OBJECTIVES: To investigate the prognostic significance of PDZ-binding kinase (PBK) in pan-cancer and its potential as a therapeutic target for pancreatic cancer. METHODS: PBK expression levels were investigated in 33 cancer types based on data from TCGA, GEO and CPTAC databases. RT-PCR and Western blotting were employed to examine PBK expression in clinical pancreatic cancer specimens and cell lines. The diagnostic and prognostic value of PBK in pancreatic cancer was evaluated using survival analysis, Cox regression analysis, ROC curve analysis, and clinical correlation studies. Gene enrichment and immune correlation analyses were conducted to explore the potential role of PBK in tumor microenvironment, and its correlation with drug sensitivity was investigated using GDSC and CTRP datasets. In pancreatic cancer BXPC-3 cells, the effects of lentivirus-mediated PBK knockdown on cell proliferation, migration, and invasion were examined using CCK-8, colony formation, and Transwell assays. The interaction between PBK and non-SMC condensin II complex subunit G2 (NCAPG2) was analyzed using co-immunoprecipitation and Western blotting. RESULTS: PBK was overexpressed in multiple cancer types, including pancreatic cancer. A high PBK expression was associated with a poor prognosis of the patients and correlated with immune infiltration and alterations in the tumor microenvironment. Elevated PBK expression was positively correlated with the sensitivity to MEK inhibitors (Trametinib) and EGFR inhibitors (Afatinib) but negatively with the sensitivity to Bcl-2 inhibitors (TW37) and niclosamide. In BXPC-3 cells, PBK knockdown significantly suppressed NCAPG2 expression and inhibited cell proliferation, migration, and invasion. Co-immunoprecipitation confirmed a direct binding between PBK and NCAPG2. CONCLUSIONS PBK is a key regulator of pancreatic cancer and interacts with NCAPG2 to promote tumor progression, suggesting its value as a potential biomarker and therapeutic target for pancreatic cancer.
Humans ; Pancreatic Neoplasms/genetics* ; Prognosis ; Biomarkers, Tumor/genetics* ; Cell Line, Tumor ; Cell Proliferation ; Adenocarcinoma/metabolism* ; Tumor Microenvironment ; Cell Movement ; Mitogen-Activated Protein Kinase Kinases

OBJECTIVE To analyse the prognosis and laryngeal function retention of patients undergoing minimally invasive and open surgery after induction chemotherapy.METHODS The clinical data of 54 hypopharyngeal carcinoma patients who received induction chemotherapy and underwent laryngeal preservation surgery in Beijing Tongren Hospital from 2016 to 2022 were retrospectively analyzed.The laryngeal function recovery and survival rate were compared between the two groups.RESULTS Twenty-eight patients underwent transoral minimally invasive surgery and 26 patients underwent partial laryngectomy and/or partial laryngectomy via external cervical approach.The 3-year survival rates of the two groups were 63%and 59%,respectively,and the difference was not statistically significant(P＞0.05).The differences were statistically significant(P＜0.05).CONCLUSION In patients with downstaged hypopharyngeal carcinoma after induction chemotherapy,the survival rate of transoral minimally invasive surgery is similar to that of open surgery,and the laryngeal function recovery of transoral minimally invasive surgery is better.

ObjectiveTo investigate the effect of supplemented Buyang Huanwutang on kidney tissue， nuclear factor-κB （NF-κB） pathway， and fibrosis factors in diabetic kidney disease （DKD） mice. MethodA total of 24 db/db mice （11-12 weeks old） were randomized into the model group （equivalent volume of distilled water， once/day， 8 weeks）， supplemented Buyang Huanwutang group （16.0 g·kg^-1， once/day， 8 weeks）， and irbesartan group （13.5 mg·kg^-1， once/day， 8 weeks） after adaptive feeding for 1 week and positive urinary protein monitoring， with 8 in each group. Another 8 db/m mice （11-12 weeks old） were included in the normal group （equivalent volume of distilled water， once/day， 8 weeks）. Then samples were collected， and the levels of fasting blood glucose （FBG）， total cholesterol （TC）， triglyceride （TG）， blood urea nitrogen （BUN）， serum creatinine （SCr）， and urinary microalbumin （mALB） were detected. The mRNA expression of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and monocyte chemoattractant protein-1 （MCP-1） was determined by real-time polymerase chain reaction （Real-time PCR）. The expression of nuclear factor-κB （NF-κB）， NF-κB inhibitor α （IκBα）， phosphorylated IκBα （p-IκBα）， transforming growth factor-β₁ （TGF-β₁）， α-smooth muscle actin （α-SMA）， and fibronectin （FN） in kidney tissue was measured by Western blot. The expression of NF-κB in renal tissue was detected by immunofluorescence. The pathological changes of kidney were observed under light microscope. ResultCompared with the normal group， the model group showed glomerular hypertrophy， increase in extracellular matrix， thickening of basement membrane， small cystic lumen， interstitial inflammatory cell infiltration， and some interstitial fibrosis （P<0.01）. Moreover， the model group had higher content of FBG， mALB， TC， TG， BUN， and SCr （P<0.01）， higher expression of inflammatory factors TNF-α， IL-1β， and MCP-1， and fibrosis-related proteins TGF-β₁， α-SMA， and FN （P<0.01）， and stronger activation of NF-κB pathway in renal tissue （P<0.01） than the normal group. Compared with the model group， supplemented Buyang Huanwutang alleviated the pathological injury in kidney （P<0.01）， decreased the content of mALB， TC， and TG， the content of BUN and SCr （P<0.01）， and the content of TNF-α， IL-1β， and MCP-1 （P<0.05， P<0.01）， and inhibited the activation of NF-κB pathway and the expression of fibrosis factors in renal tissue （P<0.05， P<0.01）， but had no significant effect on blood glucose level. ConclusionBy inhibiting NF-κB pathway and the expression of fibrosis factors in renal tissue， supplemented Buyang Huanwutang can exert anti-inflammatory and anti-fibrosis effect and alleviate the pathological damage in kidney tissue， thereby protecting the kidney.

At present, there is still no stomatology specialty in the training system of clinical pharmacists in China and the relevant research is still blank. The development of stomatological clinical pharmacy is also slow due to the lack of clinical pharmacists. By analyzing the national oral health policies, the characteristics of oral diseases and the clinical needs of stomatology, this paper provides theoretical basis for the setting of clinical pharmacist training specialty of stomatology specialty in China. This paper also makes a preliminary discussion on the construction of the training system of clinical pharmacists in the specialty of stomatology, so as to provide advice and references for the design and specific plan of the training system in the specialty of stomatology.

Objective To evaluate the changes in myocardial glucose transporter 4 ( GLUT4 ) membrane translocation in the rats with high-level spinal cord injury ( SCI ) . Methods Thirty-six clean-grade healthy adult male Sprague-Dawley rats, weighing 250-300 g, were divided into 3 groups using a random number table method: control group (group C, n=6), sham operation group (group S, n=6) and high-level SCI group (group SCI, n=24). The model of SCI was established by a modified Allen's method in anesthetized rats. The spinal cord was only exposed in group S. Six rats were selected in C and S groups and at 4, 12, 24 and 48 h after SCI ( T1-4 ) in group SCI, and blood samples were taken from the abdominal aorta to measure the activities of serum creatine kinase and creatine kinase isoenzyme-MB. The rats were then sacrificed, and myocardial specimens were collected for microscopic examination of the ultra-structure ( with a transmission electron microscope) and for determination of ATP weight ratio, phosphoryla-tion of insulin receptor substrate-1 tyrosine and expression of GLUT4 in cell membrane ( by Western blot) . Results Compared with C and S groups, the serum creatine kinase and creatine kinase isoenzyme-MB ac-tivities were significantly increased at T1-4 , the ATP weight ratio was decreased, the expression of GLUT4 in myocardial cell membrane was down-regulated, the expression of phosphorylated insulin receptor sub-strate-1 tyrosine in myocaradium was down-regulated at T2,3 (P＜0. 05), and the pathological changes of myocardial tissues were found in group SCI. There was no significant difference in the indexes mentioned a-bove between group C and group S ( P＞0. 05) . Conclusion The mechanism of myocardial energy metabo-lism disorder may be related to the reduced membrane translocation of GLUT4 in the rats with high-level SCI.

Objective: To explore the association of the glycosylated hemoglobin (HbA1c) level at admission with 90 days functional outcome in patients with spontaneous intracerebral hemorrhage (ICH). Methods: Patients admitted to the Department of Neurology, Tongji Hospital from January to December 2017 were prospectively and continuously enrolled in this study. Clinical data were collected at admission and functional outcomes 90 days after ICH were assessed by using the modified RANKIN scale. Univariate and multivariate conditional logistic regression models were constructed. Patients were divided into four groups according to the quartile of HbA1c values. The median value of HbA1c in each group was taken as the substitute value and P for trend was calculated. The logistic regression model was fitted by restricted cubic splines to investigate the association between HbA1c level and outcome of ICH. Results: A total of 345 patients with ICH were enrolled, including 214 with favorable outcomes and 131 with poor outcomes (99 severe disability cases and 32 deaths). The risk of poor 90 days outcomes was significantly associated with HbA1c level at admission indicated by multivariate logistic regression analysis, and the P for trend test was <0.001 (middle-level group vs. low-level group: OR=2.33, 95%CI: 1.07-5.07; high-level group vs. low-level group: OR=2.52, 95%CI: 1.12-5.64; extremely high-level group vs. low-level group: OR=6.80, 95%CI: 3.01-15.34). Results from the restricted cubic spline showed that there was a linear correlation between HbA1c level at admission and poor 90 days outcomes of ICH (χ²=14.81, P<0.001; non- linear test: P=0.118). Compared with patients with HbA1c level of 6.5%, the risk of poor outcomes in patients with HbA1c level of <6.5% decreased linearly with the decrease in HbA1c level at admission, and the risk in patients with HbA1c level >6.5% was higher but not significantly. Conclusion There was correlation between high HbA1c level at admission and 90 days poor outcome of ICH. High HbA1c level is an independent prediction indicator for ICH.

Objective To study the nasal mucosa absorption of paeonol ofXingbi microemulsion-based thermo-sensitive gel in rats; To evaluate the nasal mucosa absorption of medicine and the rationality of preparation form.Methods According to the nasal administration method, the blood medicine concentration of paeonol was determined at different time points.Results The nasal administration bioavailability of paeonol in Xingbi microemulsion-based thermo-sensitive gel was 78.68%, the plasma concentration reached the maximum (0.3404 μg/mL) after 3 min of administration, and the average residence time was 9.23 h. After reaching Cmax, The plasma concentration changed similar to intravenous administration of paeonol. The concentration data of paeonol in plasma was consistent with a two-compartment model, with a weight of 1.Conclusion Xingbi microemulsion-based thermo- sensitive gel has a higher bioavailability, and the preparation form was reasonable.

Objective To establish the quality standards of Gualou Guizhi Dropping Pills; To investigate the vitro dissolution. Methods HPLC was used to determine the contents of paeoniflorin, albiflorin, cinnamic acid, 6-gingerol, liquiritin, glycyrrhizic acid and liquiritigenin in the dropping pills. The vitro dissolution rate of dropping pills was determined by rotating basket method. Results The calibration curves of paeoniflorin and albiflorin were in a good linearity in the range of 0.690–6.900 μg, 0.300–2.996 μg, respectively, and the average recoveries were 101.12% and 98.52%, respectively, with RSD of 2.24%, 1.37%, respectively. Cinnamic acid was linear in the range of 0.023–0.348 μg and the average recovery was 98.21% with RSD of 2.00%. 6-Gingerol was linear in the range of 0.025–0.382 μg, and the average recovery was 99.19% with RSD of 2.18%. The calibration curves of liquiritin, glycyrrhizic acid and liquiritigenin were in a good linearity in the ranges of 0.120–2.498 μg, 0.150–2.253 μg, and 0.010–0.147 μg, respectively, and the average recoveries were 99.80%, 100.38%, and 100.62%, respectively with RSD of 2.10%, 1.91%, 1.66%, respectively. The accumulated dissolution rates of seven kinds of elements in the dropping pills all reached more than 98% in 15 min. Conclusion The method is simple and accurate, with repeatability, which can be applied to the quality control of Gualou Guizhi Dropping Pills. The vitro dissolution rates meet relevant standards.

Objective To evaluate the application efficacy of the whole-course optimized nursing in emergency treatment of patients with acute cerebral infarction (ACI).Methods A total of 93 patients with ACI received whole-course optimized nursing in emergency treatment,the time from diagnosis to intravenous thrombolysis (DNT) and triage time were recorded,and the changes of neurological function deficit severity and activities of daily living (ADL) before and after treatment and 3 months after discharge were observed.Results The DNT was all controlled within 60 min,with average of (51.84 ±6.21) min and triage time of (0.71 ± 0.19) min.After treatment and 3 months after discharge,National Institutes of Health Stroke Scale (NIHSS) score was markedly lower while Barthel index (BI) score was notably higher than treatment before,and differences were significant (P ＜ 0.05).Conclusion Application of whole-course optimized nursing is beneficial to the recovery of neurological function and the improvement of ADL in patients with ACI.

Objective To evaluate the application efficacy of the whole-course optimized nursing in emergency treatment of patients with acute cerebral infarction (ACI).Methods A total of 93 patients with ACI received whole-course optimized nursing in emergency treatment,the time from diagnosis to intravenous thrombolysis (DNT) and triage time were recorded,and the changes of neurological function deficit severity and activities of daily living (ADL) before and after treatment and 3 months after discharge were observed.Results The DNT was all controlled within 60 min,with average of (51.84 ±6.21) min and triage time of (0.71 ± 0.19) min.After treatment and 3 months after discharge,National Institutes of Health Stroke Scale (NIHSS) score was markedly lower while Barthel index (BI) score was notably higher than treatment before,and differences were significant (P ＜ 0.05).Conclusion Application of whole-course optimized nursing is beneficial to the recovery of neurological function and the improvement of ADL in patients with ACI.