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.

Diagnostic criteria, as a critical component of clinical practice guidelines, play a direct role in guiding clinicians' diagnostic and treatment decisions. Although China has increasingly emphasized the development and updating of clinical guidelines in recent years, research focusing on the diagnostic criteria within these guidelines remains limited. This paper aims to explore the types of diagnostic criteria, the issues they present, and the processes involved in their formulation. Based on this analysis, suggestions are proposed to improve the recommendation and application of diagnostic criteria in Chinese guidelines.

Diagnostic criteria, as a critical component of clinical practice guidelines, play a direct role in guiding clinicians' diagnostic and treatment decisions. Although China has increasingly emphasized the development and updating of clinical guidelines in recent years, research focusing on the diagnostic criteria within these guidelines remains limited. This paper aims to explore the types of diagnostic criteria, the issues they present, and the processes involved in their formulation. Based on this analysis, suggestions are proposed to improve the recommendation and application of diagnostic criteria in Chinese guidelines.

  Objective  To analyze the current status of the development of adaptation guidelines in China, as well as their methodological quality and the reporting quality, in order to provide reference for the development of adaptation guidelines.  Methods  We searched and collected adaptation guidelines led by Chinese researchers or institutions from 2015 to 2023 from four electronic databases, China National Knowledge Infrastructure, WanFang Data Knowledge Service Platform, SinoMed and PubMed, extracted the basic information of the adapted guidelines, and assessed their methodological quality and reporting quality using the Appraisal of Guidelines for REsearch and Evaluation (AGREE) Ⅱ and RIGHT-Ad@pt tools.  Results  A total of 14 adaptation guidelines were included, mainly focusing on nursing (42.9%, 6/14), with the most frequently used adaptation method of ADAPTE (71.4%, 10/14), and with reference to pre-existing guidelines mainly from the United States, the United Kingdom, and international organizations. Assessment by the AGREE Ⅱ tool showed that the average methodological quality score of the adapted guidelines was 36.6%. The scores were relatively high in the domains of clarity of expression and rigor of formulation (44.4% and 54.9%), and lowest in the domain of applicability (15.3%). The results of the RIGHT-Ad@pt tool showed that the reporting quality of the adaptation guidelines was relatively good, with the highest reporting rate of 91.2% and the lowest of 35.3%, and the reporting rates of seven articles were higher than 70%.  Conclusions  Adaptation guidelines in China are still in their infancy, with a relatively small number and mainly focusing on the nursing field. The most commonly used adaptation method is the ADAPTE method. The methodological quality and reporting quality of adaptation guidelines need to be further improved, and more research should be conducted on the specific conditions and timing of adaptation guidelines development.

Objective:To evaluate the therapeutic effect of glycyrrhetinic acid on cough variant asthma (CVA) mice based on molecular docking technique; To explore the possibility of its treatment for cough variant asthma.Methods:The software of Autodock Vina was used for molecular docking. The mice were divided into control group, model group, prednisone acetate group, glycyrrhetinic acid high-, medium-, and low-dosage groups according to the random number table method, with 8 mice in each group. Except for the blank control group, all other groups were induced by egg protein to establish cough variant asthma models. Glycyrrhetinic acid high-, medium-, and low-dosage groups were orally administered glycyrrhetinic acid suspension at 20, 10, and 5 mg/kg, while the prednisone acetate group was orally administered prednisone acetate at 5 mg/kg. The blank control group and model group were orally administered equal volumes of physiological saline, once per day for 14 consecutive days. The animal asthma behavior was observed after drug administration. The secretion of bronchial mucus in lung tissue were observed by AB-PAS staining and the index of spleen were recorded. The protein expressions of Gata3, IL-4 and IL-13 in the spleen tissue were determined by Western blot.Results:Molecular docking results showed that glycyrrhetinic acid had good binding ability to Th2-related factors Gata3, IL-4 and IL-13. Results of animal experiment showed that compared with the model group, the mucus secretion decreased in glycyrrhetinic acid groups, the index of the spleen of mice obviously decreased, protein expression levels of IL-4 and IL-13 in the spleen tissue of mice in glycyrrhetinic acid high-, medium-, and low-dosage groups decreased ( P<0.05), and Gata3 in glycyrrhetinic acid medium- and low-dosage groups decreased ( P<0.05). Conclusion:Glycyrrhetinic acid can correct the shift of Th2 in the immune system of cough variant asthma mice and has a certain therapeutic effect.

Objective:To evaluate CT and or MRI imaging in the diagnosis of lateral lymph node metastasis in patients of middle and low rectal cancer.Methods:In this study, 112 lateral lymph nodes were harvested in 79 patients with middle and low rectal cancer. The relationship between the preoperative imaging features of the lateral lymph nodes and the postoperative pathology was evaluated.Result:Thirty-eight cases (48%) were pathologically confirmed to have lateral lymph node metastasis. The diameter of metastasis-positive lateral lymph nodes was significantly larger than that of metastasis-negative lateral lymph nodes ( P<0.01). Multivariate analysis of clinical features and imaging features found that, tumors poorly differentiated, mucinous adenocarcinoma, signet ring cell carcinoma ( P=0.006), and the largest short diameter of the lateral lymph node ≥7 mm ( P=0.024), uneven density or signal ( P=0.022) were independent risk factors for lateral lymph node metastasis. Conclusion:Poor tumor differentiation, lateral lymph node maximum short diameter ≥7 mm, density or signal unevenness are independent risk factors for lateral lymph node metastasis in middle and low rectal carcinoma.

Objective:To explore the characteristics and evolution trend of renal disease spectrum in Ningxia.Methods:The demographic, clinical manifestations and renal pathological examination results of patients who underwent renal biopsies in the General Hospital of Ningxia Medical University from August 1, 2008 to December 31, 2019 were collected and analyzed retrospectively. According to the time period of receiving renal biopsy, the patients were divided into 2008—2013 group and 2014—2019 group. The age and sex constituent, clinical manifestation, renal disease type, pathological types of primary and secondary glomerular disease and the main clinical manifestations of patients with diabetic nephropathy were compared between the two groups. The changing trend of renal disease spectrum in Ningxia from 2008 to 2019 was analyzed.Results:A total of 3 867 patients who underwent renal biopsies were enrolled in this study, with more males (53.71%, 2 077/3 867), and age of (39.59±14.05) years old. The most common clinical manifestation of patients receiving renal biopsies was nephrotic syndrome (36.33%, 1 405/3 867). Among them, primary glomerular diseases accounted for 78.79% (3047/3 867), followed by secondary glomerular diseases (18.57%, 718/3 867), renal tubulointerstitial diseases (1.45%, 56/3 867) and hereditary nephropathy (1.19%, 46/3 867). The most common primary glomerular disease was IgA nephropathy (44.60%, 1 359/3 047), followed by membranous nephropathy (30.75%, 937/3 047). The most common secondary glomerular disease was Henoch-Sch?nlein purpura nephritis (27.44%, 197/718), followed by lupus nephritis (25.07%, 180/718). Compared with the 2008—2013 group, the proportion of membranous nephropathy increased, the proportion of mesangial proliferative glomerulonephritis (non-IgA deposition) decreased (both P<0.001), the proportions of diabetic nephropathy and hypertensive renal damage increased, and the proportions of Henoch-Sch?nlein purpura nephritis and hepatitis B virus-associated glomerulonephritis decreased in 2014—2019 group (all P<0.01). Compared with the 2008—2013 group, the proportions of acute kidney injury, chronic renal failure, simple hematuria and urinary protein≤1.0 g/24 h increased in kidney biopsy patients in 2014—2019 group, while the proportion of nephrotic syndrome decreased (all P<0.05). Compared with the 2008—2013 group, the proportion of chronic renal failure in diabetic nephropathy patients increased during renal biopsy, and the proportion of albuminuria with hematuria decreased in 2014—2019 group (all P<0.05). Conclusions:Primary glomerular disease is the most common kidney disease in Ningxia. IgA nephropathy is the most common cause, and the proportion of membranous nephropathy is increasing year by year. Henoch-Sch?nlein purpura nephritis is the most common secondary glomerular disease, and the proportions of diabetic nephropathy and hypertensive renal damage are increasing year by year, suggesting that the screening of renal complications of metabolic diseases in Ningxia should be strengthened and pay more attention to the patients with mild abnormal urine test.

Purpose: Platelet-related indices, including mean platelet volume (MPV) and plateletocrit (PCT), have been reported as new prognostic factors of overall survival (OS) in many cancers, but not yet in biliary tract cancer (BTC). We intended to assess these indices in predicting OS in BTC patients with the aim to build a new prognostic model for patients with BTC after surgical resection. Materials and Methods: Survival analysis and time receiver operating characteristic analysis were applied to screen the platelet indices. Univariate and multivariate Cox analyses were used to identify independent prognostic factors and develop a new prognostic model. Harrell’s C-statistics, calibration curves, and decisive curve analysis were used to assess the model. Results: MPV and platelet distribution width (PDW)/PCT showed the best prognostic accuracy among the platelet indices. In multivariable analysis, factors predictive of poor OS were presence of nodal involvement, Non-radical surgery, poor tumor differentiation, carbohydrate antigen 19-9 > 100 U/mL, MPV > 8.1 fl, and PDW/PCT > 190. The new model was found to be superior to the TNM staging system and our new staging system showed higher discriminative power. Conclusion MPV and PDW/PCT have high prognostic value in BTC patients, and the novel staging system based on these two indices showed good discrimination and accuracy compared with the American Joint Committee on Cancer 7th TNM staging system.

Purpose: Platelet-related indices, including mean platelet volume (MPV) and plateletocrit (PCT), have been reported as new prognostic factors of overall survival (OS) in many cancers, but not yet in biliary tract cancer (BTC). We intended to assess these indices in predicting OS in BTC patients with the aim to build a new prognostic model for patients with BTC after surgical resection. Materials and Methods: Survival analysis and time receiver operating characteristic analysis were applied to screen the platelet indices. Univariate and multivariate Cox analyses were used to identify independent prognostic factors and develop a new prognostic model. Harrell’s C-statistics, calibration curves, and decisive curve analysis were used to assess the model. Results: MPV and platelet distribution width (PDW)/PCT showed the best prognostic accuracy among the platelet indices. In multivariable analysis, factors predictive of poor OS were presence of nodal involvement, Non-radical surgery, poor tumor differentiation, carbohydrate antigen 19-9 > 100 U/mL, MPV > 8.1 fl, and PDW/PCT > 190. The new model was found to be superior to the TNM staging system and our new staging system showed higher discriminative power. Conclusion MPV and PDW/PCT have high prognostic value in BTC patients, and the novel staging system based on these two indices showed good discrimination and accuracy compared with the American Joint Committee on Cancer 7th TNM staging system.