Adenosine has been proved to have immunosuppressive effect in many different diseases, and the activity of ecto-5’-nucleotidase(CD73) on the cell surface is the rate-limiting step of extracellular adenosine production. CD73 has a profound and lasting impact on tumor immune regulation of regulatory T cells, B cells, macrophages and natural killer cells. CD73-mediated adenosine pathway is significant in signal transduction during cancer progression in tumor microenvironment, making CD73 a novel immune checkpoint. Therefore, CD73 inhibition is a emergent and promising strategy for cancer immunotherapy. At present, a variety of monoclonal antibodies and small molecule inhibitors have been in clinical development. This review comprehensively summarizes the frontier research progress of reported small molecule CD73 inhibitors, which can provide guidance for the investigation of novel CD73 inhibitors for cancer therapy.

Objective To observe the effect of non-invasive ventilator assisted vibration sputum evacuation on the level of cardiac function indicators in patients with acute heart failure in the intensive care unit(ICU).Methods A total of 120 patients with acute heart failure who received treatment in the ICU of Tongde Hospital of Zhejiang Province from September 2020 to March 2023 were selected as the study subjects.The patients were randomly divided into a control group and an experimental group using a random number table method,with 60 patients in each group.A total of 120 patients were treated with conventional symptom therapy and non-invasive ventilation.The control group received routine nursing intervention,while the experimental group received non-invasive ventilator assisted vibration sputum evacuation.Arterial partial pressure of oxygen(PaO2),arterial partial pressure of carbon dioxide(PaCO2),pulse oxygen saturation(SpO2),respiratory rate(RR),heart rate,blood pressure,central venous pressure,serum and ultrasound cardiac function indicators,and prognosis of two groups of patients were recorded after 2 weeks of intervention.Results After the intervention,PaO2,SpO2,and left ventricular ejection fraction(LVEF)were significantly increased in both groups,while PaCO2,RR,heart rate,blood pressure,central venous pressure,N-terminal pro-brain natriuretic peptide(NT-proBNP),cardiac troponin T(cTnT),left ventricular end-systolic diameter(LVESD),and left ventricular end-diastolic diameter(LVEDD)were significantly decreased compared to before the intervention(all P<0.05).Compared with the control group,the experimental group showed significant increases in PaO2,SpO2,blood pressure,central venous pressure,and LVEF after intervention[PaO2(mmHg,1 mmHg≈0.133 kPa):68.24±5.81 vs.59.63±6.86,SpO2:0.95±0.03 vs.0.87±0.04,systolic blood pressure(mmHg):116.05±4.11 vs.104.13±3.95,diastolic blood pressure(mmHg):68.19±4.13 vs.62.85±4.12,central venous pressure(mmHg):9.42±1.29 vs.8.12±4.12,LVEF:0.49±0.05 vs.0.43±0.04,all P<0.05],while PaCO2,RR,heart rate,NT-proBNP,cTnT,LVESD,and LVEDD were significantly reduced[PaCO2(mmHg):42.12±4.08 vs.52.13±4.61,RR(beats/min):18.85±1.75 vs.21.54±2.51,heart rate(bpm):89.53±8.14 vs.101.11±10.26,NT-proBNP(ng/L):1687.25±589.67 vs.2145.36±751.03,cTnT(ng/L):70.58±5.15 vs.81.45±6.89,LVESD(mm):34.51±3.11 vs.38.89±3.55,LVEDD(mm)46.11±3.22 vs.49.74±3.75,all P<0.05].The mechanical ventilation time,ICU hospitalization time,and pulmonary infection relief time of the experimental group were significantly shortened compared to the control group[mechanical ventilation time(hours):72.14±10.06 vs.78.96±12.97,ICU hospitalization time(days):10.74±2.15 vs.12.88±3.26,pulmonary infection relief time(days):3.58±0.79 vs.5.14±1.12,all P<0.05],and the incidence of pulmonary infection was significantly reduced[1.67%(1/60)vs.11.67%(7/60),P<0.05],However,there was no statistically significant difference in the mortality rate between the experimental group and the control group[10.00%(6/60)vs.21.67%(13/60),P>0.05].Conclusion The non-invasive ventilator assisted vibration sputum evacuation can improve symptoms of hypoxemia and cardiac function,stabilize hemodynamics,shorten the course of acute heart failure in ICU patients,and reduce the incidence of pulmonary infections.

Objective:To compare the effects of drug-loaded microsphere TACE (D-TACE) and iodinated oil emulsion TACE (cTACE) on liver fibrosis in the treatment of advanced hepatocellular carcinoma (HCC).Methods:Clinical data of 113 patients with HCC treated with D-TACE or cTACE at the First Affiliated Hospital of Zhengzhou University from October 2019 to September 2020 were retrospectively analyzed, including 96 males and 17 females, aged (56.8±9.8) years old. According to treatment protocol, patients were divided into two groups: the D-TACE group ( n=57) and the cTACE group ( n=56). Liver fibrosis panel, fibrosis index (FIB-4), aspartate aminotransferase to platelet ratio index (APRI), and liver stiffness measurement (LSM) were compared between the groups at four timepoints: pre-treatment, one month after the first TACE, one month after the second TACE, and 12 months after the first TACE. Follow-ups were conducted through outpatient visits or telephone reviews to assess patient survivals. Data including the progression-free survival (PFS) and number of TACE sessions were compared between the two groups. Results:The D-TACE group received 2.84±1.12 sessions of treatment during the observation period, compared to 4.05±1.44 sessions of cTACE group ( t=4.94, P<0.001). The median PFS in D-TACE and cTACE groups were 10.0 and 5.0 months, respectively ( P<0.001). At one month after the second TACE and at 12 months after the first TACE, patients in cTACE group had a higher serum levels of fibrosis markers including hyaluronic acid, type IV collagen, type III procollagen N peptide and laminin than those in D-TACE group (all P<0.05). At the same timepoints, patients in cTACE group also had higher APRI, FIB-4 and LSM than those in D-TACE group (all P<0.05). Conclusion:Compared to cTACE, patients in D-TACE group received fewer sessions of treatment during the first year after initial TACE, and the degree of liver fibrosis was also lower in D-TACE group.

Objective:To investigate the impact of elevated glucose-induced RNA oxidation on pancreatic β-cell function, activity, and underlying molecular mechanisms.Methods:Rat pancreatic islet β-cell tumour INS-1 cells were cultured in vitro and subjected to nucleic acid oxidation assessment using isotope dilution ultra-high performance liquid tandem mass spectrometry(ID LC MS/MS)following high glucose exposure.In vitro simulation of increased RNA oxidation in INS-1 cells was achieved using 8-oxoguanosine-5'-triphosphate(8-oxoGTP).Cell proliferation was evaluated through CCK-8 assay, apoptosis was measured via flow cytometry, and gene expression of insulin(INS), pancreatic-duodenal homologous cassette 1(PDX1), cysteine-aspartate proteinase 3(Casp3), and cysteine aspartate protease 6(Casp6)was analyzed at the mRNA level.Additionally, whole transcriptome sequencing was performed to elucidate the molecular mechanisms underlying the impact of RNA oxidation on INS-1 cells.Results:Elevated glucose levels induced an increase in RNA oxidation within INS-1 cells.This heightened RNA oxidation led to the inhibition of INS-1 cell proliferation, a reduction in mRNA levels of INS and PDX1 genes, and the promotion of apoptosis-related casp3 and casp6 gene mRNA synthesis.Transcriptome sequencing analysis unveiled that the elevated RNA oxidation caused differential expression of mRNA, lncRNA, miRNA, and circRNA in INS-1 cells.This included a significant down-regulation of transcription factors such as Mafa, Pdx1, Pax6, and Mnx1, alongside an up-regulation of various miRNAs like rno-miR-124-3p, rno-miR-133a-3p, rno-miR-3120, rno-miR-212-3p, and rno-miR-7a-2-3p.These molecular changes contributed to the altered expression of associated lncRNAs, ultimately hindering insulin synthesis and secretion, as well as β-cell proliferation.Conclusions:Increased RNA oxidation down-regulates the levels of key β-cell transcription factor mRNAs, contributes to the differential expression of related non-coding RNAs(ncRNAs), particularly lncRNAs, impacts β-cell insulin synthesis and secretion, hinders cell proliferation, and serves as a significant factor in β-cell dysfunction and decreased activity in type 2 diabetes mellitus(T2DM).

Iron is indispensable for the viablility of nearly all living organisms, and it is imperative for cells, tissues, and organisms to acquire this essential metal sufficiently and maintain its metabolic stability for survival. Disruption of iron homeostasis can lead to the development of various diseases. There is a robust connection between iron metabolism and infection, immunity, inflammation, and aging, suggesting that disorders in iron metabolism may contribute to the pathogenesis of arthritis. Numerous studies have focused on the significant role of iron metabolism in the development of arthritis and its potential for targeted drug therapy. Targeting iron metabolism offers a promising approach for individualized treatment of arthritis. Therefore, this review aimed to investigate the mechanisms by which the body maintains iron metabolism and the impacts of iron and iron metabolism disorders on arthritis. Furthermore, this review aimed to identify potential therapeutic targets and active substances related to iron metabolism, which could provide promising research directions in this field.

Background::The causal relationship between visceral adipose tissue (VAT) and gout is still unclear. We aimed to examine the potential association between them using observational and Mendelian randomization (MR) analyses.Methods::In the observational analyses, a total of 11,967 participants (aged 39.5 ± 11.5 years) were included from the National Health and Nutrition Examination Survey. Logistic regression models were used to investigate the association between VAT mass and the risk of gout. In two-sample MR analyses, 211 VAT mass-related independent genetic variants (derived from genome-wide association studies in 325,153 UK biobank participants) were used as instrumental variables. The random-effects inverse-variance weighted (IVW) method was used as the primary analysis. Additional sensitivity analyses were also performed to validate our results.Results::Observational analyses found that an increase in VAT mass (per standard deviation) was associated with a higher risk of gout after controlling for confounding factors (odds ratio [OR] = 1.27, 95% confidence intervals [CI] = 1.11–1.45). The two-sample MR analyses demonstrated a causal relationship between increased VAT mass and the risk of gout in primary analyses (OR = 1.78, 95% CI = 1.57–2.03). Sensitivity analyses also showed similar findings, including MR-Egger, weighted median, simple mode, weighted mode, and leave-one-out analyses.Conclusions::Observational analyses showed a robust association of VAT mass with the risk of gout. Meanwhile, MR analyses also provided evidence of a causal relationship between them. In summary, our findings suggested that targeted interventions for VAT mass may be beneficial to prevent gout.

The pathogenesis of diabetic nephropathy(DN)is very complex.Ferroptosis as a kind of new way of cell death has become a research hotspot in recent years.It is widely known that DN is closely related to ferroptosis.Deactivation of system Xc--GSH-GPX4 axis,iron overload,lipid peroxidation and mitochondrial dysfunction play important role in occurrence and development of ferroptosis of DN,antioxidant protein may be a potential target for the treatment of ferroptosis of DN.Different pathways and interactions may alleviate the occurrence and development of ferroptosis by activating antioxidant protein such as GPX4,Nrf2,Sirtuin family protein and ferritin.Traditional Chinese medicine(TCM)has the characteristics of multi-component,multi-target and multi-pathway overall regulation.The active components and compounds of TCM have potential application value in improving renal injury and ferroptosis of DN by enhancing the expression of antioxidant protein,which provides a new research direction for delaying the progress of DN.

Objective To investigate the safety and efficacy of camrelizumab added to second-line therapy after drug- eluting bead transarterial chemoembolization (DTACE) combined with apatinib for unresectable hepatocellular carcinoma (HCC). Methods A retrospective analysis was performed for 89 HCC patients with camrelizumab added to second-line therapy who attended The First Affiliated Hospital of Zhengzhou University from December 2019 to December 2020. The primary endpoints were overall survival (OS) and progression-free survival (PFS) after the application of camrelizumab, and the secondary endpoints were objective remission rate (ORR), disease control rate (DCR), and treatment-related adverse events (TRAEs). The Kaplan-Meier method was used to plot survival curves, the Log-rank test was used for stratified analysis of subgroups based on baseline characteristics, and the influencing factors for prognosis were analyzed. Results A total of 89 patients were screened and followed up in this study. The patients were followed up to December 2021, with a median follow-up time of 16 months, a median OS time of 17.0 (95% confidence interval [ CI ]: 15.3-18.7) months, and a median PFS time of 7.0 (95% CI : 6.2-7.8) months. There were significant differences in OS and PFS between the patients with different ECOG-PS scores, liver function Child-Pugh classes, portal vein invasion, patterns of progression, times of DTACE treatment, durations of oral administration of apatinib, and durations of application of camrelizumab (all P < 0.05). At 3 and 6 months after the application of camrelizumab, ORR was 39.3% and 22.4%, respectively, and DCR was 80.9% and 54.1%, respectively. The univariate analysis using the Log-rank test showed that compared with the patients receiving 0 time of DTACE treatment, the patients receiving 3-4 or 1-2 times of DTACE treatment had significant improvements in median OS [22.0 (95% CI : 21.1-22.9) months and 17.0 (95% CI : 15.8-18.2) months vs 10.0 (95% CI : 7.0-13.0) months, χ 2 =31.423, P < 0.001] and PFS [10.0 (95% CI : 7.0-13.0) months and 7.0 (95% CI : 6.2-7.8) months vs 3.0 (95% CI : 1.9-4.1) months, χ 2 =20.741, P < 0.001]; compared with the patients using apatinib for ≤4 months, the patients using apatinib for > 4 months had significant improvements in median OS [21.0 (95% CI : 19.1-22.9) months vs 14.0 (95% CI : 10.4-17.6) months, χ 2 =19.399, P < 0.001] and PFS [9.0 (95% CI : 7.3-10.7) months vs 5.0 (95% CI : 4.0-6.0) months, χ 2 =27.733, P < 0.001]; compared with the patients using camrelizumab for ≤5 months, the patients using camrelizumab for > 5 months had significant improvements in median OS [22.0 (95% CI : 20.2-23.8) months vs 13.0 (95% CI : 9.3-16.7) months, χ 2 =22.336, P < 0.001] and PFS [9.0 (95% CI : 7.0-11.0) months vs 5.0 (95% CI : 4.1-5.9) months, χ 2 =26.141, P < 0.001]. Post-embolization syndrome was the adverse event after DTACE and resolved after symptomatic treatment. Adverse reactions related to targeted drugs and immunotherapy all resolved after symptomatic supportive treatment, with no grade ≥4 adverse reactions, and no patients withdrew from target-free therapy due to TRAEs. Conclusion As for DTACE combined with apatinib in the treatment of unresectable HCC, camrelizumab added after progression has a marked therapeutic efficacy with safe and controllable TRAEs.

Objective:To explore the incidence and factors of the influence of preoperative related factors on postoperative orthopedic evaluation, through the evaluation of thoracic shape orthopedic evaluation of children pectus excavatum, during plate implantation after Nuss procedure.Methods:From April 2012 to April 2019, the clinical data were analyzed retrospectively for 159 hospitalized cases of Nuss procedure for pectus excavatum in Xi’an Children’s Hospital.The mean age was(6.8±3.4) years old(3.2-17.0 years old); males 124, females 35; Haller index 4.0±1.0(2.7-7.5); 6 cases(4%) were poor orthopedic evaluation with the thoracic shape, males 5, femal 1; 23 cases (14%) were average satisfied with the thoracic shape, males 16, femals 7; 130 cases (82%)were good orthopedic evaluation with the thoracic, males 103, femals 27. Follow-ups were conducted for at least 2 years, Retrospective analysis of the relationship between postoperative thoracic satisfaction and age, gender, Haller index, how the plates were placed during surgery and symmetry of funnel chest, t test and χ2 test were used for statistical analysis. Results:There were statistically significant differences between thoracic orthopedic evaluation after postoperative and classification of pectus excavatum ( P=0.001), and poor orthopedic evaluation after asymmetric pectus excavatum operationand ; There were no significant differences in gender, Haller index, surgical method and how the plates were placed during surgery( P>0.05). However, it can be seen from the mean and percentage that with the decrease of age, and the increase of Haller index, the orthopedic evaluation gradually becomes worse. Conclusion:According to our single-center study, asymmetric pectus excavatum is a factor for poor orthopedic evaluation during plate implantation after Nuss, especially for young children and children with larger Haller index.

Objective:To observe the short-term efficacy and safety of bronchial arterial chemoembolization (BACE) combined with anlotinib for treatment of advanced non-small cell lung cancer (NSCLC).Methods:The clinical data of 14 patients with advanced NSCLC in the First Affiliated Hospital of Zhengzhou University from June 2018 to March 2019 were retrospectively analyzed. The short-term efficacy and adverse reactions of BACE combined with anlotinib hydrochloride were evaluated.Results:All patients successfully received BACE treatment twice. The median follow-up time was 19 months (8-26 months). The objective response rate (ORR) of patients at 1, 3 and 6 months after the first treatment was 100.0% (14/14), 71.4% (10/14) and 57.1% (8/14), and the disease control rate (DCR) was 100.0% (14/14), 92.8% (13/14) and 78.6% (11/14), respectively. The median progression-free survival (PFS) time was 9.5 months (95% CI 9.0-17.3 months), and the 6-month and 12-month PFS rates were 78.6% and 28.6%, respectively. The median overall survival (OS) time was 19.0 months (95% CI 18.4-23.1 months), and the 6-month and 12-month OS rates were 100.0% and 85.7%, respectively. Anlotinib hydrochloride-related adverse reactions included hand-foot syndrome [42.9% (6/14)], fatigue [35.7% (5/14)], hypertension [35.7% (5/14)], oral mucositis [28.6% (4/14)], hemoptysis [28.6% (4/14)], elevated aminotransferases [21.4% (3/14)] and diarrhea [14.3% (2/14)]. There were no grade ≥3 adverse reactions. Conclusion:BACE combined with anlotinib is safe and effective for treatment of advanced NSCLC, and the short-term clinical efficacy is satisfactory.