To analyze the disease burden, temporal trends, and attributable risk factors of early-onset female breast cancer (EOBC) in China and globally from 1990 to 2021.

Background: Nasopharyngeal carcinoma (NPC) is characterized by high programmed death-ligand 1 (PD-L1) expression and abundant infiltration of non-malignant lymphocytes, which renders patients potentially suitable candidates for immune checkpoint blockade therapies. Palate, lung, and nasal epithelium clone (PLUNC) inhibit the growth of NPC cells and enhance cellular apoptosis and differentiation. Currently, the relationship between PLUNC (as a tumor-suppressor) and PD-L1 in NPC is unclear. Methods: We collected clinical samples of NPC to verify the relationship between PLUNC and PD-L1. PLUNC plasmid was transfected into NPC cells, and the variation of PD-L1 was verified by western blot and immunofluorescence. In NPC cells, we verified the relationship of PD-L1, activating transcription factor 3 (ATF3), and β-catenin by western blot and immunofluorescence. Later, we further verified that PLUNC regulates PD-L1 through β-catenin. Finally, the effect of PLUNC on β-catenin was verified by co-immunoprecipitation (Co-IP). Results: We found that PLUNC expression was lower in NPC tissues than in paracancer tissues. PD-L1 expression was opposite to that of PLUNC. Western blot and immunofluorescence showed that β-catenin could upregulate ATF3 and PD-L1, while PLUNC could downregulate ATF3/PD-L1 by inhibiting the expression of β-catenin. PLUNC inhibits the entry of β-catenin into the nucleus. Co-IP experiments demonstrated that PLUNC inhibited the interaction of DEAD-box helicase 17 (DDX17) and β-catenin. Conclusions PLUNC downregulates the expression of PD-L1 by inhibiting the interaction of DDX17/β-catenin in NPC.

Background: Nasopharyngeal carcinoma (NPC) is characterized by high programmed death-ligand 1 (PD-L1) expression and abundant infiltration of non-malignant lymphocytes, which renders patients potentially suitable candidates for immune checkpoint blockade therapies. Palate, lung, and nasal epithelium clone (PLUNC) inhibit the growth of NPC cells and enhance cellular apoptosis and differentiation. Currently, the relationship between PLUNC (as a tumor-suppressor) and PD-L1 in NPC is unclear. Methods: We collected clinical samples of NPC to verify the relationship between PLUNC and PD-L1. PLUNC plasmid was transfected into NPC cells, and the variation of PD-L1 was verified by western blot and immunofluorescence. In NPC cells, we verified the relationship of PD-L1, activating transcription factor 3 (ATF3), and β-catenin by western blot and immunofluorescence. Later, we further verified that PLUNC regulates PD-L1 through β-catenin. Finally, the effect of PLUNC on β-catenin was verified by co-immunoprecipitation (Co-IP). Results: We found that PLUNC expression was lower in NPC tissues than in paracancer tissues. PD-L1 expression was opposite to that of PLUNC. Western blot and immunofluorescence showed that β-catenin could upregulate ATF3 and PD-L1, while PLUNC could downregulate ATF3/PD-L1 by inhibiting the expression of β-catenin. PLUNC inhibits the entry of β-catenin into the nucleus. Co-IP experiments demonstrated that PLUNC inhibited the interaction of DEAD-box helicase 17 (DDX17) and β-catenin. Conclusions PLUNC downregulates the expression of PD-L1 by inhibiting the interaction of DDX17/β-catenin in NPC.

Background: Nasopharyngeal carcinoma (NPC) is characterized by high programmed death-ligand 1 (PD-L1) expression and abundant infiltration of non-malignant lymphocytes, which renders patients potentially suitable candidates for immune checkpoint blockade therapies. Palate, lung, and nasal epithelium clone (PLUNC) inhibit the growth of NPC cells and enhance cellular apoptosis and differentiation. Currently, the relationship between PLUNC (as a tumor-suppressor) and PD-L1 in NPC is unclear. Methods: We collected clinical samples of NPC to verify the relationship between PLUNC and PD-L1. PLUNC plasmid was transfected into NPC cells, and the variation of PD-L1 was verified by western blot and immunofluorescence. In NPC cells, we verified the relationship of PD-L1, activating transcription factor 3 (ATF3), and β-catenin by western blot and immunofluorescence. Later, we further verified that PLUNC regulates PD-L1 through β-catenin. Finally, the effect of PLUNC on β-catenin was verified by co-immunoprecipitation (Co-IP). Results: We found that PLUNC expression was lower in NPC tissues than in paracancer tissues. PD-L1 expression was opposite to that of PLUNC. Western blot and immunofluorescence showed that β-catenin could upregulate ATF3 and PD-L1, while PLUNC could downregulate ATF3/PD-L1 by inhibiting the expression of β-catenin. PLUNC inhibits the entry of β-catenin into the nucleus. Co-IP experiments demonstrated that PLUNC inhibited the interaction of DEAD-box helicase 17 (DDX17) and β-catenin. Conclusions PLUNC downregulates the expression of PD-L1 by inhibiting the interaction of DDX17/β-catenin in NPC.

Objective To explore the construction of α-1,3-galactosyltransferase (GGTA1) gene-knockout (GTKO) Diannan miniature pigs and the kidney xenotransplantation from pigs to rhesus macaques, and to assess the effectiveness of GTKO pigs. Methods The GTKO Diannan miniature pigs were constructed using the CRISPR/Cas9 gene-editing system and somatic cell cloning technology. The phenotype of GTKO pigs was verified through polymerase chain reaction, Sanger sequencing and immunofluorescence staining. Flow cytometry was used to detect antigen-antibody (IgM) binding and complement-dependent cytotoxicity. Kidney xenotransplantation was performed from GTKO pigs to rhesus macaques. The humoral immunity, cellular immunity, coagulation and physiological indicators of the recipient monkeys were monitored. The function and pathological changes of the transplanted kidneys were analyzed using ultrasonography, hematoxylin-eosin staining, immunohistochemical staining and immunofluorescence staining. Results Single-guide RNA (sgRNA) targeting exon 4 of the GGTA1 gene in Diannan miniature pigs was designed. The pGL3-GGTA1-sgRNA1-GFP vector was transfected into fetal fibroblasts of Diannan miniature pigs. After puromycin selection, two cell clones, C59# and C89#, were identified as GGTA1 gene-knockout clones. These clones were expanded to form cell lines, which were used as donor cells for somatic cell nuclear transfer. The reconstructed embryos were transferred into the oviducts of trihybrid surrogate sows, resulting in 13 fetal pigs. Among them, fetuses F04 and F11 exhibited biallelic mutations in the GGTA1 gene, and F04 had a normal karyotype. Using this GTKO fetal pig for recloning and transferring the reconstructed embryos into the oviducts of trihybrid surrogate sows, seven surviving piglets were obtained, all of which did not express α-Gal epitope. The binding of IgM from the serum of rhesus monkey 20# to GTKO pig PBMC was reduced, and the survival rate of GTKO pig PBMC in the complement-dependent cytotoxicity assay was higher than that of wild-type pig. GTKO pig kidneys were harvested and perfused until completely white. After the left kidney of the recipient monkey was removed, the pig kidney was heterotopically transplanted. Following vascular anastomosis and blood flow restoration, the pig kidney rapidly turned pink without hyperacute rejection (HAR). Urine appeared in the ureter 6 minutes later, indicating successful kidney transplantation. The right kidney of the recipient was then removed. Seven days after transplantation, the transplanted kidney had good blood flow, the recipient monkey's serum creatinine level was stable, and serum potassium and cystatin C levels were effectively controlled, although they increased 10 days after transplantation. Seven days after transplantation, the levels of white blood cells, lymphocytes, monocytes and eosinophils in the recipient monkey increased, while platelet count and fibrinogen levels decreased. The activated partial thromboplastin time, thrombin time and prothrombin time remained relatively stable but later showed an upward trend. The recipient monkey survived for 10 days. At autopsy, the transplanted kidney was found to be congested, swollen and necrotic, with a small amount of IgG deposition in the renal tissue, and a large amount of IgM, complement C3c and C4d deposition, as well as CD68⁺ macrophage infiltration. Conclusions The kidneys of GTKO Diannan miniature pigs may maintain normal renal function for a certain period in rhesus macaques and effectively overcome HAR, confirming the effectiveness of GTKO pigs for xenotransplantation.

Cervical cancer is one of the most common gynecological malignant tumors in China. Given their lack of obviously early symptoms, more than half of patients with cervical cancer are diagnosed in the middle and late stages of this malignancy, resulting in poor prognosis. Finding new therapeutic targets is the current research direction. Metabolomics, as a new omics technology, is expected to provide new targets for tumor precision diagnosis and treatment through the analysis of the changes and potential mechanisms of metabolites in tumor occurrence and development by chromatography, mass spectrometry, and other technologies. Herein, we review the research methods of metabolomics; metabolic characteristics of cervical cancer; and progress of the research on metabolomics in cervical cancer diagnosis, curative effect prediction, and prognosis evaluation to provide new ideas for the precise diagnosis and treatment of cervical cancer.

Objective To explore the mediating role of occupational well-being in the relationship between professional identity and safety behavior among nurses. Methods A total of 1 006 nurses from ten tertiary general hospitals in eight provincial administrative regions were selected as the research subjects using convenient sampling method. Their safety behavior, professional identity and occupational well-being were investigated using Nurse Safety Behavior Scale, Nurse Professional Identity Scale and Occupational Well-being Scale. Structural equation modeling was performed using AMOS 26.0 to examine the mediating effect of occupational well-being in the relationship between professional identity and safety behavior among nurses. Results The scores for safety behavior, professional identity, and occupational well-being were (53.0±6.1), (123.7±21.2) and (90.8±13.1), respectively. Safety behavior was positively correlated with both professional identity and occupational well-being (correlation coefficients were 0.50 and 0.50, respectively, both P<0.01). Professional identity was positively correlated with occupational well-being (correlation coefficient was 0.51, P<0.01). The multiple linear regression analysis results showed that the higher the professional identity and occupational well-being of nurses, the higher the level of safety behavior (both P<0.05). The result of mediating effect shows that the total effect of occupational identity on safety behavior was 0.498 [95% confidence interval (CI) was 0.405-0.576], and occupational well-being played a mediating role between professional identity and safety behavior among nurses with the mediation effect of 0.156 (95%CI was 0.112-0.205), accounting for 31.33% of the total effect. Conclusion The safety behavior of nurses is at a moderate level. Both professional identity and occupational well-being can affect the safety behavior of nurses. Professional identity can increase the safety behavior of nurses by affecting occupational well-being.

Post-endoscopic retrograde cholangiopancreatography pancreatitis(PEP)is one of the most common complications after endoscopic retrograde cholangiopancreatography(ERCP).Numerous PEP prediction models have been established based on different statistical methods at home and abroad.The PEP prediction model,as a tool for evaluating and screening high-risk populations,can provide a basis for medical staff to find high-risk PEP patients early and take effective preventive measures.In recent years,new PEP prediction models have appeared one after another,but there is still a lack of recognized reliable prediction models in clinic.This article reviews the research status of PEP risk prediction models,aim to provide a direction for establishing a more reliable,accurate,and practical PEP risk prediction model in the later period.

Objective:To explore the effects of pre-transplant controlling nutritional status(CONUT)and post-transplant minimal residual disease(MRD)on prognosis of patients with multiple myeloma(MM)after autologous hematopoietic stem cell transplantation(auto-HSCT).Methods:The clinical data of 79 patients who received auto-HSCT from 2011 to 2020 in The First Affiliated Hospital of Chongqing Medical University were retrospectively analyzed.The patients were divided into Low-CONUT group(n=62)and High-CONUT group(n=17)according to whether the CONUT score was less than 5.The differences in clinical features,hematopoietic reconstruction,adverse reactions,efficacy and survival between the two groups were compared.In addition,the prognostic risk factors were analyzed and verified by time-dependent ROC curve.Results:The proportions of male patients and bone marrow plasma cells＞30％at initial diagnosis in High-CONUT group were both higher than those in Low-CONUT group(both P＜0.05).While,there were no significant differences in hematopoietic reconstruction and adverse reactions(＞grade 2)between the two groups.The complete response(CR)rate and CR+very good partial response(VGPR)rate before transplantation in Low-CONUT group were both significantly higher than those in High-CONUT group(both P＜0.05).After 3 months of transplantation,the CR+VGPR rate still remained an advantage in Low-CONUT group compared with High-CONUT group(P＜0.01),but CR rate did not(P＞0.05).The overall survival(OS)and progression-free survival(PFS)in Low-CONUT group were both superior to those in High-CONUT group(both P＜0.05).Low CONUT score(0-4)before transplantation and negative MRD at 6 months after transplantation were favorable factors affecting OS and PFS(both P＜0.05),while the International Myeloma Working Group(IMWG)high-risk at initial diagnosis and lactate dehydrogenase(LDH)level＞250 U/L before transplantation were only risk factors for PFS(both P＜0.05).Time-dependent ROC curve analysis showed that pre-transplant CONUT score and MRD status at 6 months after transplantation could independently or jointly predict 1-and 2-year OS and PFS,and the combined prediction was more effective.Conclusion:The combination of pre-transplant CONUT and post-transplant MRD can better predict the prognosis of MM patients.

Objective:To investigate the accuracy and feasibility of applying rapid immunohistochemistry(IHC) with CK5/6 antibodies in prostate biopsy tissues to assist frozen pathology diagnosis.Methods:The data of 41 patients who underwent prostate puncture and frozen tissue rapid IHC with CK5/6 antibody in Beijing Hospital from October 2022 to April 2023 were retrospectively analyzed. The median age of the patients was 76 (69, 79) years old, and the median PSA value was 12.37 (7.07, 26.17) ng/ml.The Prostate Imaging Reporting and Data System (PI-RADS) scores of the target lesions were all ≥3. The PI-RADS score of 9 patients(21.95%) was 3, 15 (36.59%) was 4, and 17(41.46%) was 5. The median diameter of the lesions in the MRI examination was 1.40 (1.09, 2.20) cm.Fourteen lesions (34.14%) were located in the migratory zone, 23 (56.10%) were located in the peripheral zone, and 4 (9.76%) involved both peripheral and migratory zone lesions. Transperineal cognitive fusion targeted combined systematic biopsy was used, and intraoperatively, 1 additional needle was taken from each of the target and non-target areas for frozen pathology section, and hematoxylin eosin(HE) staining and rapid IHC staining with CK5/6 antibody was performed, then the frozen remaining tissue was HE staining and CK5/6 IHC staining. Data such as HE and rapid IHC results of frozen pathology sections and HE and IHC results of routine sections of the frozen remaining tissues, International Society of Urological Pathology (ISUP) grading groupings(GG), and actual diagnostic results of targeted combined systematic puncture were recorded. Using the routine IHC results of the same needle tissue as the gold standard, the sensitivity and positive predictive value of applying rapid IHC frozen pathology to diagnose prostate cancer and the accuracy of its pathological GG were analyzed.Results:Among the 41 patients, a total of 35 cases were diagnosed with prostate cancer(PCa) by HE staining in frozen section of target tissue, with a positivity rate of 85.37%(35/41). Among these, there were 17 cases (48.57%) in ISUP GG 1, 8 cases (22.86%) in GG 2, 4 cases (11.43%) in GG 3, and 6 cases (17.14%) in GG 4 to 5. In addition, a total of 35 cases were diagnosed with PCa by HE staining in frozen remaining section of target tissue, with a positivity rate of 85.37%(35/41). Among these, there were 17 cases (48.57%) in ISUP GG 1, 8 cases (22.86%) in GG 2, 4 cases (11.43%) in GG 3, and 6 cases (17.14%) in GG 4 to 5. The results of rapid IHC of target tissue: 35 cases were negative for CK5/6 expression and 6 cases were positive. The results of routine IHC of target tissue: 35 cases were negative for CK5/6 expression and 6 cases were positive. The results of rapid IHC of non-target tissue: 12 cases were negative for CK5/6 expression and 29 cases were positive. The results of routine IHC of non-target tissue: 12 cases were negative for CK5/6 expression and 29 cases were positive. Thirty-five cases of target tissue rapid IHC diagnosis of PCa were in complete agreement with routine IHC diagnosis, with a false-positive rate of 0, a sensitivity of 100.00% (35/35) and a positive predictive value of 100.00% (35/35). Twelve cases of non-target tissue rapid IHC diagnosis of PCa were in complete agreement with routine IHC diagnosis, with a false-positive rate of 0, a sensitivity of 100.00% (35/35), and a positive predictive value of 100.00% (12/12).Conclusions:The preliminarily study results confirmed that the application of rapid IHC with CK5/6 antibodies in prostate biopsy tissues assisted frozen pathology diagnosis with high accuracy, but the reliability of rapid IHC technology in assisting frozen pathological diagnosis during puncture surgery still needs further validation through large sample size prospective studies.