1.Clinical trail of vericiguat combined with sacubitril valsartan sodium in the treatment of patients with heart failure with reduced ejection fraction
Miao-jun WANG ; Shi-ping XU ; Xiao-jin PAN ; Zhi-dong YE ; Yu-fang LIAN ; Jun QIU ; Shao-tang LU ; Sheng-jie ZHOU
The Chinese Journal of Clinical Pharmacology 2025;41(1):6-10
Objective To observe the clinical efficacy and safety of vericiguat tablets combined with sacubitril valsartan sodium(Sac/Val)tablets in the treatment of patients with heart failure with reduced ejection fraction(HFrEF).Methods The HFrEF patients were divided into control group and treatment group according to the cohort method.The control group was treated with Sac/Val tablets 200 mg per time,bid,orally.On the basis of control group,the treatment group was treated with vericiguat tablets 2.5 mg per time,qd,taken with meal.Two groups were treated for 3 months.The clinical efficacy,left ventricular ejection fraction(LVEF),left ventricular end-diastolic dimension(LVEDD)and end-systolic diameter(LVESD),levels of high sensitivity C-reactive protein(hs-CRP),interleukin-6(IL-6),nitric oxide(NO),N-terminal pro-brain natriuretic peptide(NT-proBNP),blood urea nitrogen(BUN)and serum creatinine(SCr),and safety were compared between the two groups.During follow-up,the heart failure rehospitalization rates and major adverse cardiovascular events were compared between the two groups.Results Treatment group was enrolled 53 patients,control group was enrolled 53 patients.After treatment,the total effective rates of treatment and control groups were 94.34%(50 cases/53 cases)and 81.13%(43 cases/53 cases)with statistical significant difference(P<0.05).After treatment,the LVEF of treatment and control groups were(48.02±5.20)%and(43.02±4.33)%,the LVEDDs were(52.85±6.30)and(55.63±6.88)mm,the LVESDs were(41.64±6.40)and(44.22±5.85)mm,the levels of hs-CRP were(10.22±2.63)and(14.60±2.98)mg L-1,the levels of IL-6 were(14.48±2.40)and(17.36±2.52)pg·mL-1,the levels of NO were(102.60±20.16)and(92.16±16.33)μmol·L-1,the levels of NT-proBNP were(898.74±102.20)and(1315.60±182.64)ng·L-1,the levels of BUN were(12.02±2.28)and(13.45±2.33)mmol·L-1,the levels of SCr were(82.22±5.89)and(85.64±6.03)μmol·L-1,the heart failure rehospitalization rates were 5.66%and 13.21%,respectively;the differences were statistical significant between two groups(all P<0.05).The adverse drug reactions of treatment group were hyperkalemia,hypotension,renal dysfunction,dizziness and headache,while those in control group were renal dysfunction,hyperkalemia,and hypotension.The major adverse cardiovascular events of treatment group were angina pectoris and acute myocardial infarction,while those in control group were angina pectoris,acute myocardial infarction and atrial fibrillation.The incidences of total adverse drug reactions in treatment and control groups were 13.21%and 7.55%,the incidences of major adverse cardiovascular events were 5.66%and 13.21%,respectively,without statistically significant differences(all P>0.05).Conclusion Vericiguat tablets combined with Sac/Val tablets have a definitive clinical efficacy in the treatment of HFrEF patients,which can improve cardiac and endothelial function,reduce inflammatory response and readmission times,without increasing the incidences of adverse drug reactions.
2.Hemoglobin variants with low oxygen affinity:clinical diagnosis and research progress
Weidan LI ; Qiang ZENG ; Huiqin JIN ; Haiyan ZHU ; Hong ZHOU ; Lian ZHAO
Military Medical Sciences 2025;49(1):68-73
The discovery of hemoglobin variants with low oxygen affinity,diagnostic methods,prognosis of carriers,and developments in analyzing hemoglobin oxygen-carrying and-releasing abilities are reviewed in this article in order to draw the attention of related clinical departments and to provide references for optimizing the process of diagnosis and treatment.Hemoglobin variants with low oxygen affinity originate from gene mutations encoding hemoglobin and autosomal dominant inheritance.The diagnosis should be combined with clinical manifestations and family history and differentiated from methemoglobinemia.A decrease in pulse oxygen saturation(SpO2)is often the first abnormality observed in asymptomatic carriers of hemoglobin variants with low oxygen affinity.Laboratory examinations include arterial blood gas analysis,hemoglobin oxygen affinity testing,protein analysis and gene sequencing.Most carriers do not require specific treatment and have a good prognosis,who should avoid acute hypoxic injuries induced by strenuous exercise,emotional stress,or high temperature.Moreover,health practitioners should pay attention to their responses to anesthetics,agents that induce oxidative stress,drugs that increase hemoglobin oxygen affinity,and prostacyclins.Hemoglobin oxygen-carrying and-releasing analysis is a promising tool to identify carriers of hemoglobin variants with low oxygen affinity because it does not involve unnecessary or invasive examinations and is of significant values for clinical diagnosis and treatment.
3.Clinical trail of vericiguat combined with sacubitril valsartan sodium in the treatment of patients with heart failure with reduced ejection fraction
Miao-jun WANG ; Shi-ping XU ; Xiao-jin PAN ; Zhi-dong YE ; Yu-fang LIAN ; Jun QIU ; Shao-tang LU ; Sheng-jie ZHOU
The Chinese Journal of Clinical Pharmacology 2025;41(1):6-10
Objective To observe the clinical efficacy and safety of vericiguat tablets combined with sacubitril valsartan sodium(Sac/Val)tablets in the treatment of patients with heart failure with reduced ejection fraction(HFrEF).Methods The HFrEF patients were divided into control group and treatment group according to the cohort method.The control group was treated with Sac/Val tablets 200 mg per time,bid,orally.On the basis of control group,the treatment group was treated with vericiguat tablets 2.5 mg per time,qd,taken with meal.Two groups were treated for 3 months.The clinical efficacy,left ventricular ejection fraction(LVEF),left ventricular end-diastolic dimension(LVEDD)and end-systolic diameter(LVESD),levels of high sensitivity C-reactive protein(hs-CRP),interleukin-6(IL-6),nitric oxide(NO),N-terminal pro-brain natriuretic peptide(NT-proBNP),blood urea nitrogen(BUN)and serum creatinine(SCr),and safety were compared between the two groups.During follow-up,the heart failure rehospitalization rates and major adverse cardiovascular events were compared between the two groups.Results Treatment group was enrolled 53 patients,control group was enrolled 53 patients.After treatment,the total effective rates of treatment and control groups were 94.34%(50 cases/53 cases)and 81.13%(43 cases/53 cases)with statistical significant difference(P<0.05).After treatment,the LVEF of treatment and control groups were(48.02±5.20)%and(43.02±4.33)%,the LVEDDs were(52.85±6.30)and(55.63±6.88)mm,the LVESDs were(41.64±6.40)and(44.22±5.85)mm,the levels of hs-CRP were(10.22±2.63)and(14.60±2.98)mg L-1,the levels of IL-6 were(14.48±2.40)and(17.36±2.52)pg·mL-1,the levels of NO were(102.60±20.16)and(92.16±16.33)μmol·L-1,the levels of NT-proBNP were(898.74±102.20)and(1315.60±182.64)ng·L-1,the levels of BUN were(12.02±2.28)and(13.45±2.33)mmol·L-1,the levels of SCr were(82.22±5.89)and(85.64±6.03)μmol·L-1,the heart failure rehospitalization rates were 5.66%and 13.21%,respectively;the differences were statistical significant between two groups(all P<0.05).The adverse drug reactions of treatment group were hyperkalemia,hypotension,renal dysfunction,dizziness and headache,while those in control group were renal dysfunction,hyperkalemia,and hypotension.The major adverse cardiovascular events of treatment group were angina pectoris and acute myocardial infarction,while those in control group were angina pectoris,acute myocardial infarction and atrial fibrillation.The incidences of total adverse drug reactions in treatment and control groups were 13.21%and 7.55%,the incidences of major adverse cardiovascular events were 5.66%and 13.21%,respectively,without statistically significant differences(all P>0.05).Conclusion Vericiguat tablets combined with Sac/Val tablets have a definitive clinical efficacy in the treatment of HFrEF patients,which can improve cardiac and endothelial function,reduce inflammatory response and readmission times,without increasing the incidences of adverse drug reactions.
4.Efficacy of cosmetic suturing techniques combined with topical recombinant human basic fibroblast growth factor in repairing facial trauma
Huibin LIAN ; Pingsong LI ; Kunjie RONG ; Gang XU ; Jie ZHOU ; Yi LUO ; Zhongyin ZHUFU ; Haibin JU ; Junjun JIN ; Rui JIAO ; Xiaowei ZHANG ; Zhimin YIN
Chinese Journal of Medical Aesthetics and Cosmetology 2024;30(6):571-575
Objective:To observe the efficacy of cosmetic suturing techniques combined with topical recombinant human basic fibroblast growth factor (rh-bFGF) in repairing facial trauma.Methods:A prospective study was conducted on 140 patients with facial trauma admitted to the Department of Burn and Plastic Surgery, Northern Jiangsu People's Hospital from January to December 2022. Patients were divided into two groups based on different treatment methods using a random number table method: treatment group (70 cases), including 38 males and 32 females aged 3 to 54 (23.1±8.2) years, received cosmetic suturing techniques combined with topical rh-bFGF for wound repair; control group (70 cases), including 36 males and 34 females aged 2 to 49 (22.3±7.5) years, only received cosmetic suturing techniques for wound repair. Patients were followed up 2 weeks post-surgery to evaluate wound healing quality. Patient satisfaction was assessed using the visual analogue scale (VAS). Six months post-surgery, scar conditions were evaluated using the Vancouver scar scale (VSS).Results:In the treatment group, 65 cases were directly sutured, and 5 cases were repaired with skin flaps, with a first-class healing rate of 100% (70/70). In the control group, 66 cases were directly sutured, and 4 cases were repaired with skin flaps, with a first-class healing rate of 91.4% (64/70). The first-class healing rate in the treatment group was higher than that in the control group, with a statistically significant difference ( P=0.037). Two weeks post-surgery, the VAS score for surgical satisfaction in the treatment group was (1.13±0.52) scores, which was lower than that in the control group (2.56±1.32) scores, with a statistically significant difference ( P<0.001). Six months post-surgery, the VSS score for the treatment group was (2.49±1.27) scores, which was lower than that in the control group (4.67±1.93) scores, with a statistically significant difference ( P<0.001). Conclusions:In repairing facial trauma, the combination of cosmetic suturing techniques and topical rh-bFGF can improve wound healing quality, reduce wound scarring, and enhance patient satisfaction with surgery.
5.RNA SNP Detection Method With Improved Specificity Based on Dual-competitive-padlock-probe
Qin-Qin ZHANG ; Jin-Ze LI ; Wei ZHANG ; Chuan-Yu LI ; Zhi-Qi ZHANG ; Jia YAO ; Hong DU ; Lian-Qun ZHOU ; Zhen GUO
Progress in Biochemistry and Biophysics 2024;51(11):3021-3033
ObjectiveThe detection of RNA single nucleotide polymorphism (SNP) is of great importance due to their association with protein expression related to various diseases and drug responses. At present, splintR ligase-assisted methods are important approaches for RNA direct detection, but its specificity will be limited when the fidelity of ligases is not ideal. The aim of this study was to create a method to improve the specificity of splintR ligase for RNA detection. MethodsIn this study, a dual-competitive-padlock-probe (DCPLP) assay without the need for additional enzymes or reactions is proposed to improve specificity of splintR ligase ligation. To verify the method, we employed dual competitive padlock probe-mediated rolling circle amplification (DCPLP-RCA) to genotype the CYP2C9 gene. ResultsThe specificity was well improved through the competition and strand displacement of dual padlock probe, with an 83.26% reduction in nonspecific signal. By detecting synthetic RNA samples, the method demonstrated a dynamic detection range of 10 pmol/L-1 nmol/L. Furthermore, clinical samples were applied to the method to evaluate its performance, and the genotyping results were consistent with those obtained using the qPCR method. ConclusionThis study has successfully established a highly specific direct RNA SNP detection method, and provided a novel avenue for accurate identification of various types of RNAs.
6.The expression mechanism of programmed cell death 1 ligand 1 and its role in immunomodulatory ability of mesenchymal stem cells
Zhuo CHEN ; Meng-Wei YAO ; Xiang AO ; Qing-Jia GONG ; Yi YANG ; Jin-Xia LIU ; Qi-Zhou LIAN ; Xiang XU ; Ling-Jing ZUO
Chinese Journal of Traumatology 2024;27(1):1-10
Programmed cell death 1 ligand 1 (PD-L1) is an important immunosuppressive molecule, which inhibits the function of T cells and other immune cells by binding to the receptor programmed cell death-1. The PD-L1 expression disorder plays an important role in the occurrence, development, and treatment of sepsis or other inflammatory diseases, and has become an important target for the treatment of these diseases. Mesenchymal stem cells (MSCs) are a kind of pluripotent stem cells with multiple differentiation potential. In recent years, MSCs have been found to have a strong immunosuppressive ability and are used to treat various inflammatory insults caused by hyperimmune diseases. Moreover, PD-L1 is deeply involved in the immunosuppressive events of MSCs and plays an important role in the treatment of various diseases. In this review, we will summarize the main regulatory mechanism of PD-L1 expression, and discuss various biological functions of PD-L1 in the immune regulation of MSCs.
7.Cellular Temperature Imaging Technology Based on Single-molecule Quantum Coherent Modulation
Hai-Tao ZHOU ; Cheng-Bing QIN ; Lian-Tuan XIAO ; Zhi-Fang WU ; Si-Jin LI
Progress in Biochemistry and Biophysics 2024;51(5):1215-1220
ObjectiveCellular temperature imaging can assist scientists in studying and comprehending the temperature distribution within cells, revealing critical information about cellular metabolism and biochemical processes. Currently, cell temperature imaging techniques based on fluorescent temperature probes suffer from limitations such as low temperature resolution and a limited measurement range. This paper aims to develop a single-cell temperature imaging and real-time monitoring technique by leveraging the temperature-dependent properties of single-molecule quantum coherence processes. MethodsUsing femtosecond pulse lasers, we prepare delayed and phase-adjustable pairs of femtosecond pulses. These modulated pulse pairs excite fluorescent single molecules labeled within cells through a microscopic system, followed by the collection and recording of the arrival time of each fluorescent photon. By defining the quantum coherence visibility (V) of single molecules in relation to the surrounding environmental temperature, a correspondence between V and environmental temperature is established. By modulating and demodulating the arrival times of fluorescent photons, we obtain the local temperature of single molecules. Combined with scanning imaging, we finally achieve temperature imaging and real-time detection of cells. ResultsThis method achieves high precision (temperature resolution<0.1°C) and a wide temperature range (10-50°C) for temperature imaging and measurement, and it enables the observation of temperature changes related to individual cell metabolism. ConclusionThis research contributes to a deeper understanding of cellular metabolism, protein function, and disease mechanisms, providing a valuable tool for biomedical research.
8.Raman Spectroscopy Analysis of The Temporal Heterogeneity in Lung Cell Carcinogenesis Induced by Benzo(a)pyrene
Hai-Tao ZHOU ; Wei YAO ; Cao-Zhe CUI ; Xiao-Tong ZHOU ; Xi-Long LIANG ; Cheng-Bing QIN ; Lian-Tuan XIAO ; Zhi-Fang WU ; Si-Jin LI
Progress in Biochemistry and Biophysics 2024;51(6):1458-1470
ObjectiveTemporal heterogeneity in lung cancer presents as fluctuations in the biological characteristics, genomic mutations, proliferation rates, and chemotherapeutic responses of tumor cells over time, posing a significant barrier to effective treatment. The complexity of this temporal variance, coupled with the spatial diversity of lung cancer, presents formidable challenges for research. This article will pave the way for new avenues in lung cancer research, aiding in a deeper understanding of the temporal heterogeneity of lung cancer, thereby enhancing the cure rate for lung cancer. MethodsRaman spectroscopy emerges as a powerful tool for real-time surveillance of biomolecular composition changes in lung cancer at the cellular scale, thus shedding light on the disease’s temporal heterogeneity. In our investigation, we harnessed Raman spectroscopic microscopy alongside multivariate statistical analysis to scrutinize the biomolecular alterations in human lung epithelial cells across various timeframes after benzo(a)pyrene exposure. ResultsOur findings indicated a temporal reduction in nucleic acids, lipids, proteins, and carotenoids, coinciding with a rise in glucose concentration. These patterns suggest that benzo(a)pyrene induces structural damage to the genetic material, accelerates lipid peroxidation, disrupts protein metabolism, curtails carotenoid production, and alters glucose metabolic pathways. Employing Raman spectroscopy enabled us to monitor the biomolecular dynamics within lung cancer cells in a real-time, non-invasive, and non-destructive manner, facilitating the elucidation of pivotal molecular features. ConclusionThis research enhances the comprehension of lung cancer progression and supports the development of personalized therapeutic approaches, which may improve the clinical outcomes for patients.
9.Clinical effects of Supplemented Buzhong Yiqi Decoction on patients with HP-positive chronic atrophic gastritis of Spleen-Stomach Deficiency Pattern
Hui-Hu GAN ; Lian-Ning JIN ; Hong-Gen HUANG ; Wen-Bo ZHOU
Chinese Traditional Patent Medicine 2024;46(2):469-473
AIM To explore the clinical effects of Supplemented Buzhong Yiqi Decoction on patients with HP-positive chronic atrophic gastritis of Spleen-Stomach Deficiency Pattern.METHODS One hundred and thirty-two patients were randomly assigned into control group(66 cases)for 12-week intervention of conventional treatment,and observation group(66 cases)for 12-week intervention of both Supplemented Buzhong Yiqi Decoction and conventional treatment.The changes in clinical effects,HP clearance rate,miR-32,TGF-β1,IL-6,PGⅠ,PGⅡ,EGF,somatostatin,gastrin,motilin,gastroscopy pathological score and TCM symptom score were detected.RESULTS The observation group demonstrated higher total effective rate and HP clearance rate than the control group(P<0.05).After the treatment,the two groups displayed decreased miR-32,TGF-β1,IL-6,gastroscopy pathological score,TCM symptom score(P<0.05),and increased PGⅠ,PGⅡ,EGF,somatostatin,gastrin,motilin(P<0.05),especially for the observation group(P<0.05).CONCLUSION For the patients with HP-positive chronic atrophic gastritis of Spleen-Stomach Deficiency Pattern,Supplemented Buzhong Yiqi Decoction can alleviate inflammation,regulate gastrointestinal hormone levels,improve symptoms,and enhance efficacy.
10.Spatially resolved metabolomics visualizes heterogeneous distribution of metabolites in lung tissue and the anti-pulmonary fibrosis effect of Prismatomeris connate extract
Jiang HAIYAN ; Zheng BOWEN ; Hu GUANG ; Kuang LIAN ; Zhou TIANYU ; Li SIZHENG ; Chen XINYI ; Li CHUANGJUN ; Zhang DONGMING ; Zhang JINLAN ; Yang ZENGYAN ; He JIUMING ; Jin HONGTAO
Journal of Pharmaceutical Analysis 2024;14(9):1330-1346
Pulmonary fibrosis(PF)is a chronic progressive end-stage lung disease.However,the mechanisms un-derlying the progression of this disease remain elusive.Presently,clinically employed drugs are scarce for the treatment of PF.Hence,there is an urgent need for developing novel drugs to address such diseases.Our study found for the first time that a natural source of Prismatomeris connata Y.Z.Ruan(Huang Gen,HG)ethyl acetate extract(HG-2)had a significant anti-PF effect by inhibiting the expression of the transforming growth factor beta 1/suppressor of mothers against decapentaplegic(TGF-β1/Smad)pathway.Network pharmacological analysis suggested that HG-2 had effects on tyrosine kinase phosphorylation,cellular response to reactive oxygen species,and extracellular matrix(ECM)disassembly.Moreover,mass spec-trometry imaging(MSI)was used to visualize the heterogeneous distribution of endogenous metabolites in lung tissue and reveal the anti-PF metabolic mechanism of HG-2,which was related to arginine biosyn-thesis and alanine,asparate and glutamate metabolism,the downregulation of arachidonic acid meta-bolism,and the upregulation of glycerophospholipid metabolism.In conclusion,we elaborated on the relationship between metabolite distribution and the progression of PF,constructed the regulatory metabolic network of HG-2,and discovered the multi-target therapeutic effect of HG-2,which might be conducive to the development of new drugs for PF.

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