Objective:To investigate the expression of Artemin (ARTN) in malignant peripheral nerve sheath tumor (MPNST), its effect on the malignant behavior of MPNST cells, and its signaling pathway.Methods:Fifty-one MPNST paraffin embedded tissues through surgical resection at Tianjin Medical University Cancer Hospital from January 1995 to November 2011 were collected, the expression of the ARTN protein was detected by immunohistochemistry, and the relationship between the ARTN protein expression and the clinical pathological characteristics and prognosis were analyzed. In human MPNST cell lines ST-8814 (NF-1) and STS26T(sporadic), ARTN overexpression and low expression cell lines were constructed by transfecting ARTN overexpression plasmids and ARTN small interfering RNA (siRNA), respectively. The expression of ARTN mRNA was detected by real time quantitative polymerase chain reaction (RT-qPCR), the expression of the ARTN protein and Phosphoinositide 3-kinase(PI3K)/Akt signaling pathway related proteins were detected by Western blot. CCK-8 assay was used to detect cell proliferation ability, and cell invasion assay was used to detect cell invasion ability. The pathway proteins that interacted with ARTN were searched in the STRING database, and the functional pathways were clarified by Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The PI3K/Akt pathway specific inhibitor LY294002 was used to block the PI3K/Akt pathway of ST-8814 and STS26T cells to observe the changes in cell proliferation and invasion.Results:Among the 51 MPNST tissue specimens, 22 cases showed a high expression of the ARTN protein and 29 cases showed a low expression of the protein. Higher expressions of the ARTN protein was associated with larger tumor diameters and disease progression (recurrence or metastasis) (both P＜0.05). The median disease-free survival (DFS) of patients with a low expression of the ARTN protein was 26.2 months, and the median overall survival (OS) was 66.9 months. The median DFS and median OS of patients with a high expression of the ARTN protein were 10.7 months and 53.8 months, respectively. The log rank test results showed that the progression free survival rate of patients with a high expression of the ARTN protein was worse than that of patients with a low expression ( P=0.027), but the difference in overall survival rate between the two groups was not statistically significant ( P=0.790), which was also confirmed by Cox regression analysis. The CCK-8 assay results showed that after 48 hours of transfection, the absorbance ( A) values of ST-8814 and STS26T cells in the ARTN overexpression group were 1.35±0.01 and 1.10±0.02, respectively, which were higher than those in the empty plasmid control group (1.05±0.01 and 0.78±0.01, both P＜0.01), while the A values of ST-8814 and STS26T cells in the ARTN siRNA group were 0.35±0.01 and 0.61±0.01, respectively, which were lower than those in the control siRNA group (0.74±0.01 and 1.10±0.04, both P＜0.01). The results of cell invasion assay showed that the number of transmembrane cells in ST-8814 and STS26T cells overexpressing ARTN was (29.67±2.08) and (31.67±2.08), respectively, which were higher than those in the empty plasmid control group [(20.00±1.00) and (24.33±1.15), both P＜0.01]. The number of transmembrane cells in ST-8814 and STS26T cells in the ARTN siRNA group were (14.00±2.00) and (19.33±1.53), respectively, which were lower than those in the control siRNA group [(19.33±2.52) and (23.33±0.58), both P＜0.05].The KEGG results showed that ARTN is associated with multiple tumor signaling pathways, especially the PI3K/Akt signaling pathway. Western blot results showed that overexpression of ARTN upregulated the expression of p-PI3K and p-Akt proteins in ST-8814 and STS26T cells (both P＜0.01).After knocking down ARTN expression, the expression of p-PI3K and p-Akt proteins was significantly down regulated (both P＜0.01). LY294002 could significantly inhibit the effect of ARTN overexpression on ST-8814 and STS26T cells after blocking the PI3K/Akt pathway. The A values of ST-8814 and STS26T cells in the ARTN overexpression+LY294002 group were 1.09±0.06 and 0.82±0.01, respectively, which were lower than those in the ARTN overexpression group (1.50±0.01 and 1.29±0.01, respectively, both P＜0.01). The numbers of transmembrane cells in the cell invasion assay were 16.67±3.21 and 19.67±2.31, respectively, which were also lower than those in the ARTN overexpression group (29.67±2.08 and 31.67±2.08, respectively, both P＜0.01). Conclusions:In MPNST, a high expression of the ARTN protein was associated with larger tumor size, disease progression, and worse DFS. ARTN promotes the proliferation and invasion of MPNST cells through the PI3K/Akt signaling pathway.

Objective:To investigate the expression of Artemin (ARTN) in malignant peripheral nerve sheath tumor (MPNST), its effect on the malignant behavior of MPNST cells, and its signaling pathway.Methods:Fifty-one MPNST paraffin embedded tissues through surgical resection at Tianjin Medical University Cancer Hospital from January 1995 to November 2011 were collected, the expression of the ARTN protein was detected by immunohistochemistry, and the relationship between the ARTN protein expression and the clinical pathological characteristics and prognosis were analyzed. In human MPNST cell lines ST-8814 (NF-1) and STS26T(sporadic), ARTN overexpression and low expression cell lines were constructed by transfecting ARTN overexpression plasmids and ARTN small interfering RNA (siRNA), respectively. The expression of ARTN mRNA was detected by real time quantitative polymerase chain reaction (RT-qPCR), the expression of the ARTN protein and Phosphoinositide 3-kinase(PI3K)/Akt signaling pathway related proteins were detected by Western blot. CCK-8 assay was used to detect cell proliferation ability, and cell invasion assay was used to detect cell invasion ability. The pathway proteins that interacted with ARTN were searched in the STRING database, and the functional pathways were clarified by Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The PI3K/Akt pathway specific inhibitor LY294002 was used to block the PI3K/Akt pathway of ST-8814 and STS26T cells to observe the changes in cell proliferation and invasion.Results:Among the 51 MPNST tissue specimens, 22 cases showed a high expression of the ARTN protein and 29 cases showed a low expression of the protein. Higher expressions of the ARTN protein was associated with larger tumor diameters and disease progression (recurrence or metastasis) (both P＜0.05). The median disease-free survival (DFS) of patients with a low expression of the ARTN protein was 26.2 months, and the median overall survival (OS) was 66.9 months. The median DFS and median OS of patients with a high expression of the ARTN protein were 10.7 months and 53.8 months, respectively. The log rank test results showed that the progression free survival rate of patients with a high expression of the ARTN protein was worse than that of patients with a low expression ( P=0.027), but the difference in overall survival rate between the two groups was not statistically significant ( P=0.790), which was also confirmed by Cox regression analysis. The CCK-8 assay results showed that after 48 hours of transfection, the absorbance ( A) values of ST-8814 and STS26T cells in the ARTN overexpression group were 1.35±0.01 and 1.10±0.02, respectively, which were higher than those in the empty plasmid control group (1.05±0.01 and 0.78±0.01, both P＜0.01), while the A values of ST-8814 and STS26T cells in the ARTN siRNA group were 0.35±0.01 and 0.61±0.01, respectively, which were lower than those in the control siRNA group (0.74±0.01 and 1.10±0.04, both P＜0.01). The results of cell invasion assay showed that the number of transmembrane cells in ST-8814 and STS26T cells overexpressing ARTN was (29.67±2.08) and (31.67±2.08), respectively, which were higher than those in the empty plasmid control group [(20.00±1.00) and (24.33±1.15), both P＜0.01]. The number of transmembrane cells in ST-8814 and STS26T cells in the ARTN siRNA group were (14.00±2.00) and (19.33±1.53), respectively, which were lower than those in the control siRNA group [(19.33±2.52) and (23.33±0.58), both P＜0.05].The KEGG results showed that ARTN is associated with multiple tumor signaling pathways, especially the PI3K/Akt signaling pathway. Western blot results showed that overexpression of ARTN upregulated the expression of p-PI3K and p-Akt proteins in ST-8814 and STS26T cells (both P＜0.01).After knocking down ARTN expression, the expression of p-PI3K and p-Akt proteins was significantly down regulated (both P＜0.01). LY294002 could significantly inhibit the effect of ARTN overexpression on ST-8814 and STS26T cells after blocking the PI3K/Akt pathway. The A values of ST-8814 and STS26T cells in the ARTN overexpression+LY294002 group were 1.09±0.06 and 0.82±0.01, respectively, which were lower than those in the ARTN overexpression group (1.50±0.01 and 1.29±0.01, respectively, both P＜0.01). The numbers of transmembrane cells in the cell invasion assay were 16.67±3.21 and 19.67±2.31, respectively, which were also lower than those in the ARTN overexpression group (29.67±2.08 and 31.67±2.08, respectively, both P＜0.01). Conclusions:In MPNST, a high expression of the ARTN protein was associated with larger tumor size, disease progression, and worse DFS. ARTN promotes the proliferation and invasion of MPNST cells through the PI3K/Akt signaling pathway.

OBJECTIVE To investigate the implementation effects of the national centralized drug volume-based procurement policy （abbreviated as “national centralized procurement policy”） in Guangxi Zhuang Autonomous Region prefecture， and to provide a reference for the future centralized drug procurement work of the medical institution. METHODS Drug procurement data before and after policy implementation were included in the study. The six secondary indicators （such as availability， affordability， and drug safety） and eighteen third-level indicators （such as completion rate of agreed purchase volume， affordability level， drug revenue proportion） were introduced， guided by the policy objectives and issues of concern to policy beneficiaries. Descriptive statistics was adopted to analyze the data before and after policy implementation （in 2019 and 2020） in terms of differences and change trends. RESULTS In terms of accessibility， the participation rate of medical institutions in Guangxi Zhuang Autonomous Region was 92.55%， the proportion of diseases involved and median completed procurement rate were 40.16%， and 287.82% respectively， and the total centralized delivery rate was 97.20%. In terms of affordability， the total reduction amplitude in drug price was 74.80% from 2019 to 2022； the charge for medicine per capita in hospitalization， the proportion of medicine used for outpatient service and hospitalization， decreased by 17.61%， 10.22%， and 20.10% in order； the burden levels on medical fares for patients were all below 1 in addition to chronic diseases， and anti-tumor drugs. In terms of the impact on medicine， the ratio of adverse drug reaction event cases in 2022 was 66.00%， an increase of 1.29% compared to the previous； since the implementation of the policy， 12 drugs from local pharmaceutical enterprises from Guangxi Zhuang Autonomous Region had passed the consistency evaluation， and the market concentration rate of the top 8 pharmaceutical companies was less than 20.00%. In terms of the impact on healthcare and medical insurance， the public medical institutions achieved generic substitution for originator drugs mostly until 2022； about 9.12% of drugs that were non- centrally purchased in the same category were used； 63.39% of people under investigation did not show a need for a second dressing change； drug expenditure decreased by 2.459 billion yuan. CONCLUSIONS The national centralized procurement policy achieves a significant effect in Guangxi Zhuang Autonomous Region. On the other hand， attention should be paid to these suggestions as follows: expanding the category of drugs used in clinic， conducting clinically comprehensive evaluation of selected drugs， and improving reasonable allocation strategy， etc.

China is the rank 1st of gastric cancer in the world,and the incidence and mortality of gastric cancer rank the 3rd among various malignant tumors in China.It has been found that tumor cells have their own energy metabolism characteristics.Even in the presence of sufficient oxygen,tumor cells are more inclined to use glycolysis to produce energy,also known as"aerobic glycoly-sis".Aerobic glycolysis can lead to an increase in lactate,promoting the acceleration of tumor cell proliferation and invasiveness,and the key enzyme driving this phenomenon is lactate dehydrogenase(LDH).LDH levels are significantly elevated in patients with gas-tric cancer,and LDH can contribute to the occurrence and development of gastric cancer in many ways.This article will discuss the role of LDH in tumor glycolysis,which is correlated with gastric cancer as well as its clinical application value.It will also discuss the research progress of LDH in targeted therapy for gastric cancer.

Objective To systematically evaluate the efficacy and safety of hydroxychloroquine(HCQ)in obstetric antiphospholipid syndrome(OAPS).Methods PubMed,Embase,Cochrane Library,Web of Science,SinoMed,Wanfang Data,CNKI,and VIP databases were searched electronically to collect clinical research on HCQ treatment for OAPS from inception to January 31,2023.Two researchers independently screened the literature,extracted data,and assessed the risk of bias of the included studies,Meta-analysis and GRADE evaluation were performed using RevMan 5.4 software and GRADE Profile 3.6 softwares.Results Five cohort studies and three randomized controlled trias(RCTs)were included,with a total of 644 OAPS patients(732 pregnancies).The results of Meta-analysis showed that compared with conventional treatment,HCQ supplementation significantly increased the live birth rate of OAPS(RR=1.29,95％CI 1.10 to 1.51,P=0.001),the negative conversion rate of lupus anticoagulant(RR=1.29,95％CI 1.13 to 1.47,P＜0.001),the anticardiolipin antibody negative conversion rate(RR=1.27,95％CI 1.12 to 1.45,P＜0.001)and the anti-β2 glycoprotein I antibody negative conversion rate(RR=1.31,95％CI 1.12 to 1.52,P＜0.001),the rate of early abortion(＜10 weeks)was significantly reduced(RR=0.31,95％CI 0.10 to 0.93,P=0.04).However,there was no significant difference between the two groups in reducing the rate of premature birth,late abortion(＞10 weeks)and the incidence of preeclampsia(P＞0.05).In terms of safety analysis,two studies described HCQ adverse effects including skin reactions and dry eyes,symptoms are mild.Three RCTs were used to compare the incidence of adverse reactions between the two groups,the incidence of adverse reaction of HCQ group was lower than that of control group(RR=0.40,95％CI 0.25 to 0.66,P＜0.001),and no serious adverse reactions occurred in both groups.The sensitivity analysis results were robust and reliable.The results of GRADE evaluation showed that the quality of index evidence included in this study were low or very low,with weak recommendations.Conclusion HCQ can significantly improve the live birth rate of OAPS and the negative conversion rate of antiphospholipid antibody,and reduce the fetal abortion rate before 10 weeks with fewer adverse reactions,but there is insufficient evidence to reduce the incidence of premature birth,fetal abortion after 10 weeks and preeclampsia.Due to the limited number and quality of included studies,the above conclusions need to be confirmed by more high-quality studies.

Malignant biliary obstruction (MBO) refers to the obstruction of the biliary tract, which usually causes obstruction of bile discharge, leading to skin yellow staining, itching, and impaired liver function. MBO can be caused by bile duct, pancreatic head, jugular tumor or distant tumor metastasis invasion and compression. Because of its insidious symptoms and high degree of malignancy, the 5-year survival rate is extremely low, and most patients miss the opportunity of surgery. Therefore, endoscopic retrograde cholangiopancreatography combined with internal biliary stents drainage has significant advantages in the palliative treatment of MBO.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

Objective:To retrospectively compare the clinical efficacy of two PDE3 inhibitors, oplinone and Milrinone, in order to evaluate which drug has better effects on the improvement of cardiac function, protection of renal function and adverse effects of arrhythmia.Methods:A total of 41 neonates with congenital heart disease after biventricular treatment under cardiopulmonary bypass in the Department of Cardiothoracic Surgery at Soochow University Children's Hospital during 2018-2022 were collected. The experimental group was divided into two groups: Oprilinone(25 cases) and Milinone(16 cases). A retrospective study was conducted on the incidence of renal function, cardiac function improvement and arrhythmia in the children.Results:On the first day after operation, EF in both groups decreased significantly compared with that before operation( P<0.01); On day 4 after surgery, EF in the oprilinone group was significantly higher than that on day 1 after surgery( P<0.01), Milrinone group was slightly higher than that on day 1 after surgery( P<0.05), and EF in oprilinone group was significantly higher than that in Milinone group during the same period( P<0.01); EF in Milinone group continued to increase on day 7 compared with day 4( P<0.01), but there was no significant difference between the two groups. Long-term follow-up showed that there was no significant difference in EF value in the oprilinone intervention group on day 7 after surgery( P<0.05), and the long-term EF in Milinone group was higher than that at 7 days after surgery( P<0.05). The creatinine level in the oprinone intervention group continued to decrease on the 4th and 7th day after surgery( P<0.01; P<0.05); The creatinine level of Milinone group on day 4 after surgery was significantly lower than that on day 1 after surgery( P<0.01), the decrease was not significant on the 7th day after surgery compared with the 4th day after surgery; The creatinine level in the oprilinone group was lower than that in the Milrinone group on day 7 after surgery( P<0.05). The rate of arrhythmia in children was slightly decreased in the intervention group of olplinone. There was no change in the Milinone group. Conclusion:Oplinone improved cardiac function better than Milrinone, and the recovery time to normal cardiac function was shorter. In terms of renal function protection, oplinone was stronger than Milrinone, and the protective effect of oplinone on kidney lasted longer. No significant abnormalities were found with respect to adverse reactions, such as the incidence of arrhythmia.

Organ shortage is one of the important factors restricting the development of human organ transplantation. The identification and referral of potential donors determine the total scale of organ donation. Whether potential donors can be identified and referred is the most important reason for the difference of organ donation rates in different regions. This paper interprets the chapter of the identification and referral of potential donors in the Guide to the Quality and Safety of Organs for Transplantation (6th edition) issued by European Union in order to provide reference for the staff of organ procurement organization and related medical personnel in China and improve the organ donation rate in China.