Background and purpose:Plasmacytoid dendritic cells are one of the key immune cells in the tumor microenvironment(TME),which can directly or indirectly regulate tumor related immune responses and play multiple roles in the development and metastasis of tumors.This study aimed to investigate the correlation between plasmacytoid dendritic cells in lymph nodes and lymph node metastasis in patients with advanced gastric cancer.Methods:Postoperative lymph node tissue specimens and clinicopathological data from advanced gastric cancer patients who underwent D2 radical surgery in the Department of General Surgery at the First Hospital of Dandong were gathered from January 2019 to December 2023.The lymph nodes were grouped based on pTNM staging and the diameter of metastatic lesions.This study was approved by the Medical Ethics Committee of Dandong First Hospital(No.DDSDYYY-LLSC-2025-02-18-019-01),and all patients signed informed consents.Immunohistochemical staining was used to detect the expression levels of CD123-positive plasmacytoid dendritic cells in different lymph node groups,and their correlation with lymph node metastasis in advanced gastric cancer was further analyzed.Results:Of the 116 patients,plasmacytoid dendritic cells infiltrate the lymph node tissues of gastric cancer patients.As tumor differentiation decreased and pT stage,pathological stage,lymphatic/vascular invasion,and perineural invasion increased,the mean number of CD123-positive pDC in metastatic lymph nodes rose significantly(P＜0.05).The number of CD123-positive plasmacytoid dendritic cells was higher in metastatic lymph node-positive tissues than in metastatic lymph node-negative tissues,the number was higher in the macrometastasis group of pN1-3 staging than in the micrometastasis group,and the number was higher in the non-metastatic lymph node group of pN1-3 staging than in the pN0 staging lymph node group(P＜0.05).In lymph node metastasis-positive cases,the number of CD123-positive plasmacytoid dendritic cells was higher in second-station lymph nodes than in first-station lymph nodes(P＜0.05).Conclusion:The infiltration of CD123-positive plasmacytoid dendritic cells in lymph nodes of patients with advanced gastric cancer is closely associated with lymph node metastasis and may serve as a prerequisite for metastatic spread.Understanding the distribution of CD123-positive plasmacytoid dendritic cells in gastric cancer lymph nodes can help further explore their role in the immune microenvironment of gastric cancer.Targeted therapy focusing on CD123-positive plasmacytoid dendritic cells may become a new strategy for the treatment of advanced gastric cancer.

Background and purpose:Plasmacytoid dendritic cells are one of the key immune cells in the tumor microenvironment(TME),which can directly or indirectly regulate tumor related immune responses and play multiple roles in the development and metastasis of tumors.This study aimed to investigate the correlation between plasmacytoid dendritic cells in lymph nodes and lymph node metastasis in patients with advanced gastric cancer.Methods:Postoperative lymph node tissue specimens and clinicopathological data from advanced gastric cancer patients who underwent D2 radical surgery in the Department of General Surgery at the First Hospital of Dandong were gathered from January 2019 to December 2023.The lymph nodes were grouped based on pTNM staging and the diameter of metastatic lesions.This study was approved by the Medical Ethics Committee of Dandong First Hospital(No.DDSDYYY-LLSC-2025-02-18-019-01),and all patients signed informed consents.Immunohistochemical staining was used to detect the expression levels of CD123-positive plasmacytoid dendritic cells in different lymph node groups,and their correlation with lymph node metastasis in advanced gastric cancer was further analyzed.Results:Of the 116 patients,plasmacytoid dendritic cells infiltrate the lymph node tissues of gastric cancer patients.As tumor differentiation decreased and pT stage,pathological stage,lymphatic/vascular invasion,and perineural invasion increased,the mean number of CD123-positive pDC in metastatic lymph nodes rose significantly(P＜0.05).The number of CD123-positive plasmacytoid dendritic cells was higher in metastatic lymph node-positive tissues than in metastatic lymph node-negative tissues,the number was higher in the macrometastasis group of pN1-3 staging than in the micrometastasis group,and the number was higher in the non-metastatic lymph node group of pN1-3 staging than in the pN0 staging lymph node group(P＜0.05).In lymph node metastasis-positive cases,the number of CD123-positive plasmacytoid dendritic cells was higher in second-station lymph nodes than in first-station lymph nodes(P＜0.05).Conclusion:The infiltration of CD123-positive plasmacytoid dendritic cells in lymph nodes of patients with advanced gastric cancer is closely associated with lymph node metastasis and may serve as a prerequisite for metastatic spread.Understanding the distribution of CD123-positive plasmacytoid dendritic cells in gastric cancer lymph nodes can help further explore their role in the immune microenvironment of gastric cancer.Targeted therapy focusing on CD123-positive plasmacytoid dendritic cells may become a new strategy for the treatment of advanced gastric cancer.

The efficient clinical treatment of oral squamous cell carcinoma(OSCC)is still a challenge that demands the development of effective new drugs.Phenformin has been shown to produce more potent anti-tumor activities than metformin on different tumors,however,not much is known about the influence of phenformin on OSCC cells.We found that phenformin suppresses OSCC cell proliferation,and promotes OSCC cell autophagy and apoptosis to significantly inhibit OSCC cell growth both in vivo and in vitro.RNA-seq analysis revealed that autophagy pathways were the main targets of phenformin and identified two new targets DDIT4(DNA damage inducible transcript 4)and NIBAN1(niban apoptosis regulator 1).We found that phenformin significantly induces the expression of both DDIT4 and NIBAN1 to promote OSCC autophagy.Further,the enhanced expression of DDIT4 and NIBAN1 elicited by phenformin was not blocked by the knockdown of AMPK but was suppressed by the knockdown of transcription factor ATF4(activation transcription factor 4),which was induced by phenformin treatment in OSCC cells.Mechanistically,these results revealed that phenformin triggers endoplasmic reticulum(ER)stress to activate PERK(protein kinase R-like ER kinase),which phosphorylates the transitional initial factor eIF2,and the increased phosphorylation of eIF2 leads to the increased translation of ATF4.In summary,we discovered that phenformin induces its new targets DDIT4 and especially NIBAN1 to promote autophagic and apoptotic cell death to suppress OSCC cell growth.Our study supports the potential clinical utility of phenformin for OSCC treatment in the future.

Objective:To observe the clinical efficacy of mouse nerve growth factor (mNGF) combined with rehabilitation on children with global developmental delay(GDD).Methods:It was a prospective multicenter clinical randomized controlled trial (RCT) involving 120 children with GDD admitted to 5 hospitals in China from May 2020 to January 2022.They were randomly divided into mNGF group and conventional rehabilitation group using block randomization method.All children were managed by standardized rehabilitation after recruitment, and those in the mNGF group were additionally given mNGF injections.All subjects were surveyed using the Gesell Development Diagnosis Schedules(GDDS) at baseline, 90 days and 120 days after treatment, and their developmental quotient (DQ) was recorded.Clinical efficacy was analyzed by the paired t-test, rank sum test and Chi- squared test. Results:After 90 days of treatment and the continuous follow-up to 120 days, the increases in the DQ of gross motor (7.520±13.900 vs.0.450±11.459), fine motor (7.800±15.346 vs.1.250±11.581), adaptive behavior (7.730±13.428 vs.2.100±12.022) and personal-social behavior (6.780±11.651 vs.1.780±10.120) than baseline were significantly higher in mNGF group than those of conventional rehabilitation group (all P<0.05). Serious adverse events and important drug-related medical events were not reported. Conclusions:mNGF combined with rehabilitation effectively enhances the development levels of gross motor, fine motor, adaptive behavior and personal-social behavior, and continuously improves the condition of GDD in children with a high safety.

Objective:To analyze the clinical, imaging and pathological characteristics of pleomorphic xanthoastrocytoma (PXA), and to explore the effective treatment of PXA.Methods:A total of 25 patients with PXA admitted to our hospital from July 1, 2012 to December 1, 2019 were chosen in our study. Their clinical manifestations, imageology features, pathology features, treatments, and prognoses were retrospectively analyzed.Results:Headache ( n=12) and epilepsy ( n=8) were the most common first symptoms in 25 patients. The tumors in 8 patients were located in the parietal lobe, 6 were in the temporal lobe, and 6 were in the frontal lobe. Among the pathological results, the average positive rate of cell proliferation antigen Ki-67 and P53 in patients with WHO grading II was 6.4% and 21.2%, respectively; the average positive rate of Ki-67 and P53 in patients with WHO grading III was 22.2% and 48.3%, respectively. Synaptophysin protein was confirmed in 12 of the 15 patients. Twenty patients were followed up for 31 months after surgery; 19 survived; 9 had no tumor recurrence or residue, including 8 with WHO grading II and one with WHO grading III. Conclusion:Pathological result play an important role in PXA diagnosis; the prognosis of patients with WHO grading II is obviously better than that of patients with WHO grading III.

The incidence rate of biliary tract cancer is increasing year by year. Systemic therapy is the most important treatment for patients with advanced or unresectable biliary tract cancer. Gemcitabine combined with cisplatin is still the standard first-line chemotherapy, while gemcitabine combined with TS-1 and gemcitabine combined with nab-paclitaxel are also the first-line treatment options. Studies have confirmed that immunotherapy as a back-line treatment has a significant advantage in survival, and the disease control rate of nivolumab is 61% and the median overall survival is more than 1 year. In addition, targeted drugs targeting FGFR2, IDH1/2, HER-2 and other major driving genes of biliary tract cancer also show good antitumor activity, and become research hotspots in the treatment of advanced biliary tract cancer. Summarizing the research progress of systematic chemotherapy, immunotherapy and molecular targeted therapy for advanced biliary tract cancer can provide help for clinical practice.

Objective: To investigate the expressions of hypoxia inducible factor-1α (HIF-1α) and autophagy related protein Beclin-1 in colon cancer and their clinical significances. Methods: From January 2017 to December 2018, 120 patients with colon cancer who were admitted to Dandong First Hospital were selected. The expressions of HIF-1α and Beclin-1 in colon cancer and corresponding adjacent tissues were detected by immunohistochemical SABC method. The relationship of the expressions of HIF-1α and Beclin-1 with the clinicopathological features of colon cancer patients was also discussed. The expressions of HIF-1α and Beclin-1 in 20 pairs of fresh colon cancer and paracancerous tissues were detected by Western blot. Results: The results of immunohistochemistry showed that the positive expression rates of HIF-1α and Beclin-1 proteins in colon cancer tissues were significantly higher than those in paracancerous tissues [75.0% (90/120) vs. 21.7% (26/120), 60.8% (73/120) vs. 12.5% (15/120)], and the differences were statistically significant (χ ² values were 68.343 and 60.359, both P < 0.01). The results of Western blot showed that the expressions of HIF-1α and Beclin-1 proteins in 20 pairs of fresh colon cancer tissues were significantly higher than those in paracancerous tissues (1.98±0.66 vs. 0.76±0.55, 1.50±0.40 vs. 0.46±0.35), and the differences were statistically significant (t values were 6.912 and 8.315, both P < 0.01). The expressions of HIF-1α and Beclin-1 in colon cancer tissues were related to TNM stage, degree of differentiation, depth of infiltration, lymph node metastasis and nerve invasion (HIF-1α: χ ² values were 9.074, 15.215, 10.101, 11.610 and 9.979; Beclin-1: χ ² values were 11.285, 4.858, 24.436, 9.354 and 4.632; all P < 0.05), but not with age, sex, tumor location, tumor diameter and vascular tumor thrombus (all P > 0.05). There was a positive correlation between the expressions of HIF-1α and Beclin-1 proteins in colon cancer (r = 0.483, P < 0.01). Conclusion The expressions of HIF-1α and Beclin-1 proteins in colon cancer tissues are significantly increased, and the interaction between them is involved in the occurrence and development of colon cancer.

Objective To explore the efficacy of alprostadil combined with Bailing capsule in the treatment of early chronic kidney disease. Methods A total of 94 early stage chronic kidney disease patients were selected and divided into treatment group(n=46) and control group(n=48).The patients in control group were treated with Bailing capsule,5 capsules, tid,po.The patients in treatment group were treated with Bailing capsule combined with 2 mL alprostadil in 20 mL 0.9% sodium chloride injection,intravenous injection,qd.The patients were treated for 4 weeks as a course of treatment in both groups.After 2 courses of treatment,the improvement of renal function,the changes in cytokine levels including NK cells and T cell subsets CD+3, CD+4,CD+8,adverse reactions of two groups were observed. Results The effective rates of the control group and the treatment group were 60.42%,91.30%,respectively(P<0.05).The renal function index 24 h urine protein were(1.15± 0.35) g,serum creatinine were(78.52±10.63) μmol·L-1,urea nitrogen were(8.23±1.65) mmol·L-1,all of which were decreased significantly (P<0.05).The levels of NK cells were(21.89±2.73)%,T cell subsets CD+3were(71.02±5.61)%,CD+4were(38.84±3.52)%, CD+4/CD+8were(1.28 ± 0.14),which were increased significantly,while the level of CD+8were(30.21± 3.03)% was decreased significantly(P<0.05).There was no significant difference between two groups in the adverse reactions(P>0.05). Conclusion The combination of alprostadil and Bailing capsule is effective to early stage chronic kidney disease by improving the renal function and regulating the level of cytokines.

Objective To investigate the spiritual well-being (SWB) and perceived control (PC) in adult patients with heart failure (HF),and analyze the relationship between spiritual well-being and perceived control. Methods 125 patients with heart failure were surveyed with questionnaires by convenience sampling, including Control Attitudes Scale-Revised (CAS-R) and Memorial University of Newforndland Scale of Happiness (MUNSH). Results The mean score of the spiritual well-being was(6.34± 2.92), and the mean score of perceived control was (18.40±4.39). The patients’spiritual well-being was closely related to perceived control (P < 0.05). There was a positive correlation between the self-efficacy and the positive indicator of subjective well-being, r=0.46, negative correlation was between the self-efficacy and the negative indicator of subjective well-being, r=-0.17. There was a positive correlation between the locus of control and the positive indicator, r=0.38,while the negative correlation was between the locus of control and the negative indicator, r=-0.05. There was a negative correlation between the learned helpless and the positive indicator, r=-0.43, while the positive correlation was between the learned helpless and the negative indicator, r=0.06. Conclusions The spiritual well-being of patients is at a low level, as well as perceived control. The spiritual well-being of patients can be enhanced by means of improving the ability of perceived control.

Ubiquitin-proteasome pathway is one of the primary pathway in intracellular protein degrada-tion,therefore the ubiquitin conjugating enzyme D3(UbE2D3)which involved in the ubiquitin mineralization process can affect the biological effects accordingly to affect some protein and nucleic acid content and activity. The function that participate in modification and degradation of some cancer factors is vital in tumor cells,and followed by tumor biological behavior changing. Researches show that UbE2D3 correlates with human telomer-ase reverse transcriptase( hTERT),radiation sensitivity,aggressive,etc in breast cancer.