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 current status of endoscopic treatment for gastroesophageal varices in portal hypertension in China, and to provide supporting data and reference for the development of endoscopic treatment.Methods:In this study, initiated by the Liver Health Consortium in China (CHESS), a questionnaire was designed and distributed online to investigate the basic condition of endoscopic treatment for gastroesophageal varices in portal hypertension in 2022 in China. Questions included annual number and indication of endoscopic procedures, adherence to guideline for preventing esophagogastric variceal bleeding (EGVB), management and timing of emergent EGVB, management of gastric and isolated varices, and improvement of endoscopic treatment. Proportions of hospitals concerning therapeutic choices to all participant hospitals were calculated. Guideline adherence between secondary and tertiary hospitals were compared by using Chi-square test.Results:A total of 836 hospitals from 31 provinces (anotomous regions and municipalities) participated in the survey. According to the survey, the control of acute EGVB (49.3%, 412/836) and the prevention of recurrent bleeding (38.3%, 320/836) were major indications of endoscopic treatment. For primary [non-selective β-blocker (NSBB) or endoscopic therapies] and secondary prophylaxis (NSBB and endoscopic therapies) of EGVB, adherence to domestic guideline was 72.5% (606/836) and 39.2% (328/836), respectively. There were significant differences in the adherence between secondary and tertiary hospitals in primary prophylaxis of EGVB [71.0% (495/697) VS 79.9% (111/139), χ2=4.11, P=0.033] and secondary prophylaxis of EGVB [41.6% (290/697) VS 27.3% (38/139), χ2=9.31, P=0.002]. A total of 78.2% (654/836) hospitals preferred endoscopic therapies treating acute EGVB, and endoscopic therapy was more likely to be the first choice for treating acute EGVB in tertiary hospitals (82.6%, 576/697) than secondary hospitals [56.1% (78/139), χ2=46.33, P<0.001]. The optimal timing was usually within 12 hours (48.5%, 317/654) and 12-24 hours (36.9%, 241/654) after the bleeding. Regarding the management of gastroesophageal varices type 2 and isolated gastric varices type 1, most hospitals used cyanoacrylate injection in combination with sclerotherapy [48.2% (403/836) and 29.9% (250/836), respectively], but substantial proportions of hospitals preferred clip-assisted therapies [12.4% (104/836) and 26.4% (221/836), respectively]. Improving the skills of endoscopic doctors (84.2%, 704/836), and enhancing the precision of pre-procedure evaluation and quality of multidisciplinary team (78.9%, 660/836) were considered urgent needs in the development of endoscopic treatment. Conclusion:A variety of endoscopic treatments for gastroesophageal varices in portal hypertension are implemented nationwide. Participant hospitals are active to perform emergent endoscopy for acute EGVB, but are inadequate in following recommendations regarding primary and secondary prophylaxis of EGVB. Moreover, the selection of endoscopic procedures for gastric varices differs greatly among hospitals.

Objective To investigate the effects of DNA demethylation drugs combined with histone deacetylase in-hibitors on fragile X mental retardation 1 neighbor protein (FMR1NB) expression and its promoter methylation in human oral cancer cells and try to find a strategy of weakening the heterogeneity of FMR1NB expression.Methods Human oral cancer cell lines Cal27 and SCC-9 were treated with decitabine (DAC) , an inhibitor of DNA meth-yltransferase, combined with trichostatin A (TSA) and valproic acid (VPA), inhibitors of histone deacetylase.Then reverse transcription-polymerase chain reaction (RT-PCR) , quantitative real-time PCR (qRT-PCR) and Western blot were used to detect the expression of FMR1 NB and pyrosequencing was used to detect the methylation of FMR1NB promoter.Results Compared with the blank control group, DAC and its combination with TSA and VPA significantly induced the expression of FMR1NB mRNA and protein in Cal27 and SCC-9 cells.Compared with DAC alone group, FMR1NB mRNA expression of each DAC-combined drug groups significantly increased, but FMR1NB protein did not significantly change in Cal27 cells; for SCC-9 cells, except for DAC+TSA group, the mRNA and protein levels of FMR1NB significantly increased in all other groups.In addition, there was no signifi-cant difference in the expression of FMR1 NB mRNA and protein between the three-combined drugs group and two-combined drugs groups.Further methylation assay showed that the methylation level of the overall FMR1NB promot-er and its each CpG site measured were reduced to varying degrees in all treatment groups except for three-combina-tion drug group of SCC-9.Conclusion DAC and its combination with TSA and VPA can enhance the expression of FMR1NB by mediating the demethylation of FMR1NB promoter, wherein the enhanced expression effect of the com-bination of the two drugs is stronger, suggesting that they have the potential to weaken the heterogeneity of FMR1NB expression and improve the immunotherapy effect of oral cancer.

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.

The efficacy of HPV vaccine in preventing cervical cancer has been demonstrated in numerous clinical trials and clinical uses. The follow-up after clinical trials usually last for 5-6 years to evaluate the long-term efficacy, and a series of long-term follow-up studies have been conducted in some regions. The literature retrieval of HPV vaccine long term efficiency research both at home and abroad indicated that the protective efficacy of the vaccine against vaccine-type-related cervical intraepithelial neoplasia grade 2 and above is higher than 90%.
Humans ; Human Papillomavirus Viruses ; Biomedical Research ; Papillomavirus Vaccines

Objective To observe the efficacy and safety of the cocktail therapy to treat patients with Parkinson's disease with dementia ( PDD) . Methods Sixty patients with PDD were randomly divided into treatment group(30 cases)and control group(30 cases). The dose 10 mg of donepezil hydrochloride was taken 1 time a day in the control group;on the basis,the dose 0. 2 g of butylphthalide soft capsules was taken pre-dinner, 3 times a day,the dose 0. 8 g of oxiracetam was taken 3 times a day and 2 Ginkgo Biloba Leaves Extract tablets was taken 3 times a day in the treatment group,period of treatment was 6 months. The curative effect was measured by using Montreal cognitive assessment scale (MoCA),Blessed-Roth dementia table,severity of clinical dementia rating scale (WMS) rating, respectively before treatment and on the 3th, 6th month after treatment,and monitored the adverse reactions. Results There were no statistically significant differences on the scores of MoCA, WMS and Blessed-Roth dementia table between treatment group and control group before treatment ( all P>0. 05 ) . The scores of MoCA, WMS in the treatment group and control group on 6 months after treatment were significantly higher than those before treatment and 3 months after treatment, and the scores of Blessed-Roth dementia table in the treatment group and control group on 6 months after treatment were significantly lower than those before treatment and 3 months after treatment ( P<0. 05-0. 01). Compared with control group,the scores of MoCA, WMS increased obviously and the scores of Blessed-Roth dementia table decreased significantly in the treatment group on 6 months after treatment (P<0. 05-0. 01). There was no statistically significant difference on the rates of abnormal liver function after treatment betweenin the treatment group (16. 67%) and the control group (13. 33%) (P>0. 05). Conclusion The curative effect of cocktail therapy is better than traditional remedies for treating patients with PDD, and it is high safety.

Objective To study the anatomic and biomechanical characteristics of the dorsal radial ligament and anterior oblique ligament in carpometacarpal (CPC) joints of the thumb, so as to provide references for ligament repair. Methods Forty fresh hand specimens of adult male cadavers were dissected to make specimen of trapezium bone- ligament-the first metacarpal bone, of which 20 cases retained the dorsal radial ligament and 20 cases retained the anterior oblique ligament, respectively. The ligaments were tested on the biomechanical testing machine, and their length, width, thickness, the maximum load, elastic modulus and elongation rate were measured and calculated. Results For the dorsal radial ligament and anterior oblique ligament, their maximum load was (213.5±72.4) and (168.7±35.2) N, their elastic modulus was (17.2±6.7) and (9.3±2.5) N/mm2, their elongation rate was (116.2±21.3)% and (92.7±22.4)%, respectively. The maximum load, elastic modulus and elongation of the dorsal radial ligament were larger than that of the anterior oblique ligament. Conclusions In the capsular ligament in CPC joints of the thumb, the dorsal radial ligament has a higher stiffness and stronger toughness, which plays an important role in maintaining the stability of the joint. The stiffness of the anterior oblique ligament is smaller, the toughness is poor, which is easy to be damaged. The anterior oblique ligament is suggested to be reconstructed firstly to treat arthritis of CMC joints, and material whose elastic modulus and elongation rate is similar with the dorsal radial ligament should be selected.

Objective To discuss change the platelet counts by microscope rule by the platelet of Chinese people biological refer‐ence range in this laboratory blood analysis requirement .Methods Retrospectively analyzed according to the platelet of Chinese people biological reference range change the lab Sysmex XE‐5000 automatic blood cell analyzer platelet review rules .Change the platelet counts by microscope rules ,the differences between the microscopy rate and the microscopic examination of the platelet ag‐gregation rate .Results Before change the platelet counts by microscope rules the microscopy rate was 1 .94% .After change the platelet counts by microscope rules the microscopy rate was 3 .99% ,after change the platelet counts by microscope rules pushing blood piece rate increased significantly ,the difference was statistically significant(P<0 .05) .Conclusion According to the platelet of Chinese people biological reference range change the lab platelet review rules .We can increase the rate of microscopy ,and effec‐tively avoid the pseudothrombocytopenia and accurately guide clinical treatment .

Background and purpose: The morbidity of colorectal cancer in China increased year by year. This study aimed to explore the signiifcance of ADAMTS9 protein levels and promoter methylation in colorectal cancer onset and progression. Methods:ADAMTS9 promoter methylation status was detected by methylation speciifc PCR method in 162 colorectal cancer patients’ peripheral blood DNA samples; Plasmatic ADAMTS9 protein levels was detected by enzyme-linked immunosorbent assay method in 162 colorectal cancer patients and 150 healthy subjects. Results: Compared with healthy people, patients with colorectal cancer had a significant lower ADAMTS9 protein level in plasma [(65.25±9.70)μg vs (50.28±9.66)μg, P<0.001];ADAMTS9 gene promoter methylation was observed in 66 among 162 colorectal cancer patients (40.7%);The plasma level of ADAMTS9 protein in patients with methylated ADAMTS9 gene had signiifcantly reduced (P<0.001), while the plasma level of ADAMTS9 protein in patients with low ADAMTS9 protein had signiifcantly increased (P=0.007);ADAMTS9 methylation is closely related to tumor size (larger, P=0.017) and tumor differentiation degree (P=0.029), ADAMTS9 protein low expression is closely related to invasion depth (P=0.020), lymph node metastasis (P=0.019) and Dukes staging (P=0.002).Conclusion: ADAMTS9 protein downregulation induced by DNA promoter methylation may be involved in the pathogenesis, invasion and metastasis, and promote the progression in colorectal cancer.

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.