1.Mechanisms of Mahuang Lianqiao Chixiaodoutang in Improving Obesity-type Polycystic Ovary Syndrome in Rats Based on PI3K/Akt Signaling Pathway
Shiwei HU ; Biran ZHU ; Jinrong ZHANG ; Luyao RUAN ; Ji KUANG ; Jianghuan HUA ; Zhe LIU ; Yanyue YAO ; Ji WANG ; Min ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):21-31
ObjectiveTo investigate the mechanisms by which Mahuang Lianqiao Chixiaodoutang (MLC) improves obesity-type polycystic ovary syndrome (PCOS) through the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway. MethodsThirty-six female Sprague-Dawley (SD) rats were randomly divided into a blank control group (Con) and an obesity-type PCOS model preparation group. The model was induced by gavage with letrozole (1 mg·kg-1) combined with a high-fat diet (HFD). After model establishment, the obesity-type PCOS model preparation group was further divided into the model group (Mod, normal saline), metformin group (Met, 0.3 g·kg-1), low-dose MLC group (MLC-L, 4.3 g·kg-1), medium-dose MLC group (MLC-M, 8.6 g·kg-1), and high-dose MLC group (MLC-H, 17.2 g·kg-1). Active components of MLC and targets of obesity-type PCOS were screened from databases, a protein-protein interaction (PPI) network was constructed, and gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was performed. The gut microbiota structure was analyzed based on 16S rRNA sequencing and correlated with network pharmacology pathways. Body weight and estrous cycle were dynamically monitored. Ovarian morphology was observed by hematoxylin-eosin (HE) staining. Cell apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL). Enzyme-linked immunosorbent assay (ELISA) was used to detect levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), anti-Müllerian hormone (AMH), testosterone (T), and estradiol (E2). Western blot was used to detect the protein expression levels of phosphorylated PI3K/PI3K (p-PI3K/PI3K), phosphorylated Akt/Akt (p-Akt/Akt), B-cell lymphoma-2 (Bcl-2), and Bcl-2-associated X protein (Bax). ResultsNetwork pharmacology screening identified 124 active components of MLC and 408 overlapping targets between the herbal formula and the disease. Core targets such as Akt1 and Bcl-2 were revealed. As indicated by 16S rRNA sequencing, the abundances of Lachnospiraceae, Lachnoclostridium, and Dorea were increased in the MLC groups (P<0.05), while the abundance of Veillonella was decreased (P<0.05). KEGG correlation analysis integrating network pharmacology and gut microbiota data showed significant enrichment of the PI3K/Akt signaling pathway. Animal experiments showed that, compared with the Mod group, body weight decreased to normal levels in the Met, MLC-M, and MLC-H groups. The estrous cycle became regular. The number of corpora lutea increased and cystic follicles decreased. Serum levels of T, FSH, and LH/FSH were reduced (P<0.05, P<0.01), while the E2 level was increased (P<0.01). Ovarian cell apoptosis was reduced (P<0.01), and the protein expression levels of p-PI3K/PI3K, p-Akt/Akt, and Bcl-2 in ovarian tissue were significantly increased, whereas Bax protein expression was significantly decreased (P<0.05, P<0.01). ConclusionMLC can regulate gut microbiota structure, effectively improve ovarian pathology in rats with obesity-type PCOS, and inhibit ovarian granulosa cell apoptosis. The mechanism may be associated with upregulation of the PI3K/Akt signaling pathway.
2.Mechanisms of Mahuang Lianqiao Chixiaodoutang in Improving Obesity-type Polycystic Ovary Syndrome in Rats Based on PI3K/Akt Signaling Pathway
Shiwei HU ; Biran ZHU ; Jinrong ZHANG ; Luyao RUAN ; Ji KUANG ; Jianghuan HUA ; Zhe LIU ; Yanyue YAO ; Ji WANG ; Min ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):21-31
ObjectiveTo investigate the mechanisms by which Mahuang Lianqiao Chixiaodoutang (MLC) improves obesity-type polycystic ovary syndrome (PCOS) through the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway. MethodsThirty-six female Sprague-Dawley (SD) rats were randomly divided into a blank control group (Con) and an obesity-type PCOS model preparation group. The model was induced by gavage with letrozole (1 mg·kg-1) combined with a high-fat diet (HFD). After model establishment, the obesity-type PCOS model preparation group was further divided into the model group (Mod, normal saline), metformin group (Met, 0.3 g·kg-1), low-dose MLC group (MLC-L, 4.3 g·kg-1), medium-dose MLC group (MLC-M, 8.6 g·kg-1), and high-dose MLC group (MLC-H, 17.2 g·kg-1). Active components of MLC and targets of obesity-type PCOS were screened from databases, a protein-protein interaction (PPI) network was constructed, and gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was performed. The gut microbiota structure was analyzed based on 16S rRNA sequencing and correlated with network pharmacology pathways. Body weight and estrous cycle were dynamically monitored. Ovarian morphology was observed by hematoxylin-eosin (HE) staining. Cell apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL). Enzyme-linked immunosorbent assay (ELISA) was used to detect levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), anti-Müllerian hormone (AMH), testosterone (T), and estradiol (E2). Western blot was used to detect the protein expression levels of phosphorylated PI3K/PI3K (p-PI3K/PI3K), phosphorylated Akt/Akt (p-Akt/Akt), B-cell lymphoma-2 (Bcl-2), and Bcl-2-associated X protein (Bax). ResultsNetwork pharmacology screening identified 124 active components of MLC and 408 overlapping targets between the herbal formula and the disease. Core targets such as Akt1 and Bcl-2 were revealed. As indicated by 16S rRNA sequencing, the abundances of Lachnospiraceae, Lachnoclostridium, and Dorea were increased in the MLC groups (P<0.05), while the abundance of Veillonella was decreased (P<0.05). KEGG correlation analysis integrating network pharmacology and gut microbiota data showed significant enrichment of the PI3K/Akt signaling pathway. Animal experiments showed that, compared with the Mod group, body weight decreased to normal levels in the Met, MLC-M, and MLC-H groups. The estrous cycle became regular. The number of corpora lutea increased and cystic follicles decreased. Serum levels of T, FSH, and LH/FSH were reduced (P<0.05, P<0.01), while the E2 level was increased (P<0.01). Ovarian cell apoptosis was reduced (P<0.01), and the protein expression levels of p-PI3K/PI3K, p-Akt/Akt, and Bcl-2 in ovarian tissue were significantly increased, whereas Bax protein expression was significantly decreased (P<0.05, P<0.01). ConclusionMLC can regulate gut microbiota structure, effectively improve ovarian pathology in rats with obesity-type PCOS, and inhibit ovarian granulosa cell apoptosis. The mechanism may be associated with upregulation of the PI3K/Akt signaling pathway.
3.Reliable Extraction of Seawater Nd and Hf Isotope Compositions from Fe-Mn Oxyhydroxide Fraction of Marine Sediments in the Arctic Ocean
Ying ZHANG ; Lin-Sen DONG ; Hong-Min WANG ; Xiao-Jing WANG ; Lian-Hua HE ; Yan-Guang LIU ; Ji-Hua LIU
Chinese Journal of Analytical Chemistry 2025;53(8):1380-1390
Combined seawater Hf and Nd isotope compositions have been applied as reliable tracers of water mass mixing and weathering input changes.The establishment of standardized synchronous extraction methods for Fe-Mn oxyhydroxide in sediments,which serve as effective carriers for isotopic signals of ancient seawater,is a prerequisite and key for paleoceanography research.The research material of this study was the surface sediments of the Western Arctic Ocean obtained from China's 7th Arctic Scientific Expedition,and a reliable simultaneous Nd-Hf isotope extraction method in Fe-Mn oxyhydroxide fraction was established through systematic optimization of pretreatment procedures and key extraction parameters.This research focused on analyzing the effects of pretreatment(Milli-Q water pre-wash)and key extraction parameters(leaching time,solution/solid ratios,concentration of EDTA-2Na,and concentration of mixed solution of hydroxyamine hydrochloride(HH)and acetic acid(HAc))on element extraction efficiency and isotopic composition.The experimental results indicated that the Milli-Q water pre-wash was not necessary,Fe-Mn oxyhydroxide extraction could be directly performed.Nd extraction amount in Fe-Mn oxyhydroxide fraction was not sensitive to changes in extraction conditions,while the Hf extraction amount was significantly affected by leaching time,solution/solid ratios and concentration of EDTA-2Na.The optimal conditions for synchronously extracting Nd-Hf isotopes were as follows:adding 20 mL of a mixed solution of 0.005 mol/L HH+1.5%HAc+0.03 mol/L EDTA-2Na per gram of sample,and reaction at room temperature for 3 h under shaking.Through systematic verification of 87Sr/86Sr ratio,εNd value,εHf value,Al/Nd ratio and Al/Hf ratio,it was confirmed that this method could effectively avoid interferences from residual components and accurately obtain Nd-Hf isotope signals of ancient seawater preserved in sediments.The standardized method established in this work provided reliable technical support for reconstructing water mass mixing between the Arctic,North Atlantic,and North Pacific Oceans and riverine input histories.It also provided important reference for the extraction methods of Nd and Hf isotopes from marine sources in sediments from other sea areas around the world.
4.Early warning method for invasive mechanical ventilation in septic patients based on machine learning model.
Wanjun LIU ; Wenyan XIAO ; Jin ZHANG ; Juanjuan HU ; Shanshan HUANG ; Yu LIU ; Tianfeng HUA ; Min YANG
Chinese Critical Care Medicine 2025;37(7):644-650
OBJECTIVE:
To develop a method for identifying high-risk patients among septic populations requiring mechanical ventilation, and to conduct phenotypic analysis based on this method.
METHODS:
Data from four sources were utilized: the Medical Information Mart for Intensive Care (MIMIC-IV 2.0, MIMIC-III 1.4), the Philips eICU-Collaborative Research Database 2.0 (eICU-CRD 2.0), and the Anhui Medical University Second Affiliated Hospital dataset. The adult patients in intensive care unit (ICU) who met Sepsis-3 and received invasive mechanical ventilation (IMV) on the first day of first admission were enrolled. The MIMIC-IV dataset with the highest data integrity was divided into a training set and a test set at a 6:1 ratio, while the remaining datasets were served as validation sets. The demographic information, comorbidities, laboratory indicators, commonly used ICU scores, and treatment measures of patients were extracted. Clinical data collected within first day of ICU admission were used to calculate the sequential organ failure assessment (SOFA) score. K-means clustering was applied to cluster SOFA score components, and the sum of squared errors (SSE) and Davies-Bouldin index (DBI) were used to determine the optimal number of disease subtypes. For clustering results, normalized methods were employed to compare baseline characteristics by visualization, and Kaplan-Meier curves were used to analyze clinical outcomes across phenotypes.
RESULTS:
This study enrolled patients from MIMIC-IV dataset (n = 11 166), MIMIC-III dataset (n = 4 821), eICU-CRD dataset (n = 6 624), and a local dataset (n = 110), with the four datasets showing similar median ages and male proportions exceeding 50%; using 85% of the MIMIC-IV dataset as the training set, 15% as the test set, and the rest dataset as the validation set. K-means clustering based on the six-item SOFA score was performed to determine the optimal number of clusters as 3, and patients were finally classified into three phenotypes. In the training set, compared with the patients with phenotype II and phenotype III, those with phenotype I had the more severe circulatory and respiratory dysfunction, a higher proportion of vasoactive drug usage, more obvious metabolic acidosis and hypoxia, and a higher incidence of congestive heart failure. The patients with phenotype II was dominated by respiratory dysfunction with higher visceral injury. The patients with phenotype III had relatively stable organ function. The above characteristics were consistent in both the test and validation sets. Analysis of infection-related indicators showed that the patients with phenotype I had the highest SOFA score within 7 days after ICU admission, initial decreases and later increases in platelet count (PLT), and higher counts of neutrophils, lymphocytes, and monocytes as compared with those with phenotype II and phenotype III, their blood cultures had a higher positivity rates for Gram-positive bacteria, Gram-negative bacteria and fungi as compared with those with phenotype II and phenotype III. The Kaplan-Meier curve indicated that in the training, test, and validation sets, the 28-day cumulative mortality of patients with phenotype I was significantly higher than that of patients with phenotypes II and phenotype III.
CONCLUSIONS
Three distinct phenotypes in septic patients receiving IMV based on unsupervised machine learning is derived, among which phenotype I, characterized by cardiorespiratory failure, can be used for the early identification of high-risk patients in this population. Moreover, this population is more prone to bloodstream infections, posing a high risk and having a poor prognosis.
Humans
;
Machine Learning
;
Sepsis/therapy*
;
Respiration, Artificial
;
Intensive Care Units
;
Organ Dysfunction Scores
;
Male
;
Female
;
Middle Aged
;
Adult
5.Clinical characteristics and prognostic risk factors of patients with atrial fibrillation related to septic shock
Jiading XIA ; Liwei HUA ; Min XU ; Guobin LI ; Xin ZHENG ; Kun ZHANG
Journal of China Medical University 2025;54(7):631-637
Objective To analyze the clinical characteristics and prognostic risk factors of patients with atrial fibrillation(AF)related to septic shock admitted to the intensive care unit(ICU).Methods This retrospective cohort study included 152 patients with septic shock who were admitted to the ICU between January 2020 and December 2023.Patients were categorized into AF(n=48)and non-AF(n=104)groups based on the occurrence of AF.Clinical parameters were compared between the two groups,and variables with statistically significant differences(P<0.05)were entered into a multivariate logistic regression analysis to identify clinical features associated with AF.Patients were also stratified into survival(n=103)and death(n=49)groups based on 28-day outcomes.Variables showing signifi-cant intergroup differences(P<0.05)were further included in a multivariate model to identify independent risk factors for mortality.Kaplan-Meier survival analysis was performed using AF as a binary variable,and log-rank tests were applied to compare survival curves.Results The incidence of AF was 31.58%among patients with septic shock.Compared with the non-AF group,the AF group was older,received higher cumulative doses of vasoactive agents,and had elevated levels of lactate(Lac),N-terminal brain natriuretic peptide precursor(NT-proBNP),troponin I(cTnI),tumor necrosis factorα(TNF-α),and C-reactive protein(CRP).The AF group also had higher E/e'ratios,left ventricular ejection fraction(LVEF),Acute Physiology and Chronic Health Evaluation-Ⅱ(APACHEⅡ)scores,Sequen-tial Organ Failure Assessment(SOFA)scores,and 28-day mortality rates(all P<0.05).Multivariate logistic regression identified age(odds ratio[OR]=1.060,P=0.015),SOFA score(OR=1.525,P=0.001),TNF-α(OR=1.009,P=0.026),CRP(OR=1.008,P=0.002),and E/e'(OR=1.363,P=0.023)as independent risk factors for AF.The 28-day mortality rate was 32.24%.Compared with survivors,non-survivors had significantly higher Lac,cTnI,E/e',LVEF,and TNF-α levels,higher APACHEⅡand SOFA scores,longer ICU stays,and a higher incidence of AF(all P<0.05).Multivariate analysis identified SOFA score,cTnI,E/e',and AF as independent predictors of 28-day mortality.Kaplan-Meier analysis revealed significantly poorer survival in patients with AF(χ2=6.747,P=0.009).Conclusion AF is common in ICU patients with septic shock.Advanced age,greater organ dysfunction,elevated inflammatory markers,and diastolic dysfunction are associated with AF occurrence.Organ dysfunction,myocardial injury,diastolic dysfunction,and AF are inde-pendent predictors of mortality in this population.Greater clinical attention is warranted in patients with AF and septic shock due to their elevated risk of poor outcomes.
6.Effects of epifriedelanol on gene expression of P-glycoprotein in human colorectal adenocarcinoma cell line LS174T
Jie JIANG ; Xiao-li ZHANG ; Shi-jia XIANG ; Li-hua YAO ; Guo-ping ZHONG ; Min HUANG ; Yu-hua LI
The Chinese Journal of Clinical Pharmacology 2025;41(1):50-54
Objective To investigate the effect of epifriedelanol(Epi)on gene expression of P-glycoprotein(P-gp)in human colorectal adenocarcinoma cell line LS174T and its mechanism.Methods LS174T cells were divided into control group and experimental-L,-M,-H groups.Experimental-L,-M,-H groups were treated with 5,10,20 μmol·L-1 Epi,respectively.Control group was treated with 0.1%dimethyl sulfoxide.Polymerase chain reaction was used to detect the mRNA expression level of P-gp.Theeffect of Epi on multidrug resistance protein 1(MDR1/P-gp)luciferase activity was investigated by pregnane X receptor(PXR)-MDR1/P-gp dual luciferase reporter gene assay.In addition,Western Blot was used to detect the protein expression level of P-gp and the nuclear factor-κB(NF-κB)pathway related proteins.Results The relative expression levels of P-gp mRNA in experimental-M,-H groups and control group were 52.24±5.19,23.00±3.52 and 100.00±9.00;the relative expression levels of P-gp protein were 86.37±9.96,74.85±15.92 and 100.00±12.91;the relative activities P-gp luciferase were 230.19±41.32,203.10±52.84 and 279.67±19.20;the relative expression levels of p65(RelA/p65)in nucleus were 132.36±23.93,145.96±25.15 and 100.00±10.88;the relative expression levels of phosphorylation NF-κB inhibits protein kinase α/β(p-IKKα/β)in cytoplasm were 184.00±54.82,290.10±49.59 and 100.00±15.34;the relative expression levels of phosphorylated NF-κB inhibitory protein α(p-IκBα)in cytoplasm were 125.73±18.77,133.69±20.25 and 100.00±8.12;the relative expression levels of IκBα in cytoplasm were 78.36±14.83,70.44±14.57 and 100.00±22.82,respectively.The above indexes of experimental-M and experimental-H groups were compared with control group,and the differences were statistically significant(P<0.05,P<0.01,P<0.001).Conclusion Epi can down-regulate the gene expression of P-gp in human colorectal adenocarcinoma cell line LS174T,and the mechanism may be related to activation of NF-κB and suppression of PXR.
7.Effects of Schisandrae Fructus alone or in combination in viral hepatitis treatment: A systematic review and meta-analysis of randomized controlled trials
Lujie LIN ; Mingxiao ZHANG ; Huijuan XIE ; Min YANG ; Tong ZHU ; Junxuan YANG ; Bin YANG ; Hua LI
Science of Traditional Chinese Medicine 2025;3(1):69-80
Background: Viral hepatitis causes annual deaths of 1.4 million people. Antiviral therapy rarely cures the disease, and patients are usually required to maintain lifelong medication, leading to cumulative drug toxicity. Schisandrae Fructus (SF) is efficacious in the treatment of viral hepatitis. Objective: The systematic review and meta-analysis aim to examine the efficacy and safety of SF alone or in combination with specific and nonspecific treatments for treating viral hepatitis by analyzing the clinical trials performed up to date. Methods: An extensive literature was searched in 7 databases from inception to May 2023. Final outcomes were divided into the primary outcomes containing the total effective rate and virological responses, as well as the secondary outcomes containing liver biochemical functions and frequencies of adverse events. RevMan 5.3 and GRADE pro 3.6 software were used for meta-analysis and assessment of evidence quality. Subgroup analysis was conducted to explore the source of the heterogeneity. Results: Twenty-nine randomized controlled trials were included in the meta-analysis. SF treatment was comparable with western medicines or other traditional Chinese treatments in terms of primary and secondary outcomes. In combination with specific treatments with antiviral medicines, SF group reduced 18.45 U/L of alanine aminotransferase levels [weighted mean difference: 18.45, 95% confidence interval (CI): (16.12, 20.78), p < 0.000 01] and 8.37 U/L of aspartate aminotransferase levels [weighted mean difference: 8.37, 95% CI: (1.25, 15.48), p = 0.02], and it decreased the levels of hyaluronic acid (HA) [standard mean difference (SMD): 0.92, 95% CI: (0.58, 1.27), p < 0.000 01], laminin (LN) [SMD: 0.64, 95% CI: (0.38, 0.90), p < 0.000 01], and procollagen type III [SMD: 0.48, 95% CI: (0.28, 0.67), p < 0.000 01], while increasing the total effective rate by 24% [risk ratio: 1.24, 95% CI: (1.15, 1.32), p < 0.000 01]. There were no severe adverse events during treatment. Conclusions: SF was a potential adjuvant for antiviral therapy in restoring liver function. However, the poor quality of the included randomized controlled trials limited the recommendations. More long-term, randomized, and double-blind studies should be performed to assess the efficacy and safety of combination therapy.
8.Effects of Schisandrae Fructus alone or in combination in viral hepatitis treatment: A systematic review and meta-analysis of randomized controlled trials
Lujie LIN ; Mingxiao ZHANG ; Huijuan XIE ; Min YANG ; Tong ZHU ; Junxuan YANG ; Bin YANG ; Hua LI
Science of Traditional Chinese Medicine 2025;3(1):69-80
Background: Viral hepatitis causes annual deaths of 1.4 million people. Antiviral therapy rarely cures the disease, and patients are usually required to maintain lifelong medication, leading to cumulative drug toxicity. Schisandrae Fructus (SF) is efficacious in the treatment of viral hepatitis. Objective: The systematic review and meta-analysis aim to examine the efficacy and safety of SF alone or in combination with specific and nonspecific treatments for treating viral hepatitis by analyzing the clinical trials performed up to date. Methods: An extensive literature was searched in 7 databases from inception to May 2023. Final outcomes were divided into the primary outcomes containing the total effective rate and virological responses, as well as the secondary outcomes containing liver biochemical functions and frequencies of adverse events. RevMan 5.3 and GRADE pro 3.6 software were used for meta-analysis and assessment of evidence quality. Subgroup analysis was conducted to explore the source of the heterogeneity. Results: Twenty-nine randomized controlled trials were included in the meta-analysis. SF treatment was comparable with western medicines or other traditional Chinese treatments in terms of primary and secondary outcomes. In combination with specific treatments with antiviral medicines, SF group reduced 18.45 U/L of alanine aminotransferase levels [weighted mean difference: 18.45, 95% confidence interval (CI): (16.12, 20.78), p < 0.000 01] and 8.37 U/L of aspartate aminotransferase levels [weighted mean difference: 8.37, 95% CI: (1.25, 15.48), p = 0.02], and it decreased the levels of hyaluronic acid (HA) [standard mean difference (SMD): 0.92, 95% CI: (0.58, 1.27), p < 0.000 01], laminin (LN) [SMD: 0.64, 95% CI: (0.38, 0.90), p < 0.000 01], and procollagen type III [SMD: 0.48, 95% CI: (0.28, 0.67), p < 0.000 01], while increasing the total effective rate by 24% [risk ratio: 1.24, 95% CI: (1.15, 1.32), p < 0.000 01]. There were no severe adverse events during treatment. Conclusions: SF was a potential adjuvant for antiviral therapy in restoring liver function. However, the poor quality of the included randomized controlled trials limited the recommendations. More long-term, randomized, and double-blind studies should be performed to assess the efficacy and safety of combination therapy.
9.Effects of Schisandrae Fructus alone or in combination in viral hepatitis treatment: A systematic review and meta-analysis of randomized controlled trials
Lujie LIN ; Mingxiao ZHANG ; Huijuan XIE ; Min YANG ; Tong ZHU ; Junxuan YANG ; Bin YANG ; Hua LI
Science of Traditional Chinese Medicine 2025;3(1):69-80
Background: Viral hepatitis causes annual deaths of 1.4 million people. Antiviral therapy rarely cures the disease, and patients are usually required to maintain lifelong medication, leading to cumulative drug toxicity. Schisandrae Fructus (SF) is efficacious in the treatment of viral hepatitis. Objective: The systematic review and meta-analysis aim to examine the efficacy and safety of SF alone or in combination with specific and nonspecific treatments for treating viral hepatitis by analyzing the clinical trials performed up to date. Methods: An extensive literature was searched in 7 databases from inception to May 2023. Final outcomes were divided into the primary outcomes containing the total effective rate and virological responses, as well as the secondary outcomes containing liver biochemical functions and frequencies of adverse events. RevMan 5.3 and GRADE pro 3.6 software were used for meta-analysis and assessment of evidence quality. Subgroup analysis was conducted to explore the source of the heterogeneity. Results: Twenty-nine randomized controlled trials were included in the meta-analysis. SF treatment was comparable with western medicines or other traditional Chinese treatments in terms of primary and secondary outcomes. In combination with specific treatments with antiviral medicines, SF group reduced 18.45 U/L of alanine aminotransferase levels [weighted mean difference: 18.45, 95% confidence interval (CI): (16.12, 20.78), p < 0.000 01] and 8.37 U/L of aspartate aminotransferase levels [weighted mean difference: 8.37, 95% CI: (1.25, 15.48), p = 0.02], and it decreased the levels of hyaluronic acid (HA) [standard mean difference (SMD): 0.92, 95% CI: (0.58, 1.27), p < 0.000 01], laminin (LN) [SMD: 0.64, 95% CI: (0.38, 0.90), p < 0.000 01], and procollagen type III [SMD: 0.48, 95% CI: (0.28, 0.67), p < 0.000 01], while increasing the total effective rate by 24% [risk ratio: 1.24, 95% CI: (1.15, 1.32), p < 0.000 01]. There were no severe adverse events during treatment. Conclusions: SF was a potential adjuvant for antiviral therapy in restoring liver function. However, the poor quality of the included randomized controlled trials limited the recommendations. More long-term, randomized, and double-blind studies should be performed to assess the efficacy and safety of combination therapy.
10.A multicenter retrospective study on the clinicopathological features, genetic variant profiles and prognosis of patients with previously untreated Diffuse large B-cell lymphoma.
Yongning JIANG ; Jie ZHANG ; Yaping ZHANG ; Yi XIA ; Yi MIAO ; Haiwen NI ; Jinning SHI ; Xiaohui ZHANG ; Min XU ; Haiying HUA ; Yun ZHUANG ; Wenzhong WU ; Maozhong XU ; Xiaoyan XIE ; Zhuxia JIA ; Yuqing MIAO ; Min ZHAO ; Jianyong LI ; Wenyu SHI
Chinese Journal of Medical Genetics 2025;42(9):1069-1077
OBJECTIVE:
To explore the impact of age on the genetic variant spectrum and prognosis of patients with previously untreated Diffuse large B-cell lymphoma (DLBCL).
METHODS:
A retrospective analysis was conducted on the clinical data and follow-up information of 254 previously untreated DLBCL patients from 14 hospitals in the Jiangsu Cooperative Lymphoma Group (JCLG) enrolled from July 2018 and July 2023. Following extraction of DNA from tumor tissue samples, next-generation sequencing (NGS) technique was employed to analyze the genetic variant spectrum of the DLBCL patients, with an evaluation of the relationship between age and genetic variants as well as prognosis. This study was approved by the Medical Ethics Committee of the Affiliated Hospital of Nantong University (Ethics No.: 2023-K048-01).
RESULTS:
The median age of the 254 DLBCL patients was 62 years old, with 55% of patients aged 60 years or above. Clinical evaluation showed that younger (< 60 years) patients had higher complete response (CR) (70% vs. 59%), and objective response rate (ORR) (88% vs. 79%) than older patients, though the difference between the two groups was not statistically. Survival analysis indicated that both the five-year overall survival (OS) (82.7% vs. 71.7%, P = 0.006) and progression-free survival (PFS) (70.6% vs. 50.2%, P < 0.05) rates were significantly higher in younger patients. NGS showed that 99.6% of the patients harbored genetic variants, with PIM1, KMT2D, TP53, MYD88, and CD79B being the most common genes. Age significantly affected the variant frequency of certain genes, with MYC variants serving an adverse prognostic factor for OS in younger patients (P = 0.002), while TP53 (P = 0.024) and BCL2 (P = 0.002) variants significantly impacted OS in older patients. Prognostic analysis identified age ≥ 60 years (HR = 3.439, 95%CI: 1.318~9.874), presence of B symptoms (HR = 2.871, 95%CI = 1.133~7.307), and elevated lactate dehydrogenase (HR = 3.528, 95%CI = 1.231~10.66) as independent adverse prognostic factors.
CONCLUSION
Age, genetic variants, and clinical factors may significantly affect the prognosis of the DLBCL patients. Younger patients have better survival compared to older patients. Variants of the MYC, BCL2, and TP53 genes are closely associated with poor prognosis.
Humans
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Lymphoma, Large B-Cell, Diffuse/diagnosis*
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Middle Aged
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Female
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Male
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Retrospective Studies
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Aged
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Prognosis
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Adult
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Aged, 80 and over
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High-Throughput Nucleotide Sequencing
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Young Adult
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Adolescent
;
Genetic Variation

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