1.Mechanism of action of ginsenoside Rg_2 on diabetic retinopathy and angiogenesis based on YAP/TLRs pathway.
Zhuo-Rong LIU ; Yong-Li SONG ; Shang-Qiu NING ; Yue-Ying YUAN ; Yu-Ting ZHANG ; Gai-Mei HAO ; Jing HAN
China Journal of Chinese Materia Medica 2025;50(6):1659-1669
Ginsenoside Rg_2(GRg2) is a triterpenoid compound found in Panax notoginseng. This study explored its effects and mechanisms on diabetic retinopathy and angiogenesis. The study employed endothelial cell models induced by glucose or vascular endothelial growth factor(VEGF), the chorioallantoic membrane(CAM) model, the oxygen-induced retinopathy(OIR) mouse model, and the db/db mouse model to evaluate the therapeutic effects of GRg2 on diabetic retinopathy and angiogenesis. Transwell assays and endothelial tube formation experiments were conducted to assess cell migration and tube formation, while vascular area measurements were applied to detect angiogenesis. The impact of GRg2 on the retinal structure and function of db/db mice was evaluated through retinal thickness and electroretinogram(ERG) analyses. The study investigated the mechanisms of GRg2 by analyzing the activation of Yes-associated protein(YAP) and Toll-like receptors(TLRs) pathways. The results indicated that GRg2 significantly reduced cell migration numbers and tube formation lengths in vitro. In the CAM model, GRg2 exhibited a dose-dependent decrease in the vascular area ratio. In the OIR model, GRg2 notably decreased the avascular and neovascular areas, ameliorating retinal structural disarray. In the db/db mouse model, GRg2 increased the total retinal thickness and enhanced the amplitudes of the a-wave, b-wave, and oscillatory potentials(OPs) in the ERG, improving retinal structural disarray. Transcriptomic analysis revealed that the TLR signaling pathway was significantly down-regulated following YAP knockdown, with PCR results consistent with the transcriptome sequencing findings. Concurrently, GRg2 downregulated the expression of Toll-like receptor 4(TLR4), TNF receptor-associated factor 6(TRAF6), and nuclear factor-kappaB(NF-κB) proteins in high-glucose-induced endothelial cells. Collectively, GRg2 inhibits cell migration and tube formation and significantly reduces angiogenesis in CAM and OIR models, improving retinal structure and function in db/db mice, with its pharmacological mechanism likely involving the down-regulation of YAP expression.
Animals
;
Ginsenosides/pharmacology*
;
Diabetic Retinopathy/physiopathology*
;
Mice
;
YAP-Signaling Proteins
;
Humans
;
Male
;
Signal Transduction/drug effects*
;
Cell Movement/drug effects*
;
Adaptor Proteins, Signal Transducing/genetics*
;
Mice, Inbred C57BL
;
Neovascularization, Pathologic/metabolism*
;
Drugs, Chinese Herbal/administration & dosage*
;
Panax notoginseng/chemistry*
;
Endothelial Cells/metabolism*
;
Transcription Factors/genetics*
;
Angiogenesis
2.Does Prenatal SARS-CoV-2 Infection Exacerbate Postpartum Lower Urinary Tract Symptoms? A Multicenter Retrospective Cohort Study.
Yu Han LYU ; Min LI ; Hui Qing YAO ; Tian Zi GAI ; Lin LIANG ; Su PAN ; Ping Ping LI ; Ya Xin LIANG ; Yue YU ; Xiao Mei WU ; Min LI
Biomedical and Environmental Sciences 2025;38(9):1095-1104
OBJECTIVE:
Coronavirus disease 2019 (COVID-19) can result in fatigue and post-exertional malaise; however, whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection exacerbates lower urinary tract symptoms (LUTS) is unclear. This study investigated the association between prenatal SARS-CoV-2 infection and postpartum LUTS.
METHODS:
A multicenter, retrospective cohort study was conducted at two tertiary hospitals in China from November 1, 2022, to November 1, 2023. Participants were classified into infected and uninfected groups based on SARS-CoV-2 antigen results. LUTS prevalence and severity were assessed using self-reported symptoms and the Incontinence Impact Questionnaire-Short Form (IIQ-7). Pelvic floor muscle activity was measured using electromyography following the Glazer protocol. Group comparisons were performed to evaluate the association of SARS-CoV-2 infection with LUTS and electromyography parameters, with stratified analyses conducted using SPSS version 26.0.
RESULTS:
Among 3,652 participants (681 infected, 2,971 uninfected), no significant differences in LUTS prevalence or IIQ-7 scores were observed. However, SARS-CoV-2 infection was an independent factor influencing the electromyographic activity of the pelvic floor muscles (mean tonic contraction amplitudes), regardless of delivery mode ( P = 0.001).
CONCLUSION
Prenatal SARS-CoV-2 infection was not significantly associated with an increased risk of postpartum LUTS but independently altered pelvic floor muscle electromyographic activity, suggesting potential neuromuscular effects.
Humans
;
Female
;
COVID-19/epidemiology*
;
Retrospective Studies
;
Adult
;
Pregnancy
;
Lower Urinary Tract Symptoms/virology*
;
Postpartum Period
;
Pregnancy Complications, Infectious/virology*
;
China/epidemiology*
;
Electromyography
;
SARS-CoV-2/physiology*
;
Pelvic Floor/physiopathology*
;
Prevalence
3.Effect and mechanism of dandelion flavonoids in alleviating lipopolysaccharide-induced colon epithelial cell injury
Jia-Qi ZHANG ; Dong-Xue MEI ; Sha LI ; Sheng-Gai GAO ; Jia ZHENG ; Hong-Xia LIANG ; Yi WANG
The Chinese Journal of Clinical Pharmacology 2024;40(4):549-553
Objective To investigate the protective effect of dandelion flavone(DF)on lipopolysaccharide(LPS)-induced colon epithelial cell injury by intervening oxidative stress and inflammation with AT-specific binding protein 2(SATB2).Methods Colon epithelial cells FHC were cultured.FHC cells were randomly divided into control group(normal cultured),LPS group(10 μg·mL-1 LPS),experimental-L group(10 μg·mL-1 LPS+1 μmol·L-1 DF),experimental-H group(10 μg·mL-1 LPS+5 μmol·L-1 DF),experimental-H+sh-NC group(transfected with sh-NC+10 μg·mL-1 LPS+5 μmol·mL-1 DF),experimental-H+sh-SATB2 group(transfected with sh-SATB2+10 μg·mL-1 LPS+5μmol·L-1 DF).The relative expression level of SATB2 protein in FHC cells was detected by Western blotting.The survival rate of FHC cells in each group was determined by tetramethylazolium blue(MTT).The apoptosis rate of FHC cells in each group was detected by flow cytometry.The levels of malondialdehyde(MDA)and interleukin-6(IL-6)in FHC cells were detected by the kit.Results The relative expression levels of SATB2 protein in control group,LPS group,experimental-H group,experimental-H+sh-NC group and experimental-H+sh-SATB2 group were 0.83±0.09,0.19±0.03,0.66±0.05,0.62±0.07 and 0.23±0.03,respectively;cell viability rates were(100.00±1.00)%,(48.16±4.31)%,(85.31±5.83)%,(81.39±6.47)%and(58.75±5.24)%,respectively;cell apoptosis rates were(3.27±0.81)%,(41.26±2.09)%,(11.35±1.04)%,(10.29±1.26)%and(35.87±2.15)%,respectively;MDA levels were(13.16±1.73),(52.87±3.49),(23.19±2.05),(20.98±3.17)and(44.87±3.05)μmol·L-1,respectively;IL-6 levels were(507.18±103.26),(2 132.09±198.15),(883.16±136.92),(801.69±119.85)and(1 736.29±206.91)pg·mL-1,respectively.The above indicators in the LPS group showed significant differences compared to the control group(all P<0.05);the above indicators in the experimental-H group showed significant differences compared to the LPS group(all P<0.05);the above indicators in the experimental-H+sh-SATB2 group showed significant differences compared to the experimental-H+sh-NC group(all P<0.05).Conclusion DF has a protective effect on LPS-induced colon epithelial cell injury by intervening oxidative stress and inflammation through SATB2.
4.Investigation and disposal of a skin anthrax outbreak in the 164th Regiment,9th Division,Xinjiang Production and Construction Corps
Yong-Nian ZHAO ; Yue WANG ; Wei LIU ; Li-Li DUAN ; Gai-Mei DONG ; Delina·Sairike
Chinese Journal of Zoonoses 2024;40(6):595-598
Field epidemiological investigation and treatment of a human skin anthrax outbreak were performed,including tracing of the infection source,case searching,management of close contacts,sampling and testing,and on-site elimination.Additional training and public outreach,and anthrax prevention and control measures are recommended.This case involved a sporadic outbreak of human skin anthrax,with sick cattle as the source of infection.On July 20,our patient slaughtered a cow at his home without taking any protective measures.Three days earlier,he had been stabbed at the second joint of the middle finger of his right hand,and he became infected with anthrax bacilli through the wound.Fever appeared on the day after expo-sure,and on the fourth day(July 24),a black scab mass of approximately(3X3)cm was visible at the wound site,without rupture or discharge of pus.He was hospitalized with fever at the 164th Regiment Hospital,Tacheng People's Hospital,Tacheng District People's Hospital,and Tacheng Jingcheng Hospital.His stay at the Tacheng District People's Hospital was from the 24th to 25th.He had seven close contacts,none of whom were infected,and no common exposures were identified.On the 27th,the PCR results for smear samples around the black scab were positive,the serum antibody results were positive,and the fecal samples were negative.The PCR test results for five environmental specimens were negative,and the isolation and culture results for bone surface specimens from dead cattle were positive.Strengthened efforts are necessary in training and public education regarding zoonotic disease prevention and control;establishment of local corps integration and joint prevention and control;and detection and mitigation of epi-demics in early stages.
5.Distribution of non-bacterial pathogens in 1 788 children with community-acquired pneumonia.
Shuang WANG ; Xue-Feng WANG ; Na LI ; Yue-Xin ZHANG ; Jing CHEN ; Gai-Mei WANG
Chinese Journal of Contemporary Pediatrics 2023;25(6):633-638
OBJECTIVES:
To investigate the distribution characteristics of non-bacterial pathogens in community-acquired pneumonia (CAP) in children.
METHODS:
A total of 1 788 CAP children admitted to Shenyang Children's Hospital from December 2021 to November 2022 were selected. Multiple RT-PCR and capillary electrophoresis were used to detect 10 viral pathogens and 2 atypical pathogens, and serum antibodies of Chlamydial pneumoniae (Ch) and Mycoplasma pneumoniae (MP) were detected. The distribution characteristics of different pathogens were analyzed.
RESULTS:
Among the 1 788 CAP children, 1 295 children were pathogen-positive, with a positive rate of 72.43% (1 295/1 788), including a viral pathogen positive rate of 59.68% (1 067/1 788) and an atypical pathogen positive rate of 22.04% (394/1 788). The positive rates from high to low were MP, respiratory syncytial virus (RSV), influenza B virus (IVB), human metapneumovirus (HMPV), human rhinovirus (HRV), human parainfluenza virus (HPIV), influenza A virus (IVA), bocavirus (BoV), human adenovirus (HADV), Ch, and human coronavirus (HCOV). RSV and MP were the main pathogens in spring; MP had the highest positive rate in summer, followed by IVA; HMPV had the highest positive rate in autumn; IVB and RSV were the main pathogens in winter. The positive rate of MP in girls was higher than that in boys (P<0.05), and there were no significant differences in other pathogens between genders (P>0.05). The positivity rates of certain pathogens differed among age groups (P<0.05): the positivity rate of MP was highest in the >6 year-old group; the positivity rates of RSV and Ch were highest in the <1 year-old group; the positivity rates of HPIV and IVB were highest in the 1 to <3 year-old group. RSV, MP, HRV, and HMPV were the main pathogens in children with severe pneumonia, while MP was the primary pathogen in children with lobar pneumonia, and MP, IVB, HMPV, RSV, and HRV were the top 5 pathogens in acute bronchopneumonia.
CONCLUSIONS
MP, RSV, IVB, HMPV, and HRV are the main pathogens of CAP in children, and there are certain differences in the positive rates of respiratory pathogens among children of different ages, genders, and seasons.
Humans
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Child
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Female
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Male
;
Infant
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Child, Preschool
;
Pneumonia
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Respiratory Syncytial Virus, Human
;
Antibodies
;
Community-Acquired Infections
;
Hospitalization
;
Influenza B virus
;
Mycoplasma pneumoniae
7.Effect of Fufang Huangbai Fluid Paint on Virulence and Biofilm of Methicillin-resistant Staphylococcus aureus
Jin-ze LI ; Kai-yu CUI ; Dong-ying LI ; Shu-hua MA ; Gai-ying HE ; Ya-nan SUN ; Yi WANG ; Zhong-mei HE ; Wei-feng YANG
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(8):54-62
ObjectiveTo study the virulence and biofilm inhibition effect of Fufang Huangbai Fluid Paint (FFHBFP) on methicillin-resistant Staphylococcus aureus (MRSA), and to explore the antibacterial effect of FFHBFP on MRSA, which provides a theoretical basis and reference for clinical medication. MethodFirstly, the microdilution method and time–growth curve were used to determine the minimum inhibitory concentration (MIC) of FFHBFP and vancomycin (VAN) against MRSA and the effect on bacterial growth. The effects of FFHBFP and VAN on the inhibition of MRSA virulence factor lipase and restoration of hydrogen peroxide (H2O2) sensitivity were detected under sub-minimum inhibitory concentration (sub-MIC). The inhibitory effect of FFHBFP and VAN on MRSA biofilm formation and maturation was detected by the microplate method. The morphological changes of mature biofilms before and after administration were observed under a scanning electron microscope (SEM). Real-time polymerase chain reaction (Real-time PCR) was utilized to detect the effect of 50.600 g·L-1 concentration of FFHBFP on the expression of MRSA virulence gene crtM and biofilm-forming genes fnbA and icaA. Finally, molecular docking technology was used to predict the mechanism of potential antibacterial active ingredients of FFHBFP in inhibiting the virulence and biofilm of MRSA. ResultThe MIC of VAN was 2 mg·L-1, and VAN below 1 mg·L-1 exerted no effect on MRSA growth. The MIC of FFHBFP was not determined, while the 101.200-202.400 g·L-1 original solution inhibited MRSA growth. Compared with the blank group and the VAN group, sub-MIC (25.300-50.600 g·L-1 original solution) inhibited lipase and recovered MRSA sensitivity to H2O2 (P<0.01). The results of the microplate method showed that FFHBFP (25.300-202.400 g·L-1 original solution) inhibited biofilm formation and maturation (P<0.05, P<0.01). The SEM exhibited that FFHBFP made the structure of biofilm loose and the size of the bacteria varied. FFHBFP at 50.600 g·L-1 concentration can inhibit the expression of related virulence genes and biofilm-forming genes (P<0.05, P<0.01), and molecular docking results also showed that the main antibacterial active ingredients in FFHBFP have good binding ability to the target. ConclusionFFHBFP that cannot directly kill MRSA exerts clinical efficacy by impairing virulence expression, biofilm formation, and other pathogenic properties.
8.Clinical effect of different maintenance doses of caffeine citrate in the treatment of preterm infants requiring assisted ventilation: a pilot multicenter study.
Yang YANG ; Ke-Yu LU ; Rui CHENG ; Qin ZHOU ; Guang-Dong FANG ; Hong LI ; Jie SHAO ; Huai-Yan WANG ; Zheng-Ying LI ; Song-Lin LIU ; Zhen-Guang LI ; Jin-Lan CAI ; Mei XUE ; Xiao-Qing CHEN ; Zhao-Jun PAN ; Yan GAO ; Li HUANG ; Hai-Ying LI ; Lei SONG ; San-Nan WANG ; Gui-Hua SHU ; Wei WU ; Meng-Zhu YU ; Zhun XU ; Hong-Xin LI ; Yan XU ; Zhi-Dan BAO ; Xin-Ping WU ; Li YE ; Xue-Ping DONG ; Qi-Gai YIN ; Xiao-Ping YIN ; Jin-Jun ZHOU
Chinese Journal of Contemporary Pediatrics 2022;24(3):240-248
OBJECTIVES:
To explore the optimal maintenance dose of caffeine citrate for preterm infants requiring assisted ventilation and caffeine citrate treatment.
METHODS:
A retrospective analysis was performed on the medical data of 566 preterm infants (gestational age ≤34 weeks) who were treated and required assisted ventilation and caffeine citrate treatment in the neonatal intensive care unit of 30 tertiary hospitals in Jiangsu Province of China between January 1 and December 31, 2019. The 405 preterm infants receiving high-dose (10 mg/kg per day) caffeine citrate after a loading dose of 20 mg/kg within 24 hours after birth were enrolled as the high-dose group. The 161 preterm infants receiving low-dose (5 mg/kg per day) caffeine citrate were enrolled as the low-dose group.
RESULTS:
Compared with the low-dose group, the high-dose group had significant reductions in the need for high-concentration oxygen during assisted ventilation (P=0.044), the duration of oxygen inhalation after weaning from noninvasive ventilation (P<0.01), total oxygen inhalation time during hospitalization (P<0.01), the proportion of preterm infants requiring noninvasive ventilation again (P<0.01), the rate of use of pulmonary surfactant and budesonide (P<0.05), and the incidence rates of apnea and bronchopulmonary dysplasia (P<0.01), but the high-dose group had a significantly increased incidence rate of feeding intolerance (P=0.032). There were no significant differences between the two groups in the body weight change, the incidence rates of retinopathy of prematurity, intraventricular hemorrhage or necrotizing enterocolitis, the mortality rate, and the duration of caffeine use (P>0.05).
CONCLUSIONS
This pilot multicenter study shows that the high maintenance dose (10 mg/kg per day) is generally beneficial to preterm infants in China and does not increase the incidence rate of common adverse reactions. For the risk of feeding intolerance, further research is needed to eliminate the interference of confounding factors as far as possible.
Caffeine/therapeutic use*
;
Citrates
;
Humans
;
Infant
;
Infant, Newborn
;
Infant, Premature
;
Respiration, Artificial
;
Retrospective Studies
9.Efficacy and Safety of Mulberry Twig Alkaloids Tablet for Treatment of Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Multicenter Clinical Study.
Ling QU ; Xiao-Chun LIANG ; Guo-Qing TIAN ; Gai-Li ZHANG ; Qun-Li WU ; Xiu-Mei HUANG ; Ya-Zhong CUI ; Yu-Ling LIU ; Zhu-Fang SHEN ; Guo-Qing MA ; Hao LU ; Yi LI ; Hong JIANG ; Xi-Yan YANG ; Guang-de ZHANG ; Chen-Hua YANG
Chinese journal of integrative medicine 2022;28(4):304-311
OBJECTIVE:
To assess the efficacy and safety of mulberry twig alkaloids (Sangzhi alkaloids, SZ-A) for treatment of type 2 diabetes in a randomized, double-blind, placebo-controlled multicenter clinical trial.
METHODS:
A total of 200 patients were randomized to receive SZ-A (n=100) or placebo (n=100) for 16 weeks. The data analysis system for electronic data capture clinical trial central randomization system was used for randomization and dispensing of drugs. The primary outcome was the change in glycosylated hemoglobin (HbA1c) level. The secondary outcome included the proportions of cases with HbA1c <7.0% and HbA1c <6.5%, fasting blood glucose (FBG), postprandial blood glucose (PBG), area under curve for the PBG (AUC0-2h), body weight, and body mass index (BMI). Adverse events (AEs), severe adverse events (SAEs), treatment-related adverse events (TAEs), gastrointestinal disorders (GDs), blood pressure, routine blood tests, and liver and kidney function were monitored.
RESULTS:
Compared with baseline, the change of HbA1c at week 16 was -0.80% (95% CI: -0.98% to -0.62%) and -0.09% (95% CI: -0.27% to 0.09%) in SZ-A group and placebo group, respectively. The proportion of patients with HbA1c <7% and <6.5% was higher in the SZ-A group than in the placebo group (46.8% vs. 21.6% and 29.9% vs. 10.8%). The observed values and changes in FBG, 1 h-PBG, 2 h-PBG, and AUC0-2h differed significantly between groups (P<0.001), but differences were not significant in body weight and BMI (P>0.05). The incidence rates of AEs, TAEs, and GDs differed significantly between groups (P=0.010, P=0.005, and P=0.006, respectively), whereas the incidence rates of SAEs showed no significant differences between groups (P=1.000).
CONCLUSION
SZ-A are effective and safe for treatment of type 2 diabetes. The protocol was registered in http://www.chictr.org.cn/showproj.aspx?proj=60117 (ChiCTR2000038550).
Alkaloids
;
Blood Glucose
;
Diabetes Mellitus, Type 2/drug therapy*
;
Double-Blind Method
;
Glycated Hemoglobin A
;
Humans
;
Hypoglycemic Agents/therapeutic use*
;
Morus
;
Tablets/therapeutic use*
;
Treatment Outcome
10.The Effect and Mechanism of Novel Telomerase Inhibitor Nilo 22 on Leukemia Cells.
Jing-Jing YIN ; Qian TANG ; Jia-Li GU ; Ya-Fang LI ; Hui-Er GAO ; Mei HE ; Ming YANG ; Wen-Shan ZHANG ; Hui XU ; Chao-Qun WANG ; Ying-Hui LI ; Cui-Gai BAI ; Ying-Dai GAO
Journal of Experimental Hematology 2021;29(4):1056-1064
OBJECTIVE:
To investigate the cytotoxic effect and its mechanism of the micromolecule compound on the leukemia cells.
METHODS:
The cytotoxic effects of 28 Nilotinib derivatives on K562, KA, KG, HA and 32D cell lines were detected by MTT assays, and the compound Nilo 22 was screen out. Cell apoptosis and cell cycle on leukemia cells were detected by flow cytometry. The effect of compound screened out on leukemogenesis potential of MLL-AF9 leukemia mice GFP
RESULTS:
Nilo 22 serves as the most outstanding candidate out of 28 Nilotinib derivatives, which impairs leukemia cell lines, but spares normal hematopoietic cell line. Comparing with Nilotinib, Nilo 22 could induce the apoptosis of GFP
CONCLUSION
Nilo 22 shows a significant cytotoxic effect on mice and human leukemia cells, especially for drug resistance cells. Nilo 22 is a promising anti-leukemia agent to solve the common clinical problems of drug resistance and relapse of leukemia.
Animals
;
Apoptosis/drug effects*
;
Cell Cycle/drug effects*
;
Cell Line, Tumor
;
Humans
;
Leukemia
;
Mice
;
Myeloid-Lymphoid Leukemia Protein/genetics*
;
Telomerase/metabolism*
;
Telomere/metabolism*

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