OBJECTIVES: To investigate the expression of parathyroid hormone-like hormone (PTHLH) in hepatocellular carcinoma (HCC) and analyze its correlation with clinical prognosis, its regulatory effects on HCC cell behaviors, and the signaling pathways mediating its effects. METHODS: We analyzed the differential expression of PTHLH in HCC and adjacent tissues and its association with patient prognosis based on data from TCGA and GEO databases and from 70 HCC patients treated in our hospital. The effects of PTHLH knockdown and overexpression on proliferation, migration, and invasion of cultured HCC cells were investigated using CCK-8 assay, colony formation assay, Transwell migration and invasion assays, and the signaling pathways activated by PTHLH were detected using Western blotting. RESULTS: TCGA and GEO database analysis showed significant overexpression of PTHLH mRNA in HCC tissues, which was associated with poor prognosis of the patients (P<0.05). High PTHLH mRNA expression was a probable independent prognostic risk factor for HCC (P<0.05). In the clinical samples, PTHLH mRNA and protein expressions were significantly higher in HCC tissues than in the adjacent tissues (P<0.001 or 0.01). Univariate and multivariate Cox regression analyses suggested that high PTHLH mRNA expression was an independent risk factor to affect postoperative disease-free survival of HCC patients (P<0.05). The prognostic prediction model based on PTHLH mRNA expression showed an improved accuracy for predicting the risk of postoperative recurrence in HCC patients. In cultured HCC cells, PTHLH overexpression significantly promoted cell proliferation, colony formation, migration and invasion, and caused activation of the ERK/JNK signaling pathway in Huh7 and Hep3B cells. CONCLUSIONS High PTHLH expression promotes HCC progression and is associated with poor patient prognosis. Its pro-tumor effects may be mediated by activation of the ERK/JNK signaling pathway.
Humans ; Carcinoma, Hepatocellular/metabolism* ; Liver Neoplasms/metabolism* ; Prognosis ; Cell Proliferation ; Parathyroid Hormone-Related Protein/genetics* ; Cell Line, Tumor ; Cell Movement ; Disease Progression ; Signal Transduction ; Male ; RNA, Messenger/genetics* ; Female

Objectives:To evaluate the diagnostic value of echocardiography in unroofed coronary sinus syndrome(UCSS)with endocardial cushion defect(ECD). Methods:The echocardiographic data of 43 patients of UCSS with ECD who underwent surgical treatment in our hospital from July 2017 to May 2022 were retrospectively analyzed.The diagnostic accuracy was evaluated by comparing the echocardiographic findings with the intraoperative exploration results. Results:According to Kirklin and Barratt-Boyes classification,there were 26 cases of type Ⅰ(60.5%),9 cases of type Ⅱ(20.9%),2 cases of type Ⅲ(4.7%),4 cases of type Ⅳ(9.3%),and 2 cases of type Ⅲ combined with type Ⅳ(4.7%).There were 26 cases(60.5%)of partial ECD,7 cases(16.3%)of intermediate ECD,10 cases(23.3%)of total ECD.Twenty two cases(51.2%)were associated with single atrium.Twenty seven cases(62.8%)were associated with persistent left superior vena cava(PLSVC).Other coexisting complicated malformations were as follows:2 cases of double outlet of right ventricle,1 case of pulmonary atresia,1 case of total anomalous pulmonary venous connection,and 1 case of aplenia syndrome.The coexisting simple malformations included 4 cases of ostium secundum atrial septal defect,2 cases of ventricular septal defect,3 cases of patent ductus arterial,and 6 cases of patent foramen ovale.Other abnormalities included 5 cases of absence of hepatic segment of inferior vena cava,1 case of hypoplasia of right superior vena cava,1 case of absence of right superior vena cava,3 cases of cor triatriatum,1 case of isolated levocardia,1 case of mirror image dextrocardia,4 cases of right aortic arch.Of the 43 patients,30(69.8%)were correctly diagnosed by preoperative echocardiography and 13(30.2%)by intraoperative exploration.UCSS was misdiagnosed as inferior vena cava type sinus septal defect and PLSVC was missed in 1 case.UCSS was missed in 12 cases,and PLSVC was missed in 3 cases of them. Conclusions:Diagnosis UCSS with ECD by echocardiography is valuable and challenging.It is necessary to strengthen the understanding of the embryonic development and pathological anatomy characteristics of these malformations to improve the diagnostic accuracy.

Severe muscle injury is hard to heal and always results in a poor prognosis. Recent studies found that extracellular vesicle-based therapy has promising prospects for regeneration medicine, however, whether extracellular vesicles have therapeutic effects on severe muscle injury is still unknown. Herein, we extracted apoptotic extracellular vesicles derived from mesenchymal stem cells (MSCs-ApoEVs) to treat cardiotoxin induced tibialis anterior (TA) injury and found that MSCs-ApoEVs promoted muscles regeneration and increased the proportion of multinucleated cells. Besides that, we also found that apoptosis was synchronized during myoblasts fusion and MSCs-ApoEVs promoted the apoptosis ratio as well as the fusion index of myoblasts. Furthermore, we revealed that MSCs-ApoEVs increased the relative level of creatine during myoblasts fusion, which was released via activated Pannexin 1 channel. Moreover, we also found that activated Pannexin 1 channel was highly expressed on the membrane of myoblasts-derived ApoEVs (Myo-ApoEVs) instead of apoptotic myoblasts, and creatine was the pivotal metabolite involved in myoblasts fusion. Collectively, our findings firstly revealed that MSCs-ApoEVs can promote muscle regeneration and elucidated that the new function of ApoEVs as passing inter-cell messages through releasing metabolites from activated Pannexin 1 channel, which will provide new evidence for extracellular vesicles-based therapy as well as improving the understanding of new functions of extracellular vesicles.
Creatine/metabolism* ; Extracellular Vesicles ; Muscle, Skeletal/metabolism* ; Myoblasts/metabolism* ; Regeneration ; Connexins/metabolism*

Zika virus (ZIKV) is an emerging pathogen associated with neurological complications, such as Guillain-Barré syndrome in adults and microcephaly in fetuses and newborns. This mosquito-borne flavivirus causes important social and sanitary problems owing to its rapid dissemination. However, the development of antivirals against ZIKV is lagging. Although various strategies have been used to study anti-ZIKV agents, approved drugs or vaccines for the treatment (or prevention) of ZIKV infections are currently unavailable. Repurposing clinically approved drugs could be an effective approach to quickly respond to an emergency outbreak of ZIKV infections. The well-established safety profiles and optimal dosage of these clinically approved drugs could provide an economical, safe, and efficacious approach to address ZIKV infections. This review focuses on the recent research and development of agents against ZIKV infection by repurposing clinical drugs. Their characteristics, targets, and potential use in anti-ZIKV therapy are presented. This review provides an update and some successful strategies in the search for anti-ZIKV agents are given.
Adult ; Animals ; Drug Repositioning ; Humans ; Infant, Newborn ; Microcephaly ; Pharmaceutical Preparations ; Zika Virus ; Zika Virus Infection/prevention & control*

Objective:To analyze the echocardiographic features of operation-related aorto-cardiac fistula(ACF) after surgery or transcatheter procedure, to explore the value of echocardiography on diagnosis of operation-related ACF, and summarize the key points of its diagnosis.Methods:Eight patients with operation-related ACF who were admitted to Fuwai Hospital were collected from July 2002 to December 2020. Echocardiographic features of the 8 patients with operation-related ACF were reviewed and analyzed. The diagnosis methodology was summarized.Results:Of the 8 patients with operation-related ACF, 3 had aortic right atrial fistula and 5 had aortic right ventricular fistula. The fistula was single, which can be located but not limited to the aortic sinus. The median size of the fistula was 4 mm (range: 3-5 mm). There was no aneurysmal dilation of the aortic sinus where the fistula was located. The fractured end of the fistula did not thin, and the fistula had a regular shape. Six of the 8 patients undertook cardiac catheterization and occlusion. One patient received surgical repairment. One patient was treated conservatively.Conclusions:Echocardiography can help diagnose operation-related ACF and provide valuable information for further clinical diagnosis and treatment. Sonographers should avoid missed diagnosis and pay attention to distinguishing from other causes of aortic-cardiac shunt disease.

Objective:To find the risk assessment model of [di (2-ethylhexyl) phthalate, DEHP] fitting well for producing companies.Methods:The Cluster Sampling method was used in selecting a DEHP producing company in the occupational health and workplace environment monitoring study conducted between July and August in 2017. Data was collected by site evaluating and workplace environment monitoring. According to GBZ/T 298-2017《Technical Guidelines for Occupational Health Risk Assessment of Chemical Hazards in the Workplace》, a qualitative assessment method and a semi-quantitative comprehensive index method were chosen as the models and were compared.Results:The occupational health risk of the two methods rated 4 (high risk) and 2 (negligible risk) .Conclusion:The semi-quantitative comprehensive index method is more comprehensive and accurate when used to assess the occupational health risk caused by DEHP.

Objective:To find the risk assessment model of [di (2-ethylhexyl) phthalate, DEHP] fitting well for producing companies.Methods:The Cluster Sampling method was used in selecting a DEHP producing company in the occupational health and workplace environment monitoring study conducted between July and August in 2017. Data was collected by site evaluating and workplace environment monitoring. According to GBZ/T 298-2017《Technical Guidelines for Occupational Health Risk Assessment of Chemical Hazards in the Workplace》, a qualitative assessment method and a semi-quantitative comprehensive index method were chosen as the models and were compared.Results:The occupational health risk of the two methods rated 4 (high risk) and 2 (negligible risk) .Conclusion:The semi-quantitative comprehensive index method is more comprehensive and accurate when used to assess the occupational health risk caused by DEHP.

Objective To systematically assess the relation between angiotensin-I converting enzyme(ACE) gene insertion/deletion (I/D) variation and type 2 diabetic nephropathy (T2DN) onset risk among Chinese population.Methods The related literatures were retrieved from the China National Knowledge Infrastructure (CNKI) and Wanfang Data until June 1st,2016.The RevMan 5.0 was used to conduct the statistical analysis.The merge OR value and corresponding 95% confidence interval(95%CI) were used to assess ACE gene I/D polymorphism and T2DN onset risk.Results Totally 29 papers with 4 357 subjects were included according to the inclusion and exclusion standard,including 2 208 cases of DN and 2 149 cases of T2DM without DN.Meta analysis showed that compared with ACE gene I/D polymorphism I allele,D allele could significantly increase the risk of T2DM patients suffering from DN,the OR value and corresponding 95%CI were 1.44(1.25,1.66);the gene analysis showed that ACE gene I/D polymorphism loci were significantly correlated with DN onset risk in the Asian population.The corresponding relative onset risk OR and 95%CI were 1.42(1.15,1.76) and 1.75(1.46,2.10) in the dominant and recessive genetic model.The Begg′s test showed that the included data had no obvious publication bias existence.Conclusion ACE gene I/D polymorphism is closely correlated with the onset risk of T2DN,and D allele might be a risk genetic factor for DN occurrence in the patients with T2DM.

Objective:To explore the regulatory effects of proliferation and apoptosis on THC-8307 by MMS2 siRNA and P53 siRNA.Methods:We experimentally suppressed the MMS2 and P53 expression in human colon cancer cells by the interference RNA technology ( RNAi) as monitored by Real-time qRT-PCR and Western blot.THC-8307 cells that express rate significantly reduced were collected as case group , while using untreated cells as the blank control group , and mock-treated cells as the negative control group.After separately interfering the target genes in each group ,test the relationship and expression level of the two genes.Utilizing flow cytometry techniques to test cells proliferation and apoptosis rate of each group.Results: Compared to the control group , colon cancer cells in which MMS2 and P53 were silenced displayed significant increase of P53,MMS2 mRNA and protein levels(P<0.05).MMS2-depleted cells displayed increase in apoptosis rates ,for both early and later stages ( P<0.05 ).Conclusion: MMS2 and P53 negatively regulate each other in colon cancer cells proliferation and apoptosis .

The impact of maintenance therapy on progression?free survival and overall survival as well as quality of life of Chi?nese patients with metastatic colorectal cancer has long been under discussion. Recently, some phase III clinical trials have revealed that maintenance therapy can signiifcantly prolong the progression?free survival while maintain an acceptable safety proifle. Based on this evidence and common treatment practice in China, we now generated one Expert Consensus on Maintenance Treatment for Metastatic Colorectal Cancer in China to further specify the neces?sity of maintenance therapy, suitable candidates for such treatment, and appropriate regimens.