1.Mechanism of salvianolic acid B protecting H9C2 from OGD/R injury based on mitochondrial fission and fusion
Zi-xin LIU ; Gao-jie XIN ; Yue YOU ; Yuan-yuan CHEN ; Jia-ming GAO ; Ling-mei LI ; Hong-xu MENG ; Xiao HAN ; Lei LI ; Ye-hao ZHANG ; Jian-hua FU ; Jian-xun LIU
Acta Pharmaceutica Sinica 2024;59(2):374-381
This study aims to investigate the effect of salvianolic acid B (Sal B), the active ingredient of Salvia miltiorrhiza, on H9C2 cardiomyocytes injured by oxygen and glucose deprivation/reperfusion (OGD/R) through regulating mitochondrial fission and fusion. The process of myocardial ischemia-reperfusion injury was simulated by establishing OGD/R model. The cell proliferation and cytotoxicity detection kit (cell counting kit-8, CCK-8) was used to detect cell viability; the kit method was used to detect intracellular reactive oxygen species (ROS), total glutathione (t-GSH), nitric oxide (NO) content, protein expression levels of mitochondrial fission and fusion, apoptosis-related detection by Western blot. Mitochondrial permeability transition pore (MPTP) detection kit and Hoechst 33342 fluorescence was used to observe the opening level of MPTP, and molecular docking technology was used to determine the molecular target of Sal B. The results showed that relative to control group, OGD/R injury reduced cell viability, increased the content of ROS, decreased the content of t-GSH and NO. Furthermore, OGD/R injury increased the protein expression levels of dynamin-related protein 1 (Drp1), mitofusions 2 (Mfn2), Bcl-2 associated X protein (Bax) and cysteinyl aspartate specific proteinase 3 (caspase 3), and decreased the protein expression levels of Mfn1, increased MPTP opening level. Compared with the OGD/R group, it was observed that Sal B had a protective effect at concentrations ranging from 6.25 to 100 μmol·L-1. Sal B decreased the content of ROS, increased the content of t-GSH and NO, and Western blot showed that Sal B decreased the protein expression levels of Drp1, Mfn2, Bax and caspase 3, increased the protein expression level of Mfn1, and decreased the opening level of MPTP. In summary, Sal B may inhibit the opening of MPTP, reduce cell apoptosis and reduce OGD/R damage in H9C2 cells by regulating the balance of oxidation and anti-oxidation, mitochondrial fission and fusion, thereby providing a scientific basis for the use of Sal B in the treatment of myocardial ischemia reperfusion injury.
2.Data-independent Acquisition-Based Quantitative Proteomic Analysis Reveals Potential Salivary Biomarkers of Primary Sj?gren's Syndrome
Tian YI-CHAO ; Guo CHUN-LAN ; Li ZHEN ; You XIN ; Liu XIAO-YAN ; Su JIN-MEI ; Zhao SI-JIA ; Mu YUE ; Sun WEI ; Li QIAN
Chinese Medical Sciences Journal 2024;39(1):19-28,中插3
Objective As primary Sj?gren's syndrome(pSS)primarily affects the salivary glands,saliva can serve as an indicator of the glands'pathophysiology and the disease's status.This study aims to illustrate the salivary proteomic profiles of pSS patients and identify potential candidate biomarkers for diagnosis. Methods The discovery set contained 49 samples(24 from pSS and 25 from age-and gender-matched healthy controls[HCs])and the validation set included 25 samples(12 from pSS and 13 from HCs).Totally 36 pSS patients and 38 HCs were centrally randomized into the discovery set or to the validation set at a 2:1 ratio.Unstimulated whole saliva samples from pSS patients and HCs were analyzed using a data-independent acquisition(DIA)strategy on a 2D LC-HRMS/MS platform to reveal differential proteins.The crucial proteins were verified using DIA analysis and annotated using gene ontology(GO)and International Pharmaceutical Abstracts(IPA)analysis.A prediction model for SS was established using random forests. Results A total of 1,963 proteins were discovered,and 136 proteins exhibited differential representation in pSS patients.The bioinformatic research indicated that these proteins were primarily linked to immunological functions,metabolism,and inflammation.A panel of 19 protein biomarkers was identified by ranking order based on P-value and random forest algorichm,and was validated as the predictive biomarkers exhibiting good performance with area under the curve(AUC)of 0.817 for discovery set and 0.882 for validation set. Conclusions The candidate protein panel discovered may aid in pSS diagnosis.Salivary proteomic analysis is a promising non-invasive method for prognostic evaluation and early and precise treatments for pSS patients.DIA offers the best time efficiency and data dependability and may be a suitable option for future research on the salivary proteome.
3.Palatability evaluation of oral iron for children based on in vivo and in vitro evaluation techniques
Dong MEI ; Long-tai YOU ; Huan ZHANG ; Xiao-ling WANG
Acta Pharmaceutica Sinica 2024;59(6):1847-1853
Oral iron is a commonly used preparation for the treatment of iron deficiency and iron-deficiency anemia in children, but its undesirable taste has become a major factor affecting clinical adherence to the medication. No studies have been conducted to evaluate the palatability of oral iron supplements. Thirteen representative oral iron supplements were selected to evaluate the palatability of oral iron supplements from different perspectives of
4.Sensitive Detection of Hypochlorous Acid Using Porphyrin-pyridyl Conjugated Oligomer-based Fluorescent Nanoprobe
Ji-Yan HUANG ; Mi-Xue CHEN ; Jin-Ling LI ; Yi XIAO ; Hong-Mei HUANG ; You-Yu ZHANG
Chinese Journal of Analytical Chemistry 2024;52(8):1132-1140,中插6-中插11
Conjugated oligomers,as analogues of conjugated polymers,allow for constructing ultrafine fluorescent nanoparticles with improved sensing sensitivity due to their more precisely defined molecular structure and smaller size.Herein,a new porphyrin-pyridyl conjugated oligomer,i.e.,Zn-TPP-OMe,was designed and synthesized via Sonogashira coupling strategy and a super-small(~2.0 nm)water-soluble fluorescent nanoprobe(Zn-TPP-OMe nanoparticles(NPs))was subsequent obtained by nanoprecipitation method.Due to the addition reaction of chlorine atom to porphyrin ring,the fluorescence intensity of Zn-TPP-OMe NPs at 619-660 nm significantly decreased with increasing HCLO concentration.Meanwhile,Zn-TPP-OMe NPs aggregated obviously after adding HClO,achieving enhanced fluorescence quenching.The fluorescence detection mechanism was verified by transmission electron microscopy(TEM),proton nuclear magnetic resonance(1H NMR)and high resolution mass spectrometry(HRMS)analyses.The experimental results indicated that the porphyrin-pyridyl conjugated oligomer nanosystem had high sensitivity(LOD=0.005 μmol/L)and excellent selectivity in detection of HClO,and was successfully applied to the sensing of HClO in actual water samples.
5.Clinical Study on the Treatment of Insomnia in the Elderly with the Spleen-Strengthening,Blood-Activating and Phlegm-Resolving Chinese Herbal Medicine Based on the Theory of "Muscular Atrophy,Qi-Passage Blockage" Recorded in the Huang Di Nei Jing
Chao WANG ; Jian-Qiang MEI ; Sai-Qiang YAN ; Xun ZHANG ; Ao LIU ; Xiao-Yan YOU ; Li CHENG
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(7):1730-1737
Objective To explore the clinical efficacy of Chinese herbal medicine with the actions of invigorating spleen,activating blood and resolving phlegm in the treatment of senile insomnia based on the theory of"muscular atrophy,qi-passage blockage"recorded in Huang Di Nei Jing(The Yellow Emperor's Inner Classic,shortened as Nei Jing).Methods A total of 120 elderly patients with insomnia were randomly divided into observation group and control group,with 60 cases in each group.The control group was treated with oral use of Dexzopiclone Tablets,and the observation group was treated with oral use of decoction of Chinese herbal medicine for invigorating spleen,activating blood and resolving phlegm.The course of treatment covered 4 weeks.Before and after treatment,the two groups were observed in the changes of Pittsburgh Sleep Quality Index(PSQI)score,Insomnia Severity Index(ISI)score,polysomnography(PSG)related parameters of total sleep time(TST),number of awakenings(AN)and sleep latency(SL),mean blood flow velocity of anterior cerebral artery(ACA),middle cerebral artery(MCA),and posterior cerebral artery(PCA),and serum levels of 5-hydroxytryptamine(5-HT)and melatonin(MT).After treatment,the clinical efficacy and safety of the two groups were evaluated.Results(1)After 4 weeks of treatment,the total effective rate of the observation group was 93.33%(56/60),which was slightly higher than 90.00%(54/60)of the control group,but the difference was not statistically significant(P>0.05).(2)After treatment,the item scores and total scores of PSQI in the two groups were lower than those before treatment(P<0.05),and the decrease of the scores of sleep quality,sleep time,sleep efficiency,and daytime function as well as total scores in the observation group was significantly superior to that in the control group(P<0.05).However,there was no significant difference of time for falling asleep and sleep disorder scores between the two groups(P>0.05).After 4 weeks of drug withdrawal,the item scores of PSQI in the observation group continued to decrease compared with those after treatment(P<0.05),but there was no significant difference in the control group(P<0.05).(3)After treatment,the ISI scores in the two groups were decreased when compared with those before treatment(P<0.05),and the decrease in the observation group was superior to that in the control group(P<0.05).After 4 weeks of drug withdrawal,the ISI score of the observation group continued to decrease compared with that after treatment(P<0.05),while the control group had no significant change,and the difference was not statistically significant(P>0.05).(4)After treatment,the PSG related parameters such as TST,AN and SL in the two groups were improved when compared with those before treatment(P>0.05),and the improvement of TST and AN in the observation group was superior to that in the control group(P>0.05).(5)After treatment,the mean blood flow velocity of ACA,MCA and PCA in the observation group was improved compared with that before treatment(P<0.05),while there was no significant change in the control group compared with that before treatment(P>0.05).The improvement of the mean blood flow velocity of ACA,MCA and PCA in the observation group was significantly superior to that in the control group(P<0.05).(6)After treatment,the levels of serum 5-HT and MT in the two groups were increased when compared with those before treatment(P<0.05),and the increase in the observation group was superior to that in the control group(P<0.05).(7)The incidence of adverse reactions in the observation group was 5.00%(3/60),which was slightly lower than 13.33%(8/60)in the control group,but the difference was not statistically significant(P>0.05).Conclusion Based on the theory of"muscular atrophy,qi-passage blockage"recorded in Nei Jing,the Chinese herbal medicine for invigorating spleen,activating blood and resolving phlegm exerts certain effect in treating senile insomnia.It can effectively improve the sleep quality and daytime function of patients,enhance sleep efficiency,increase sleep time,reduce the number of awakenings,alleviate the severity of insomnia,improve brain function,and regulate the level of neurotransmitters,with remarkably long-term effect and reliable safety.
6.Clinical characteristics of 267 children with eosinophilic gastrointestinal disease:a multicenter study
Chun-Lei ZHAN ; Jie-Yu YOU ; Xiao-Qin LI ; Yong WANG ; Xian-Qin MEI ; Sheng-Hua WAN
Chinese Journal of Contemporary Pediatrics 2024;26(2):139-144
Objective To explore the clinical manifestations,endoscopic findings,histopathological changes,treatment,and prognosis of eosinophilic gastrointestinal disease(EGID)in children,with the aim of enhancing awareness among pediatricians about this condition.Methods Data of 267 children with EGID were prospectively collected from January 2019 to July 2022 at Jiangxi Children's Hospital,Hunan Children's Hospital,and Henan Children's Hospital.The age of onset,symptoms,physical signs,laboratory examination results,endoscopic findings,histopathological changes,and treatment outcomes were observed.Results Among the 267 children with EGID,the majority had mild(164 cases,61.4% )or moderate(96 cases,35.6% )clinical severity.The disease occurred at any age,with a higher prevalence observed in school-age children(178 cases).The main symptoms in infants were vomiting and hematemesis,while in toddlers,vomiting and bloody stools were prominent.Abdominal pain and vomiting were the primary symptoms in preschool and school-age children.Nearly half(49.4% )of the affected children showed elevated platelet counts on hematological examination,but there was no significant difference in platelet counts among children with mild,moderate,and severe EGID(P>0.05).Endoscopic findings in EGID children did not reveal significant specificity,and histopathological examination showed no specific structural damage.Among them,85.0% (227 cases)received acid suppression therapy,34.5% (92 cases)practiced dietary avoidance,20.9% (56 cases)received anti-allergic medication,and a small proportion(24 cases,9.0% )were treated with prednisone.Clinical symptoms were relieved in all patients after treatment,but three cases with peptic ulcers experienced recurrence after drug discontinuation.Conclusions Mild and moderate EGID are more common in children,with no specific endoscopic findings.Dietary avoidance,acid suppression therapy,and anti-allergic medication are the main treatment methods.The prognosis of EGID is generally favorable in children.[Chinese Journal of Contemporary Pediatrics,2024,26(2):139-144]
7.Ionizing radiation-induced damage(IRD)to and repair mechanisms of the male reproductive system:Report of testicular function changes in a case of IRD
Neng-Liang DUAN ; Hua-Pei WANG ; Yuan-Shuai RAN ; Zhi-Xiang GAO ; Feng-Mei CUI ; Qiu CHEN ; Yu-Long LIU ; You-You WANG ; Bo-Xin XUE ; Xiao-Long LIU
National Journal of Andrology 2024;30(8):687-695
Objective:To investigate the impact of ionizing radiation(IR)on the structure and function of the testis and pro-vide some strategies for the prevention and treatment of IR-induced damage(IRD).Methods:Using radiation dose simulation,se-men analysis,hormone testing,electron microscopy and single-cell transcriptome sequencing,we assessed and analyzed a case of IRD.We established a mouse model of IRD to validate the results of single-cell sequencing,and investigated the specific biological mecha-nisms of IRD and potential strategies for its intervention.Results:IR at 1-2 Gy significantly reduced sperm concentration and mo-tility,which gradually recovered after 12 months but the percentage of morphologically normal sperm remained low.It also caused im-balanced levels of various steroid hormones,decreased testosterone and dehydroepiandrosterone sulfate,increased progesterone,prolac-tin,luteinizing hormone,and follicle-stimulating hormone.Electron microscopy revealed damages to the testis structure,including loss of germ cells,atrophy of the seminiferous tubules,nuclear membrane depression of the spermatocytes,mitochondrial atrophy and de-formation,and reduction of mitochondrial cristae.Single-cell sequencing indicated significant changes in the function of the Leydig cells and macrophages and disrupted lipid-related metabolic pathways after IRD.Administration of L-carnitine to the mouse model im-proved lipid metabolism disorders and partially alleviated IRD to the germ cells.Conclusion:Ionizing radiation can cause disorders of testicular spermatogenesis and sexual hormones and inhibit lipid metabolism pathways in Leydig cells and macrophages.Improving lipid metabolism can alleviate IRD to germ cells.
8.Chinese Guideline on the Management of Polypoidal Choroidal Vasculopathy (2022).
You-Xin CHEN ; Yu-Qing ZHANG ; Chang-Zheng CHEN ; Hong DAI ; Su-Yan LI ; Xiang MA ; Xiao-Dong SUN ; Shi-Bo TANG ; Yu-Sheng WANG ; Wen-Bin WEI ; Feng WEN ; Ge-Zhi XU ; Wei-Hong YU ; Mei-Xia ZHANG ; Ming-Wei ZHAO ; Yang ZHANG ; Fang QI ; Xun XU ; Xiao-Xin LI
Chinese Medical Sciences Journal 2023;38(2):77-93
Background In mainland China, patients with neovascular age-related macular degeneration (nAMD) have approximately an 40% prevalence of polypoidal choroidal vasculopathy (PCV). This disease leads to recurrent retinal pigment epithelium detachment (PED), extensive subretinal or vitreous hemorrhages, and severe vision loss. China has introduced various treatment modalities in the past years and gained comprehensive experience in treating PCV.Methods A total of 14 retinal specialists nationwide with expertise in PCV were empaneled to prioritize six questions and address their corresponding outcomes, regarding opinions on inactive PCV, choices of anti-vascular endothelial growth factor (anti-VEGF) monotherapy, photodynamic therapy (PDT) monotherapy or combined therapy, patients with persistent subretinal fluid (SRF) or intraretinal fluid (IRF) after loading dose anti-VEGF, and patients with massive subretinal hemorrhage. An evidence synthesis team conducted systematic reviews, which informed the recommendations that address these questions. This guideline used the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach to assess the certainty of evidence and grade the strengths of recommendations. Results The panel proposed the following six conditional recommendations regarding treatment choices. (1) For patients with inactive PCV, we suggest observation over treatment. (2) For treatment-na?ve PCV patients, we suggest either anti-VEGF monotherapy or combined anti-VEGF and PDT rather than PDT monotherapy. (3) For patients with PCV who plan to initiate combined anti-VEGF and PDT treatment, we suggest later/rescue PDT over initiate PDT. (4) For PCV patients who plan to initiate anti-VEGF monotherapy, we suggest the treat and extend (T&E) regimen rather than the pro re nata (PRN) regimen following three monthly loading doses. (5) For patients with persistent SRF or IRF on optical coherence tomography (OCT) after three monthly anti-VEGF treatments, we suggest proceeding with anti-VEGF treatment rather than observation. (6) For PCV patients with massive subretinal hemorrhage (equal to or more than four optic disc areas) involving the central macula, we suggest surgery (vitrectomy in combination with tissue-plasminogen activator (tPA) intraocular injection and gas tamponade) rather than anti-VEGF monotherapy. Conclusions Six evidence-based recommendations support optimal care for PCV patients' management.
9.Application of Worst lacrimal probe combined with modified lacrimal duct threading intubation in anastomosis of complex canalicular laceration
Tai-Ying CHENG ; Hong-Tao LIU ; Ming-Bo LI ; Yang LI ; Su-Jun ZHOU ; Xiao-Mei NIE ; You-Huan CAI
International Eye Science 2023;23(2):334-338
AIM: To investigate the application value of Worst lacrimal probe combined with modified lacrimal duct intubation in anastomosis of complex canalicular laceration.METHODS: Retrospective study. A total of 68 cases(68 eyes)with complex traumatic canalicular laceration treated in the ophthalmology department of the Second Affiliated Hospital of Zunyi Medical University from March 1, 2019 to March 31, 2021 were selected. They were divided into two groups according to the surgical methods, with 36 patients(36 eyes)who were treated with the Worst lacrimal probe to find the broken end of lacrimal duct combined with improved lacrimal duct threading intubation in group A, and 32 patients(32 eyes)who were treated with microscope to find the broken end of lacrimal duct and two-way intubation anastomosis canaliculus intubation in group B. The clinical efficacy, success rate of intraoperative search for the broken end of lacrimal duct, searching time, operation time, the degree of pain, postoperative ocular foreign body sensation and complications were compared between the two groups.RESULTS: The total effective rate of clinical efficacy in patients of group A was higher than that in group B(94% vs. 38%), the success rate of intraoperative search for broken end of lacrimal duct was higher than that in group B(100% vs. 47%), the searching time and operation time were shorter than those in group B, and the score of pain degree was lower than that in group B(all P<0.05). The postoperative follow-up for 6mo-1a showed that the ocular foreign body sensation score, the incidence of lacrimal punctum rupture and morphological change, and the degree of tear overflow in group A were all lower than those in group B(all P<0.05).CONCLUSION: Worst lacrimal probe combined with modified lacrimal duct intubation for the treatment of complex traumatic canalicular laceration can find the broken end of lacrimal duct more accurately, shorten the operation time, reduce the pain and foreign body sensation of patients, improve clinical efficacy and reduce the incidence of complications.
10.Correlation of DNA Damage Repair Gene FANCI with Prognosis and Immune Infiltration of Hepatocellular Carcinoma
Ying YOU ; Mei-hua MEI ; Ning-xin TAN ; Yi-li CHEN ; Pei-dong CHI ; Xiao-shun HE ; Jun-qi HUANG
Journal of Sun Yat-sen University(Medical Sciences) 2023;44(1):51-62
ObjectiveTo evaluate the expression level of DNA damage repair gene FANCI in hepatocellular carcinoma (HCC) and its relationship with prognosis, clinical stage and immune infiltration. MethodsIn this study, TCGA, GTEx, TIMER2.0, HPA database and qRT-PCR, western blot and immunohistochemistry were used to analyze the expression of FANCI in HCC and its correlation with different clinical stages; Kaplan-Meier Plotter database was used to explore the relationship between FANCI and the prognosis of HCC; the TISIDB database was used to analyze the relationship between FANCI and immune cell infiltration and immune checkpoints in HCC; the STRING database was used to detect the protein binding with FANCI; the TCGA and GTEx databases were used for GO and KEGG enrichment analysis; Cell experiments were used to explore the role of FANCI in HCC. ResultsCompared with normal tissues, the mRNA and protein expression levels of FANCI in tumor tissues were up-regulated (P<0.001); and HCC patients with high expression of FANCI had poor prognosis (P<0.001); the expression of FANCI in tumor tissues was positively correlated with the number of activated CD4+ T cells, the number of Th2 cells and the expression of immune checkpoints, and B-cell and macrophage infiltration was significantly lower in the FANCI high expression group (P<0.01); GO and KEGG enrichment analysis showed that FANCI-related genes were enriched in various biological processes such as amino acid transmembrane transporter activity; Cell experiments showed that knockdown of FANCI could inhibit the proliferation, invasion and migration of HCC (P<0.05). ConclusionsFANCI is highly expressed in hepatocellular carcinoma tissues, which may play a role in suppressing anti-tumor immunity and acting on pathways such as amino acid transmembrane transport, and is associated with poor prognosis. The proliferation, invasion and migration ability of hepatocellular carcinoma are inhibited after knocking down FANCI.

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