Damage to organelles plays a significant role in myocardial ischemia/reperfusion injury,which results in the dysfunction of mitochondria and other related organelles.The communication between mitochondria and other organ-elles can also affect the development of myocardial ischemia/reperfusion injury.For instance,the mitochondria-associated endoplasmic reticulum membrane provides a"seamless connection"and regulates the exchange of organelles and metabolites(such as ions,lipids and proteins)between the mitochondria and the endoplasmic reticulum,which subse-quently affects myocardial ischemia/reperfusion injury.However,there is a lack of studies regarding the interaction be-tween mitochondria and related organelles,which is a critical component in triggering myocardial ischemia/reperfusion inju-ry.Therefore,this article describes the role of mitochondrial crosstalk with endoplasmic reticulum,lysosomes and nuclei in myocardial ischemia/reperfusion injury,and aims to provide a theoretical basis for targeting mitochondrial crosstalk with other organelles in the treatment of myocardial ischemia/reperfusion injury.

Objective:To summarize the ultrasonographic characteristics, genetic etiology, and perinatal prognosis of fetuses with absence of ductus venosus (ADV).Methods:A retrospective study enrolled 84 singleton pregnancies that underwent prenatal ultrasound examination and were diagnosed with fetal ADV at the First Affiliated Hospital of Zhengzhou University from June 2017 to July 2022. Based on prenatal ultrasonographic findings, the cases were divided into isolated ADV group ( n=37), ADV with ultrasound soft markers group ( n=9), and ADV with definite ultrasound abnormalities group ( n=38). According to the gestational age at the initial diagnosis of ADV, they were categorized into early pregnancy group (11-13 weeks of 6 days) with 17 cases, mid-pregnancy group (14-27 weeks of 6 days) with 45 cases, and late pregnancy group (≥28 weeks) with 22 cases. Depending on the direction of blood flow in the intra-abdominal segment of the umbilical vein, they were classified into umbilical vein directly entering the portal sinus group ( n=75), intrahepatic umbilical vein abnormal shunt group ( n=4), and extrahepatic umbilical vein shunt group ( n=5). The clinical characteristics of each group were summarized, and compared using the Chi-square, trend Chi-square tests, Fisher's exact test and Bonferroni correction test. Results:The common ultrasonographic abnormalities in the 84 cases of ADV fetuses were cardiac anomalies (27.4%, 23/84), cystic hygroma (10.7%, 9/84), fetal hydrops (9.5%, 8/84), and body cavity effusion (8.3%, 7/84). The proportions of fetuses with ADV and definite ultrasound abnormalities detected in the early, mid, and late pregnancy were 16/17, 44.4% (20/45), and 9.1% (2/22), respectively, with a higher proportion of definite ultrasound abnormalities associated with earlier detection of ADV ( χ 2trend=27.25, P<0.001). Among them, 21 cases underwent chromosomal karyotyping and/or chromosomal copy number variation sequencing or expanded non-invasive prenatal testing, with five abnormalities detected, including 45,X, trisomy 13, trisomy 22 mosaicism, trisomy 7 mosaicism, and a 14 Mb duplication at 22q12.3q13.33. The neonatal survival (28 days after birth) rates with ADV detected in the early, mid, and late pregnancy gradually increased, at 1/17, 43.9% (18/41), and 90.5% (19/21), respectively ( χ 2trend=27.04, P<0.001). The neonatal survival rates of the isolated ADV group and the group with ultrasound soft markers were higher than that of the group with definite ultrasound abnormalities [93.9% (31/33) and 6/9 vs. 2.7% (1/37), Bonferroni corrected, both P<0.001]. The neonatal survival rates of the umbilical vein directly entering the portal sinus group, intrahepatic umbilical vein abnormal shunt group, and extrahepatic umbilical vein shunt group were 50.0% (35/70), 0/4, and 1/5, respectively, with no statistically significant difference (Fisher's exact test, P=0.105). Conclusions:The earlier the detection of fetal ADV, the more likely it is to be associated with definite ultrasound abnormalities and have lower neonatal survival rates. This highlights the importance of ultrasonographic examination of the fetal ductus venosus. Once ADV is detected, attention should be paid to other potential ultrasound abnormalities, and genetic testing should be completed.

A resurging interest in targeted covalent inhibitors (TCIs) focus on compounds capable of irreversibly reacting with nucleophilic amino acids in a druggable target. p97 is an emerging protein target for cancer therapy, viral infections and neurodegenerative diseases. Extensive efforts were devoted to the development of p97 inhibitors. The most promising inhibitor of p97 was in phase 1 clinical trials, but failed due to the off-target-induced toxicity, suggesting the selective inhibitors of p97 are highly needed. We report herein a new type of TCIs (i.e., FL-18) that showed proteome-wide selectivity towards p97. Equipped with a Michael acceptor and a basic imidazole, FL-18 showed potent inhibition towards U87MG tumor cells, and in proteome-wide profiling, selectively modified endogenous p97 as confirmed by in situ fluorescence scanning, label-free quantitative proteomics and functional validations. FL-18 selectively modified cysteine residues located within the D2 ATP site of p97. This covalent labeling of cysteine residue in p97 was verified by LC‒MS/MS-based site-mapping and site-directed mutagenesis. Further structure-activity relationship (SAR) studies with FL-18 analogs were established. Collectively, FL-18 is the first known small-molecule TCI capable of covalent engagement of p97 with proteome-wide selectivity, thus providing a promising scaffold for cancer therapy.

Primary Sj(o)gren's syndrome (pSS) is a chronic autoimmune disease characterized by lymphoplasmacytic infiltration of the exocrine glands that results in multiple organs and systems damage.Renal injury affects 0.3％-27.0％ patients,The most frequent form of nephropathy in pSS is tubulointerstitial nephritis.The main clinical manifestation is renal tubular acidosis.The renal prognosis in patients with pSS is usually favorable,but renal failure may occur.At present,it still lacks of strict consensus or guideline for the treatment.

With the discovery of exosomes,new pathways of intercellular information and material exchange mediated by exosomes are attracting more and more attention from researchers. The process of exo-some production overlaps with many viral assembly and outflow pathways,suggesting that exosomes may be related to viral infections. In vitro experiments also show that exosomes play a very important role in viral in-fections. On one hand,exosomes can transfer viral nucleic acids and proteins,and may change microenviron-ment to promote the spread of infection. On the other hand,exosomes can induce immune responses by activa-ting antiviral pathways or transferring antiviral molecules. Do they promote or suppress the spread of infec-tion? What are the factors that affect their functions? In this paper,we review the role of exosomes in viral in-fection in order to provide a reference for better understanding the process of viral infection and immune re-sponses,and to provide a new train of thoughts for the prevention,diagnosis and treatment of viral diseases.

PurposeWith the extensive use of percutaneous radiofrequency ablation (RFA) for the treatment of hepatic carcinoma (HC), the study of MRI findings and its clinical signiifcance after RFA of HC have important value and can improve the complete ablation rate.Materials and MethodsA retrospective analysis of post-procedure MRI ifndings of 79 patients (114 lesions) with HC were performed, the size of the lesion, the signal changes and enhancement condition were observed at the ifrst, fourth and seventh month after RFA; the two different ifndings of high signal ring on MRI T1WI and local recurrence rate were analyzed.ResultsOne month after RFA, peripheral region of RFA lesion showed high signal on T1WI, and slightly lower signal on T2WI, the size of lesions was slightly larger than pre-procedure, enhancement scan showed the thin homogeneous ring enhanced around the non-enhanced lesions; 4 months later, the size of lesions were relative stable and the periphery enhancement was weaken; 7 months later, the size of lesions were reduced and showed no enhancement. For recurrence lesions, the high signal ring was incomplete on TIWI, the incomplete area showed nodular enhancement on the arterial phase, and most of nodule showed slightly lower signal on the delay phase demonstrated a feature of quick wash-in and wash-out; 7 months after RFA, recurrence rate was 6.12% in patients with complete high signal ring and 43.75% in patients with incomplete high signal ring, the difference was statistically significant (P<0.05). The total survival rate and accumulated survival rate of the patients with complete high signal ring on T1WI were higher than the patients with incomplete ring, the difference was statistically signiifcant (P<0.05).ConclusionThere are characteristic ifndings of MRI examination of liver cancer after percutaneous RFA, observation of the integrity of high signal ring on T1WI image and ifnding of dynamic enhancement scan can early evaluate efifcacy of RFA guide the selection of treatment plan.

Background and purpose:Urothelial carcinoma of the bladder (UCB) is the most common cancer in urinary system. Yes associated protein (YAP) gene is closely associated with urothelial carcinoma of the bladder. The study was aimed to explore the effect of siRNA targeting the YAP gene on cell proliferation and migration of T24 cells. Methods:Small interfering RNA (siRNA) was transfected together with LipofectamineTM2000 in T24 human bladder cancer cells to block the YAP signal pathway. The effect of siRNA on cell proliferation and invasiveness was assessed by cell counting kit-8 (CCK-8) assay, Transwell migration assay and wound healing assay. Quantitative real time-Polymerase chain reaction (qRT-PCR) and Western blot analysis were used to conifrm the successful suppression of YAP gene and protein by siRNA. Results:Expression of YAP gene and protein was successfully suppressed after transfected with siRNA which verified by qRT-PCR and Western blot(RNA:F=93.91, P<0.000 1; Protein: F=4.62, P<0.05). As CCK-8 test showed, the proliferation of T24 bladder cancer cells was successfully restrained by inhibition of YAP gene compared with blank control and negative control(12 h: F=6.00, P=0.037;24 h: F=41.72, P=0.000 3;36 h:F=462.8, P<0.000 1;48 h:F=236.6, P<0.000 1;72 h:F=140.5, P<0.000 1). Transwell and wound healing test were performed after YAP gene was interfered by siRNA. The result demonstrated that migration of T24 bladder cancer cells was signiifcantly inhibited (Transwell: F=43.55, P<0.05;Wound healing: F=43.55, P<0.05). Conclusion:This study suggested that YAP gene was an important enhancer for the proliferation and migration of bladder cancer cells.

OBJECTIVETo study chemical constituents contained in Desmodium caudatum.

METHODThe chemical compounds were separated by using such chromatographic methods as macroporous resin, Sephadex LH-20, ODS and normal phase silicagel column, and their structures were identified by spectroscopic data analysis.

RESULTFifteen compounds were separated and identified as stigmasterol (1), beta-sitosterol (2), citrusinol (3), hibiscone A (4), yukovanol (5), kenusanone I (6), neophellamuretin (7), desmodol (8), erythrotriol (9), hibiscone D (10), kaempferol (11), 8-prenylquercetin (12), leachianone G (13), 5,7,4'-trihydroxy-dihydroflavonol (14), and 4H-1-benzopyran-4-one, 2-(3,4-dihydroxyphenyl) -2, 3-dihydro-3,5,7-trihydroxy-8-( 3-methyl-2-butenyl) -, (2R-trans)-(9CI) (15).

CONCLUSIONAll of the compounds were separated from D. caudatum for the first time except compound 8.

Drugs, Chinese Herbal ; chemistry ; Fabaceae ; chemistry ; Organic Chemicals ; analysis ; isolation & purification ; Spectrum Analysis

OBJECTIVETo study on pharmacologic actions on quail hyperlipidemia and atherosclerosis model.

METHODTo duplicate quail hyperlipidemia model by ectogenesis cholesterol and high fat forage, induce to atherosclerosis model, observe influence of sugarcane alkane alcohol to model animals' blood fat level, formation of atherosclerosis plaque, pathological changes of coronary vessels and vascular intimal.

RESULTTC, TG, LDL-C level in blood serum of quail hyperlipidemia markedly decreased after administered sugarcane alkane alcohol by dose of 30, 15, 7.5 mg x kg(-1), proliferation of aorta and brachiocephalic artery tunica intima foam cells was suppressed.

CONCLUSIONSugarcane alkane alcohol has satisfactory pharmacologic actions on hyperlipidemia and atherosclerosis animal model by regulating blood fat.

Alkanes ; chemistry ; therapeutic use ; Animals ; Atherosclerosis ; drug therapy ; Cholesterol ; blood ; Disease Models, Animal ; Ethanol ; chemistry ; therapeutic use ; Hyperlipidemias ; drug therapy ; Male ; Plant Extracts ; chemistry ; therapeutic use ; Quail ; Random Allocation ; Saccharum ; chemistry

OBJECTIVETo investigate the anti-proliferative effect of Protobioside on the HepG2 cells and its mechanism.

METHODThe inhibitory effects of Protobioside on 3 kinds of human cancer cell line was measured by MTT assay. Apoptotic morphological changes was observed by Hoechst33528 staining technique. Cell cycle were analyzed using flow cytometry. The expression of cell cycle related protein and apoptosis related protein were determined using Western blotting.

RESULTProtobioside shows strong cytotoxic power on HepG2 cells and IC50 were 20 micromol x L(-1). The nucleus became pyknosis at 36 hours. The cells in G2/M phase increase in a dose-dependent and time-dependent manner. And the protein level of CyclinB1 was down-regulated, that of Bax was up-regulated and that of Bcl-2 was down-regulated.

CONCLUSIONThe growth inhibition of Protobioside on HepG2 cells is highly related to cell cycle arrest at G2/M phase which was well correlated with the down-regulation of expression of Cyclin B1, and the induction of apoptosis via up-regulating of Bax and down-regulating Bcl-2 expression.

Apoptosis ; drug effects ; Blotting, Western ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; Flow Cytometry ; Hep G2 Cells ; Humans