OBJECTIVE:To observe the clinical efficacy and ADR of Mirabilite combined with intrapetitoneal in the treatment of elderly colorectal malignant ascites. METHODS:77 cases of patients with elderly colorectal malignant ascites were randomly di-vided into treatment group (n=40) and control group (n=37). The control group received the treatment of intraperitoneal alone, while the treatment group was based on the control group additionally received Mirabilite combined with intrapetitoneal. The clini-cal efficacy,quality of life (QOL),and ADR in 2 groups were compared and statistically analyzed. RESULTS:Compared with control group,the effective rate in treatment group was 77.5% and the disease control rate was 87.5%,with significant difference (P<0.05);the QOL score in treatment group was better than control group,with significant difference(P<0.05);the incidence of local ADR in Mirabilite for external use was low. CONCLUSIONS:Mirabilite combined with intraperitoneal has better efficacy in the elderly colorectal malignant ascites and better QOL.

Objective To construct Neuropilins-2 eukaryotic expression vector for RNA interference.Methods Recombinant targeting on gene NRP2 was designed and established with plasmid pGenSil-1 based on NRP2 cDNA equences of Genomes.Two pairs of oligonucleotides were synthesized according to the Tuschl and inserted into plasmid pGenSil-l to generate siRNA eukaryotic expression vector,DH5? strains were transformed,plasmid were extracted,and recombinant vectors were identified by the restriction map and the sequence analysis.The recombinant plasmid(pGenSil-NRP2) was transfected into the cultured LOVO cells.At 48 h after transfection,the whole cell protein was extracted,and the protein level was detected by Western blotting with mouse-anti-human NRP2 monoclonal antibody.Results Recombinant plasmids were completely coincided with the designs by the restriction map and the sequence analysis.pGenSil-NRP2 expression vector into LOVO cells down-regulated the protein level of NRP2 at 48 h after transfection.The recombinant eukaryotic expression vector were constructed successfully.Conclusion siRNA recombinant can be constructed successfully by RNAi technique for inhibiting NRP2 expression.

Objective To evaluate the utility of serum thymidine kinase 1(STK1)in health screening.Methods A total of 8896 adults who participated in health check-up during November 2009 and November 2010 were tested for STK1 by using sensitive chemiluminescence's dot blot assay.Results The level of STK1 of group A(STK1 ＞ 2 pmol/L)was much higher than that of the group B(STK1 ＜ 2 pmol/L)[(5.47 ±4.23)vs(0.62 ±0.48)pmol/L;t =11.90,P =0.00].The STK1 level was not correlated with gender.However,the mean age of individuals in the group A was higher than that in the group B[(48.2 ± 12.0)vs(41.8 ± 12.3)years; t =5.37,P =0.00].The positive detection rate of STK1 was 1.2％(108/ 8896).In the group A,there were 1.9％ pre-or post-treatment malignancy,27.8％ pre-malignant tumor or benign disease,36.0％ nontumorous proliferation disease,14.8％ hepatitis B virus/HP infection,10.2％fatty liver,and 9.3％ other diseases.No pre-treatment malignancy and pre-malignancy were found in the group B.Conclusion STK1 measurement could reflect the situation of cell proliferation and predict the risk of any type of malignancy.

Objective To explore the status of histone acetylation modification and their regulatory effect to hMSH2 gene and hMLH1 gene expression in acute leukemia. Methods Reverse transcription-polymerase chain reaction (RT-PCR) was used to measure the expression of hMSH2 and hMLH1 mRNA, and Western blot was used to measure the expression of histone H3, H4, HDACi, hMSH2 and hMLH1 protein in mononuclear cells of 56 acute leukemia patients and 30 healthy volunteers. The mononuclear cells of 30 acute leukemia patients were treated with histone deacetylase inhibitors trichostatin A (TSA), and measured the expression difference of histone H3, H4, HDAC1, hMSH2 and hMLH1 in the mononuclear cells treated with TSA. Results The protein expression levels of hMSH2, hMLH1, histone H3 and histone H4 in those mononuclear cells of acute leukemia patients were 0.4610±0.1211, 0.4013±0.1143, 0.4103±0.1241 and 0.4251±0.1081, respectively, which were significantly decreased comparing with those of healthy volunteers (0.9461±0. 1841, 0.996±0.2021, 0.8971±0. 1194 and 0.9513±0.1953) (t = 3.341, 3.935, 2.843 and 3.575,respectinely, P ＜0.05). The protein expression levels of HDAC1 (0.8841±0.2018) of acute leukemia patients was significantly increased comparing with those of healthy volunteers (0.5142±0.1340) (t= 2.634, P ＜0.05).After treatment with TSA for 48 hours, the protein expression of hMSH2 was increased nearly 1.5-fold, hMLH1 about 1.6-fold, H3 about 2.9-fold and H4 about 3.4-fold comparing with the negative control groups (P ＜0.05),while the protein expression of HDAC1 were decreased comparing with the negative control groups by 40 %.Conclusion There was an low expression phenomenon of histone acetylation in acute leukemia, and histone acetylation played an important role in regulation of the mismatch repair gene expression in acute leukemia.

OBJECTIVE: To determine the application of serum thymidine kinase 1 (STK1) in general health screening for early detection of premalignant/early malignant tumors. METHODS: A cross sectional study was carried out in 26 055 health screenings from 8 centers of Changsha in 2011. The concentration of STK1 was determined by a sensitive chemiluminescent dot blot ECL assay. RESULTS: In the elevated STK1 group 60.35% showed diseases with a higher risk of premalignant/ early cancerous progression. The positive rate of elevated STK1 (>2.0 pmol/L) was 2.61%. There was a significantly higher rate with moderate/severe type of hyperplasia of breasts and prostate with elevated STK1 than people with normal STK1 values. CONCLUSION STK1 may be a reliable marker for risk assessment of premalignant/early malignant tumors.
Biomarkers, Tumor ; blood ; Breast ; pathology ; Cross-Sectional Studies ; Early Detection of Cancer ; Female ; Humans ; Hyperplasia ; Male ; Neoplasms ; diagnosis ; Precancerous Conditions ; diagnosis ; Prostate ; pathology ; Thymidine Kinase ; blood

Objective: To analyze the related factors of postoperative complications after laparoscopic assisted D2 radical resection for advanced gastric cancer. Methods: From August 2015 to July 2017, 80 patients with advanced gastric cancer admitted to the First Hospital of Jiaxing were selected.All the patients were treated with laparoscopic-assisted D2 radical resection, and the risk factors related to postoperative complications were analyzed by logistic regression analysis model. Results: There were 33 cases (41.25%) with postoperative system complications, 19 cases (23.75%) with complications of level Ⅱ and above; 15 cases (18.75%) with postoperative local complications, among them 12 cases (15.00%) appeared level Ⅱ and above local complications.The number of concomitant diseases and age were related risk factors for systemic complications in patients with advanced gastric cancer after laparoscopic D2 radical resection (OR=1.982, 95%CI: 2.183-34.405, OR=6.587, 95%CI: 1.738-23.495, all P<0.05). The preoperative neoadjuvant chemotherapy, reconstruction method and age were the risk factors for local complications in patients with advanced gastric cancer after laparoscopic D2 radical resection (OR=8.273, 95%CI: 4.982-35.394, OR=12.304, 95%CI: 2.384-88.921, OR=6.365, 95%CI: 2.183-21.384, all P<0.05). Conclusion Treatment of advanced gastric cancer patients with laparoscopic D2 radical mastectomy, attention should be paid to control the patients' age, preoperative neoadjuvant chemotherapy, reconstruction mode, associated disease and other related risk factors.In order to ensure the safety of patients and to avoid postoperative complications.

Objective: To discuss the application of three dimentional(3D)visualization technologies in treatment plan of hepatic malignant tumor. Methods: The clinical data of 300 patients with liver malignant tumor who received treatment from January 2016 to January 2017 in the Third Department of Hepatic Surgery of Eastern Hepatobiliary Surgery Hospital was retrospectively analyzed in this study, including 221 male and 79 female patients aged from 7 to 76 years with median age of 54 years. The median height was 168 cm (115-183 cm), the median weight was 65 kg (20-105 kg) and the median tumor volume was 142 ml (23-2 493 ml). Three-dimensional visualization technology was used in all patients to reconstruct liver three-dimensional graphics. Also, two and three-dimensional methods were taken respectively to evaluate patients and develop treatment strategy. The change of treatment strategy caused by 3D evaluation, actual surgical plan, operation time, time of hepatic vascular occlusion, intraoperative blood loss, volumes of blood transfusion and postoperative complications was observed. Results: After three-dimensional visualization technology was applied, 75(25%) of 300 patients′ treatment strategies had been changed. The range of hepatectomy was extended in 25 patients. And 7 of them were due to hepatic venous variation, which resulted in increasing drainage area. In other 4 patients, liver resections were extended due to lack of perfusion of the liver parenchyma after the removal of portal vein. And hepatectomy was expanded in 14 patients in order to increase the surgical margin. The range of hepatectomy was reduced in 8 patients, 4 of which were due to hepatic venous variation, such as hepatic vein of segment 4 or lower right posterior hepatic vein. The remaining 4 cases were because of insufficient residual liver volume.The surgical resection was performed in 278 cases, 257 of which received operation directly. Left hepatectomy was performed in 24 patients and right hepatectomy was performed in 33 patients. Left trisectionectomy was carried out in 12 patients and right trisectionectomy was carried out in 11 patients. Caudate lobectomy was applied in 10 patients. There were 18 cases of left lateral sectionectomy, 7 cases of right anterior sectionectomy, 25 cases of right posterior sectionectomy and 18 cases of mesohepatectomy. Single or multi segment resection was performed in 99 patients. The treatment strategy of thirty-six patients was converted to staged hepatectomy (ALPPS 11 cases and portal vein embolization 25 cases). The median operation time was 130 minutes (90-360 minutes) and the median inflow blood occlusion time was 20 minutes (0-75 minutes). Median blood loss volume was 200 ml (20-1 600 ml). Thirty-seven of 278 patients received transfusions, and the average red blood transfusion volume was (4.4±1.7)units (0-8 units). Median hepatic resection volume was 530 ml(30-2 600 ml). There were 117 cases of pleural effusion after operation, including 3 patients needing invasive therapy. Ascites occurred in 23 patients, 6 of whom needed invasive therapy. Biliary leakage was observed in 30 patients. Eight patients occurred hepatic cutting surface hemorrhage, 6 of whom received blood transfusion, and 4 of whom underwent laparotomy to stop bleeding. Three patients had pulmonary infection after surgery and 3 patients appeared biliary obstruction. Deep vein thrombosis took place in 2 patients and portal vein thrombosis was observed in 4 patients. No postoperative liver failure and death ever happened in our study group. Conclusion Three-dimensional visualization technique can optimize the treatment strategy of patients with liver malignant tumor, improve surgical safety.

BACKGROUND:It is known that N6-methyladenosine(m6A)plays a role in the pathogenesis of various diseases and studies have suggested its involvement in the pathologic changes of steroid-induced femoral head necrosis(SNFH).However,research on m6A methylation modifications in steroid-induced femoral head necrosis is limited. OBJECTIVE:Using bioinformatics methods to identify the differential expression of m6A-related genes in steroid-induced femoral head necrosis and to predict miRNAs associated with these genes to further elucidate the role and mechanism of m6A methylation in steroid-induced femoral head necrosis. METHODS:Differential gene expression between steroid-induced femoral head necrosis and control groups was analyzed using GSE123568 gene expression data and identified using the"limma"package in R.Functional enrichment analysis was performed on the differentially expressed genes.Differential analysis of the related genes was carried out using the"ggstatsplot"package in R.The differential genes were cross-validated using the GSE74089 dataset.An mRNA-miRNA regulatory network was constructed,and co-expression analysis was performed on the module genes followed by enrichment analysis.Differences in immune cell infiltration between steroid-induced femoral head necrosis and control groups were quantified using the ssGSEA method. RESULTS AND CONCLUSION:Correlation analysis revealed 13 m6A-related genes,and further analysis through the protein-protein interaction network identification and receiver operating characteristic curve analysis showed that YTHDF2 was expected to be a core differential gene as a potential early biomarker.Enrichment analysis indicated that differentially expressed genes were mainly involved in inflammation and immune response and were closely related to osteoclasts.Cross-validation analysis showed that differential gene expression results between the two datasets were consistent.mRNA-miRNA regulatory network analysis revealed that YTHDF2 was negatively correlated with miRNA-27a.Immune infiltration analysis revealed an increase in immune cell infiltration in steroid-induced femoral head necrosis,and YTHDF2 was positively correlated with the infiltration of CD4+T cells.To conclude,m6A-related gene YTHDF2 can serve as a potential biomarker of steroid-induced femoral head necrosis and is valuable for the early clinical diagnosis and treatment of steroid-induced femoral head necrosis.The negative correlation between YTHDF2 and mir-27a and the positive correlation between YTHDF2 and CD4+T cell infiltration provide new insights into the early diagnosis and treatment of steroid-induced femoral head necrosis and shed light on the mechanism of m6A in steroid-induced femoral head necrosis.

Objective:To investigate the efficacy of the nomogram model based on multiparametric MRI combined with clinical features for differential diagnosis of benign and malignant breast imaging reporting and data system (BI-RADS) 4 lesions.Methods:This study was a cross-sectional study. Clinical and imaging data of 56 patients (66 lesions) with pathologically confirmed BI-RADS 4 breast lesions from January 2020 to June 2022 at Second Affiliated Hospital of Shantou University Medical College were retrospectively analyzed. The patients were all females aged 42 (17, 71) years old. All patients underwent the breast MRI, including T 1WI, T 2WI, diffusion-weighted imaging, diffusion kurtosis imaging (DKI), and dynamic-enhanced MRI (DCE-MRI), and the patient clinical characteristics, imaging characteristics as well as relevant MRI quantitative parameters were recorded. Comparisons of the indicators of benign and malignant BI-RADS 4 lesions were performed by sample t-test , Mann-Whitney U, or χ 2 test. The least absolute shrinkage and selection operator regression was utilized to further select indicators with statistically significant differences in univariate analyses, and finally, nomogram models were constructed and reclassified all the lesions. Results:Of the 66 lesions in 56 patients, 24 lesions were found in 24 malignant patients and 42 lesions in 32 benign patients. The differences in age, body mass index, and menopausal status between benign and malignant patients were statistically significant (all P<0.05); the differences in tumor longest diameter, type of lesion enhancement, time-single intensity curve type, mean diffusivity and mean kurtosis (MK) between benign and malignant lesions were statistically significant (all P<0.05). After feature selection, MK ( OR=27.952, 95% CI 1.301-600.348, P=0.033), age ( OR=1.140, 95%CI 1.040-1.249, P=0.005), and the type of lesion enhancement ( OR=0.045, 95%CI 0.006-0.316, P=0.005) were the independent influences in predicting BI-RADS 4 malignant lesions. Using this to construct a nomogram model, its area under the curve for predicting BI-RADS 4 malignant lesions was 0.946, and the accuracy of reclassifying 66 BI-RADS 4 lesions as benign versus malignant was 86.36% (57/66). Conclusion:The nomogram model constructed with MK from DKI parameters, the type of lesion enhancement from DCE-MRI, and age is valuable in diagnosing the benign and malignant nature of BI-RADS 4 lesions.

In recent years, modeling and simulation technology based on pharmacometrics has received increasing attention in the development of innovation drugs. In August of 2021, FDA issued a guidance named Pharmacokinetic-Based Criteria for Supporting Alternative Dosing Regimens of Programmed Cell Death Receptor-1 (PD-1) or Programmed Cell Death-Ligand 1 (PD-L1) Blocking Antibodies for Treatment of Patients with Cancer Guidance for Industry, claiming the necessity of using population PK-based simulation method for the optimization of dosing regimens, and the corresponding implementation standards. This article first summarized the existing therapeutic regimens of PD-1/PD-L1 blocking antibodies in clinic as well as the main content of the guidance, and then cited some actual examples where population PK-based simulation method did contribute to the approval of the alternative dosing regimens. Besides, some critical considerations for the dosing regimen optimization of PD-1/PD-L1 blocking antibodies were also analyzed. In our view, this guidance would have positive impacts on the development of PD-1/PD-L1 blocking antibodies in the future. We hope that this article may provide some references for the colleagues in China.