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 explore the direct⁃on⁃target micro⁃droplet growth assay (DOT⁃MGA) for rapid detection of the susceptibility of tigecycline and polymyxin. Methods: A total of 67 strains of Klebsiella pneumoniae were collected for DOT⁃MGA. 6 μl droplets with or without tigecycline or polymyxin (The final drug concentration is 2 μg/ml) were added in triplicate into the wells of the MALDI plate with four incubation time points (3 h ,4 h ,6 h , and 8 h) . The results were classified as susceptible (score < 1. 7) and non⁃susceptible (score≥1 . 7) according to the Bruker Biotype software Results: After incubation for 4 h , the growth efficiency, specificity and positive predictive value of tigecycline and polymyxin were both 100. 00% . The classification consistency rate was 98. 15% and 96. 15% , the sensitivity was 96. 30% and 92. 31% , and the negative predictive value was 96. 45% and 92. 86% , respectively. Conclusion DOT⁃MGA can provide rapid and reliable drug susceptibility diagnosis of tigecycline and polymyxin ,which is of great significance for the clinical anti⁃infective treatment.

Molar-incisor hypomineralization (MIH) is defined as an enamel mineralization defect caused by systemic factors, which is characterized by demarcated opacities. These opacities are liable to result in brittle hypomineralized enamel breakdown, which expediting the eventual development of cavities, even tooth loss. Early diagnosis and prompt intervention are essential. The MIH scoring system based on the diagnostic criteria of the European Academy of Paediatric Dentistry (EAPD) is internationally recognized. This system is particularly helpful to diagnose and evaluate the MIH, as well as conductive to the performance of epidemiological investigations. This paper gives a presentation on the EAPD judgment criteria and scoring system as well as their applications, based on the current situation of MIH studies and our findings of MIH epidemiological investigation.

Objective:To explore the safety and efficacy of immune checkpoint inhibitors(ICI)for patients with tumor recurrence after liver transplantation(LT).Methods:A single-center retrospective study was conducted for 6 recipients of tumor recurrence after LT on a therapy of ICI admitted into Shulan(Hang Zhou)Hospital from September 2015 to June 2018.The authors examined the occurrences of graft rejection and clinical outcomes of overall response rate, progression-free survival and overall survival after dosing of PD-1/PD-L1 inhibitors.Results:Six patients enrolled with tumor recurrence on a therapy of ICI undergoing LT due to hepatocellular carcinoma (HCC). Nivolumab (n=4) and duvalizumab (n=2) were administrated.The median session of treatment was 8.3(2-31) cycles.The disease outcomes were stable (3/6, 50%) and progressive (3/6, 50%), The progression-free survival time of 3 disease-controlled patients was 1.5, 16.2 and 18 months and the median survival time after recurrence was 19.75(10.8-37.8) months.Rejection occurred in 1 patients (1/6, 16.7%) and the occurring time of rejection was 28 days after PD-1 inhibitor dosing.After acute rejection, high-dose corticosteroids and immunoglobulin were ineffective and the patient died from acute rejection related liver failure.Conclusions:ICI may be employed as a salvage treatment for tumor recurrence after LT for HCC.Due to a possibility of severe acute rejection, usage should be cautious under close monitoring of liver function.

Objective:To investigate the effects of anxiety and depressive symptoms in mediation of pain catastrophizing on disability in patients with low back pain.Methods:A cross-sectional survey was conducted among 97 patients with low back pain in the Changjiang Subdistrict community health center from July to October 2021. Oswestry Disability Index, pain catastrophic subscale in Coping Strategies Questionnaire-24, Generalized Anxiety Disorder Scale-short version, Patient Health Depression Questionnaire-short version were used to evaluate the activity dysfunction, pain catastrophic cognition and anxiety and depression levels of patients,respectively. Path analysis was implemented to test the mediation model, and the indirect effects were assessed using the bootstrap procedure with bias-corrected 95 %CI. Results:Results suggested significant positive correlations among pain catastrophizing, anxiety, depressive symptoms and disability of patients. In addition, both anxiety and depressive symptoms significantly mediated the impact of pain catastrophizing on disability (standardized indirect effects were 0.183 and 0.197, P<0.05). Patients with higher levels of pain catastrophic cognition showed higher levels of anxiety and depressive symptoms (β=0.757, 0.720; P<0.01), and reported more severe motor dysfunction (β=0.241, 0.274; P<0.05). Conclusions:Our findings suggest that anxiety and depression may be the psychological pathways through which pain catastrophizing predicts disability in patients with low back pain. Effective psychological interventions, such as emotion regulation and stress reduction strategies should be considered in treatment and supportive care for patients with low back pain.

Microcystis aeruginosa, a type of algal bloom microalgae, is widely distributed in water, causing serious deteriorated effects on humans and the ecological environment. As a biocontrol microorganism, Bacillus subtilis can synthesize various bioactive substances through non-ribosomal peptide synthetase, to inhibit the growth of M. aeruginosa. Thus, it is imperative to investigate the non-ribosomal peptide (NRP) metabolites of B. subtilis fmb60. Three NRP metabolites from B. subtilis fmb60 including bacillibactin, surfactin and fengycin were extracted and identified by genome mining technology. The growth inhibition of M. aeruginosa was studied by adding various concentrations of NRP metabolites. The half-effect concentration value (EC50.4 d) of M. aeruginosa was 26.5 mg/L after incubation for 4 days. With the increasing concentration, the inhibitory effects of NRP metabolites of B. subtilis fmb60 on M. aeruginosa was enhanced significantly. Compared with the control group, with the addition of 50 mg/L NRP metabolites to the M. aeruginosa, the content of Fv/Fm, Fv/Fo and Yield parameter after cultured for 4 days were decreased by 2.8%, 1.7% and 2.0%, respectively. Those findings indicate that the NRP metabolites of B. subtilis fmb60 can significantly inhibit the photosynthesis and metabolism of M. aeruginosa, which provides a theoretical foundation for the development of biological algae inhibitor of B. subtilis.
Bacillus subtilis ; Humans ; Microcystis ; Peptides ; Photosynthesis

Objective:The aim of the study is analyze the recurrence, metastasis and prognosis of early breast cancer patients and evaluate the long-term safety of tracer sentinel lymph node biopsy (SLNB) using indocyanine green (ICG) and methylene blue (MB) in early breast cancer.Methods:A total of 394 breast cancer patients were enrolled from January 1, 2014 to December 31, 2014 in Affiliated Hospital of Chengde Medical University. The baseline data and clinical characteristics of 222 patients who met the inclusion criteria were analyzed.Results:The median follow-up time of 222 patients was 57 months. The detection rate of sentinel lymph nodes (SLNs) using ICG or MB alone was 96.4% and 84.7% ( P=0.02); the number of SLNs detected was 740 and 604 ( P<0.001); the positive SLN detection rates were 100% and 91% ( P=0.014), and the positive SLNs were 221 and 195 ( P<0.001). The local recurrence rates were 0.7% in patients without axillary lymph node dissection (ALND) and 1.4% ( P=0.57) in patients with ALND, and the distant metastasis rates were 5.3% and 15.7% ( P=0.01), respectively. The 5-year overall survival (OS) was 4.7% and 91.7% ( P=0.421), and the disease-free survival (DFS) was 90.5% and 85.9% ( P=0.285). The OS and DFS of the 222 patients were 100%, 96.8%, 94.1% and 100%, 96.4% and 89.2% respectively at 1, 3 and 5 years after operation. Multivariate COX regression model showed that age ≤50 years old, triple negative molecular classification and primary tumor >2 cm were independent risk factors for prognosis, and HR were 3.254, 7.321 and 3.507, respectively (all P<0.05). Conclusions:Sentinel lymph node biopsy with indocyanine green combined with methylene blue is a safe and reliable method for axillary staging of breast cancer. The COX regression models showed that patients with younger age, three-negative molecular type and larger primary tumor were more likely to have adverse events.

Objective:To investigate the effect of volar plate internal fixation with modified Henry approach with pronator quadratus preservation for distal radius fractures in elderly patients.Methods:A retrospective case control analysis was performed on 78 elderly patients with distal radius fractures treated with volar plate internal fixation from February 2016 to December 2018 in Second Affiliated Hospital of Wenzhou Medical University and People's Hospital of Qingtian. There were 36 males and 42 females, aged 60-79 years [(66.5±5.6)years]. According to AO classification, there were 16 patients with type B1 fractures, 15 with type B2, 11 with type B3, 12 with type C1, 14 with type C2 and 10 with type C3. Of all, 40 patients were operated using modified Henry approach with pronator quadratus preservation (improvement group) and 38 using Henry approach with pronator quadratus cutting (traditional group). All patients were treated with volar plate internal fixation. The fracture healing, internal fixation and complications were observed. The wrist pain visual analogue score (VAS), forearm rotation range and grip strength were compared between the two groups at 1 week, 1 month, 3 months and 12 months postoperatively. The wrist joint function score of the two groups was compared by using the upper limb function assessment table (DASH) at 3 months and 12 months postoperatively.Results:All patients were followed up for 12-24 months [(15.2±6.3)months]. All fractures were healed after 3 months. The position of internal fixation was good, and there were no complications of infection, nonunion, plate loosening and tendon injury. During the follow-up period, 2 patients in traditional group had carpal tunnel syndrome, which was relieved after removal of internal fixation. The VAS in improvement group was lower than that in traditional group at 1 week, 1 month and 3 months postoperatively [(6.17±0.40)points vs. (6.80±0.45)points, (5.54±0.40)points vs. (6.08±0.70)points, (3.18±0.30)points vs. (3.75±0.40)points, respectively] ( P<0.05). The forearm rotation range in improvement group was larger than that in traditional group at 1 week, 1 month and 3 months postoperatively [(49.40±17.5)% vs. (40.3±13.2)%, (66.7±14.3)% vs. (54.2±18.7)%, (87.3±7.2)% vs. (80.7±8.1)%, respectively] ( P<0.05). There was no significant difference in VAS and forearm rotation range between the two groups at 12 months postoperatively ( P>0.05). There was no significant difference in grip strength between the two groups at 1 week, 1 month, 3 months and 12 months postoperatively ( P>0.05). There was no significant difference in DASH score between the two groups at 3 months and 12 months postoperatively ( P>0.05). Conclusion:For elderly patients with distal radius fracture, modified Henry approach with pronator quadratus preservation combined with volar plates is relatively better in alleviating postoperative pain, improving early rotation function and promoting early functional recovery.

Objective This paper focuses on the field of clinical medicine,with the aim of verifying the feasibility of interdisciplinary literature evaluation model based on feature matching method,to provide support for further interdisciplinary scientific research evaluation.Methods Feature matching method,Delphi expert enquiry,and normalization method were adopted to establish an evaluation system in clinical medicine,which was further verified by case studies.Results The normalization coefficient reflects the difficulty of publishing articles with high impact factors.Through the process of feature matching and normalization,it was found that compared with the fields of Neurology,Psychiatry and Surgery,researchers in the fields of Oncology and Internal Medicine were more likely to publish articles with high impact factors.Conclusions Through case analysis,this study verifies the feasibility of interdisciplinary scientific paper evaluation system.The interdisciplinary paper evaluation system based on feature matching method and normalized evaluation method comprehensively considers the characteristics of various disciplines of clinical medicine and provides a new idea for the evaluation of clinical scientific research talents.

BACKGROUND: For the patients with benign osteopathy, the patients usually get a good life cycle after surgical treatment. Through continuous improvement of the operation mode, the stress of the proximal femur after the operation of benign osteopathy is studied by using the finite element analysis. The risk of pathological fracture and secondary fracture is predicted and reduced. To explore the best operation and prognosis is of great significance for prolonging and improving the quality of life of patients. OBJECTIVE: Three-dimensional finite element technique was used to analyze the different surgical models of benign proximal femoral lesions. The differences of different surgical models were compared and the rationality and effectiveness of internal fixation were verified. The reliability of the finite element model was verified in the follow-up of patients after operation. METHODS: Preoperative CT examination was conducted in 10 patients with benign proximal femoral lesions who met the inclusion criteria. Three models of limbs scraping (group A), cavity internal nail re-infusion bone cement (group B) and intracavitary bone cement joint plate screw (group C) were established by MIMICS. The maximum stress values of the left and right side windows of the cortical model of group A, B and C were measured under simulated conditions, and the stress values of the three groups were compared. All patients signed the informed consent. This study was approved by the Hospital Ethics Committee. RESULTS AND CONCLUSION: (1) The comparison of the maximum stress values of the anterior and posterior sides of the cortical fenestration in the three groups of models was group A > group B > group C (P < 0.05). The risk of fracture was high in group A, and the risk of fracture in group B was large. The stress in group C was controlled within a reasonable range, and the risk of fracture was low. (2) Therefore, 10 subjects underwent the treatment in group C. The prognosis was good and there were no secondary fractures. The Musculoskeletal Tumor Society score was 27-30 points 1 year after surgery. (3) The model stress is prone to increase the local stress after opening the window. After adding bone cement and steel plate, the stress value of the model window is significantly reduced. After the benign lesions of the proximal femur are scraped, the stress of the fenestration can be effectively reduced by placing the bone cement and the steel plate, and the fracture probability at the surgical site is significantly reduced. Steel plate placement is reasonable.