Recent studies have indicated that the expression of ubiquitin-specific protease 51 (USP51), a novel deubiquitinating enzyme (DUB) that mediates protein degradation as part of the ubiquitin‒proteasome system (UPS), is associated with tumor progression and therapeutic resistance in multiple malignancies. However, the underlying mechanisms and signaling networks involved in USP51-mediated regulation of malignant phenotypes remain largely unknown. The present study provides evidence of USP51's functions as the prominent DUB in chemoresistant triple-negative breast cancer (TNBC) cells. At the molecular level, ectopic expression of USP51 stabilized the 78 kDa Glucose-Regulated Protein (GRP78) protein through deubiquitination, thereby increasing its expression and localization on the cell surface. Furthermore, the upregulation of cell surface GRP78 increased the activity of ATP binding cassette subfamily B member 1 (ABCB1), the main efflux pump of doxorubicin (DOX), ultimately decreasing its accumulation in TNBC cells and promoting the development of drug resistance both in vitro and in vivo. Clinically, we found significant correlations among USP51, GRP78, and ABCB1 expression in TNBC patients with chemoresistance. Elevated USP51, GRP78, and ABCB1 levels were also strongly associated with a poor patient prognosis. Importantly, we revealed an alternative intervention for specific pharmacological targeting of USP51 for TNBC cell chemosensitization. In conclusion, these findings collectively indicate that the USP51/GRP78/ABCB1 network is a key contributor to the malignant progression and chemotherapeutic resistance of TNBC cells, underscoring the pivotal role of USP51 as a novel therapeutic target for cancer management.

Objective To investigate the microstructural changes of temporal lobe epilepsy(TLE)in patients with sleep disorders based on diffusion kurtosis imaging(DKI).Methods This research prospectively included 38 TLE patients(case group)and 20 healthy controls(HC)(HC group).Participants used sleep questionnaires to evaluate their sleep status.All TLE patients were divided into groups with and without sleep disorders according to the diagnostic criteria and scale scores of sleep disorders.The mean kurtosis(MK),mean diffusivity(MD),and fractional anisotropy(FA)of the relevant region of interest(ROI)were measured by DKI sequence.The differences of sleep quality scores and DKI parameters between groups were further compared via independent samples t-test and one-way analysis of variance.Results The Epworth sleepiness scale(ESS),Athens insomnia scale(AIS),and Pittsburgh sleep qual-ity index(PSQI)scores of TLE patients with sleep disorders were significantly higher than those of HC group(P＜0.05).The FA and MK values in TLE patients were significantly lower than those in HC group,while the MD value of TLE patients were substan-tially higher than that of HC group(P＜0.05).The values of MK and FA in left TLE patients with sleep disorders were significantly lower than those of without sleep disorders(P＜0.05),while there was no significant difference in MD value between the two groups(P＞0.05).MK value of right TLE patients with sleep disor-ders was significantly lower than that of without sleep disorders(P＜0.05),however,there were no significant differences in MD and FA values between the two groups(P＞0.05).Conclusion Quantitative DKI analysis revealed differences in DKI parameters in TLE patients combined with sleep disorders,inferring a specific white matter fiber damage in this group and providing imaging data to support the personalized treatment and prognostic assessment of these patients.

Objective:To compare the perioperative conditions of open pancreaticoduodenectomy (OPD), laparoscopic pancreaticoduodenectomy (LPD) and LPD conversion OPD, and analyze the short-term prognosis and risk factors for LPD conversion OPD.Methods:The clinical data of 167 patients undergoing pancreaticoduodenectomy (PD) in the Beijing Friendship Hospital, Capital Medical University from February 2020 to March 2023 were retrospectively analyzed. Of 167 patients, 63 patients underwent OPD surgery (OPD group), 91 patients underwent LPD surgery (LPD group), and 13 patients were converted to OPD during LPD surgery (LPD conversion OPD group). The measurement data with non-normal distribution were expressed as median (interquartile range) [ M( Q1, Q3)], and comparison between groups was analyzed using the Kruskal-Wallis H test. The count data were expressed as the number of cases and percentage, and the Chi-square test was used for ordered categorical variable, Kruskal-Wallis H test was used for un-ordered categorical variable. The risk factors of LPD conversion OPD were analyzed by multivariate Logistic regression. Results:The intraoperative blood loss [600(350, 1 000) mL], bilio-intestinal drainage stay time [10(8, 15) d] and bilio-intestinal drainage volume [995(505, 1 502) mL] in the LPD conversion OPD group were significantly higher than those in the LPD group [200(100, 300) mL, 7(6, 6) 10) d, 450(175, 874) mL], the differences were statistically significant ( P<0.05). The operation time of the LPD conversion OPD group [335(293, 385) d] was significantly longer than that of the OPD group [230 (195, 290)d], and the difference was statistically significant ( P<0.05). Multivariate Logistic regression analysis revealed that preoperative complications of chronic pancreatitis ( OR=19.714) and maximum diameter of the lesion ( OR=5.583) has a significant impact on the LPD conversion OPD ( P<0.05). Conclusions:Patients who plan to undergo PD should prefer LPD if the technology and physical condition permit. Preoperative complication of chronic pancreatitis, maximum diameter of lesion > 3.5 cm are the risk factors for LPD conversion OPD, which may significantly increase intraoperative blood loss, prolong the indwelling time of biliary drainage tube, and increase the drainage volume of biliary drainage tube. Therefore, the surgical method should be carefully selected.

Purpose: Inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal malignancy that occurs primarily in children and adolescents. The clinical and pathological features of IMT in adult patients are not well understood. Materials and Methods: We retrospectively searched for records of adult patients with IMT at Fudan University Shanghai Cancer Center from 2006 to 2021. Clinicopathological data, treatments, and outcomes were collected and analyzed. Results: Thirty adult patients with IMT, mostly women (60.0%), were included. The median age of the patients was 38 (21-77). The most common primary site was abdominopelvic region (53.3%), followed by lungs (20.0%). Seven patients had an abdominal epithelioid inflammatory myofibroblast sarcoma (EIMS). The positivity rate of anaplastic lymphoma kinase (ALK) was 81.5% (22/27). Sixteen patients with advanced ALK-positive disease received crizotinib, with an objective response rate (ORR) of 81.3% and a disease control rate of 87.5%. The median progression-free survival was 20.8 months. EIMS was associated with more aggressive behavior; however, the prognosis was similar to that of non-EIMS patients after treatment with an ALK inhibitor. At a median follow-up time of 30 months (95% confidence interval [CI], 13.6 to 46.4), the 5-year overall survival was 77% (95% CI, 66 to 88) in all patients. Conclusion Adult IMTs appeared more aggressive, with a higher incidence of recurrence and metastases, and patients with EIMS had more aggressive cases. Treatment with ALK inhibitors resulted in a high ORR and a durable response, which suggested that ALK inhibitors could be used as a first-line treatment option in adult patients with ALK-positive advanced IMT.

Objective:To explore the effect of health education based on Green's model combined with individualized systematic nutrition management on the knowledge of disease, nutritional status and immune function of patients with esophageal cancer undergoing radiotherapy.Methods:From May 2019 to June 2021, 102 patients with esophageal cancer treated by radiotherapy in the Affiliated Cancer Hospital of Zhengzhou University were selected as the subject by convenient sampling. A total of 51 patients from May 2019 to May 2020 were set as control group and given routine nursing. A total of 51 patients from June 2020 to June 2021 were assigned to the observation group, and the health education based on the Green's model combined with individualized systematic nutrition was given. Albumin (ALB), prealbumin (PA), hemoglobin (Hb), transferrin (TRF), body weight, body mass index (BMI), knowledge of esophageal cancer radiotherapy, CD3 +, CD4 +, CD8 + and CD4 +/CD8 +, Hamilton Anxiety Scale (HAMA) and Hamilton Depression Scale (HAMD) scores were compared between the two groups. Results:Before radiotherapy, there was no statistically significant difference in body weight, BMI, Hb, ALB, PA, TRF, CD3 +, CD4 +, CD8 +, CD4 +/CD8 +, HAMA score and HAMD score between the two groups ( P>0.05). After three and six months of radiotherapy, body weight, BMI, Hb, ALB, PA and TRF in the observation group were higher than those in the control group. Six months after radiotherapy, the CD3 +, CD4 +, CD4 +/CD8 + in the observation group were higher than those in the control group, while the CD8 +, HAMA score and HAMD score in the observation group were lower than those in the control group. The above differences were statistically significant ( P<0.05). The scores of admission instructions, disease knowledge, radiotherapy knowledge, diet care, skin care, radiotherapy complications, rehabilitation knowledge and total score in the observation group were higher than those in the control group, and the differences were statistically significant ( P<0.05) . Conclusions:Health education based on Green's model combined with individualized systematic nutrition management in esophageal cancer patients undergoing radiotherapy has a certain effect, which is conducive to increasing patients' knowledge of esophageal cancer radiotherapy, improving patients' immune function, and reducing the occurrence of malnutrition.

Human epidermal growth factor receptor 2 (HER2) proteins are overexpressed in a high proportion of gastric cancer (GC) cases and affect the maintenance of cancer stem cell (CSC) subpopulations, which are used as targets for the clinical treatment of patients with HER2-positive GC. Despite improvements in survival, numerous HER2-positive patients fail treatment with trastuzumab, highlighting the need for more effective therapies. In this study, we generated a novel type of genetically modified human T cells, expressing a chimeric antigen receptor (CAR), and targeting the GC cell antigen HER2, which harbors the CD137 and CD3ζ moieties. Our findings show that the expanded CAR-T cells, expressing an increased central memory phenotype, were activated by the specific recognition of HER2 antigens in an MHC-independent manner, and effectively killed patient-derived HER2-positive GC cells. In HER2-positive xenograft tumors, CAR-T cells exhibited considerably enhanced tumor inhibition ability, long-term survival, and homing to targets, compared with those of non-transduced T cells. The sphere-forming ability and in vivo tumorigenicity of patient-derived gastric cancer stem-like cells, expressing HER2 and the CD44 protein, were also inhibited. Our results support the future development and clinical application of this adoptive immunotherapy in patients with HER2-positive advanced GC.
Animals ; Humans ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasms, Experimental ; immunology ; pathology ; therapy ; Receptor, ErbB-2 ; immunology ; Receptors, Antigen, T-Cell ; immunology ; Stomach Neoplasms ; immunology ; pathology ; therapy ; Tumor Cells, Cultured

Objective: An innovative technique was established to rapidly construct various cell lines that could be induced to express multiple influenza A virus (IAV) proteins. Method: The HA protein genes of multiple IAVs were cloned into the Cumate-induced expression system which was positioned between two PiggyBac transposon sites. These HA plasmids were transfected into the HEK293A cell line with the PiggyBac transposase plasmids. The transfected cells were screened with puromycin, and after that the corresponding virus proteins were induced with Cumate. Results: The results of flow cytometry and Western blotting showed that the virus proteins were expressed in most of the cells in corresponding lines after the induction of Cumate. Conclusion Cell lines which were inducible to express IVA HA protein can be efficiently constructed by using the PiggyBac transposon system.

Objective To investigate the effects of different wavelength (595 nm,755 nm and 1064 nm) lasers on the mRNA expression of types Ⅰ and Ⅲ procollagen in cultured fibroblasts.Methods Fibroblasts from Kunming mice were cultured in vitro.They were divided into 595 nm laser group,755 nm laser group,1064 nm laser group and no laser irradiating group.The mRNA expression of the types Ⅰ and Ⅲ procollagen was detected by RT-PCR.Results The mRNA expression level of type Ⅰ procollagen in 1064 nm group was higher than that of 755 nm group,595 nm group and control group (P＜0.05).The expression levels of 755 nm group and 595 nm group were higher than that of control group (P＜0.05).But the difference between 755 nm group and 595 nm group was not statistically significant (P＞0.05).The mRNA expression level of type Ⅲ procollagen in 1064 nm group was higher than that in 755 nm group,595 nm group and control group (P＜0.05).755 nm group had higher expression than 595 nm group and control group (P＜0.05).But the difference between 595 nm group and the control group was not statistically significant (P ＞ 0.05).Conclusions Three wavelength lasers can directly promote mRNA expression of types Ⅰ and Ⅲ procollagen in fibroblasts.595 nm laser mainly promotes mRNA expression of type Ⅰ procollagen,and 755 nm laser promotes more mRNA expression of type Ⅲ procollagen than 595 nm laser.The most mRNA expression of types Ⅰ and Ⅲ procollagen is promoted by 1064 nm laser.

ObjectiveTo evaluate the curative effect of supplementedGanmai-Dazaodecoction for malignant tumor correlation with depression.MethodsA total of 98 patients with malignant tumor-related depression were divided into a treatment group and acontrol group according to the random number table. The control group were treated with flupentixol and melitracen tablets (Deanxit) combined with conventional treatment, the treatment group were treated with oral administration of traditional Chinese medicine supplemented Ganmai-Dazaodecoction combined with conventional treatment for 8 weeks. The Hamilton Depression Scale (HAMD) was used to evaluate the curative effect.ResultsThe effective rate showed no significant difference between the treatment groupand the control group (79.59%vs.75.51%;χ2=0.059,P=0.809). HAMD scores in both groups were significantly decreased after the treatment than before treatment (12.8±3.4 vs. 29.4±4.7 in the treatment group, 12.3±3.6vs.28.7±4.5 in the controlgroup, allP<0.05), there was no significant difference in HAMD scores after the treatment between the treatment group and the control group (t=0.707,P=0.481). ConclusionCurative effect of supplementedGanmai-Dazaodecoction is equal to flupentixol andmelitracen tablets in patients with malignant tumor-related depression.

AIM: To investigate the effect of injection stauntoniae ( IS) on inflammatory pain responses in mice.METHODS:The carrageenan test was used to determine the anti-inflammatory and analgesic effects of IS .Except for control group, the mice in other groups received an injection of λ-carrageenan solution (1%, 50 μL) into the plantar region of the left hind paws , followed by a subcutaneous injection of IS at doses of 12.5%, 50%and 100%or equal vol-ume of 0.9%NaCl.Both paw edema and hyperalgesia to thermal stimulation were measured 4 h, 12 h, 24 h and 48 h after the injection of λ-carrageenan solution.The lumbar-5 (L5) dorsal root ganglions (DRGs) of the mice were taken to inves-tigate the cyclooxygenase 2 ( COX-2) expression by immunohistochemical staining .RESULTS:Subcutaneous injection of IS potently inhibited paw edema and hyperalgesia induced by λ-carrageenan in the mice accompanied with the inhibition of COX-2 protein expression in L 5 DRGs.CONCLUSION:IS exerts the anti-inflammatory and analgesic effects on the in-flammatory responses by inhibiting the protein expression of COX-2 in DRGs.