1.Modified Ditan Tang Regulates Biorhythm-related Genes in Rat Model of Non-alcoholic Fatty Liver Disease
Zhiwen PANG ; Yu LIU ; Nan SONG ; Jie WANG ; Jingxuan ZHU ; Zhen HUA ; Yupeng PEI ; Qun WANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(6):115-124
ObjectiveTo investigate the effects of modified Ditan tang on genes related to the transcription-translation feedback loop (TTFL) of biorhythm in the rat model of non-alcoholic fatty liver disease (NAFLD) and its mechanism for prevention and treatment of NAFLD. MethodsSixty-five healthy SPF male SD rats were randomly assigned into blank (n=20), model (n=15), and low-, medium-, and high-dose (2.68, 5.36, and 10.72 g·kg-1·d-1, respectively) modified Ditan tang (n=10) groups. Other groups except the blank group were fed a high-fat diet for 12 weeks. The modified Ditan tang groups were treated with the decoction at corresponding doses by gavage, and the blank and model groups were treated with an equal volume of normal saline from the 9th week for 4 weeks. The levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) in the serum were measured by an automatic biochemical analyzer. TG and non-esterified fatty acid (NEFA) assay kits were used to measure the levels of TG and NEFA in the liver. The pathological changes in the hypothalamus and liver were observed by hematoxylin-eosin staining, and the lipid deposition in the liver was observed by oil red O staining. The levels of brain-muscle ARNT-like protein 1 (BMAL1/ARNTL) in the hypothalamus and liver were determined by immunohistochemical staining. The mRNA and protein levels of BMAL1, circadian locomotor output cycles kaput (CLOCK), period circadian clock 2 (PER2), and cryptochrome1 (Cry1) in the hypothalamus and liver were determined by Real-time PCR and Western blot, respectively. ResultsCompared with the blank group, the model group showed elevated levels of TG, TC, LDL-C, AST, and ALT (P<0.01) and a lowered level of HDL-C (P<0.05) in the serum, elevated levels of TG and NEFA in the liver (P<0.01), pyknosis and deep staining of hypothalamic neuron cells, and a large number of vacuoles in the brain area. In addition, the model group showed lipid deposition in the liver, up-regulated mRNA and protein levels of CLOCK and BMAL1 (P<0.01), and down-regulated mRNA and protein levels of Cry1 and PER2 (P<0.01) in the hypothalamus and liver. Compared with the model group, all the three modified Ditan tang groups showed lowered levels of TG, TC, LDL-C, ALT, and AST (P<0.05, P<0.01) and an elevated level of HDL-C (P<0.05) in the serum, and lowered levels of TG and NEFA (P<0.05, P<0.01) in the liver. Furthermore, the three groups showed alleviated pyknosis and deep staining of hypothalamic neuron cells, reduced lipid deposition in the liver, down-regulated mRNA and protein levels of CLOCK and BMAL1 (P<0.05, P<0.01), and up-regulated mRNA and protein levels of Cry1 and PER2 (P<0.05, P<0.01) in the hypothalamus and liver. ConclusionModified Ditan tang can reduce lipid deposition in the liver and regulate the expression of CLOCK, BMAL1, Cry1, and PER2 in the TTFL of NAFLD rats.
2.Effect of finite element method in treatment of developmental dysplasia of the hip in children
Xiaojun SUN ; Huaming WANG ; Dehong ZHANG ; Xuewen SONG ; Jin HUANG ; Chen ZHANG ; Shengtai PEI
Chinese Journal of Tissue Engineering Research 2025;29(9):1897-1904
BACKGROUND:Developmental dysplasia of the hip often leads to limb deformities in children,and the research related to its diagnosis and treatment has been gradually clarified.Recently,the finite element method has been paid attention to by scholars in the research related to developmental dysplasia of the hip because of its advantages. OBJECTIVE:Through literature search and review of the relevant research progress of finite element method in children's developmental dysplasia of the hip and treatment,analyze and summarize its advantages and disadvantages,and explore the direction of further research in the future. METHODS:PubMed,SCI,CBM,and CNKI were searched for relevant articles published from January 2014 to November 2023 with the key words of"developmental dysplasia(dislocation)of the hip,dysplasia of the hip,finite element analysis(method),pavlik harness,fixation in herringbone position,biomechanics,pelvic osteotomies,pemberton,salter,dega,periacetabular osteotomy,children"in Chinese and English.A small number of long-term articles were included,and 62 articles were finally included for analysis through screening. RESULTS AND CONCLUSION:(1)The mechanical environment of hip joint in children with developmental dysplasia of the hip was abnormal.The pressure in acetabulum was uneven.The stress increased and concentrated;the joint contact area decreased,and the local stress concentrated in femoral neck.(2)In the Pavlik sling and herringbone fixation,the mechanical environment of the hip was improved;the concentrated high stress area disappeared and the joint contact area increased,but the excessive abduction angle led to the increase of stress in the acetabulum and the lateral femoral head.(3)After pelvic osteotomy,the stress environment of hip joint and sacroiliac joint was improved.There was no single hinge in the three kinds of osteotomy,and the stress load position was different according to the age of the children.(4)After peri-acetabular osteotomy,the joint contact pressure was close to normal,but it was difficult to recover in patients with non-spherical femoral head.(5)The postoperative X-ray film findings could not show that the joint contact mechanics was the best.(6)It is indicated that the information that cannot be measured in the body can be obtained by using the finite element method,which can be operated in a virtual environment without the limitation of time and ethics.It can directly see the stress change area of normal and developmental dysplasia of the hip,explain the effectiveness of treatment from the point of view of mechanics,establish a specific finite element model and tailor-made operation plan for patients who need osteotomy.There is no standard or unified standard for the finite element modeling of developmental dysplasia of the hip and the material characteristic parameters of children's hip joint.Due to the inherent limitations of finite element method,it is impossible to analyze the model that contains bone,cartilage,ligament,muscle and other elements at the same time.The operation of finite element analysis is difficult,although it has advantages,it is not universal,and the current research sample size is small,which needs to be further expanded and verified.
3.Clinical study on the treatment of chronic atrophic gastritis with spleen and stomach weakness syndrome by Piwei Peiyuan Pill combined with moxibustion
Kairui WU ; Yu YE ; Bei PEI ; Biao SONG ; Yi ZHANG ; Tingting LI ; Qi YANG ; Yun LIU ; Xuejun LI
Journal of Beijing University of Traditional Chinese Medicine 2025;48(2):280-290
Objective:
To determine the clinical efficacy and mechanism of Piwei Peiyuan Pill (PPP) combined with moxibustion for treating patients with chronic atrophic gastritis (CAG) with spleen and stomach weakness syndrome.
Methods:
Ninety-six CAG patients with spleen and stomach weakness syndrome who met the inclusion and exclusion criteria were enrolled at the Department of Spleen and Stomach Diseases of the Second Affiliated Hospital of Anhui University of Chinese Medicine from June 2022 to December 2023. The patients were randomly divided into a control, a Chinese medicine, and a combined group using a random number table method, with 32 cases in each group (two cases per group were excluded). The control group was treated with rabeprazole combined with folic acid tablets (both thrice daily), the Chinese medicine group was treated with PPP (8 g, thrice daily), and the combined group was treated with moxa stick moxibustion (once daily) on the basis of the Chinese medicine group for 12 consecutive weeks. Gastric mucosa atrophy in the three groups was observed before and after treatment. The gastric mucosal pathological score was evaluated. The Patient Reported Outcome (PRO) scale was used to evaluate the patients′ physical and mental health status and quality of life.An enzyme-linked immunosorbent assay was used to detect serum tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-4, IL-10, IL-37, and transforming growth factor (TGF)-β levels in each group. Real-time fluorescence PCR was used to detect the relative expression levels of signal transducer and activator of transcription 3 (STAT3) and mammalian target of rapamycin (mTOR) mRNA in each group. Western blotting was used to detect the relative expression levels of proteins related to the STAT3/mTOR signaling pathway, and the adverse drug reactions and events were recorded and compared.
Results:
There was no statistical difference in age, gender, disease duration, family history of gastrointestinal tumors, alcohol consumption history, and body mass index among the three groups of patients.The total therapeutic efficacy rates of the control, Chinese medicine, and combined groups in treating gastric mucosal atrophy were 66.67% (20/30), 86.67% (26/30), and 90.00% (27/30), respectively (P<0.05). Compared to before treatment, the pathological and PRO scale scores of gastric mucosa in each group decreased after treatment, and TNF-α, IL-1β, IL-37, and TGF-β levels decreased. The relative STAT3 and mTOR mRNA expression levels, as well as the relative STAT3, p-STAT3, mTOR, and p-mTOR protein expression levels decreased (P<0.05), whereas the IL-4 and IL-10 levels increased (P<0.05). After treatment, compared to the control group, the pathological score of gastric mucosa, PRO scale score, TNF-α, IL-1β, IL-37, TGF-β content, relative STAT3 and mTOR mRNA expression levels, and relative STAT3, p-STAT3, mTOR, and p-mTOR protein expression levels in the Chinese medicine and combined groups after treatment were reduced (P<0.05), whereas the IL-4 and IL-10 levels increased (P<0.05). After treatment, compared to the Chinese medicine group, the combined group showed a decrease in relative STAT3, mTOR mRNA expression levels, and STAT3, p-STAT3, mTOR, and p-mTOR protein expression levels (P<0.05).
Conclusion
The combination of PPP and moxibustion may regulate the inflammatory mechanism of the body by inhibiting the abnormal activation of the STAT3/mTOR signaling pathway, upregulating related anti-inflammatory factor levels, downregulating pro-inflammatory factor expression, and increasing related repair factor expression, thereby promoting the recovery of atrophic gastric mucosa, reducing discomfort symptoms, and improving the physical and mental state of CAG patients with spleen and stomach weakness syndrome.
4.Effect of Gypenosides on MAFLD Mice and Its Molecular Mechanism Based on Classical/Non-classical Ferroptosis Pathways
Yu LIU ; Yupeng PEI ; Jiaxin WANG ; Jingxuan ZHU ; Xiaofei SUN ; Qun WANG ; Peng CUI ; Nan SONG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(17):99-107
ObjectiveTo explore the effect of gypenosides (GPs) on liver lipid deposition in metabolism-associated fatty liver disease (MAFLD) mice and its mechanism based on classical/non-classical ferroptosis. MethodsEight male C57BL/6 mice in a blank group and 32 male apolipoprotein E gene knockout (ApoE-/-) mice were randomly divided into a model group, a low-dose GPs (GPs-L) group, a high-dose GPs (GPs-H) group, and a simvastatin (SV) group. Starting from the second week, mice in the blank group were given a maintenance diet, and the other four groups were fed a high-fat diet daily. After eight weeks of feeding, mice in the GPs-L and GPs-H groups were given GPs of 1.487 mg·kg-1·d-1 and 2.973 mg·kg-1·d-1, respectively, and mice in the SV group were given simvastatin of 2.275 mg·kg-1·d-1. Mice in the blank group and the model group were given saline of equal volume by gavage for four weeks. The content of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) in the serum of mice in each group was detected by an automatic biochemical analyzer. The level of non-esterified fatty acid (NEFA) and TG in the mouse liver was measured by the kit. The change in liver tissue structure and lipid deposition was observed by hematoxylin-eosin (HE) and oil red O staining. The levels of coenzyme Q10 (CoQ10), glutathione (GSH), malondialdehyde (MDA), and Fe2+ in serum, as well as nicotinamide adenine dinucleotide phosphate [NAD(P)H] in the liver were detected by enzyme-linked immunosorbent assay (ELISA). The expression of ferroptosis suppressor protein 1 (FSP1) in the liver of mice was observed by the immunohistochemical (IHC) method, and the expression of genes and proteins related to classical and non-classical ferroptosis pathways was analyzed by real-time polymerase chain reaction (Real-time PCR) and Wes automated protein expression analysis system. ResultsCompared with those in the blank group, the levels of TC, TG, LDL-C, ALT, and AST in serum and TG and NEFA in the liver in the model group were significantly increased, and the level of HDL-C in serum was significantly decreased (P<0.01). The liver tissue structure changed, and there were fat vacuoles of different sizes and a large number of red lipid droplets, with obvious lipid deposition. The level of CoQ10 and GSH in serum and NADH in the liver were significantly decreased, while the level of MDA and Fe2+ in serum was significantly increased (P<0.01). The mRNA and protein expressions of cystine/glutamate transporter (xCT/SLC7A11), glutathione peroxidase (GPX4), p62, nuclear factor E2-related factor 2 (Nrf2), and FSP1 were significantly decreased, and the mRNA and protein expressions of tumor antigen (p53), spermidine/spermine N1-acetyltransferase 1 (SAT1), arachidonate 15-lipoxygenase (ALOX15), and Kelch-like epichlorohydrin-associated protein-1 (Keap1) were significantly increased (P<0.01). Compared with those in the model group, the level of TC, TG, LDL-C, ALT, and AST in serum and TG and NEFA in the liver of mice in the GPs-L, GPs-H, and SV groups were decreased, while the level of HDL-C in serum was significantly increased (P<0.05, P<0.01). The liver tissue structure and lipid deposition were improved. The levels of CoQ10 and GSH in serum and NADH in the liver were significantly increased, while the levels of MDA and Fe2+ in serum were significantly decreased (P<0.05, P<0.01). The mRNA and protein expressions of xCT, GPX4, p62, Nrf2, and FSP1 were significantly increased, while the mRNA and protein expressions of p53, SAT1, ALOX15, and Keap1 were significantly decreased (P<0.05, P<0.01). ConclusionGPs can interfere with liver lipid deposition in MAFLD mice through classical/non-classical ferroptosis pathways.
5.Effect of Gypenosides on MAFLD Mice and Its Molecular Mechanism Based on Classical/Non-classical Ferroptosis Pathways
Yu LIU ; Yupeng PEI ; Jiaxin WANG ; Jingxuan ZHU ; Xiaofei SUN ; Qun WANG ; Peng CUI ; Nan SONG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(17):99-107
ObjectiveTo explore the effect of gypenosides (GPs) on liver lipid deposition in metabolism-associated fatty liver disease (MAFLD) mice and its mechanism based on classical/non-classical ferroptosis. MethodsEight male C57BL/6 mice in a blank group and 32 male apolipoprotein E gene knockout (ApoE-/-) mice were randomly divided into a model group, a low-dose GPs (GPs-L) group, a high-dose GPs (GPs-H) group, and a simvastatin (SV) group. Starting from the second week, mice in the blank group were given a maintenance diet, and the other four groups were fed a high-fat diet daily. After eight weeks of feeding, mice in the GPs-L and GPs-H groups were given GPs of 1.487 mg·kg-1·d-1 and 2.973 mg·kg-1·d-1, respectively, and mice in the SV group were given simvastatin of 2.275 mg·kg-1·d-1. Mice in the blank group and the model group were given saline of equal volume by gavage for four weeks. The content of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) in the serum of mice in each group was detected by an automatic biochemical analyzer. The level of non-esterified fatty acid (NEFA) and TG in the mouse liver was measured by the kit. The change in liver tissue structure and lipid deposition was observed by hematoxylin-eosin (HE) and oil red O staining. The levels of coenzyme Q10 (CoQ10), glutathione (GSH), malondialdehyde (MDA), and Fe2+ in serum, as well as nicotinamide adenine dinucleotide phosphate [NAD(P)H] in the liver were detected by enzyme-linked immunosorbent assay (ELISA). The expression of ferroptosis suppressor protein 1 (FSP1) in the liver of mice was observed by the immunohistochemical (IHC) method, and the expression of genes and proteins related to classical and non-classical ferroptosis pathways was analyzed by real-time polymerase chain reaction (Real-time PCR) and Wes automated protein expression analysis system. ResultsCompared with those in the blank group, the levels of TC, TG, LDL-C, ALT, and AST in serum and TG and NEFA in the liver in the model group were significantly increased, and the level of HDL-C in serum was significantly decreased (P<0.01). The liver tissue structure changed, and there were fat vacuoles of different sizes and a large number of red lipid droplets, with obvious lipid deposition. The level of CoQ10 and GSH in serum and NADH in the liver were significantly decreased, while the level of MDA and Fe2+ in serum was significantly increased (P<0.01). The mRNA and protein expressions of cystine/glutamate transporter (xCT/SLC7A11), glutathione peroxidase (GPX4), p62, nuclear factor E2-related factor 2 (Nrf2), and FSP1 were significantly decreased, and the mRNA and protein expressions of tumor antigen (p53), spermidine/spermine N1-acetyltransferase 1 (SAT1), arachidonate 15-lipoxygenase (ALOX15), and Kelch-like epichlorohydrin-associated protein-1 (Keap1) were significantly increased (P<0.01). Compared with those in the model group, the level of TC, TG, LDL-C, ALT, and AST in serum and TG and NEFA in the liver of mice in the GPs-L, GPs-H, and SV groups were decreased, while the level of HDL-C in serum was significantly increased (P<0.05, P<0.01). The liver tissue structure and lipid deposition were improved. The levels of CoQ10 and GSH in serum and NADH in the liver were significantly increased, while the levels of MDA and Fe2+ in serum were significantly decreased (P<0.05, P<0.01). The mRNA and protein expressions of xCT, GPX4, p62, Nrf2, and FSP1 were significantly increased, while the mRNA and protein expressions of p53, SAT1, ALOX15, and Keap1 were significantly decreased (P<0.05, P<0.01). ConclusionGPs can interfere with liver lipid deposition in MAFLD mice through classical/non-classical ferroptosis pathways.
6.Activation of Nrf2/HO-1/NQO1 Signaling Pathway by Shenqi Tangluo Pill Improves Oxidative Stress Injury of Skeletal Muscle of Type 2 Diabetes Mellitus Mice
Xiaoli PEI ; Yonglin LIANG ; ⁎ ; Yongqiang DUAN ; ⁎ ; Xiangdong ZHU ; Bing SONG ; Min BAI ; Yunhui ZHAO ; Sichen ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(7):131-139
ObjectiveTo investigate the effect and mechanism of Shenqi Tangluo pill (SQTLP) on oxidative stress injury of skeletal muscle of type 2 diabetes mellitus (T2DM) mice based on nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1)/NAD(P)H quinone oxidoreductase 1 (NQO1) pathway. MethodA total of 60 7-week-old male db/db mice [specific pathogen-free (SPF) grade] were selected and fed for one week for adaption. They were divided into the model control group, SQTLP low-, medium- and high-dose (19, 38, and 76 g·kg-1) groups and metformin group (0.26 g·kg-1) by gavage. Each group consisted of 12 mice. Twelve male db/m mice of the same age were selected as the blank group. The intervention was implemented continuously for 8 weeks. Fasting blood glucose (FBG) was detected. Fasting serum insulin (FINS) levels were detected by enzyme-linked immunosorbent assay (ELISA), and the homeostasis model assessment-insulin resistance (HOMA-IR) index and the homeostasis model assessment-insulin sensitivity index (HOMA-ISI) were calculated. Oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) were conducted. The activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and the contents of malondialdehyde (MDA) and reduced nicotinamide adenine dinucleotide phosphate (NADPH) in skeletal muscle tissues were detected by biochemical kits. Hematoxylin-eosin (HE) staining was used to observe the pathological changes in skeletal muscle tissues. The levels of reactive oxygen species (ROS) and 4-hydroxynonenal (4-HNE) in skeletal muscle tissue were detected by immunofluorescence (IF). The expression levels of Nrf2, HO-1, NQO1 and glutamate-cysteine ligase catalytic subunit (GCLC) proteins in skeletal muscle tissues were detected by Western blot. ResultCompared with those in the blank group, FBG, FINS and HOMA-IR in the model group were significantly increased (P<0.05), while HOMA-ISI was decreased (P<0.05). The results of OGTT and ITT showed that blood glucose was significantly increased at all time points (P<0.05), and glucose tolerance and insulin tolerance were significantly impaired. SOD and GSH-Px activities in skeletal muscle tissues were significantly decreased (P<0.05), and MDA and NADPH contents were significantly increased (P<0.05). In skeletal muscle tissues, the arrangement of muscle fibers was loose, the nucleus was disordered, and inflammatory cells were infiltrated. The expression levels of ROS and 4-HNE in skeletal muscle tissues were significantly increased (P<0.05). The protein expression levels of Nrf2, HO-1, NQO1 and GCLC in skeletal muscle tissues were significantly decreased (P<0.05). Compared with those in the model group, FBG, FINS and HOMA-IR in the metformin group were significantly decreased (P<0.05), while HOMA-ISI was increased (P<0.05). The results of OGTT and ITT showed that blood glucose in the metformin group was significantly decreased at all time points (P<0.05). The activities of SOD and GSH-Px in skeletal muscle tissues were significantly increased (P<0.05), while the contents of MDA and NADPH were significantly decreased (P<0.05). No obvious abnormality was found in the skeletal muscle tissue of the metformin group. The expressions of ROS and 4-HNE in skeletal muscle tissues were decreased (P<0.05). The protein expression levels of Nrf2, HO-1, NQO1 and GCLC in skeletal muscle tissues were significantly increased (P<0.05). Compared with those in the model group, FBG, FINS and HOMA-IR in the SQTLP medium- and high-dose groups were significantly decreased (P<0.05), while HOMA-ISI was increased (P<0.05). The results of OGTT and ITT showed that the glucose tolerance and insulin tolerance of mice were improved in each dose group of SQTLP. The GSH-Px activity in the SQTLP low-dose group was significantly increased (P<0.05), and the NADPH content was decreased (P<0.05). The activities of SOD and GSH-Px in the SQTLP medium- and high-dose groups were significantly increased (P<0.05), while the contents of MDA and NADPH were significantly decreased (P<0.05). The skeletal muscle tissue injury of mice in each dose group of SQTLP was ameliorated to different degrees. In the SQTLP medium- and high-dose groups, the expressions of ROS and 4-HNE were decreased (P<0.05), and the protein expression levels of Nrf2, HO-1, NQO1 and GCLC were significantly increased (P<0.05). Compared with those in the SQTLP low-dose group, FBG and HOMA-IR in the SQTLP high-dose group were significantly decreased (P<0.05), while HOMA-ISI was increased (P<0.05). The results of OGTT and ITT showed that the SQTLP high-dose group significantly improved the glucose tolerance and insulin tolerance of mice. The activities of SOD and GSH-Px in skeletal muscle tissues were significantly increased (P<0.05), while the contents of MDA and NADPH were significantly decreased (P<0.05). No obvious abnormality was found in the skeletal muscle tissue, the expressions of ROS and 4-HNE were decreased (P<0.05), and the protein expression levels of Nrf2, HO-1, NQO1 and GCLC were significantly increased (P<0.05) in the skeletal muscle tissue of the SQTLP high-dose group. ConclusionSQTLP can significantly improve IR in T2DM mice, and the mechanism is related to SQTLP activating the Nrf2/HO-1/NQO1 signaling pathway, promoting the expression of antioxidant enzymes, and thus improving the oxidative stress injury in the skeletal muscle.
7. Advances in relationship between pyroptosis and pulmonary arterial hypertension and therapeutic drugs
Qian YAN ; Yang SUN ; Jun-Peng LONG ; Jiao YAO ; Yu-Ting LIN ; Song-Wei YANG ; Yan-Tao YANG ; Gang PEI ; Qi-Di AI ; Nai-Hong CHEN ; Qian YAN ; Yang SUN ; Jun-Peng LONG ; Jiao YAO ; Yu-Ting LIN ; Song-Wei YANG ; Yan-Tao YANG ; Gang PEI ; Qi-Di AI ; Nai-Hong CHEN ; Sha-Sha LIU ; Nai-Hong CHEN
Chinese Pharmacological Bulletin 2024;40(1):25-30
Pyroptosis is the programmed death of cells accompanied by an inflammatory response and is widely involved in the development of a variety of diseases, such as infectious diseases, cardiovascular diseases, and neurodegeneration. It has been shown that cellular scorching is involved in the pathogenesis of pulmonary arterial hypertension ( PAH) in cardiovascular diseases. Patients with PAH have perivascular inflammatory infiltrates in lungs, pulmonary vasculopathy exists in an extremely inflam-matory microenvironment, and pro-inflammatory factors in cellular scorching drive pulmonary vascular remodelling in PAH patients. This article reviews the role of cellular scorch in the pathogenesis of PAH and the related research on drugs for the treatment of PAH, with the aim of providing new ideas for clinical treatment of PAH.
8.Forty years of changes and thinking on China’s drug regulation
Ruilin SONG ; Xinyi LI ; Fan ZHANG ; Yangyang ZHANG ; Xiaoyu PEI
China Pharmacy 2024;35(24):2965-2971
Since the first Drug Administration Law was issued in 1984, the drug regulation of China has undergone a forty- year process. During these four decades, China’s drug regulatory system has gradually transitioned from being extensive to refined, and the concept of supervision has become increasingly scientific. This paper first outlines the historical evolution of China’s drug regulatory laws and regulations since the founding of the People’s Republic of China, with a focus on the historical origins of the revision of the Drug Administration Law during 1984-2001. It also clarifies the new challenges faced by drug regulation as the industry innovates and develops, as well as the corresponding reform of the drug review and approval system. The paper summarizes the reform achievements of drug regulation. By studying and analyzing the challenges faced by drug regulation in terms of regulatory capacity, regulatory resources, and regulatory system in the context of internationalization of the industry, the paper proposes policy suggestions such as establishing a cross-regional regulatory system, reforming the review mechanism, strengthening the construction of the review team, and enhancing transparency in regulatory practices, with the aim of promoting the high-quality development of the pharmaceutical industry.
9.Neuro-ophthalmic features of SARS-CoV-2 associated acute macular neuroretinopathy
Pei LIU ; Zhaojie CHU ; Bo LI ; Xuemei LIN ; Yan LIU ; Chensheng SONG ; Yan SUO ; Jun ZHAO ; Songdi WU
International Eye Science 2024;24(7):1173-1178
AIM: To explore the neuro-ophthalmological characteristics of acute macular neuroretinopathy(AMN)after SARS-CoV-2 infection.METHODS: A total of 8 patients(14 eyes), including 6 females and 2 males, who were diagnosed with AMN in the neuro-ophthalmology department of Xi'an No.1 Hospital(The First Affiliated Hospital of Northwest University)from December 27, 2022 to February 1, 2023 were included in the study. All patients had a history of SARS-CoV-2 infection before the disease, and the results of best corrected visual acuity(BCVA), non-contact indirect intraocular pressure measurement, fundus color photography, near infrared(IR), spectral-domain optical coherence tomography(SD-OCT), OCT angiography(OCTA), fundus fluorescein angiography(FFA), indocyanine green angiography(ICGA), visual field, visual evoked potential(VEP), and electroretinogram(ERG)were collected. Furthermore, the neuro-opthalmology characteristics of the included patients were analyzed and summarized.RESULTS: The included 8 patients aged from 20 to 43, with an average age of(30±6.63)years old. The patients had a history of SARS-CoV-2 infection 3 to 11(mean 5±3.51)d before the disease, and 6 out of 8 patients developed visual symptoms within 5 d of infection with SARS-CoV-2, with manifestated with decreased vision or visual scotoma. The visual acuity varied from 0.08 to 1.0, with visual field defect characterized by central, paracentral or peripheral scotoma. VEP showed prolongation latency of P100 or P2, and ERG revealed impaired function of retinal photoreceptor cell. In the early stage of the disease, the size and shape of early visual acuity, visual field, and extraretinal lesions in patients with AMN associated with SARS-CoV-2 infection may not match, and the lower the visual acuity, the later the VEP peaks.CONCLUSION: The neuro-ophthalmic features of SARS-CoV-2 infection-associated AMN require the attention of clinicians. In addition to multi-mode fundus imaging, clinicians should use a variety of methods to comprehensively evaluate visual function and prognosis of patients.
10.A Rapid Non-invasive Method for Skin Tumor Tissue Early Detection Based on Bioimpedance Spectroscopy
Jun-Wen PENG ; Song-Pei HU ; Zhi-Yang HONG ; Li-Li WANG ; Kai LIU ; Jia-Feng YAO
Progress in Biochemistry and Biophysics 2024;51(5):1161-1173
ObjectiveIn recent years, with the intensification of environmental issues and the depletion of ozone layer, incidence of skin tumors has also significantly increased, becoming one of the major threats to people’s lives and health. However, due to factors such as high concealment in the early stage of skin tumors, unclear symptoms, and large human skin area, most cases are detected in the middle to late stage. Early detection plays a crucial role in postoperative survival of skin tumors, which can significantly improve the treatment and survival rates of patients. We proposed a rapid non-invasive electrical impedance detection method for early screening of skin tumors based on bioimpedance spectroscopy (BIS) technology. MethodsFirstly, we have established a complete skin stratification model, including stratum corneum, epidermis, dermis, and subcutaneous tissue. And the numerical analysis method was used to investigate the effect of dehydrated and dry skin stratum corneum on contact impedance in BIS measurement. Secondly, differentiation effect of different diameter skin tumor tissues was studied using a skin model after removing the stratum corneum. Then, in order to demonstrate that BIS technology can be used for detecting the microinvasion stage of skin tumors, we conducted a simulation study on the differentiation effect of skin tumors under different infiltration depths. Finally, in order to verify that the designed BIS detection system can distinguish between tumor microinvasion periods, we conducted tumor invasion experiments using hydrogel treated pig skin tissue. ResultsThe simulation results show that a dry and high impedance stratum corneum will bring about huge contact impedance, which will lead to larger measurement errors and affect the accuracy of measurement results. We extracted the core evaluation parameter of relaxed imaginary impedance (Zimag-relax) from the simulation results of the skin tumor model. When the tumor radius (Rtumor) and invasion depth (h)>1.5 mm, the designed BIS detection system can distinguish between tumor tissue and normal tissue. At the same time, in order to evaluate the degree of canceration in skin tissue, the degree of tissue lesion (εworse) is defined by the relaxed imaginary impedance (Zimag-relax) of normal and tumor tissue (εworse is the percentage change in virtual impedance of tumor tissue relative to that of normal tissue), and we fitted a Depth-Zimag-relax curve using relaxation imaginary impedance data at different infiltration depths, which can be applied to quickly determine the infiltration depth of skin tumors after being supplemented with a large amount of clinical data in the future. The experimental results proved that when εworse=0.492 0, BIS could identify microinvasive tumor tissue, and the fitting curve correction coefficient of determination was 0.946 8, with good fitting effect. The simulation using pig skin tissue correlated the results of real human skin simulation with the experimental results of pig skin tissue, proving the reliability of this study, and laying the foundation for further clinical research in the future. ConclusionOur proposed BIS method has the advantages of fast, real-time, and non-invasive detection, as well as high sensitivity to skin tumors, which can be identified during the stage of tumor microinvasion.


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