Reactive oxygen species (ROS) are major contributors to radiation therapy-induced side effects in cancer patients. A fusion antioxidant enzyme comprising glutathione S-transferase (GST), superoxide dismutase 1 (SOD1), and a transmembrane peptide has been shown to effectively mitigate ROS-induced damage. To enhance its targeting capability, the fusion protein was further modified by incorporating a matrix metalloproteinase-2/9 substrate peptide (X) and the transmembrane peptide R9, yielding the antioxidant enzyme GST-SOD1-X-R9 (GS1XR). This modification reduced its transmembrane ability in tumor cells, thereby selectively protecting normal cells from oxidative stress. However, the use of non-human GST poses potential immunogenicity risks. In this study, we employed seamless cloning technology to construct an expression vector containing the human GST gene to replace the non-human GST gene, and then expressed and purified novel fusion antioxidant enzymes GS1R and GS1XR. The protective effects of newly constructed GS1R and GS1XR against hydrogen peroxide (H₂O₂)-induced oxidative damage in L-02 cells were then evaluated using GS1 as a control. Enzymatic activity assays revealed that the specific activity of GST in GS1XR remained unchanged compared to the unmodified protein, while SOD activity was enhanced. Exposure to 200 μmol/L H₂O₂ transiently activated the nuclear factor-erythroid 2-related factor 2 (Nrf2) pathway; however, this activation diminished after 24 h, reducing cell viability to 48.4%. Both GS1R and GS1XR effectively scavenged intracellular ROS, directly counteracting oxidative stress and promoting Nrf2 nuclear translocation, thereby activating antioxidant pathways and restoring cell viability to normal levels. The two enzymes showed comparable efficacy. In contrast, GS1, lacking transmembrane capability, was restricted to scavenging extracellular ROS and provided only limited protection. In conclusion, both novel fusion antioxidant enzymes demonstrated significant potential in safeguarding normal cells from ROS-mediated oxidative damage. The findings provide a foundation for further investigation in related field.
Humans ; Oxidative Stress/drug effects* ; Hydrogen Peroxide ; Antioxidants/metabolism* ; Glutathione Transferase/metabolism* ; Recombinant Fusion Proteins/pharmacology* ; Superoxide Dismutase-1 ; Reactive Oxygen Species/metabolism* ; Superoxide Dismutase/biosynthesis*

Objective:To analyze the clinical phenotypes and genotypes of fetal Zellweger spectrum disorders (ZSD).Methods:A retrospective analysis was conducted on the clinical data of three fetuses diagnosed with ZSD and their parents, who underwent family genetic testing at the Prenatal Diagnosis Center of the Third Affiliated Hospital of Zhengzhou University (Maternal and Child Health Hospital of Henan Province) from June 2020 to December 2021. The prenatal phenotypic and genotypic characteristics were summarized in combination with previous literature. Descriptive statistical analysis was used for the data.Results:The mothers of the three fetuses were all primiparous, aged 32, 29, and 33 years, respectively. The gestational weeks at the first detection of fetal abnormalities were 23 weeks and 2 days, 24 weeks, and 33 weeks and 3 days, respectively. Case 1 only showed increased nuchal translucency, while Case 2 and 3 showed brain structural abnormalities. Chromosomal microarray analysis of the three cases did not detect any pathogenic or potentially pathogenic copy number variations. However, heterozygous deletions of unknown significance at 6q13q15 and 7q21.13q22.1 were detected in Case 1. All three fetuses were found to have pathogenic PEX1 variants, which were inherited from their parents. A novel heterozygous variant c.1 246_1247del detected in Case 3 was not previously reported in China. All three families chose to terminate the pregnancies. The mother in family 2 conceived naturally six months later, and an early pregnancy test revealed a pathogenic heterozygous variant c.892_895dup (p.N299Ifs*2) in the PEX1 gene, leading to a diagnosis of being a carrier of the pathogenic PEX1 variant. She continued the pregnancy to full term, and the newborn was followed up with good health. The remaining two families did not have any further pregnancies. Conclusions:PEX1 gene variants may predominantly characterize the mutation spectrum of ZSD. When prenatal examinations reveal fetal craniofacial malformations, brain structural abnormalities, increased nuchal translucency, or high echogenicity of the liver and kidneys, heightened vigilance and comprehensive genetic testing are warranted to reduce birth defects.

Objective:To evaluate the short-term antiviral efficacy and safety profile of tenofovir amibufenamide (TMF) in patients with hepatitis B cirrhosis.Methods:The biochemical indexes, renal function, and complication status in patients with hepatitis B cirrhosis who were treated with tenofovir amibufenamide (TMF) in Beijing You'an Hospital Affiliated to Capital Medical University from March 2022 to June 2024 were retrospectively analyzed.Results:A total of 98 cases with hepatitis B cirrhosis were included. Among them, 62 and 36 cases with hepatitis B cirrhosis had previously undergone partial resection for hepatocellular carcinoma. 66.7% (62/93) of the treated patients were HBV DNA negative before treatment. The longest follow-up time for medication was 24 months, with an average follow-up of (14.1±4.7) months. There were no statistically significant differences in aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin (TBil) levels at 18 months of treatment compared with those before treatment ( P>0.05). The ALT return to normal rate was 91.3%. The HBV DNA negativity rate was 90.6% and 93.5% at 18 and 12 months of follow-up, respectively. There were no significant changes in the estimated glomerular filtration rate (eGFR) and low-density lipoprotein cholesterol (LDL-C) compared with those before treatment ( P>0.05). 36 cases were still HBV DNA positive (including 31 treated and 5 never treated) before treatment. A total of 29 cases were followed up for 12 months, and 24 cases (82.8%) had HBV DNA negative conversion. Conclusion:TMF antiviral therapies have an HBV DNA negative rate of over 80% at 12 months and can improve the liver function in patients with hepatitis B cirrhosis. However, there were no significant changes in renal function and blood lipids before and after treatment.

Objective:To analyze the clinical phenotypes and genotypes of fetal Zellweger spectrum disorders (ZSD).Methods:A retrospective analysis was conducted on the clinical data of three fetuses diagnosed with ZSD and their parents, who underwent family genetic testing at the Prenatal Diagnosis Center of the Third Affiliated Hospital of Zhengzhou University (Maternal and Child Health Hospital of Henan Province) from June 2020 to December 2021. The prenatal phenotypic and genotypic characteristics were summarized in combination with previous literature. Descriptive statistical analysis was used for the data.Results:The mothers of the three fetuses were all primiparous, aged 32, 29, and 33 years, respectively. The gestational weeks at the first detection of fetal abnormalities were 23 weeks and 2 days, 24 weeks, and 33 weeks and 3 days, respectively. Case 1 only showed increased nuchal translucency, while Case 2 and 3 showed brain structural abnormalities. Chromosomal microarray analysis of the three cases did not detect any pathogenic or potentially pathogenic copy number variations. However, heterozygous deletions of unknown significance at 6q13q15 and 7q21.13q22.1 were detected in Case 1. All three fetuses were found to have pathogenic PEX1 variants, which were inherited from their parents. A novel heterozygous variant c.1 246_1247del detected in Case 3 was not previously reported in China. All three families chose to terminate the pregnancies. The mother in family 2 conceived naturally six months later, and an early pregnancy test revealed a pathogenic heterozygous variant c.892_895dup (p.N299Ifs*2) in the PEX1 gene, leading to a diagnosis of being a carrier of the pathogenic PEX1 variant. She continued the pregnancy to full term, and the newborn was followed up with good health. The remaining two families did not have any further pregnancies. Conclusions:PEX1 gene variants may predominantly characterize the mutation spectrum of ZSD. When prenatal examinations reveal fetal craniofacial malformations, brain structural abnormalities, increased nuchal translucency, or high echogenicity of the liver and kidneys, heightened vigilance and comprehensive genetic testing are warranted to reduce birth defects.

Objective:To evaluate the short-term antiviral efficacy and safety profile of tenofovir amibufenamide (TMF) in patients with hepatitis B cirrhosis.Methods:The biochemical indexes, renal function, and complication status in patients with hepatitis B cirrhosis who were treated with tenofovir amibufenamide (TMF) in Beijing You'an Hospital Affiliated to Capital Medical University from March 2022 to June 2024 were retrospectively analyzed.Results:A total of 98 cases with hepatitis B cirrhosis were included. Among them, 62 and 36 cases with hepatitis B cirrhosis had previously undergone partial resection for hepatocellular carcinoma. 66.7% (62/93) of the treated patients were HBV DNA negative before treatment. The longest follow-up time for medication was 24 months, with an average follow-up of (14.1±4.7) months. There were no statistically significant differences in aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin (TBil) levels at 18 months of treatment compared with those before treatment ( P>0.05). The ALT return to normal rate was 91.3%. The HBV DNA negativity rate was 90.6% and 93.5% at 18 and 12 months of follow-up, respectively. There were no significant changes in the estimated glomerular filtration rate (eGFR) and low-density lipoprotein cholesterol (LDL-C) compared with those before treatment ( P>0.05). 36 cases were still HBV DNA positive (including 31 treated and 5 never treated) before treatment. A total of 29 cases were followed up for 12 months, and 24 cases (82.8%) had HBV DNA negative conversion. Conclusion:TMF antiviral therapies have an HBV DNA negative rate of over 80% at 12 months and can improve the liver function in patients with hepatitis B cirrhosis. However, there were no significant changes in renal function and blood lipids before and after treatment.

Objective:To explore the effect of Tai chi ball combined with Baduanjin in patients with acute myocardial infarction after PCI.Methods:From October 2018 to October 2019, a total of 118 patients with acute myocardial infarction after PCI in Department of Cardiology of Shangqiu First People's Hospital were selected as the research objects using the convenient sampling method, and divided into the observation group (57 cases) and the control group (61 cases) by the random number table method. The control group adopted conventional treatment and nursing, and the observation group conducted Tai Chi ball combined with Baduanjin exercise program on the basis of conventional treatment and nursing. One month after discharge, the ability of activity of daily living and quality of life were compared between the two groups.Results:One month after discharge, the total score of the ability of activity of daily living and the score of each dimension of the observation group were lower than those of the control group, and the differences were statistiocally significant ( P<0.05) ; the total score of the quality of life and the score of each dimension of the observation group were higher than those of the control group, and the differences were statistically significant ( P<0.05) . Conclusions:Tai Chi ball combined with Baduanjin can effectively improve the ability of activity of daily living and quality of life of patients with acute myocardial infarction after PCI.

ObjectiveTo determine the mechanism of Yitangkang in correcting excessive apoptosis of skeletal muscle cells to improve insulin resistance （IR） by inhibiting the advanced glycation end product （AGE）/receptor for the advanced glycation end product （RAGE） signaling pathway. Method① In vitro experiments. Yitangkang-medicated serum was prepared. C2C12 cells were divided into a blank group， a model group， high-， medium-， and low-dose Yitangkang-medicated serum groups （40， 20， and 10 g·kg^-1）， and a RAGE inhibitor group. The IR model was induced by palmitic acid in C2C12 cells except for those in the blank group. After the corresponding intervention methods were conducted，the cell viability and glucose consumption level of each group were determined. In addition，the apoptosis rate was determined using flow cytometry. The mRNA and protein expression levels of the important apoptotic proteins ［B-cell lymphoma 2 （Bcl-2）， Bcl-2-associated X protein （Bax）， p53， cysteinyl aspartate-specific protease-3 （Caspase-3）， and cysteinyl aspartate-specific protease-9 （Caspase-9）］ were determined using Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot. ② In vivo experiments. Ninety-six eligible Wistar rats were divided into a blank group， a model group， high-，medium-，and low-dose Yitangkang groups （40， 20， and 10 g·kg^-1）， and a western medicine group （pioglitazone hydrochloride，1.35 mg·kg^-1）. The IR model was induced using high-glucose and high-fat feed for diabetes combined with intraperitoneal injection of low-dose streptozotocin （STZ） in animals and verified by the hyperinsulinemic-euglycemic clamp （HEC） test. After the model was determined successfully， the rats in each group were given intragastric administration of drugs as required. Terminal deoxynucleotidyl transferase dUTP nick end labeling （TUNEL） assay was performed to determine the number of positive apoptotic cells in the skeletal muscle tissues of rats in each group，while Real-time polymerase chain reaction（Real-time PCR） and Western blot were performed to determine the mRNA and protein expression levels of the important apoptotic proteins Bcl-2， Bax， p53， Caspase-3， and Caspase-9. Result① In vitro experiments. compared with the blank group， the model groups showed increased apoptosis rate of C2C12 cells and decreased cell viability and glucose consumption （P<0.01）. Compared with the model group， the Yitangkang-medicated serum groups and the RAGE inhibitor group showed decreased apoptosis rate of C2C12 cells and increased cell viability and glucose consumption （P<0.01）. Compared with the blank group， the model group showed decreased expression levels of Bcl-2 mRNA and protein in C2C12 cells and increased mRNA and protein expression levels of Bax， p53， Caspase-3， and Caspase-9 （P<0.01）. Compared with the model group， the Yitangkang-medicated serum groups and the RAGE inhibitor group showed increased expression levels of Bcl-2 mRNA and protein in C2C12 cells （P<0.01） and decreased mRNA and protein expression levels of Bax， p53， Caspase-3， and Caspase-9 （P<0.05， P<0.01）. ② In vivo experiments. The number of positive apoptotic cells in the skeletal muscle tissues of rats in the model group significantly increased as compared with that in the blank group （P<0.01）. The number of positive apoptotic cells in the skeletal muscle tissues of rats in the Yitangkang groups and the western medicine group decreased as compared with that in the model group （P<0.01）. Compared with the blank group， the model group showed decreased expression levels of Bcl-2 mRNA and protein in skeletal muscle tissues of rats and increased mRNA and protein expression levels of Bax， p53， Caspase-3， and Caspase-9 （P<0.01）. Compared with the model group， the Yitangkang groups and the western medicine group showed increased expression levels of Bcl-2 mRNA and protein in skeletal muscle tissues of rats （P<0.01） and decreased mRNA and protein expression levels of Bax， p53， Caspase-3， and Caspase-9 （P<0.05， P<0.01）. The medium-dose Yitangkang showed a similar effect as RAGE inhibitor， and the effect was equivalent to that of pioglitazone hydrochloride. ConclusionYitangkang can inhibit skeletal muscle cell apoptosis by inhibiting the AGE/RAGE signaling pathway.

ObjectiveTo observe the effects of Yuejuwan in the treatment of psychological and heart diseases （PHD） and explore its mechanism. MethodThirty 6-week-old healthy male SPF AopE^-/- mice and 10 homologous C57BL/6J mice were selected for the experiment. The 30 AopE^-/- mice were divided into a model group， low-dose （7.58 g·kg^-1·d^-1） and high-dose （30.32 g·kg^-1·d^-1） Yuejuwan groups， with 10 mice in each group， and 10 C57BL/6J mice were assigned to the blank control group. Intragastrical administration lasted 12 weeks. During feeding， the PHD model was induced by chronic unpredictable mild stress （CUMS） combined with high-fat diet in mice. After intragastric administration， the behavioral results ［open field test （OFT） and sucrose preference test （SPT）］ of mice in each group， the content of aspartic transaminase （AST）， alanine aminotransferase （ALT）， 5-hydroxytryptamine （5-HT）， noradrenaline （NE）， high-density lipoprotein cholesterol （HDL-C）， low-density lipoprotein cholesterol （LDL-C）， total cholesterol （TC）， and triglyceride （TG） in serum of mice detected by the automatic biochemical analyzer， the oil red O staining and HE staining of aorta and liver and Masson staining of myocardial tissues were used for model evaluation. Finally， liver TMT-labeled quantitative proteomics was used to explore the mechanism of action. ResultThe model mice showed obvious manifestations of depression， anxiety， loss of interest， and despair， manifest lipid deposition in the aorta and liver by pathological observation， and increased myocardial fibrosis in myocardial tissues. After intragastric administration of Yuejuwan， the above symptoms and indexes of the PHD model mice were improved. Compared with the blank control group， the model group showed decreased standing times， cumulative time in the central area， total moving distance， moving speed， and sucrose preference at week 12 （P<0.01）. Compared with the model group， the Yuejuwan groups showed decreased indexes mentioned above （P<0.01）. After sample collection， AST， ALT， and TG levels in the model group were higher （P<0.01） and the levels of 5-HT， NE， and HDL-C were lower than those in the blank control group （P<0.01）. The results of liver TMT labeled quantitative proteomics suggested that the PHD model mainly caused the changes in protein expression levels such as ApoE， UGT1A5， and FASN in mice，involving acetyl CoA metabolism，response to bacteria，cellular amino acid catabolism， and other processes，which were related to the abnormal metabolic function of the liver. The efficacy of Yuejuwan against PHD was achieved mainly through the regulation of high mobility group nucleosomal-binding domain 2 （HMGN2）， CALD1， and Mup7 protein expression levels and correcting the biological processes and abnormal pathways related to the pathogenesis of PHD，including muscle contraction，tight junction pathway，myocardial contraction pathway，and focal adhesion pathway. ConclusionCUMS combined with high-fat diet is reasonable in the induction of the PHD model in AopE^-/- mice. Yuejuwan can correct the depression and anxiety conditions of PHD model mice，reduce the aortic plaque， and recover the abnormal blood lipid and liver function levels. Furthermore， Yuejuwan can correct abnormal biological processes and pathways of PHD model mice. The differential proteins screened throughout the experiment and the involved physiological and pathological changes are the focus of the next experiment.

ObjectiveTo compare the therapeutic effects of oral Chinese medicines （including Chinese patent medicines） on coronary artery disease （CAD） by the Bayesian network Meta-analysis. MethodThe randomized controlled trials of treating CAD with oral Chinese medicines were retrieved from the China National Knowledge Infrastructure （CNKI）， Wanfang Data， VIP， PubMed， Web of Science， Embase， and Cochrane Library from the inception to December 1， 2022. The Cochrane risk of bias assessment tool was used to evaluate the quality of the included articles. The direct meta-analysis was performed to compare the performance of oral Chinese medicines alone and in combination with Western medicine in the treatment of CAD in terms of intima-media thickness （IMT）， vascular endothelial function， plaque score， hypersensitive C-reactive protein （hs-CRP）， total cholesterol （TC）， triglyceride （TG）， high-density lipoprotein cholesterol （HDL-C）， low-density lipoprotein cholesterol （LDL-C）， and total response rate. Furthermore， the Bayesian network Meta-analysis was performed to compare the therapeutic effects of different Chinese medicines. ResultA total of 41 articles were included. The direct meta-analysis results showed that Chinese medicines combined with Western medicine outperformed Western medicine alone in recovering all the indicators of CAD. The Bayesian network meta-analysis yielded the following results. In terms of the total response rate， modified Huangqi Guizhi Wuwutang and Sanqi Huayu pills had obvious advantages over other Chinese medicines. In terms of IMT and plaque score， Xiaoban Huazhuo decoction， Yiqi Tongluo formula， Ruangan Jiangzhi capsules， and Guanxin Shutong capsules had obvious advantages over other Chinese medicines. In terms of blood lipid indicators， Shenqi Roumai mixture， Ruangan Jiangzhi capsules， Xiaoban Huazhuo decoction， Qiwei Sanxiong decoction， and Sanqi Huayu pills were superior to other Chinese medicines. The Chinese medicines above mainly had the functions of activating blood， resolving stasis， resolving phlegm， and dredging vessels. ConclusionThe combination of oral Chinese medicines and Western medicine is effective in treating CAD. Clinicians can use the drugs targeting abnormal indicators according to the results of this Bayesian network meta-analysis combined with the actual situation of patients to achieve better therapeutic effects.