1.Apoptosis Regulation by Buzhong Yiqitang via PERK/eIF2α/ATF4/CHOP Pathway to Enhance Pulmonary Surfactant-associated Protein C Expression and Ameliorate Lung Injury in CIH Mice
Luyao ZHANG ; Yangjing WANG ; Bingbing LIU ; Jieru LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(15):19-27
ObjectiveTo investigate the effects of Buzhong Yiqitang on the abnormal expression of pulmonary surfactant-associated protein C (SFTPC) and lung injury induced by chronic intermittent hypoxia (CIH) and the mechanism of action. MethodsForty healthy adult male SPF-grade C57BL/6 mice were randomly allocated into five experimental groups: a normoxia group, a CIH group, and low-, medium-, and high-dose Buzhong Yiqitang groups, with eight mice in each group. During the modeling, mice in the normoxia group were housed under standard oxygen concentrations, while the CIH and all Buzhong Yiqitang groups were placed in a hypoxic chamber for 8 h daily over 35 d. Prior to each chamber session, mice in the low-, medium-, and high-dose Buzhong Yiqitang groups were administered decoctions by gavage at corresponding doses (8.1, 16.2, 32.4 g·kg-1·d-1 of crude drug, respectively), while those in normoxia and CIH groups received an equivalent volume of saline by gavage. The general conditions of the mice were recorded before and after the experiment. Pulmonary function was assessed using a non-invasive detection system. Serum SFTPC levels were measured using enzyme-linked immunosorbent assay (ELISA). Histopathological changes in lung tissue were evaluated using hematoxylin-eosin (HE) staining. Apoptosis in lung tissue was detected using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). Protein expression of SFTPC, B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), protein kinase R-like endoplasmic reticulum kinase (PERK), phosphorylated PERK (p-PERK), eukaryotic initiation factor 2α (eIF2α), phosphorylated eIF2α (p-eIF2α), activating transcript factor 4 (ATF4), and CCAAT/enhancer-binding protein homologous protein (CHOP) in lung tissue was analyzed by Western blot. Immunofluorescence staining was employed to assess the expression of SFTPC and CHOP proteins in lung tissue. ResultsCompared to those in the normoxia group, mice in the CIH group showed significantly impaired pulmonary function and increased histopathological lung injury scores (P<0.05, P<0.01). Serum SFTPC levels increased, while SFTPC expression in lung tissue was reduced (P<0.05, P<0.01). The rate of apoptotic cells in lung tissue increased, and the expression of endoplasmic reticulum stress markers p-PERK, p-eIF2α, ATF4, and CHOP was upregulated (P<0.05, P<0.01). Compared with the CIH group, Buzhong Yiqitang intervention improved pulmonary function indicators and decreased the histopathological lung injury scores (P<0.05, P<0.01). Serum SFTPC levels were decreased, and lung tissue SFTPC expression was recovered (P<0.05, P<0.01). The apoptotic rate of lung tissue cells was significantly reduced, with downregulation of pro-apoptotic Bax and upregulation of anti-apoptotic Bcl-2 expression (P<0.05, P<0.01). Activation and expression of p-PERK, p-eIF2α, ATF4, and CHOP were also decreased (P<0.05, P<0.01). ConclusionBuzhong Yiqitang can alleviate lung injury and improve pulmonary function by reducing lung cell apoptosis and enhancing alveolar surfactant secretion, which may be related to the modulation of the PERK/eIF2α/ATF4/CHOP signaling pathway.
2.Analysis of human parvovirus B19 nucleic acid detection in blood products in China
Yue WANG ; Xiaobei ZHENG ; Qin GONG ; Ying ZHAO ; Yuanxiu LUO ; Dandan YANG ; Linlin ZHANG ; Zheng JIANG ; Gan PENG ; Jin ZHANG ; Bingbing KE
Chinese Journal of Blood Transfusion 2025;38(7):950-957
Objective: To analyze the nucleic acid load of human parvovirus B19 in major commercially available blood products in China, including human albumin, human intravenous immunoglobulin, human rabies immunoglobulin and various coagulation factor products, aiming to provide evidence for improving blood product manufacturing processes and quality control of source plasma. Methods: A total of 98 batches of coagulation factor products were tested for human parvovirus B19 nucleic acid using real-time fluorescent quantitative PCR, including 42 batches of human prothrombin complex, 35 batches of human coagulation factor Ⅷ, and 21 batches of human fibrinogen. Additionally, 6 batches of human albumin, 6 batches of human intravenous immunoglobulin, and 38 batches of human rabies immunoglobulin were tested for human parvovirus B19 nucleic acid. Results: Human parvovirus B19 nucleic acid were undetectable in human albumin, human intravenous immunoglobulin and human rabies immunoglobulin. Among the 98 batches of coagulation factor products tested for human parvovirus B19 nucleic acid, B19 nucleic acid reactivity rate was 69.0% (29/42) for human prothrombin complex batches, but nucleic acid concentration were all significantly lower than 10
IU/mL. The reactivity rate of B19 nucleic acid in 35 batches of human coagulation factor Ⅷ was 48.6% (17/35), with nucleic acid concentration all below 10
IU/mL. The reactivity rate of B19 nucleic acid in 21 batches of human fibrinogen was 61.9% (13/21), with nucleic acid concentration all below 10
IU/mL. Conclusion: No human parvovirus B19 has been detected in human albumin, human intravenous immunoglobulin, or human rabies immunoglobulin. Human parvovirus B19 nucleic acid may exist in commercially available coagulation factor products, highlighting the need for enhanced screening of human parvovirus B19 nucleic acid in these products. It is also recommended that B19 viral nucleic acid testing be conducted on source plasma, particularly for coagulation factor products.
3.Analysis of human parvovirus B19 nucleic acid detection in blood products in China
Yue WANG ; Xiaobei ZHENG ; Qin GONG ; Ying ZHAO ; Yuanxiu LUO ; Dandan YANG ; Linlin ZHANG ; Zheng JIANG ; Gan PENG ; Jin ZHANG ; Bingbing KE
Chinese Journal of Blood Transfusion 2025;38(7):950-957
Objective: To analyze the nucleic acid load of human parvovirus B19 in major commercially available blood products in China, including human albumin, human intravenous immunoglobulin, human rabies immunoglobulin and various coagulation factor products, aiming to provide evidence for improving blood product manufacturing processes and quality control of source plasma. Methods: A total of 98 batches of coagulation factor products were tested for human parvovirus B19 nucleic acid using real-time fluorescent quantitative PCR, including 42 batches of human prothrombin complex, 35 batches of human coagulation factor Ⅷ, and 21 batches of human fibrinogen. Additionally, 6 batches of human albumin, 6 batches of human intravenous immunoglobulin, and 38 batches of human rabies immunoglobulin were tested for human parvovirus B19 nucleic acid. Results: Human parvovirus B19 nucleic acid were undetectable in human albumin, human intravenous immunoglobulin and human rabies immunoglobulin. Among the 98 batches of coagulation factor products tested for human parvovirus B19 nucleic acid, B19 nucleic acid reactivity rate was 69.0% (29/42) for human prothrombin complex batches, but nucleic acid concentration were all significantly lower than 10
IU/mL. The reactivity rate of B19 nucleic acid in 35 batches of human coagulation factor Ⅷ was 48.6% (17/35), with nucleic acid concentration all below 10
IU/mL. The reactivity rate of B19 nucleic acid in 21 batches of human fibrinogen was 61.9% (13/21), with nucleic acid concentration all below 10
IU/mL. Conclusion: No human parvovirus B19 has been detected in human albumin, human intravenous immunoglobulin, or human rabies immunoglobulin. Human parvovirus B19 nucleic acid may exist in commercially available coagulation factor products, highlighting the need for enhanced screening of human parvovirus B19 nucleic acid in these products. It is also recommended that B19 viral nucleic acid testing be conducted on source plasma, particularly for coagulation factor products.
4.Transcranial magnetic stimulation can alleviate sleep disorders in children with cerebral palsy
Jun WANG ; Yuhang ZHANG ; Lijie ZHOU ; Yangyang CAO ; Ru WANG ; Chunya SU ; Junhui WANG ; Bingbing LI ; Dengna ZHU ; Huachun XIONG
Chinese Journal of Physical Medicine and Rehabilitation 2024;46(2):134-138
Objective:To observe any effect of repetitive transcranial magnetic stimulation (rTMS) on sleep disorders among children with cerebral palsy (CP).Methods:A total of 102 children with CP and disordered sleep were randomly divided into an experimental group and a control group, each of 51. All were given routine rehabilitation and sleep health education, but the experimental group additionally received rTMS for two weeks. The polysomnography (PSG) results of the two groups were recorded and analyzed.Results:The PSG parameters had improved greatly in both groups after the treatment. The percentage of N2 sleep (depth of sleep during light sleep) in the severe cerebral palsy group and of N3 sleep (depth of sleep during deep sleep) in the moderate cerebral palsy group had increased significantly more than in the mild cerebral palsy group, on average. After the intervention the percentages of N2 and N3 in those with mixed cerebral palsy and of N3 in those with involuntary motor cerebral palsy had increased significantly more than in those with spastic cerebral palsy, on average.Conclusion:rTMS treatment can improve the sleep disorders of children with cerebral palsy, especially N2 sleep among children with moderate to severe cerebral palsy, N3 sleep in cases of mixed or dyskinetic CP.
5.Mechanisms of Fufang Biejia Ruangan Pills Against Alcoholic Liver Disease via Regulating Liver-brain Dialogue Mediated by HMGB1-BDNF Axis
Yudong LIU ; Xiangying YAN ; Tao LI ; Chu ZHANG ; Bingbing CAI ; Zhaochen MA ; Na LIN ; Yanqiong ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(23):214-223
ObjectiveTo systematically and objectively characterize the pharmacological effects of Fufang Biejia Ruangan pills (FBRP) in the intervention of alcoholic liver disease (ALD) using acute and chronic ALD mouse models and to elucidate its molecular mechanisms. MethodFifty SPF-grade male BALB/c mice were randomly divided into the normal group, model group, and FBRP low-, medium-, and high-dose groups (9.6, 19.2, 38.4 mg·kg-1). Except for the normal group, the remaining groups were given 56° white wine by gavage to establish the acute ALD model, with samples collected after 4 weeks. Thirty SPF-grade male C57BL/6N mice were randomly divided into the normal group, model group, and FBRP medium-dose group (19.2 mg·kg-1). The chronic ALD mouse model was established using the Lieber-DeCarli method over a 10-week period. Inflammatory markers in liver tissues were assessed using hematoxylin-eosin (HE), Sirius Red, oil red O staining, and enzyme-linked immunosorbent assay (ELISA). Intoxication behaviors of each group were objectively evaluated through sobering-up time, net-catching, and pole-climbing tests. Further bioinformatics analyses based on clinical transcriptomic data were conducted to identify key targets and molecular mechanisms of FBRP in alleviating ALD through liver-brain dialogue, with experimental validation by ELISA, Western blot, and immunohistochemical staining. ResultCompared with the normal group, the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in liver tissues of mice in the acute and chronic ALD model groups were significantly increased (P<0.05). Compared with the model group, the levels of AST and ALT in liver tissue of mice in FBRP groups were significantly decreased (P<0.05). Compared with the normal group, the time of grasping the net and climbing the pole in the acute ALD model group was significantly decreased within 4 weeks (P<0.01). Compared with the model group, the grasping and climbing time of FBRP high dose groups increased significantly within 4 weeks (P<0.05). Compared with the normal group, the expression of high mobility group protein B1 (HMGB1) protein in liver tissue and prefrontal lobe tissue of mice in the chronic ALD model group was significantly increased (P<0.01). Compared with the model group, the expression of HMGB1 protein in FBRP medium dose group was significantly decreased (P<0.05,P<0.01). Compared with the normal group, the expression of brain-derived neurotrophic factor (BDNF) protein and the release of γ-aminobutyric acid (GABA) in the prefrontal cortex of the model group were significantly decreased (P<0.01). Compared with the model group, the expression of BDNF protein and the release of GABA in the FBRP medium dose group were significantly increased (P<0.05). ConclusionThis study revealed that FBRP improved key pathological changes in ALD by modulating liver-brain dialogue mediated by the HMGB1-BDNF axis. These findings provide experimental evidence for the clinical use of FBRP in treating ALD and offer new insights for the development of ALD therapeutic agents.
6.Identification of in Vitro and in vivo Chemical Constituents of Ruyi Zhenbaowan Based on UHPLC-Q Exactive Orbitrap HRMS
Kedian CHEN ; Zhaochen MA ; Bingbing CAI ; Ying LIU ; Yudong LIU ; Tao LI ; Mingzhu XU ; Haiping WANG ; Na LIN ; Yanqiong ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(24):78-84
ObjectiveTo identify the chemical constituents of Ruyi Zhenbaowan in vitro and in vivo. MethodThe chemical constituents of Ruyi Zhenbaowan were identified based on UHPLC-Q Exactive Orbitrap HRMS. A total of 12 male SD rats were randomized into two groups: control (pure water) and Ruyi Zhenbaowan (1.8 g·kg-1). The rats were administrated with the suspension of Ruyi Zhenbaowan or pure water by gavage. After 1.5 h, the plasma and cerebrospinal fluid were collected. Chromatographic separation was performed on a Waters ACQUITY UPLC BEH C18 column (2.1 mm × 150 mm, 1.7 μm) with a mixture of 0.1% formic acid aqueous solution (A) and acetonitrile (B) as the mobile phase. Gradient elution was carried out according to the procedure of 0~15 min,97%~80%A;15~30 min ,80%~60%A;30~40 min,60%~30%A;40~45 min,30%~5%A. The ion source was electrospray ionization, and scan range was m/z 100-1 500. The prototype components and the components in the plasma and cerebrospinal fluid were analyzed qualitatively by scanning in positive and negative ion modes and identified by comparison with the data in published literature and the information of standard substances. ResultA total of 126 chemical constituents were identified from the 80% methanol solution of Ruyi Zhenbaowan, and 14 and 7 prototype constituents were detected in the plasma and the cerebrospinal fluid, respectively. In addition, the fragmentation rules of apigenin, apigenin-7-O-glucuronide, galangin, liquiritin, piperine, glycyrrhizic acid, eugenol, gallic acid, and cholic acid were deduced. ConclusionThis study achieved rapid multicomponent characterization and identification of Ruyi Zhenbaowan in vitro and in vivo, providing theoretical support for exploring active substances and performing quality control.l.
7.Health impact assessment of the development of employment and social security in Deqing County, Zhejiang Province
Shiyu HAN ; Bingbing ZHU ; Yiming ZHANG ; Yuting YANG ; Chaowei FU
Shanghai Journal of Preventive Medicine 2024;36(3):274-279
ObjectiveTo identify the possible health impact of the 14th five⁃year plan for the development of employment and social security in Deqing County and propose improvement measures through health impact assessment. MethodsBased on the data of Deqing County, stakeholder interviews and Delphi Consultation Method, this study described the current status of employment and social security and analyzed the potential health impacts of implementing the 14th five⁃year plan for the development of employment and social security in Deqing County. ResultsThrough a quick assessment process, the results showed that the implementation of the plan would bring mixed health impacts. Positive impacts included enhanced social security capacity, improved health levels of low-income populations and families, increased convenience of medical treatment, and improved efficiency of health services. Negative impacts included reduced accessibility of digital services for the elderly, increased gap in benefits for retirees, increased risk of discrimination against disabled individuals, increased risks of layoffs and unemployment for vulnerable groups, and increased employment instability for middle-aged and elderly populations. ConclusionThe 14th five⁃year plan for the development of employment and social security in Deqing County will bring a series of positive health impacts, but negative health impacts also warrant attention.
8.GLUT1-targeted Nano-delivery System for Active Ingredients of Traditional Chinese Medicine:A Review
Hua ZHU ; Huimin LUO ; Si LIN ; Bingbing WANG ; Jinwei LI ; Liba XU ; Miao ZHANG ; Fengfeng XIE ; Long CHEN ; Meilin LI ; Lu LU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(12):270-280
Tumor cells use glycolysis to provide material and energy under hypoxic conditions to meet the energy requirements for rapid growth and proliferation, namely the Warburg effect. Even under aerobic conditions, tumor cells mainly rely on glycolysis to provide energy. Therefore, glucose transporter protein 1(GLUT1), which is involved in the process of glucose metabolism, plays an important role in tumorigenesis, development and drug resistance, and is considered to be one of the important targets in the treatment of malignant tumors. In recent years, research on tumor glucose metabolism has gradually become a hot spot. It has been shown that various factors are involved in the regulation of tumor energy metabolism, among which the role of GLUT1 is the most critical. In this paper, the authors reviewed the latest research progress of GLUT1-targeted traditional Chinese medicine(TCM) active ingredient nano-delivery system in tumor therapy, aiming to reveal the feasibility and effectiveness of this system in the delivery of chemotherapeutic drugs. The GLUT1-targeted TCM active ingredient nano-delivery system can overcome the bottleneck of the traditional targeting strategy as well as the high-permeability long retention(EPR) effect. In summary, the authors believe that the GLUT1-targeted TCM active ingredient nano-delivery system provides a new strategy for targeted treatment of tumors and has a broad application prospect in tumor prevention and treatment.
9.A retrospective study:The efficacy and safety of immunotherapy combined with radiochemotherapy for advanced esophageal cancer
China Modern Doctor 2024;62(1):39-42
Objective To contrast the efficacy and safety of immune checkpoint inhibitor(ICI)combined with radiochemotherapy and concomitant radiochemotherapy in the treatment of advanced esophageal cancer.Methods The clinical data of 67 patients with advanced esophageal cancer who were treated in the Second Hospital of Anhui Medical University from January 2019 to January 2023 were retrospectively analyzed.Patients were divided into combination group(n=35)and radiochemotherapy group(n=32)according to different treatment plans.Progress free survival(PFS),objective remission rate(ORR),disease control rate(DCR)and adverse reactions were compared between two groups.Results The median PFS in combination group was significantly longer than that in radiochemotherapy group(12.6 months vs.6.3 months,χ2=16.288,P<0.001).ORR in combination group was significantly higher than that in radiochemotherapy group(54.3%vs.21.9%,P=0.011).DCR in combination group was significantly higher than that in radiochemotherapy group(77.1%vs.53.1%,P=0.045).The incidence of treatment-related adverse reactions and radiochemotherapy-related adverse reactions in combination group were significantly lower than those in radiochemotherapy group(P<0.05).There were 11 cases of immune-related adverse reactions in combination group,all of which were grade 1-2 adverse reactions.Conclusion ICI combined with radiochemotherapy can improve the curative effect of patients with advanced esophageal cancer,and the adverse reactions are acceptable.
10.Influence of different compressed sensing factors on susceptibility weighted imaging for displaying cerebral medullary vein
Jiajun CAO ; Jing YANG ; Yukun ZHANG ; Na LIU ; Bingbing GAO ; Yangyingqiu LIU ; Qingwei SONG ; Yanwei MIAO
Chinese Journal of Interventional Imaging and Therapy 2024;21(3):139-144
Objective To observe the influence of different acceleration factors(AF)on compressed sensing susceptibility weighted imaging(CS-SWI)for cerebral medullary veins of healthy people,and to screen the best AF.Methods Forty healthy volunteers were prospectively enrolled.Axial brain SWI images were obtained with CS technique under different AF(AF0,CS2,CS4,CS6,CS8 and CS10),and the phase value(PV)and standard deviation(SD)of bilateral septal vein(SV),internal cerebral vein(ICV),thalamus vein(TV),basal vein(BV)and dentate nucleus vein(DNV)were measured.Taken PV and SD of parietal white matter as controls,the signal-to-noise ratio(SNR)and contrast-to-noise ratio(CNR)of venous images were calculated.Then the original images were reconstructed with minimum intensity projection,and the subjective quality scoring of reconstructed images were performed using a 5-point scale.SNR,CNR,PV and quality score were compared among images under different AF,and the best AF,i.e.with the best performances for displaying and quantitatively analyzing cerebral medullary veins in healthy people was obtained.Results Compared with those acquired with AF0,SNR and CNR of all cerebral medullary veins acquired with CS6,CS8 and CS10 were significantly different(all adjusted P<0.05).Meanwhile,significant differences of PV in bilateral SV and right TV were found among CS6,CS8 and CS10,also in bilateral ICV,left TV and bilateral BV between CS8 and CS10(all adjusted P<0.05).Conclusion Excessive AF might decrease image quality of CS-SWI for cerebral medullary veins.CS4 was the best AF for displaying and quantitatively analyzing cerebral medullary veins in healthy people.

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