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.

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 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.

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.

Objective To investigate the effect of capsaicin on hepatic stellate cells (HSCs) and liver fibrogenesis.Methods HSCs were cultured.The reactive oxygen in HSCs under capsaicin at different concentrations was tested by DCFH-DA kit.The proliferation of HSCs was detected by CCK-8 test kit.Smoothmuscle α-actin (α-SMA) expression of HSCs was evaluated by Western blot.The fibrosisrelated genes were tested by RT-PCR.The apoptosis of HSCs was measured by flow cytometer.Bcl-2,bax and cyt-c was detected by Western blot.A murine model of liver fibrogenes was established.Capsaicin of different concentration was injected intraperitoneally.Liver pathology was observed using HE staining.Hydroxyproline content of liver and levels of collagen Ⅲ and hyaluronic acid in serum were tested.Results In dose dependent manner capsaicin inhibited the generation of the reactive oxygen species.Proliferation and activation of HSCs was inhibited by capsaicin (respectively F =13.267,57.392,all P ＜ 0.05) and the apoptosis of HSCs was promoted by capsaicin (F =235.571,P ＜ 0.05).Bax,cyt-c and caspase-3 was increased obviously (respectively F =29.334,38.274,138.329,all P ＜ 0.05).Capsaicin changed the expression of fibrosis-related genes (TGF-β1,TIMP-1) in HSCs (respectively F =376.534,253.751,all P ＜0.05).Capsaicin downregulated the level of hydroxyproline,collagen Ⅲ and hyaluronic acid in the rat model (respectively F =153.397,27.149,38.392,all P ＜ 0.05).Conclusions Capsaicin inhibits the proliferation and activation of hepatic stellate cells.Capsaicin promotes the apoptosis of hepatic stellate cells,and inhibits liver fibrogenesis.

Objective To compare the dosimetric parameters of volumetric modulated arc therapy(VMAT),fixed field intensity modulated radiation therapy(IMRT)and three-dimensional conformal radiotherapy(3D-CRT)in the radiotherapy for the patients with locally recurrent nasopharyngeal carcinoma, and to analyze their characteristics. Methods Twelve patients with locally recurrent nasopharyngeal carcinoma were treated with VMAT, IMRT and 3D-CRT plan designed by Pinnacle 9.2 and Preciseplan 2.03 treatment planning system.The dosimetric parameters of targeted volumes and organs at risk were compared between three groups. Results The conformation indexes (CI)of VMAT and IMRT plans were similar,and they were both better than 3D-CRT plan,the difference was significant(P<0.05).The homogeneity index(HI)in three groups were similar,there were no statistically significant differences between them(P>0.05).The monitor units(MU)and beam time in 3D-CRT group were better than those in other two groups,and VMRT group was better than IMRT group,the statistical differences were observed between three groups (P<0.05 ).There were no statistical differences of organs at risk such as brainstem and lens between three groups(P>0.05).The doses of the spinal cord,optic nerve,optic chiasm and temporal lobe of brain in VMAT and IMRT groups were better than those in 3D-CRT group,there were statistical differences between them(P<0.05),and the data in VMAT and IMRT groups were similar,and there were no statistical differences(P>0.05).Conclusion There are differences of the targeted dose distribution between the three kinds of radiation technology, while VMAT and IMRT plans can cover the targeted areas and reduce the received doses of organs at risk.The CI,MU and beam time of VMAT plan are better than those of IMRT plan. 3D-CRT plan only has advantage in the MU and beam time.