1.Mechanisms of Xiaozhi Qinggan Decoction in Treatment of Metabolic Dysfunction-associated Steatotic Liver Disease by Regulating Ferroptosis
Haihang DONG ; Yuying TU ; Xingrong LI ; Yujie CAI ; Yi REN ; Huiqin ZHANG ; Yinqiang ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(6):109-119
ObjectiveTo investigate the mechanism of Xiaozhi Qinggan decoction (XQD) in preventing and treating metabolic dysfunction-associated steatotic liver disease (MASLD) by regulating ferroptosis, network pharmacology, in vitro and in vivo experiments. MethodsIn the in vivo experiment, mouse MASLD models were established by high-fat diet (HFD) induction. The model mice were randomly assigned to a positive control group (silybin, 50 mg·kg-1), low-, medium- and high-dose XQD groups (4.725, 9.45, 18.9 g·kg-1), with a normal control group. After 4 weeks of modeling, mice except the normal group were administered intragastrically for 8 consecutive weeks. Liver function, serum lipid levels, hepatic histopathology, as well as the levels of malondialdehyde (MDA), superoxide dismutase (SOD), reduced glutathione (GSH) and oxidized glutathione (GSSG) and Fe2+ were detected. The mRNA and protein expression of p53, SLC7A11 and GPX4 were determined by quantitative Real-time quantitative polymerase chain reaction(Real-time PCR) and Western blot. In the network pharmacology analysis, active components and potential targets of XQD for MASLD were screened, followed by functional and pathway enrichment analyses, and molecular docking was performed to verify the target binding activity. In the in vitro experiment, the optimal concentration of XQD-containing serum was screened by cytotoxicity assay. HepG2 cells were transfected with ov-NC or ov-p53 plasmid, and a lipid accumulation model was induced by free fatty acid (FFA, 1.0 mmol·L-1). Cells were divided into a normal group, FFA model group, ov-NC+XQD (15%) group and ov-p53+XQD (15%) group. Intracellular Fe2+ level and lipid accumulation were evaluated, and the protein expression of p53, SLC7A11 and GPX4 was measured by Western blot. ResultsCompared with the normal group, the model group exhibited markedly elevated body weight, liver weight, liver index, fasting blood glucose, AUC of glucose tolerance test, serum liver function and blood lipid levels at week 12 (P<0.01). Hepatic steatosis and inflammatory infiltration were observed by pathological staining. Additionally, hepatic levels of MDA, SOD and Fe2+ were increased (P<0.01), while GSH, GSSG and the GSH/GSSG ratio were decreased (P<0.01). The mRNA and protein expression of hepatic p53 was upregulated (P<0.01), whereas the expression of SLC7A11 and GPX4 was downregulated (P<0.01). Compared with the model group, the low- and medium-dose XQD groups showed significantly decreased body weight at week 12 (P<0.05). The silybin group, together with the medium- and high-dose XQD groups, presented reduced liver weight and liver index (P<0.05). Fasting blood glucose and the AUC of glucose tolerance test were lowered in all four treatment groups (P<0.05, P<0.01). Pathological staining revealed alleviated hepatic steatosis and inflammation, accompanied by decreased serum liver function and blood lipid levels (P<0.05, P<0.01). Moreover, hepatic MDA and SOD levels were markedly reduced, while GSH, GSSG and the GSH/GSSG ratio were significantly elevated (P<0.05, P<0.01). Hepatic Fe2+ level was decreased (P<0.01). The mRNA and protein expression of hepatic p53 was downregulated, and the expression of SLC7A11 and GPX4 was upregulated (P<0.05, P<0.01). Network pharmacology analysis identified quercetin, kaempferol, luteolin, tanshinone IIA and isorhamnetin as the core active components of XQD, with p53 serving as the key target. Stable binding was verified between these active components and the p53 protein. The optimal concentration of XQD-containing serum in vitro was determined to be 15%. Compared with the normal group, the model group showed increased intracellular Fe2+ and lipid accumulation, significantly upregulated p53 protein expression (P<0.01), and markedly downregulated SLC7A11 and GPX4 protein expression (P<0.01). Compared with the model group, the ov-NC group exhibited reduced Fe2+ and lipid accumulation, downregulated p53 expression, and upregulated SLC7A11 and GPX4 expression. In the ov-p53 group, p53 expression was upregulated (P<0.01), while SLC7A11 and GPX4 expression was downregulated (P<0.01). ConclusionXQD inhibits ferroptosis by downregulating p53 and upregulating SLC7A11 and GPX4, thereby alleviating oxidative stress and lipid peroxidation in hepatocytes and improving MASLD.
2.Experience in Staged Differentiation and Treatment of Cirrhotic Ascites Based on the Theory of Tonification and Purging
Haihang DONG ; Yujie CAI ; Huiqin ZHANG ; Yan CHEN ; Yuying TU ; Dongling WANG ; Yinqiang ZHANG
Journal of Traditional Chinese Medicine 2025;66(5):532-536
It is believed that patients with cirrhotic ascites exhibit a pathological mechanism characterized by the decline of healthy qi and the accumulation of pathogenic factors. Clinically, treatment should be based on the theory of tonification and purging, with a staged approach distinguishing between the active phase and the remission phase. The balance between tonification and purging should be adjusted according to the progression of pathogenic and healthy actors. In the acute phase, purging should take precedence over tonification, using purging as a means of tonification to facilitate the flow of water and qi through the triple energizer. The severity of water retention, dampness, blood stasis, and heat should be carefully assessed to ensure thorough elimination of pathogenic factors while avoiding harm to healthy qi. Medication adjustments should be made once the pathogenic factors are significantly weakened. In the remission phase, an integrated approach combining both tonification and purging should be adopted, incorporating purging within tonification to clear residual pathogens and prevent recurrence. Concurrently, proactive treatment of the underlying disease is essential to achieve complete recovery and prevent the recurrence of ascites.
3.Effects of wogonin on joint inflammation in collagen-induced arthritis rats via the endoplasmic reticulum stress pathway
Yuru WANG ; Siyuan LI ; Ye XU ; Yumeng ZHANG ; Yang LIU ; Huiqin HAO
Chinese Journal of Tissue Engineering Research 2025;29(5):1026-1035
BACKGROUND:Rheumatoid arthritis is an inflammatory disease.Many studies have shown that wogonin has a good anti-inflammatory effect on rheumatoid arthritis,but its exact efficacy and specific mechanism of action remain to be clarified. OBJECTIVE:To investigate the mechanism of wogonin ameliorating joint inflammation by regulating endoplasmic reticulum stress pathway in rats with collagen-induced arthritis. METHODS:(1)At the animal level:Female Wistar rats were divided into healthy control group,arthritis model group and wogonin treatment group.Rat models of arthritis in the latter two groups were established by subcutaneous injection of bovine type Ⅱ collagen and adjuvant.In the wogonin group,wogonin was given by gavage for 28 consecutive days after modeling.During this period,the rats in each group were weighed,and arthritis score and ankle swelling were measured every 7 days.After the experiment,the pathological changes of the joint were observed,the mRNA and protein levels of endoplasmic reticulum stress pathway GRP78 and CHOP were detected by qRT-PCR,western blot,and immunohistochemistry.(2)At the cellular level,cell counting kit-8 was used to detect the cytotoxic effect of wogonin on fibroblast-like synoviocytes from rats with collagen-induced arthritis.The fibroblast-like synoviocytes induced by thapsigargin were treated with different concentrations of wogonin.The levels of interleukin-1β and tumor necrosis factor-α in the cell supernatant were detected by ELISA,and the intracellular reactive oxygen species in each group were determined by DCFH-DA probe method.The mRNA and protein levels of GRP78,IRE1α,XBP1s and CHOP were detected by qRT-PCR and western blot,respectively. RESULTS AND CONCLUSION:Compared with the healthy control group,arthritis index score and ankle swelling degree in the arthritis model group were increased(P<0.01),synovial hyperplasia,inflammatory cell infiltration,cartilage destruction and bone erosion were observed in pathological sections,and the mRNA and protein expressions of GRP78 and CHOP in the ankle were significantly increased(P<0.01),which were mainly located in synovial tissue and articular surface.Compared with the arthritis model group,the arthritis index score and ankle swelling degree in the wogonin treatment group were decreased(P<0.05),synovial hyperplasia and the number of inflammatory cells were decreased,cartilage destruction and bone erosion were alleviated,the mRNA and protein expression levels of GRP78 and CHOP in the ankle were decreased(P<0.05),particularly in synovial tissue and on the articular surface.There was no significant difference in body mass among the three groups(P>0.05).In the cell experiment,200 μmol/L wogonin significantly reduced the survival rate of fibroblast-like synoviocytes(P<0.01).Compared with the blank control group,the levels of interleukin-1β,tumor necrosis factor-α,content of reactive oxygen species,and mRNA and protein expression of GRP78,IRE1α,XBP1s,and CHOP in the thapsigargin group were significantly increased(P<0.05);compared with the thapsigargin group,50 and 100 μmol/L wogonin significantly reduced the levels of interleukin-1β and tumor necrosis factor-α in the cell supernatant(P<0.05,P<0.01),and 100 μmol/L wogonin significantly reduced the content of reactive oxygen species(P<0.01)and down-regulated the mRNA and protein expression levels of GRP78,IRE1α,XBP1s and CHOP(all P<0.05).These results suggest that wogonin can effectively alleviate joint inflammatory responses in rats with collagen-induced arthritis,and the endoplasmic reticulum stress pathway may be the key target of its intervention.
4.Genetic detection for hereditary cancer syndrome among general population
Xinning CHEN ; Li ZHANG ; Li YU ; Huiqin JIANG ; Fei HUANG ; Chunyan ZHANG ; Baishen PAN ; Beili WANG ; Wei GUO
Chinese Journal of Clinical Medicine 2025;32(4):627-633
Objective To examine the significance of susceptible gene detection for hereditary cancer syndrome (HCS) among general population. Methods A total of 2 928 individuals undergoing routine health examinations in Healthcare Center of Zhongshan Hospital, Fudan University, from September 2021 to April 2024 were enrolled retrospectively. Next generation sequencing was employed to identify susceptible genes for HCS. American College of Medical Genetics and Genomics (ACMG) guideline was used to analyze the pathogenicity of variants. Clinical data, imagings, follow-up data were also collected. Results The overall mutation rate of HCS panel was 3.59% (105/2 928), with 0.61% (18/2 928) for MutY DNA glycosylase (MUTYH), 0.27% (8/2 928) for breast cancer susceptibility gene 1/2 (BRCA1/2) and 0.23% (7/2 928) for mismatch repair (MMR) genes. Conclusions Healthy individuals carrying tumor susceptible genes usually lack the relevant clinical phenotypes. Whether comprehensive testing needs to be carried out among healthy people remains to be further explored.
5.Relationship between eNOS gene polymorphism and main complications in premature infants
Xiaoyan Li ; Bing Li ; Jia' ; an Wang ; Xian Dong ; Huiqin Wang ; Haijuan Zhu ; Bin Zhang
Acta Universitatis Medicinalis Anhui 2025;60(4):719-724
Objective :
To explore the polymorphism of endothelial nitric oxide synthase(eNOS) gene in umbilical cord blood of preterm infants and its relationship with major complications in preterm infants.
Methods :
A total of 254 preterm infants(<37 weeks) who were hospitalized were selected as the study subjects. Umbilical cord blood was collected at delivery to determine the genotypes and alleles of eNOS gene at three loci: rs61722009, rs2070744,and rs1799983. Clinical data of the preterm infants were recorded, and the relationship between eNOS gene polymorphism and major complications in preterm infants was analyzed.
Results:
(1) The TC+CC genotype at locus rs2070744 was an independent risk factor for bronchopulmonary dysplasia(BPD) in preterm infants, with an OR(95%CI) of 1.266(1.017-1.577).(2) The GT+TT genotype at locus rs1799983 was an independent risk factor for retinopathy prematurity(ROP), with an OR(95%CI) of 1.184(1.008-1.391).(3) The AB+AA genotype at locus rs61722009 was also an independent risk factor for ROP,with an OR(95%CI) of 1.335(1.033-1. 726).(4) There was no significant relationship between gene polymorphism and the occurrence of respiratory distress syndrome( RDS) and periventricular-intraventricular hemorrhage( PIVH).
Conclusion
eNOS gene polymorphism is associated with the occurrence of BPD and ROP in preterm infants. The evaluation of e NOS gene polymorphism by umbilical cord blood measurement is helpful for the prevention and correct management of some serious complications.
6.The current situation and influencing factors of patient perception for humanistic care in 30 provincial hospitals
Fengjian ZHANG ; Haixin ZHANG ; Yilan LIU ; Shaoshan PAN ; Shujie GUO ; Xia XIN ; Yan YANG ; Huiqin XI ; Xiue LI ; Yuanjuan CHENG ; Beirong MO ; Weihua LI ; Xiaohong ZHANG ; Fang WANG ; Hongxia WANG
Chinese Journal of Nursing 2024;59(3):324-330
Objective To understand the current status and influencing factors of patient perception for humanistic care in China hospitals,and to provide a basis for developing nursing humanistic care measures and improving the quality of nursing humanistic care services.Methods A total of 30,099 outpatients and inpatients from 107 hospitals in 30 provinces(autonomous regions and municipalities)from July to August 2022 as survey subjects.A general information questionnaire and the Relational Caring Questionnaire-Patient Form were used for a cross-sectional survey,and a single-factor analysis was used to analyze the influencing factors of patient relationship care.Results Finally,29 108 valid questionnaires were collected,and the effective questionnaire recovery rate was 96.7%.The patient evaluation of relationship care was(65.72±8.61)points.Single-factor analysis showed that gender,age,marital status,children's situation,education level,occupation,place of residence,average family income,medical insurance type,visiting department,and location of the visiting hospital,and whether or not surgery were influencing factors of patient relationship care(P<0.05).Conclusion The evaluation score of caregiver-patient relationship care among Chinese hospital patients is above average,but there is still room for improvement in western and rural regions,seriously ill and outpatient patients,low-income and low-medical insurance reimbursement populations,and non-surgical patients.Medical institutions at all levels should optimize and improve nursing humanistic care services based on influencing factors,and further enhance patients'perception of nursing humanistic care.
7.Comparison of clinical manifestations, laboratory characteristics and treatment of 153 patients with acute and chronic brucellosis
Huiqin YANG ; Haipeng ZHENG ; Xudan CHEN ; Ying TAN ; Fuchun ZHANG ; Linghua LI ; Jian WANG
Chinese Journal of Endemiology 2024;43(5):398-403
Objective:To learn about the clinical manifestations, laboratory characteristics and treatment of patients with acute and chronic brucellosis.Methods:Clinical data of 153 brucellosis patients admitted to the Guangzhou Eighth People's Hospital, Guangzhou Medical University from 2012 to 2022 were retrospectively collected, including general information, epidemiological characteristics, clinical manifestations, laboratory test results, imaging examination results, treatment and prognosis. According to the course of disease < 180 d and ≥180 d, these patients were divided into acute brucellosis group and chronic brucellosis group, and the clinical data of the two groups of patients were compared and analyzed.Results:A total of 153 patients with brucellosis were included, including 119 in the acute brucellosis group and 34 in the chronic brucellosis group. The age was (46.2 ± 13.8) years old, with 115 males (75.2%) and 38 females (24.8%), and 85 patients (55.6%) were occupational exposed. Complications occurred in 90 patients (58.8%), and the incidence of complications in the acute brucellosis group was lower than that in the chronic brucellosis group [76.5% (26/34) vs 53.8% (64/119), χ 2 = 5.62, P = 0.018]. The most common clinical manifestations were fever and arthralgia, with 128 cases (83.7%) and 124 cases (81.0%), respectively. The incidence of fever in the acute brucellosis group was higher than that in the chronic brucellosis group [87.4% (104/119) vs 70.6% (24/34), χ 2 = 5.46, P = 0.019], while the incidence of arthralgia was lower than that in the chronic brucellosis group [77.3% (92/119) vs 94.1% (32/34), χ 2 = 4.83, P = 0.027]. In laboratory tests, the positive rate of blood culture was 59.5% (91/153), and it was higher in the acute brucellosis group than that in the chronic brucellosis group [67.2% (80/119) vs 32.4% (11/34), P < 0.05]. The incidence of elevated procalcitonin [PCT, 58.6% (58/99) vs 24.1% (7/29), χ 2 = 10.65, P = 0.001] and the incidence of liver dysfunction [33.9% (40/118) vs 15.2% (5/33), χ 2 = 4.33, P = 0.037] in the acute brucellosis group were higher than those in the chronic brucellosis group. In the imaging examination, 61 patients (39.9%) experienced bone destruction, and the incidence of bone destruction in the chronic brucellosis group was higher than that in the acute brucellosis group [55.9% (19/34) vs 35.3% (42/119), χ 2 = 4.68, P = 0.031]. All patients were treated with antibiotics, with a median of 3 and 4 types of antibiotics used in the acute and chronic brucellosis groups, respectively. The overall incidence of adverse drug reactions was 5.2% (8/153). After treatment, 65 cases (42.5%) recovered, 70 cases (45.8%) improved, and 18 cases (11.8%) did not recover. Conclusions:The main clinical manifestations of brucellosis patients are fever and arthralgia, with a high incidence of complications. All patients are treated with combined antibiotics therapy. Patients in acute brucellosis group have a higher incidence of fever, positive blood culture, elevated PCT and abnormal liver function, while patients in chronic brucellosis group have a higher incidence of complications, arthralgia and bone destruction.
8.Analysis of the suspected cases of measles and rubella in Pudong New Area of Shanghai, 2013‒2022
Xiao WANG ; Aihua ZHANG ; Huiqin FU ; Yuying YANG ; Xiaoxian CUI ; Lipeng HAO ; Yanqiu ZHOU ; Lifeng PAN
Shanghai Journal of Preventive Medicine 2024;36(6):534-539
ObjectiveTo analyze the epidemic characteristics of measles and rubella in Pudong New Area of Shanghai from 2013 to 2022, and to provide data support for the elimination of measles and rubella. MethodsEnzyme linked immunosorbent assay was used to detect IgM antibodies in serum samples. The sequence of 630 nucleotides at the C-terminal of N gene of measles virus was amplified by reverse transcription-polymerase chain reaction and the phylogenic tree was constructed. ResultsA total of 1 529 suspected cases of measles were detected from 2013 to 2022, among which the positive rate of measles IgM antibody was 33.55% (513/1 529). The highest positive rate (20.73%) was from March to May , and the positive rate of rubella IgM antibody was 6.80% (104/1 529). The positive rate of both IgM was higher in males than that in females (P<0.05). The IgM against measles was mainly detected in 0‒ years old (63.16%, 96/152) and 20‒ years old (45.61%, 161/353). The IgM against rubella was mainly detected in 10‒20 years old (27.27%, 18/66). The IgM antibody could be detected more easily from 4 to 28 days after eruption, and the IgM antibody positive rate of measles/rubella from 2020 to 2022 was significantly lower than previous years (2013‒2019). There were 2 D8 genotype strains, and the rest were H1a gene subtypes. ConclusionThe positive rate of IgM antibodies against measles/rubella in Pudong New Area of Shanghai decreased significantly. People aged 0‒ years and 20‒ years old are more susceptible to measles, and rubella is concentrated in 10‒ years old. It is necessary to strengthen the vaccination of school-age children, in order to achieve the goal of eliminating measles. The age group with high risk of exposure should be checked for vaccination status to ensure the enhanced immunization, and the surveillance of imported measles cases should be strengthened.
9.Transesophageal echocardiography for guiding left atrial appendage closure with LAmbre occluder
Meng ZHANG ; Wen HE ; Lijuan DU ; Tingyu LAN ; Yifei LYU ; Huiqin ZHANG ; Fengxia DUAN ; Wei ZHANG
Chinese Journal of Medical Imaging Technology 2024;40(2):177-181
Objective To observe the value of transesophageal echocardiography(TEE)for guiding left atrial appendage closure(LAAC)with LAmbre occluder.Methods Data of 40 non-valvular atrial fibrillation(NVAF)patients who underwent LA AC with LAmbre occluder were retrospectively analyzed.CT angiography(CTA)before treatment,TEE and digital subtraction angiography(DSA)findings during LAAC were comparatively observed,and the correlations of the anchor area diameter and left atrial appendage opening diameter measured with the above three as well as occluder size were analyzed,and TEE and DSA for evaluating peri-device leak(PDL)were compared.Results LAAC were successfully performed with LAmbre occlude in all 40 cases.The diameter of the fixed umbrella was positively correlated with anchor area diameter measured with CTA,TEE and DSA(r=0.79,0.82,0.91,all P<0.01),of occlusion umbrella was positively correlated with left atrial appendage opening diameter measured with CTA,TEE and DSA(r=0.56,0.89,0.86,all P<0.01).Immediately after the release of occluder in LAAC,PDL occurred in 16 cases and were detected with both TEE and DSA,while in the rest 24 cases no PDL was found with neither TEE nor DSA.Conclusion TEE had comparable value to DSA for guiding LAAC using LAmbre occluder.
10.Family analysis of primary microcephaly caused by complex heterozygous variants of the RTTN gene and literature review
Chenyue ZHAO ; Jinsong JIANG ; Lixue ZHANG ; Min GUO ; Jingbo GAO ; Xiayu SUN ; Rong GUO ; Hongyong LU ; Jianrui WU ; Huiqin XUE
Chinese Journal of Child Health Care 2024;32(2):212-217
【Objective】 To analyze the genetic variation characteristics and clinical phenotypes of a family with primary microcephaly (MCPH) caused by RTTN gene variation, and to provide reference for genetic counseling and prenatal diagnosis. 【Methods】 Clinical data of the three patients (including 2 fetuses and 2-year-old proband,and one fetus with clinical diagnosis) and their parents were collected and analyzed. Two of the children and their parents were tested by trio whole exome sequencing (trio-WES), sanger sequencing validation sites, and the hazard of their compound heterozygous variants was predicted. Literature review was conducted through domestic and international databases to collect reported RTTN gene mutation cases. 【Results】 Three patients in this family had anomalies of the septum pellucidum, hypoplasia of the corpus callosum and other brain malformations during fetal period. The proband (G2) and fetus (G3) showed intrauterine growth retardation and MCPH in late pregnancy; besides, G2 was born with global developmental delay. Trio-WES detected a c.2101(exon16)C>T(p.Arg701Ter,1526) nonsense and a c.2863(exon22)G>A(p.Glu955Lys)missense in the RTTN gene of G2 and G3, which were inherited from their father and mother, forming a compound heterozygous variant. According to the American College of Medical Genetics and Genomics (ACMG) variant classification guidelines, two variants were likely to be pathogenic (LP) and uncertain significance (VUS). Among them, c.2863(exon22)G>A was a newly discovered missense, which was predicted by the software to be harmful to the gene product. 【Conclusions】 Complex heterozygous variations of RTTN gene (c.2101C>T and c.2863G>A) are the genetic cause of MCPH in this family. This report has enriched the variation spectrum of RTTN gene, provided guidance for prenatal diagnosis and reproduction of this family, as well as material and reference for further understanding of the diseases caused by this gene mutation.


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