Objective:To investigate the impact of Tumor-Infiltrating Lymphocytes (TILs) density in the tumor stroma on the long-term prognosis of hepatocellular carcinoma (HCC) liver transplant patients meeting the Hangzhou criteria.Methods:This study is a retrospective cohort study. The clinical data of 83 patients with hepatocellular carcinoma who met the Hangzhou criteria and underwent allogeneic liver transplantation from January 2018 to December 2023 in the Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital affiliated to Capital Medical University were collected and analyzed. Hematoxylin and Eosin (HE) staining was used to study the density of TILs in the resected liver grafts. Patients were divided into TILs-negative group (TILs<10%, n=31) and TILs-positive group (TILs≥10%, n=52) based on whether the TILs density exceeded 10%. Clinical and pathological characteristics were analyzed, and the significance of alpha-fetoprotein (AFP), TILs density, and microvascular invasion on the prognosis of HCC patients who met the Hangzhou criteria was studied. Measurement data with normal distribution were expressed as mean±standard deviation ( ± s) and compared between groups using t-test. Measurement data with skewed distribution were expressed as M ( Q1, Q3) and compared using rank-sum tests. Categorical data were compared using chi-square test. Kaplan-Meier method was used to study the relationship between various observation indicators and overall survival, and survival curves were plotted. Log-rank test was used to compare the survival rates between groups, and multivariate Cox regression model was used to adjust for the distribution of risk factors between groups. Results:The preoperative AFP level in the TILs-negative group was (15.69±1.21) U/mL, and in the TILs-positive group was (12.17±0.13) U/mL, with a statistically significant difference between the two groups ( P<0.05). In the TILs-negative group, 8 cases had microvascular invasion, and the number of low, moderate, and high differentiation tumors was 8, 23, and 0, respectively. In the TILs-positive group, 3 cases had microvascular invasion, and the number of low, moderate, and high differentiation tumors was 2, 31, and 19, respectively. The results indicated that patients in the TILs-negative group were more likely to have microvascular invasion and poorer tumor differentiation ( P<0.05). All patients were regularly followed up, and the 1-, 2-, and 3-year survival rates in the TILs-negative group and TILs-positive group were 84.0%, 77.6%, 69.8%, and 94.7%, 91.7%, 86.6%, respectively ( P<0.01). Cox proportional hazards model indicated that microvascular invasion ( RR=4.474, 95% CI: 1.172-17.072, P=0.028) and TILs-negative status ( RR=5.081, 95% CI: 1.420-18.184, P=0.012) were independent risk factors for the long-term prognosis of HCC patients who met the Hangzhou criteria. Conclusions:Among HCC patients meeting the Hangzhou criteria, the density of TILs in the tumor stroma is related to AFP levels, tumor differentiation, and the presence of microvascular invasion. TILs-negative status indicates a poorer prognosis for these patients.

Objective:To observe the effect of acupuncture in the treatment of accommodative myopia in children.Methods:A total of 76 children with accommodative myopia who met the inclusion criteria were divided into a control group or a test group according to the random number table method,with 38 cases in each group.The control group was given education on eye hygiene,and the test group was treated with acupuncture twice a week for 2 months in addition to the intervention used in the control group.The patient's uncorrected visual acuity(UCVA),refraction,and axial length(AL)were measured before treatment and 1 month and 2 months after treatment.Results:After 1 month of treatment,there was no significant difference in the UCVA between the two groups(P＞0.05);after 2 months of treatment,the UCVA of the test group was better than that of the control group(P＜0.05).After 1 and 2 months of treatment,the refraction of the two groups was significantly different from that before treatment(P＜0.01),but there was no significant difference between the two groups(P＞0.05).After 1 and 2 months of treatment,the AL in the control group was increased compared with that before treatment(P＜0.05),while there was no significant change in the test group(P＞0.05),and there was no significant difference between the two groups(P＞0.05).Conclusion:Acupuncture treatment can improve UCVA in children with accommodative myopia.

P2X7 receptor is an ion channel receptor with adenosine triphosphate (ATP) as its ligand, which is widely expressed in various immune cells and tissues. Activated P2X7 receptor is involved in a variety of physiological and pathological processes. P2X7 receptor is abnormally expressed in colon cancer, and plays a duel role of cancer-promoting and cancer-suppressing in colon cancer progression. When P2X7 receptor is activated by extracellular ATP, it can effectively inhibit proliferation and induce apoptosis of colon cancer cells through various mechanisms. In addition, P2X7 receptor can also promote the growth, invasion and metastasis of colon cancer. Understanding the activation of P2X7 receptor and its effect mechanism is of great significance for the treatment of colon cancer.

Objective:To identify new prognostic markers and therapeutic targets for gastric adenocarcinoma.Methods:The public datasets of gastric adenocarcinoma collected from GEO database (GSE33335 and GSE63089) were downloaded for analysis. There were 70 GC tissues and paired normal tissues in the two profile datasets. Differentially expressed genes (DEGs) between GC tissues and normal stomach tissues were selected by the R software. Protein-protein interaction (PPI) of these DEGs were visualized by the Search Tool for the Retrieval of Interacting Genes (STRING). The key gene sets were analyzed by Cytoscape and Molecular Complex Detection (MCODE). The mRNA and protein expression levels of prognosis related genes identified by public database were confirmed by using GC tissues and paired normal tissues collected from July 2019 to September 2019 in Affiliated Hospital of Nantong University.Results:DEGs were identified in the two datasets by using R software. A total of 128 DEGs were detected, including 85 up-regulated genes ( log2FC>1.2 and FDR<0.01) and 43 down-regulated genes ( log2FC<-1.2 and FDR<0.01) in the GC tissues. PPI network model and MCODE model were established by using the Online String tool and Cytoscape software, and 27 key genes were obtained, including 25 genes related with prognosis of GC patients ( P<0.05). We identified 14 significant DEGs in GC tissues, including cyclin B1 (CCNB1), polo-like kinase 1 (PLK1) and pituitary-tumor transforming gene (PTTG1), which were significantly enriched in the cell cycle pathway through KEGG pathway enrichment analysis. The positive expression rate of PTTG1 in GC tissues was 68.8% (22/32), significantly higher than 18.8% (6/32) in normal gastric tissues ( P<0.05). Conclusions:The expression of PTTG1 is different in GC and gastric tissues, implicates it is the key gene in gastric carcinogenesis. The prognoses of GC patients with higher PTTG1 expression are worse. PTTG1 might participate in the development of gastric adenocarcinoma by regulating cell cycle.

Objective:To identify new prognostic markers and therapeutic targets for gastric adenocarcinoma.Methods:The public datasets of gastric adenocarcinoma collected from GEO database (GSE33335 and GSE63089) were downloaded for analysis. There were 70 GC tissues and paired normal tissues in the two profile datasets. Differentially expressed genes (DEGs) between GC tissues and normal stomach tissues were selected by the R software. Protein-protein interaction (PPI) of these DEGs were visualized by the Search Tool for the Retrieval of Interacting Genes (STRING). The key gene sets were analyzed by Cytoscape and Molecular Complex Detection (MCODE). The mRNA and protein expression levels of prognosis related genes identified by public database were confirmed by using GC tissues and paired normal tissues collected from July 2019 to September 2019 in Affiliated Hospital of Nantong University.Results:DEGs were identified in the two datasets by using R software. A total of 128 DEGs were detected, including 85 up-regulated genes ( log2FC>1.2 and FDR<0.01) and 43 down-regulated genes ( log2FC<-1.2 and FDR<0.01) in the GC tissues. PPI network model and MCODE model were established by using the Online String tool and Cytoscape software, and 27 key genes were obtained, including 25 genes related with prognosis of GC patients ( P<0.05). We identified 14 significant DEGs in GC tissues, including cyclin B1 (CCNB1), polo-like kinase 1 (PLK1) and pituitary-tumor transforming gene (PTTG1), which were significantly enriched in the cell cycle pathway through KEGG pathway enrichment analysis. The positive expression rate of PTTG1 in GC tissues was 68.8% (22/32), significantly higher than 18.8% (6/32) in normal gastric tissues ( P<0.05). Conclusions:The expression of PTTG1 is different in GC and gastric tissues, implicates it is the key gene in gastric carcinogenesis. The prognoses of GC patients with higher PTTG1 expression are worse. PTTG1 might participate in the development of gastric adenocarcinoma by regulating cell cycle.

Objective To investigate influencing factors of serum small and dense low-density lipoprotein cholesterol (sd LDL-C) levels in patients with chronic diseases in Zhoujiadu community, and to provide a scientific basis for the treatment of sd LDL-C related chronic diseases. Methods A total of 200 patients with common chronic diseases who were admitted to our hospital from November 2017-November 2019 were selected. Basic data including height, weight, past medical history and family history of the patients were collected. Biochemical indicators were measured to understand dietary structure. The influencing factors of serum sd LDL-C were analyzed by multiple stepwise regression. Results The levels of serum sd LDL-C in patients with advanced age, increased BMI, thickened IMT, fatty liver and coronary heart disease were significantly increased (P<0.05). Pearson linear correlation analysis showed that serum sd LDL-C level of patients with chronic diseases was positively correlated with TC, TG, LDL, ALT and AST, and negatively correlated with HDL (P<0.05). Multiple linear regression showed that TG, BMI, IMT, fatty liver, oil heating (frying and frying) and the use of mixed oil were independent risk factors of sd LDL-C level in patients with common chronic diseases, while HDL-C was a protective factor (P<0.05). Conclusion The levels of serum sd LDL-C in patients with common chronic diseases in Zhoujiadu community were correlated with dyslipidemia, BMI, thickening of IMT, fatty liver, oil heating (frying and frying), and use of mixed oil.

G protein-coupled receptors (GPCRs) are membrane receptors whose agonist-induced dynamic conformational changes trigger heterotrimeric G protein activation, followed by GRK-mediated phosphorylation and arrestin-mediated desensitization. Cytosolic regions of GPCRs have been studied extensively because they are direct contact sites with G proteins, GRKs, and arrestins. Among various cytosolic regions, the role of helix 8 is least understood, although a few studies have suggested that it is involved in G protein activation, receptor localization, and/or internalization. In the present study, we investigated the role of helix 8 in dopamine receptor signaling focusing on dopamine D1 receptor (D1R) and dopamine D2 receptor (D2R). D1R couples exclusively to Gs, whereas D2R couples exclusively to Gi. Bioinformatic analysis implied that the sequences of helix 8 may affect GPCR-G protein coupling selectivity; therefore, we evaluated if swapping helix 8 between D1R and D2R changed G protein selectivity. Our results suggest that helix 8 is not involved in D1R-Gs or D2R-Gi coupling selectivity. Instead, we observed that D1R with D2R helix 8 or D1R with an increased number of hydrophobic residues in helix 8 relative to wild-type showed diminished β-arrestin-mediated desensitization, resulting in increased Gs signaling.
Arrestin ; Arrestins ; Computational Biology ; Cytosol ; Dopamine ; Family Characteristics ; GTP-Binding Proteins ; Membranes ; Phosphorylation ; Receptors, Dopamine D1 ; Receptors, Dopamine D2 ; Receptors, Dopamine

OBJECTIVE:To provide reference for promoting the rational use of Dexamethasone sodium phosphate injection in the clinic. METHODS:Special comment criteria and evaluation rules was formulated,medical records of 1273 inpatients receiving Dexamethasone sodium phosphate injection were collected from our hospital during Jul. 2014-Jun. 2015. Rationality of drug use was evaluated and analyzed retrospectively. RESULTS:The most use amount and case number of Dexamethasone sodium phosphate injection were in the departments of blood/oncology,obstetrics,emergency minimally invasive surgery,gastrointestinal surgery,emergency trauma of orthopedics and thyroid breast surgery;while much less were in departments of new pediatrics, infection and rehabilitation. There were 138 cases of irrational use of Dexamethasone sodium phosphate injection found in special comment, and the total irrational use rate was 10.84％ . The types of irrational use included inappropriate indication (contraindication,59.42％),inappropriate drug combination(18.84％),inappropriate drug selection (15.94％),inappropriate usage and dosage(3.62％)and inappropriate drug dosage forms or drug delivery methods(2.17％),etc. The irrational use rate of Dexamethasone sodium phosphate injection monthly declined steadily by month from 30.35％ in Jul. 2014 to 7.81％ in Jun. 2015 through the special comment;then a consensus of 5 points for the drug use formed in our hospital. CONCLUSIONS:There are irrational situations in the clinical use of Dexamethasone sodium phosphate injection in our hospital,especially in the cases of inappropriate indications. The rationality of the drug can be improved by the development of the special comment. This work should continue to be carried out in the future and perfected.

Objective To analyze of the effect of artificial lengthening femoral head replacement in elderly patients with stage Ⅰ of unstable femoral intertrochanteric fracture.Methods 203 patients with stage Ⅰ of unstable femoral intertrochanteric fracture were selected as the research object,and they were taken artificial lengthening femoral head replacement,among which 65caese were male,female in 138 cases.The Harris scoring,SF-36,VAS pain scores on admission,2 weeks after operation,postoperative follow-up limb were counted,and the pain of the affected limb and the hip scores were compared amond 3 time periods.Results All 203 cases of senile patients with follow-up,average operation time was 83.64 minutes,the intraoperative blood loss was 355.41mL.The curative effect was evaluated according to the Harris score,SF-36 and VAS pain scoring criteria,and the Harris scores of the affected limbs at admission,at 2 weeks after the operation and after the follow-up were (28.26 ± 5.50) points,(68.26 ±5.50) points,(93.13 ± 5.31) points,respectively,the differences were statistically significant (t =-71.27,-1 397.55,-46.07,all P ＜ 0.01);The VAS pain scores were (8.19 ± 0.48) points,(3.53 ± 0.71) points,(0.23 ± 0.42) points,respectively,the differences were statistically significant (t =88.06,324.17,60.84,all P ＜ 0.01).The sf-36 scores:physiological [(8.35 ± 1.24) points,(15.23 ± 2.17) points,(19.21 ± 2.12) points],social/family [(7.01 ±1.13) points,(14.12 ± 2.12) points,(19.85 ± 2.24) points],emotional [(4.83 ± 1.01) points,(10.12 ±1.22)points,(14.87 ± 1.32) points],function [(6.35 ± 1.21) points,(13.67 ± 1.87) points,(16.81 ±2.12) points],additional focus [(8.85 ± 1.45) points,(16.38 ± 2.12) points,(20.21 ± 2.42) points],total quality of life [(47.35 ± 4.76) points,(74.69 ± 5.87) points,(89.21 ± 6.12) points],the differences were statistically significant(-39.77,-62.92,-20.21,-44.87,-71.89,-26.79,-45.04,-89.01,-38.25,-45.79,-63.41,-15.29,-45.20,-60.39,-17.54,-52.12,-76.49,-22.58,all P＜0.O1).Conclusion Artificial lengthening femoral head replacement in elderly patients with stage Ⅰ of unstable femoral intertrochanteric fracture has good clinical effect,intraoperative high safety,less postoperative complications,postoperative limb functional recovery is good,and it is worthy of clinical promotion and application.

Objective To detect miR-181d expression levels in colon cancer cell lines,and to study the functions of miR-181d on colon cancer cell proliferation and apoptosis.Methods RT qPCR was employed to study miR-181d cxpression levels in colon cancer cell line HCT116,HT29,LoVo,SW480 and SW620 cells,as well as in colon normal epithelial cell line HIEC.miR-181d mimic and control were transfected into LoVo cells while miR-181d inhibitor and control were transfected into SW620 cells.qRT-PCR was performed to validate the transfection efficiency.MTT assay was performed to measure cell proliferation while flow cytometry was performed to detect cell cycle and apoptosis rate.Results miR-181d was universally downregulated in all colon cancer cell lines compared to the colon normal epithelial cell line HIEC (F=29.34,P＜0.01).Overexpression of miR-181d in LoVo cells significantly decreased in vitro cell proliferation rate (F=5.403,P＜0.01).Flow cytometry indicated that cells at S phase were greatly decreased (t=4.71,P＜0.05) and apoptotic cells were gready increased compared to the control cells (t=3.47,P＜0.05).On the contrary,inhibition of miR-181d in SW620 cells significantly promoted cell proliferation (F=20.82,P＜0.01).Cell cycle was accelerated with significant increase in S phase compared to the control cells (t=2.92,P＜0.05),whereas apoptosis rano was significantly decreased (t=4.14,P＜0.05).Conclusion miR-181d was universally downregulated in colon cancer cell lines compared to the normal epithelial cell line.miR-181d inhibits cell proliferation and induces apoptosis,thus functions as an tumor suppressive miRNA.