2018
Lixin HAO ; Yu WU ; Liusen WANG ; Lili CHEN ; Boya ZHAO ; Zhongting LU ; Zhihong WANG ; Bing ZHANG ; Hongru JIANG ; Huijun WANG
Journal of Environmental and Occupational Medicine 2026;43(2):160-167
Background The global prevalence of obesity is on the rise and is closely associated with various chronic non-communicable diseases such as cardiovascular diseases and diabetes. There is a relative lack of long-term dynamic studies on compound obesity among occupational populations. Objective To explore the changing trends of compound obesity among different occupational groups aged 18–59 years in nine provinces (autonomous regions, municipalities) of China from 1993 to 2018, and to provide a scientific basis for formulating targeted weight management strategies for occupational populations. Methods A total of
3.Exploring on Processing Mechanism of Enhanced "Invigorating Spleen and Stopping Diarrhea" Effect of Soil-fried Atractylodis Macrocephalae Rhizoma Based on "Microscopic Characterization, Chemical Analysis and Pharmacodynamic Evaluation" Trinity
Guoshun SHAN ; Yuyan XIAO ; Chu YUAN ; Xiuai CHEN ; Qimiao ZHAO ; Xiang LIU ; Hao WU ; Ke ZHANG ; Siqi LIU ; Yongduo YU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):182-193
ObjectiveTo analyze the processing mechanism underlying the enhanced effect of invigorating spleen and stopping diarrhea of soil-fried Atractylodis Macrocephalae Rhizoma(AMR) by analyzing the changes of microstructure, chemical composition and anti-ulcerative colitis(UC) activity before and after soil stir-frying. MethodsThe microstructure and elemental composition of AMR before and after soil stir-frying were analyzed by scanning electron microscopy-energy dispersive spectroscopy(SEM-EDS), to investigate the differences in microstructure and the underlying causes. Ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS) coupled with UNIFI 1.9.2 natural product analysis platform were used to analyze and identify the chemical constituents in raw and soil-fried products, and multivariate statistical methods including principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA) were used to explore the differences and sources of chemical constituents between them. A dextran sulfate sodium(DSS)-induced UC mouse model was established. The method of disease activity index(DAI) was used to evaluate the severity of intestinal inflammation. Hematoxylin-eosin(HE) staining was used to observe the pathological changes of colon tissue, enzyme-linked immunosorbent assay(ELISA) was used to detect the levels of inflammatory factors, Real-time quantitative polymerase chain reaction(Real-time PCR) and Western blot were used to analyze the expressions of key genes and proteins involved in the intestinal mucosal barrier. The 16S rRNA sequencing was used to evaluate the diversity of intestinal flora, headspace gas chromatography-mass spectrometry(HS-GC-MS) was used to explore the levels of short-chain fatty acids(SCFAs) in feces. Base on the above findings, this paper investigated the effects of raw and soil-fried AMR on the biological, chemical, mechanical and immune barriers of model animals, and the differences in pharmacological effects and underlying mechanisms from the perspective of regulating the intestinal mucosal barrier in UC mice. ResultsSEM observation revealed numerous hearth soil particles on the surface of soil-fried AMR, accompanied by bubble-like bulges. At the same time, there were many cracks and folds on the surface of the hearth soil. EDS analysis revealed that the contents of Si, Al, Mg and Ca in soil-fried AMR were significantly higher than those of raw products, and these elements constituted the primary components of hearth soil. UPLC-Q-TOF-MS combined with database comparison was used to identify the chemical constituents of raw and soil-fried AMR. In positive ion mode, a total of 132 components were identified, primarily comprising three categories of terpenoids, polyphenols and amino acids. In negative ion mode, a total of 40 components were identified, primarily polyphenolic and glycoside compounds. Among them, the contents of sesquiterpenes and polyphenolic acids were changed significantly before and after processing. Soil-fried AMR could reduce the DAI score of UC mice, alleviate the shortening of colon length, reduce the levels of pro-inflammatory factors such as interleukin(IL)-17, IL-18, γ-interferon(IFN-γ) and tumor necrosis factor(TNF)-α in serum, increase the levels of anti-inflammatory factors such as secretory immunoglobulin A(sIgA), IL-10, IL-4 and transforming growth factor-β(TGF-β) in serum, increase the expressions of key genes and proteins of intestinal mucosal barrier such as tight junction protein-1(ZO-1), Occludin, Claudin-1 and mucin 2(MUC2) in colonic mucosa, and improve the disorders of intestinal flora diversity and the levels of SCFAs(P<0.05, P<0.01). The raw and stir-fried products of AMR also exhibited the aforementioned effects, but they were weaker than the soil-fried products. Additionally, the auxiliary material hearth soil also had a certain pharmacodynamic effect. ConclusionSoil-fried AMR can enhance the protective effect on intestinal mucosal barrier in UC mice. These changes or heating-induced alterations in the microscopic structure and chemical composition of AMR may be attributed to the dual effects of adsorption of hearth soil.
4.Risk Factors Analysis and Predictive Model Construction for Acute Kidney Injury Following Amphotericin B Deoxycholate Use in Hospitalized Patients
Hao XIE ; Yixun SHI ; Zhiqing XU ; Minquan LI ; Xiaoli DU ; Gang CHEN ; Bin ZHAO
Medical Journal of Peking Union Medical College Hospital 2026;17(2):429-437
To investigate the risk factors for acute kidney injury (AKI) following the use of amphotericin B deoxycholate and to develop a predictive model to guide clinical monitoring and intervention. A retrospective analysis was conducted on hospitalized patients who received amphotericin B deoxycholate between January 2014 and September 2024. Patients were divided into a training set and a validation set. Demographic data, laboratory findings, and medication orders were collected. Based on the occurrence of AKI during treatment and within 7 days after discontinuation, patients were classified into an AKI group and a non-AKI group. Univariate analysis was used to screen for potential risk factors, multivariate logistic regression was employed to construct a predictive model, and model performance was evaluated using the area under the receiver operating characteristic curve (AUC) and the Hosmer-Lemeshow test. The training set included 473 patients, comprising 255 males (53.91%) and 218 females (46.09%), with a median age of 52(35, 62) years. The AKI group consisted of 191 cases (40.38%), and the non-AKI group consisted of 282 cases (59.62%). The validation set included 114 patients, comprising 80 males (70.18%) and 34 females (29.82%), with a median age of 43.5 (31.0, 58.5) years. The AKI group consisted of 42 cases (36.84%), and the non-AKI group consisted of 72 cases (63.16%). Univariate analysis revealed statistically significant differences between the two groups in 23 factors (all Admission to the ICU, elevated serum creatinine at admission, and comorbid cardiac insufficiency as potential risk factors for AKI, while prophylactic use of diphenhydramine/promethazine or sodium bicarbonate showed a protective association. A predictive model with good discrimina-tion and calibration was developed, which may provide a basis for early identification of high-risk patients and timely adjustment of treatment strategies in clinical practice.
5.Effects of human umbilical cord blood platelet-rich plasma,mononuclear cells,and mesenchymal stem cells in repairing thin endometrium in rats
Yanli MU ; Anchun HU ; Wenchi XU ; Panpan CHEN ; Hao CHEN ; Shuyun ZHAO ; Guanyou HUANG ; Xiaojuan CHEN
Chinese Journal of Tissue Engineering Research 2026;30(1):78-92
BACKGROUND:Research has found that human umbilical cord blood platelet rich plasma and human umbilical cord blood derived mesenchymal stem cells have certain therapeutic effects on thin endometrium.However,there are currently no reports on the study of human umbilical cord blood mononuclear cells on thin endometrium,and there is a lack of relevant research comparing the three.OBJECTIVE:To explore the effects and mechanisms of human umbilical cord blood platelet rich plasma,monocytes,and mesenchymal stem cells in repairing thin endometrium in rats.METHODS:Sixty female SPF grade SD rats were randomly divided into sham operation group,model group,human umbilical cord blood platelet rich plasma group,human umbilical cord blood mononuclear cell group,and human umbilical cord blood derived mesenchymal stem cell group,with 12 rats in each group.The sham operation group received 0.5 mL physiological saline injection into the uterine horn,followed by 0.5 mL of PBS infusion after 5 minutes;The model group,human umbilical cord blood platelet rich plasma group,human umbilical cord blood mononuclear cell group,and human umbilical cord blood derived mesenchymal stem cell group were injected with 0.5 mL of 95%ethanol by volume.After 5 minutes,the remaining ethanol was aspirated and washed twice with physiological saline.Then,0.5 mL of PBS,human umbilical cord blood platelet rich plasma,human umbilical cord blood mononuclear cells(1×107 cells/mL),and human umbilical cord blood derived mesenchymal stem cells(1×107 cells/mL)were perfused separately.During the third normal estrus cycle after reperfusion,organs,tissues and serum were collected for testing of relevant indicators.RESULTS AND CONCLUSION:(1)The macroscopic view of uterine tissue,hematoxylin eosin staining and Masson staining results:the sham operation group had intact structure,moderate endometrial thickness,and clear vascular structure.Compared with the sham operation group,the model group showed uterine atrophy,incomplete structure,significantly reduced endometrial thickness and glandular quantity,disordered vascular structure,and increased fibrosis.Compared with the model group,after treatment with human umbilical cord blood derivatives,the size,structure,and endometrial thickness of the uterus were restored(all P<0.01),and fibrosis was reduced,with the most significant recovery observed in the human umbilical cord blood mononuclear cell group.The increase in glandular quantity was most significant in the human umbilical cord blood platelet rich plasma group(P<0.000 1).(2)The immunohistochemistry and immunofluorescence results of uterine tissue showed that compared with the sham operation group,the expression levels of cell proliferation related indicators such as keratin 9 and vimentin,endometrial receptivity related indicators such as leukemia inhibitory factor and integrin αyβ3,platelet endothelial cell adhesion molecule,basic fibroblast growth factor,and vascular endothelial growth factor were all reduced in the model group(all P<0.05).Compared with the model group,the above indicators were significantly increased after treatment with human umbilical cord blood derivatives.Comparison of human umbilical cord blood derivatives among groups showed that keratin 9 and vascular endothelial growth factor protein:human umbilical cord blood mononuclear cell group>human umbilical cord blood derived mesenchymal stem cell group>human umbilical cord blood platelet rich plasma group;Wave shaped protein and leukemia inhibitory factor protein:human umbilical cord blood derived mesenchymal stem cell group>human umbilical cord blood mononuclear cell group>human umbilical cord blood platelet rich plasma group;Integrin αyβ3 protein:human umbilical cord blood platelet rich plasma group>human umbilical cord blood derived mesenchymal stem cell group>human umbilical cord blood mononuclear cell group;Platelet endothelial cell adhesion molecule protein:human umbilical cord blood platelet rich plasma group>human umbilical cord blood mononuclear cell group>human umbilical cord blood derived mesenchymal stem cell group;Basic fibroblast growth factor protein:human umbilical cord blood mononuclear cell group>human umbilical cord blood platelet rich plasma group>human umbilical cord blood derived mesenchymal stem cell group.(3)Western blot analysis showed that compared with the sham operation group,the protein levels of interleukin-6,interleukin-1β,and tumor necrosis factor alpha in the model group were significantly increased(all P<0.001),and their expression levels decreased after treatment(all P<0.05).(4)ELISA assay showed that compared with the sham operation group,the model group had lower levels of anti Mullerian hormone,estradiol,and progesterone,and increased levels of follicle stimulating hormone and luteinizing hormone(except for luteinizing hormone,all P<0.05).After treatment,there was a certain degree of recovery in the levels of sex hormones and anti Mullerian hormones.(5)Fertility experiments showed that compared with the sham operation group,the model group had an increase in conception time and a significant decrease in litter size(all P<0.05).After treatment with human umbilical cord blood derivatives,the litter size of all three groups increased(P<0.05),and no significant differences were found between the groups.This study preliminarily reveals that human umbilical cord blood mononuclear cells have a certain therapeutic effect on thin endometrium,and human umbilical cord blood platelet rich plasma,human umbilical cord blood mononuclear cells,and human umbilical cord blood derived mesenchymal stem cells have different advantages and differences in improving endometrial regeneration function,endometrial receptivity,angiogenesis,inflammation regulation,and improving pregnancy outcomes in thin endometrium.
6.Effects of human umbilical cord blood platelet-rich plasma,mononuclear cells,and mesenchymal stem cells in repairing thin endometrium in rats
Yanli MU ; Anchun HU ; Wenchi XU ; Panpan CHEN ; Hao CHEN ; Shuyun ZHAO ; Guanyou HUANG ; Xiaojuan CHEN
Chinese Journal of Tissue Engineering Research 2026;30(1):78-92
BACKGROUND:Research has found that human umbilical cord blood platelet rich plasma and human umbilical cord blood derived mesenchymal stem cells have certain therapeutic effects on thin endometrium.However,there are currently no reports on the study of human umbilical cord blood mononuclear cells on thin endometrium,and there is a lack of relevant research comparing the three.OBJECTIVE:To explore the effects and mechanisms of human umbilical cord blood platelet rich plasma,monocytes,and mesenchymal stem cells in repairing thin endometrium in rats.METHODS:Sixty female SPF grade SD rats were randomly divided into sham operation group,model group,human umbilical cord blood platelet rich plasma group,human umbilical cord blood mononuclear cell group,and human umbilical cord blood derived mesenchymal stem cell group,with 12 rats in each group.The sham operation group received 0.5 mL physiological saline injection into the uterine horn,followed by 0.5 mL of PBS infusion after 5 minutes;The model group,human umbilical cord blood platelet rich plasma group,human umbilical cord blood mononuclear cell group,and human umbilical cord blood derived mesenchymal stem cell group were injected with 0.5 mL of 95%ethanol by volume.After 5 minutes,the remaining ethanol was aspirated and washed twice with physiological saline.Then,0.5 mL of PBS,human umbilical cord blood platelet rich plasma,human umbilical cord blood mononuclear cells(1×107 cells/mL),and human umbilical cord blood derived mesenchymal stem cells(1×107 cells/mL)were perfused separately.During the third normal estrus cycle after reperfusion,organs,tissues and serum were collected for testing of relevant indicators.RESULTS AND CONCLUSION:(1)The macroscopic view of uterine tissue,hematoxylin eosin staining and Masson staining results:the sham operation group had intact structure,moderate endometrial thickness,and clear vascular structure.Compared with the sham operation group,the model group showed uterine atrophy,incomplete structure,significantly reduced endometrial thickness and glandular quantity,disordered vascular structure,and increased fibrosis.Compared with the model group,after treatment with human umbilical cord blood derivatives,the size,structure,and endometrial thickness of the uterus were restored(all P<0.01),and fibrosis was reduced,with the most significant recovery observed in the human umbilical cord blood mononuclear cell group.The increase in glandular quantity was most significant in the human umbilical cord blood platelet rich plasma group(P<0.000 1).(2)The immunohistochemistry and immunofluorescence results of uterine tissue showed that compared with the sham operation group,the expression levels of cell proliferation related indicators such as keratin 9 and vimentin,endometrial receptivity related indicators such as leukemia inhibitory factor and integrin αyβ3,platelet endothelial cell adhesion molecule,basic fibroblast growth factor,and vascular endothelial growth factor were all reduced in the model group(all P<0.05).Compared with the model group,the above indicators were significantly increased after treatment with human umbilical cord blood derivatives.Comparison of human umbilical cord blood derivatives among groups showed that keratin 9 and vascular endothelial growth factor protein:human umbilical cord blood mononuclear cell group>human umbilical cord blood derived mesenchymal stem cell group>human umbilical cord blood platelet rich plasma group;Wave shaped protein and leukemia inhibitory factor protein:human umbilical cord blood derived mesenchymal stem cell group>human umbilical cord blood mononuclear cell group>human umbilical cord blood platelet rich plasma group;Integrin αyβ3 protein:human umbilical cord blood platelet rich plasma group>human umbilical cord blood derived mesenchymal stem cell group>human umbilical cord blood mononuclear cell group;Platelet endothelial cell adhesion molecule protein:human umbilical cord blood platelet rich plasma group>human umbilical cord blood mononuclear cell group>human umbilical cord blood derived mesenchymal stem cell group;Basic fibroblast growth factor protein:human umbilical cord blood mononuclear cell group>human umbilical cord blood platelet rich plasma group>human umbilical cord blood derived mesenchymal stem cell group.(3)Western blot analysis showed that compared with the sham operation group,the protein levels of interleukin-6,interleukin-1β,and tumor necrosis factor alpha in the model group were significantly increased(all P<0.001),and their expression levels decreased after treatment(all P<0.05).(4)ELISA assay showed that compared with the sham operation group,the model group had lower levels of anti Mullerian hormone,estradiol,and progesterone,and increased levels of follicle stimulating hormone and luteinizing hormone(except for luteinizing hormone,all P<0.05).After treatment,there was a certain degree of recovery in the levels of sex hormones and anti Mullerian hormones.(5)Fertility experiments showed that compared with the sham operation group,the model group had an increase in conception time and a significant decrease in litter size(all P<0.05).After treatment with human umbilical cord blood derivatives,the litter size of all three groups increased(P<0.05),and no significant differences were found between the groups.This study preliminarily reveals that human umbilical cord blood mononuclear cells have a certain therapeutic effect on thin endometrium,and human umbilical cord blood platelet rich plasma,human umbilical cord blood mononuclear cells,and human umbilical cord blood derived mesenchymal stem cells have different advantages and differences in improving endometrial regeneration function,endometrial receptivity,angiogenesis,inflammation regulation,and improving pregnancy outcomes in thin endometrium.
7.Treatment Modalities and Long-Term Outcomes in Unruptured Vertebrobasilar Fusiform Aneurysms: A Nationwide Observational Cohort Study
Linggen DONG ; Dachao WEI ; Xiheng CHEN ; Mingtao LI ; Yang ZHAO ; Yong SUN ; Qingbin NIE ; Jun FENG ; Guomin XIAO ; Jinghua ZHOU ; Shengli HU ; Lifei FENG ; Lifeng QI ; Hongen LIU ; Geng GUO ; Yufang LI ; Renfu TIAN ; Jianghua YU ; Dianshi JIN ; Liang HAO ; Tian TIAN ; Shizhong ZHANG ; Yang WANG ; Liping LIU ; Ming LV
Journal of Stroke 2026;28(2):250-262
Background:
and Purpose Vertebrobasilar fusiform aneurysms (VBFAs) carry substantial morbidity and mortality, but optimal management for unruptured VBFAs remains unclear. We compared the safety and efficacy of conservative management (CM), stent-assisted coiling (SAC), and flow diverters (FDs) in patients with unruptured VBFAs, focusing on long-term prognosis.
Methods:
This study included data from a nationwide Chinese cohort of patients with vertebrobasilar dissecting aneurysms. Inverse probability of treatment weighting (IPTW) balanced confounders across groups. The primary outcome was poor prognosis (modified Rankin Scale score >2). Secondary outcomes included aneurysm rupture, ischemic stroke, compression symptoms, and VBFA-related deaths. Logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CIs). Subgroup and sensitivity analyses were performed.
Results:
Among 1,115 patients with unruptured VBFAs, 838 (median age, 54 years; 655 men) were included. After IPTW, baseline characteristics were balanced. Median follow-up was 54 months. FD was associated with a lower risk of poor prognosis than CM (OR, 0.48 [95% CI, 0.30 to 0.77]; p=0.002), with no difference between CM and SAC. FD also reduced aneurysm rupture (OR, 0.20 [95% CI, 0.07 to 0.60]; p=0.004) and compression symptoms (OR, 0.30 [95% CI, 0.13 to 0.68]; p=0.004) versus CM. Time-to-event analyses further revealed significant differences in vertebral artery lesions and Type I–II VBFAs, whereas no significant differences were observed in basilar or vertebrobasilar junction lesions or in Type III–IV VBFAs.
Conclusions
Compared with CM, FD was associated with improved long-term outcomes in unruptured VBFAs, particularly in vertebral artery lesions and Type I–II VBFAs, although residual confounding cannot be excluded.
8.SIRT5 Potentiates Hepatocarcinogenesis by Modulating Protein Acylation in Mice
Yu ZHANG ; Feng-Rui REN ; Jia-Yun LI ; Xiang-Yu CHEN ; Zi-Yi WANG ; Qi SUN ; Jun-Cheng ZHAO ; Ye ZHANG ; Zhen HUANG ; Hao HU ; Tao-Tao WEI ; Min XIAO
Progress in Biochemistry and Biophysics 2026;53(6):1712-1722
ObjectiveHepatocellular carcinoma (HCC) represents 90% of all primary liver cancers. The main risk factors associated with HCC include viral hepatitis (B and/or C), alcohol abuse, and metabolic dysfunction-associated steatotic liver disease (MASLD), which progressively advance to liver fibrosis, cirrhosis, and ultimately evolve into HCC. Surgical resection represents the most effective treatment for HCC, while recent advances in immunotherapy, including immune checkpoint inhibitors and adoptive cell therapies, have provided improved treatment prospects for patients with unresectable HCC. However, the complex metabolic heterogeneity of HCC limits the therapeutic efficacy. Metabolic intermediates acyl-CoA not only provide energy and substrates for numerous biochemical reactions but also serve as donors for protein lysine acylation, a major class of post-translational modification (PTM). Therefore, a deeper understanding of the molecular mechanisms underlying protein lysine acylation and hepatocarcinogenesis is urgently needed. MethodsThe levels of protein lysine acylation and silence information regulator 5 (SIRT5) expression levels in clinical HCC samples were analyzed by Western blot. Quantitative malonylome and succinylome of HCC samples were analyzed by antibody-based affinity enrichment coupled with tandem mass spectrometry. The proliferation of HCC cells was analyzed with Cell Counting Kit-8 (CCK-8) assays, the apoptosis was quantified by Annexin V-FITC/propidium iodide (PI) staining coupled with flow cytometry, and the ability of cells to migrate was assayed by Transwell assays. The enzymatic activity of glutathione S-transferase Mu 1 (GSTM1) was quantified. Transgenic mice with hepatic overexpression of SIRT5 were constructed using CRISPR-Cas9, and primary hepatocarcinogenesis was induced by administration of diethylnitrosamine. ResultsWestern blot analysis indicated that the expression level of SIRT5 was elevated in clinical samples from HCC patients, and the levels of lysine malonylation, glutarylation, and succinylation were significantly reduced in HCC tissues. Knockout of SIRT5 in MHCC-97H and MHCC-97L hepatoma cells suppressed cell proliferation, and increased the percentage of apoptotic cells significantly. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the differentially malonylome and succinylome of HCC samples revealed significant enrichment in two major classes of biological processes: core energy metabolism (e.g., glycolysis/gluconeogenesis, tricarboxylic acid metabolic process, fatty acid beta oxidation) and detoxification and oxidative stress response (e.g., response to toxic substance, chemical carcinogenesis, reactive oxygen species (ROS)). SIRT5 removes malonylation from lysine residues in GSTM1 and restores its detoxification activity, which is crucial for the survival of hepatocytes under stressed conditions. More importantly, in vivo experiment indicated that hepatic-specific overexpression of SIRT5 in mice accelerated diethylnitrosamine-induced liver fibrosis and hepatocarcinogenesis, indicating the critical role of SIRT5 in HCC progression. ConclusionThis study highlights the previously unrecognized SIRT5-GSTM1 axis as a key regulator in hepatocarcinogenesis, and suggests a potential target for the treatment of patients with HCC.
9.Gut microbiota and osteoporotic fractures
Wensheng ZHAO ; Xiaolin LI ; Changhua PENG ; Jia DENG ; Hao SHENG ; Hongwei CHEN ; Chaoju ZHANG ; Chuan HE
Chinese Journal of Tissue Engineering Research 2025;29(6):1296-1304
BACKGROUND:Osteoporotic fracture is the most serious complication of osteoporosis.Previous studies have demonstrated that gut microbiota has a regulatory effect on skeletal tissue and that gut microbiota has an important relationship with osteoporotic fracture,but the causal relationship between the two is unclear. OBJECTIVE:To explore the causal relationship between gut microbiota and osteoporotic fractures using Mendelian randomization method. METHODS:The genome-wide association study(GWAS)datasets of gut microbiota and osteoporotic fracture were obtained from the IEU Open GWAS database and the Finnish database R9,respectively.Using gut microbiota as the exposure factor and osteoporotic fracture as the outcome variable,Mendelian randomization analyses with random-effects inverse variance weighted,MR-Egger regression,weighted median,simple model,and weighted model methods were performed to assess whether there is a causal relationship between gut microbiota and osteoporotic fracture.Sensitivity analyses were performed to test the reliability and robustness of the results.Reverse Mendelian randomization analyses were performed to further validate the causal relationship identified in the forward Mendelian randomization analyses. RESULTS AND CONCLUSION:The results of this Mendelian randomization analysis indicated a causal relationship between gut microbiota and osteoporotic fracture.Elevated abundance of Actinomycetales[odds ratio(OR)=1.562,95%confidence interval(CI):1.027-2.375,P=0.037),Actinomycetaceae(OR=1.561,95%CI:1.027-2.374,P=0.037),Actinomyces(OR=1.544,95%CI:1.130-2.110,P=0.006),Butyricicoccus(OR=1.781,95%CI:1.194-2.657,P=0.005),Coprococcus 2(OR=1.550,95%CI:1.068-2.251,P=0.021),Family ⅩⅢ UCG-001(OR=1.473,95%CI:1.001-2.168,P=0.049),Methanobrevibacter(OR=1.274,95%CI:1.001-1.621,P=0.049),and Roseburia(OR=1.429,95%CI:1.015-2.013,P=0.041)would increase the risk of osteoporotic fractures in patients.Elevated abundance of Bacteroidia(OR=0.660,95%CI:0.455-0.959,P=0.029),Bacteroidales(OR=0.660,95%CI:0.455-0.959,P=0.029),Christensenellacea(OR=0.725,95%CI:0.529-0.995,P=0.047),Ruminococcaceae(OR=0.643,95%CI:0.443-0.933,P=0.020),Enterorhabdus(OR=0.558,95%CI:0.395-0.788,P=0.001),Eubacterium rectale group(OR=0.631,95%CI:0.435-0.916,P=0.016),Lachnospiraceae UCG008(OR=0.738,95%CI:0.546-0.998,P=0.048),and Ruminiclostridium 9(OR=0.492,95%CI:0.324-0.746,P=0.001)would reduce the risk of osteoporotic fractures in patients.We identified 16 gut microbiota associated with osteoporotic fracture by the Mendelian randomization method.That is,using gut microbiota as the exposure factor and osteoporotic fracture as the outcome variable,eight gut microbiota showed positive causal associations with osteoporotic fracture and another eight gut microbiota showed negative causal associations with osteoporotic fracture.The results of this study not only identify new biomarkers for the early prediction of osteoporotic fracture and potential therapeutic targets in clinical practice,but also provide an experimental basis and theoretical basis for the study of improving the occurrence and prognosis of osteoporotic fracture through gut microbiota in bone tissue engineering.
10.Principles, technical specifications, and clinical application of lung watershed topography map 2.0: A thoracic surgery expert consensus (2024 version)
Wenzhao ZHONG ; Fan YANG ; Jian HU ; Fengwei TAN ; Xuening YANG ; Qiang PU ; Wei JIANG ; Deping ZHAO ; Hecheng LI ; Xiaolong YAN ; Lijie TAN ; Junqiang FAN ; Guibin QIAO ; Qiang NIE ; Mingqiang KANG ; Weibing WU ; Hao ZHANG ; Zhigang LI ; Zihao CHEN ; Shugeng GAO ; Yilong WU
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(02):141-152
With the widespread adoption of low-dose CT screening and the extensive application of high-resolution CT, the detection rate of sub-centimeter lung nodules has significantly increased. How to scientifically manage these nodules while avoiding overtreatment and diagnostic delays has become an important clinical issue. Among them, lung nodules with a consolidation tumor ratio less than 0.25, dominated by ground-glass shadows, are particularly worthy of attention. The therapeutic challenge for this group is how to achieve precise and complete resection of nodules during surgery while maximizing the preservation of the patient's lung function. The "watershed topography map" is a new technology based on big data and artificial intelligence algorithms. This method uses Dicom data from conventional dose CT scans, combined with microscopic (22-24 levels) capillary network anatomical watershed features, to generate high-precision simulated natural segmentation planes of lung sub-segments through specific textures and forms. This technology forms fluorescent watershed boundaries on the lung surface, which highly fit the actual lung anatomical structure. By analyzing the adjacent relationship between the nodule and the watershed boundary, real-time, visually accurate positioning of the nodule can be achieved. This innovative technology provides a new solution for the intraoperative positioning and resection of lung nodules. This consensus was led by four major domestic societies, jointly with expert teams in related fields, oriented to clinical practical needs, referring to domestic and foreign guidelines and consensus, and finally formed after multiple rounds of consultation, discussion, and voting. The main content covers the theoretical basis of the "watershed topography map" technology, indications, operation procedures, surgical planning details, and postoperative evaluation standards, aiming to provide scientific guidance and exploration directions for clinical peers who are currently or plan to carry out lung nodule resection using the fluorescent microscope watershed analysis method.

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