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 construct a risk prediction model for early post-injury respiratory failure in patients with traumatic cervical spinal cord injury (TCSCI) and validate its efficacy.Methods:A retrospective cohort study was conducted to analyze the clinical data of 393 TCSCI patients admitted to Zhengzhou Central Hospital Affiliated to Zhengzhou University from January 2020 to October 2024, including 294 males and 99 females, aged 18-82 years [59(45, 72)years]. Among them, 76 patients had respiratory failure (19.3%). The patients were randomly divided into the training set ( n=275) and validation set ( n=118) at a ratio of 7∶3. According to the presence of respiratory failure within one week after admission, 275 patients in the training set were divided into respiratory failure group ( n=53) and non-respiratory failure group ( n=222). The demographic data, injury characteristics, laboratory test results, and imaging findings of the patients were collected. Risk factors were determined through univariate analysis and multivariate Logistic regression analysis and a nomogram prediction model was constructed. The area under the receiver operating characteristic (ROC) curve (AUC) and Hosmer-Lemeshow test were used to evaluate the discrimination and calibration of the model. Decision curve analysis (DCA) was plotted to evaluate the clinical effectiveness of the prediction model. Results:The results of the univariate analysis showed that there were significant differences in history of respiratory diseases, causes of injury, Glasgow coma scale (GCS), American Spinal Injury Association (ASIA) classification, ASIA-motor score (AMS), injury severity score (ISS), clinical pulmonary infection score (CPIS), hypoproteinemia and cervical vertebra fracture and dislocation between the respiratory failure group and non-respiratory failure group in the training set ( P<0.05). The results of multivariate Logistic regression analysis indicated that GCS, ASIA classification, CPIS, and hypoproteinemia were independent risk factors for early post-injury respiratory failure in TCSCI patients ( P<0.05). Based on the above four variables, a Logistic regression equation was constructed: Logit( P)=2.361-0.675×ASIA classification+0.419×CPIS-0.358×GCS+0.854×hypoproteinemia. In the prediction model established based on this equation, the AUC was 0.96 (95% CI 0.94, 0.99) in the training set and 0.89 (95% CI 0.82, 0.96) in the validation set. In the calibration curves of the training set and validation set, the prediction curve and reference curve were approximately overlapping, with the average absolute errors of 0.04 and 0.03. DCA results demonstrated that both the training and validation sets exhibited positive net benefits when threshold probabilities fell within ranges of 0%-78% and 0%-87%, respectively. Conclusion:The risk prediction model for early post-injury respiratory failure in TCSCI patients based on GCS, ASIA classification, CPIS and hypoproteinemia has good predictive efficacy and clinical practicability.

Objective:To construct a risk prediction model for early post-injury respiratory failure in patients with traumatic cervical spinal cord injury (TCSCI) and validate its efficacy.Methods:A retrospective cohort study was conducted to analyze the clinical data of 393 TCSCI patients admitted to Zhengzhou Central Hospital Affiliated to Zhengzhou University from January 2020 to October 2024, including 294 males and 99 females, aged 18-82 years [59(45, 72)years]. Among them, 76 patients had respiratory failure (19.3%). The patients were randomly divided into the training set ( n=275) and validation set ( n=118) at a ratio of 7∶3. According to the presence of respiratory failure within one week after admission, 275 patients in the training set were divided into respiratory failure group ( n=53) and non-respiratory failure group ( n=222). The demographic data, injury characteristics, laboratory test results, and imaging findings of the patients were collected. Risk factors were determined through univariate analysis and multivariate Logistic regression analysis and a nomogram prediction model was constructed. The area under the receiver operating characteristic (ROC) curve (AUC) and Hosmer-Lemeshow test were used to evaluate the discrimination and calibration of the model. Decision curve analysis (DCA) was plotted to evaluate the clinical effectiveness of the prediction model. Results:The results of the univariate analysis showed that there were significant differences in history of respiratory diseases, causes of injury, Glasgow coma scale (GCS), American Spinal Injury Association (ASIA) classification, ASIA-motor score (AMS), injury severity score (ISS), clinical pulmonary infection score (CPIS), hypoproteinemia and cervical vertebra fracture and dislocation between the respiratory failure group and non-respiratory failure group in the training set ( P<0.05). The results of multivariate Logistic regression analysis indicated that GCS, ASIA classification, CPIS, and hypoproteinemia were independent risk factors for early post-injury respiratory failure in TCSCI patients ( P<0.05). Based on the above four variables, a Logistic regression equation was constructed: Logit( P)=2.361-0.675×ASIA classification+0.419×CPIS-0.358×GCS+0.854×hypoproteinemia. In the prediction model established based on this equation, the AUC was 0.96 (95% CI 0.94, 0.99) in the training set and 0.89 (95% CI 0.82, 0.96) in the validation set. In the calibration curves of the training set and validation set, the prediction curve and reference curve were approximately overlapping, with the average absolute errors of 0.04 and 0.03. DCA results demonstrated that both the training and validation sets exhibited positive net benefits when threshold probabilities fell within ranges of 0%-78% and 0%-87%, respectively. Conclusion:The risk prediction model for early post-injury respiratory failure in TCSCI patients based on GCS, ASIA classification, CPIS and hypoproteinemia has good predictive efficacy and clinical practicability.

The development of animal early embryos commences with the reprogramming of terminally differentiated gametes into totipotent zygotes following fertilization. During the initial stages of embryonic development, the transcriptional levels of zygotic genome remain silent and maternal gene products dominate the regulation of development. As embryonic development progresses, the maternal gene products undergo phased degradation while the zygotic genome gradually activates transcription, marking the transition from the maternal regulation to the zygotic genome regulation in early embryonic development, which is also referred to as the maternal-zygotic transition (MZT). Zygotic genome activation (ZGA) is a critical turning process in this transition, and its accurate occurrence is crucial for early embryonic development and cell fate decisions. However, the regulatory factors and molecular mechanisms of ZGA remain poorly understood. Studies have shown that ZGA varies greatly among different species and may be affected by a variety of regulatory factors such as DNA methylation, histone modification, non-coding RNA, chromatin remodeling and ZGA related factors. Here, we review the research progress of the above regulatory factors affecting ZGA, which can provide valuable insights for further investigations into the ZGA related mechanisms of early embryos.

OBJECTIVES: To examine the global, regional, and national disease burden of neonatal jaundice. METHODS: The 2019 Global Burden of Disease database was searched to collect incident cases/incidence and deaths/mortality of neonatal jaundice, as well as global socio-demographic index (SDI) and universal health coverage index (UHCI). The epidemiological trend of neonatal jaundice from 1990 to 2019 was analyzed. The correlations between incidence/mortality of neonatal jaundice and SDI and UHCI were evaluated. RESULTS: From 601 681 in 1990 to 626 005 in 2019, with a 4.04% increase in global incident cases of neonatal jaundice. The overall age-standardized incidence rate exhibited an increase [estimated annual percent change=0.13 (95%CI: 0.03 to 0.23)] during this period. Additionally, deaths due to neonatal jaundice decreased by 58.83%, from 128 119 in 1990 to 52 742 in 2019. The overall age-standardized mortality rate showed a decrease [estimated annual percent change=-2.78 (95%CI: -3.00 to -2.57)] over the same period. Countries with lower SDI, such as India, Pakistan, and Nigeria, reported a higher proportion of neonatal morbidity and mortality. In 2019, a negative correlation was observed between estimated annual percent change in age-standardized mortality rate and SDI (ρ=-0.320, P<0.05) or UHCI (ρ=-0.252, P<0.05). CONCLUSIONS The global incidence of neonatal jaundice is on the rise, while the mortality rate is declining. The burden of neonatal jaundice is influenced by social development, economic factors, and the level of medical care.
Infant, Newborn ; Humans ; Global Burden of Disease ; Jaundice, Neonatal/epidemiology* ; Incidence

To assess the reliability, validity and responsiveness of the Chinese version of the atopic dermatitis control tool (ADCT). After this study obtained authorization for the Chinese version of the ADCT scale. 114 patients with atopic dermatitis were enrolled from the Department of Dermatology, Peking University First Hospital using convenience sampling from October 2022. Patients were surveyed using the General Information Questionnaire, Chinese version of ADCT, patient-oriented eczema measure (POEM),peak pruritus numerical rating scale (PP-NRS),dermatology life quality index (DLQI) and the global patient self-assessment for disease severity. Mann-Whitney rank sum test and Spearman correlation analysis were used for item analysis; content validity was assessed using content validity index (CVI); exploratory factor analysis was used to assess structural validity; Cronbach' alpha coefficient was used to assess internal consistency; Spearman correlation analysis was used to assess the correlation of ADCT with other scales to assess external responsiveness. The results showed that all items were retained by item analysis. I-CVI was 0.9-1, and S-CVI/Average was 0.983; the scale extracted one common factor by factor analysis, the cumulative variance explanation rate was 77.927%; the Cronbach' alpha coefficient of the scale was 0.937; the correlation coefficients of the Chinese version of ADCT with POEM, PP-NRS, and DLQI were 0.805, 0.861, and 0.709 respectively. In conclusion, the Chinese version of the ADCT has adequate reliability, validity and responsiveness, and is suitable for measuring disease control in Chinese patients with atopic dermatitis.
Humans ; Dermatitis, Atopic ; Quality of Life ; Reproducibility of Results ; Surveys and Questionnaires

Inductively coupled plasma mass spectrometry (ICP-MS) was applied to determine the concentrations of lead (Pb), cadmium (Cd) and arsenic (As) in Lindera aggregata (Sims) Kosterm. The physiologically based extraction test (PBET) digestion in vitro/Caco-2 cell model was established to investigate the bioaccessible contents of Pb, Cd and As in decoction of Lindera aggregata (Sims) Kosterm. The target-organ toxicity dose modification of HI method (TTD) was used to evaluate the cumulative risk caused by the combined exposure of the total levels of Pb, Cd and As in Lindera aggregata (Sims) Kosterm. and the bioaccessible contents in the decoction. The results showed that the total contents of Pb, Cd and As in 4 batches of samples were in the range of 2.901-3.872, 1.299-1.800 and 0.062-0.216 mg·kg^-1, respectively. After transportation by Cacco-2 cells, the bioaccessible contents of Pb, Cd, and As in the decoction were in the range of 0.045-0.080, 0.070-0.112 and 0.004-0.018 mg·kg^-1. The results of risk assessment showed that calculated by the total amounts of heavy metals in the Lindera aggregata (Sims) Kosterm., for the end points of nervous system, the cumulative risks of co-exposure of heavy metals in 3 batches of samples were of concern. After decoction and transportation by Caco-2 cells, for the end points of cardiovascular system, blood, nervous system, kidney and testis, the TTD modification of HI values of all batches of samples were less than 1, and the health risks were acceptable. The study provided methodology basis for a more objective assessment of the health risks of heavy metals and harmful elements in traditional Chinese medicine and for a more scientific limit standard of heavy metals and harmful elements.

Objective:To construct a health education program for enterostomy patients based on the guideline of Facilitating Client Centered Learning. Methods:From July to October 2022, based on the adaptability survey and literature research of the previous guidelines, the first draft of the health education program for enterostomy patients was formed. A total of 13 experts were selected using purposive sampling method, and two rounds of expert consultation were conducted through the Delphi method on the first draft of the program to build the final health education program for enterostomy patients. We calculated the authority, enthusiasm, coordination, and concentration of experts.Results:The health education program for enterostomy patients included 3 first-level indicators, 9 second-level indicators, and 31 third-level indicators. The effective response rates of the first and second rounds of consultation questionnaires were both 100.0%, and the authority coefficients of experts were both greater than 0.7. In the second round of consultation, the Kendal coordination coefficients of the importance of the first, second and third level indicators were 0.231, 0.154 and 0.182 ( P<0.05), and the Kendal coordination coefficients of the feasibility of the first, second and third level indicators were 0.216, 0.154 and 0.129 ( P<0.05), with coefficients of variation < 0.25. Conclusions:The health education program for enterostomy patients based on the guideline of Facilitating Client Centered Learning is practical and scientific, and can provide guidance for clinical practice.

In order to establish the probabilistic risk assessment method for heavy metals and harmful elements in line with the characteristics of traditional Chinese medicine (TCM) and provide guidance for the safe use of TCM, the contents of lead (Pb), cadmium (Cd), arsenic (as), mercury (Hg) and copper (Cu) in 21 batches of Plantago asiatica L. were determined by inductively coupled plasma mass spectrometry (ICP-MS). By the comprehensive use of investigation of TCM consumption pattern and Monte Carlo simulation technology, the non-carcinogenic and carcinogenic health risks of heavy metals and harmful elements in TCM were assessed by hazard quotient (HQ) and cancer risk (CR), respectively. The greatest risk contributors were screened through sensitivity analysis. The results revealed that the mean contents of Pb, Cd, As, Hg and Cu in Plantago asiatica L. were 9.01, 0.28, 3.83, 0.01 and 12.82 mg·kg^-1, respectively. The P95, P99 and maximum values of HQ for males were 1.41, 2.83 and 10.97 mg·kg^-1, respectively. The P95, P99 and maximum values of HQ for females were 1.27, 2.63 and 9.80 mg·kg^-1, respectively. The P95, P99 and maximum values of HI for males were 1.44, 2.85 and 11.0 mg·kg^-1, respectively. The P95, P99 and maximum values of HI for females were 1.29, 2.66 and 10.0 mg·kg^-1, respectively. The P99 and maximum values for CR_As and total carcinogenic risk (TCR) were greater than 10^-4 for both men and women. The risk assessment results indicated that the non-carcinogenic and carcinogenic health risks of high exposure population caused by arsenic exposure are needed to be concern. The results of sensitivity analysis showed that the exposure frequency of TCM and the arsenic concentrations in Plantago asiatica L. were the main risk contributors. Based on Monte Carlo simulation technology and considering the characteristics of TCM, this study puts forward the first example of probabilistic risk assessment of heavy metals and harmful elements in Chinese herbal medicine, which provides a novel perspective for health risk assessment of heavy metals in TCM.