Objective To provide technical support for the formulation of scientific and reasonable supervision measures for enterprises engaged in the exploitation and utilization of ores with associated radionuclides in Guangxi Province, China. Methods A radionuclide analysis was performed on solid materials generated during production processes such as zirconium-titanium ore dressing and processing in multiple enterprises in Guangxi Province. The radiation levels of effluents was measured. Measurement and analysis were performed on the environmental air radon concentration levels and environmental γ-radiation dose rates at the factory boundaries of these enterprises and the surrounding environmental protection targets. Results The air absorption dose rate of γ radiation, the concentrations of radon and its daughters, and the radiation levels of surface water and aerosols at the factory boundaries and in the surrounding environment were all at normal levels. The specific activities of nuclides ²³⁸U, ²³²Th, and ²²⁶Ra in the raw ore, zirconium products, rutile products, and monazite products within the factory area were relatively high. The γ radiation air absorption dose rates in the corresponding workshops were also relatively high, with the zirconium-rutile workshop being the area with the highest values. Materials such as zirconium products, rutile, and monazite all showed a certain amount of radon exhalation. Conclusion The radiation level of tailings met the criteria of monitoring exemption, and the enterprises did not generate radioactive solid waste. Attention should be paid to the personal dose of the staff in areas with high radiation dose rates.

Rare diseases are a collective term for diseases with extremely low prevalence and incidence rates.Up to now,China has released two lists identifying a total of 207 rare diseases.Given that most rare diseases do not have drugs with corresponding indications,physicians frequently resort to using off-label drugs when treating patients with rare diseases.However,there is currently no systematic guideline or expert consensus for the use of off-label medications in China.To comprehensively collect existing evidence of off-label drug use for rare diseases,fully analyze and evaluate the rationality of off-label drug use for rare diseases,and standardize the management of off-label drug use for rare diseases,the Rare Disease Branch of Beijing Medical Association,Chinese Pharmaceutical Association,Beijing Pharmaceutical Association,and the School of Public Health,Peking University have jointly initiated the drafting of the Expert Consensus on Off-label Use of Drugs for Rare Diseases.This consensus refer to the WHO Handbook for Guideline Development,the Guidelines for Developing/Revising Clinical Diagnostic and Treatment Guidelines in China(2022 Edition),the AGREE Ⅱ and the STAR tools.This protocol outlines the background and purpose of consensus,as well as the comprehensive framework for consensus development,encompassing panel formation,clinical issue identification,evidence retrieval,data extraction,and evidence-based recommendation formulation.

The aim of this updated guideline is to provide comprehensive recommendations for the management of gout in patients with common comorbidities, such as chronic kidney disease(CKD), cardiovascular disease(CVD), diabetes, osteoarthritis(OA), and gastrointestinal disorders. This guideline was developed by a multidisciplinary expert panel consisting of specialists in endocrinology, rheumatology, nephrology, cardiology, gastroenterology, and methodology. The development process adhered to standard methodologies, including PICO(population, intervention, comparator, and outcomes) question deconstruction, systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation(GRADE) for evidence and recommendation evaluation, Delphi voting, and expert consensus. The guideline presents 26 evidence-based recommendations addressing 7 clinical questions for patients with hyperuricemia and gout in the context of comorbidities. Key recommendations include the maintenance of strict serum urate targets, particularly for patients with CKD stage≥3, chronic gouty arthritis, and OA, in order to prevent disease progression. In patients with CVD or diabetes, intra-articular triamcinolone is preferred over systemic glucocorticoids. Prioritized anti-inflammatory treatments for patients with CKD, gastrointestinal diseases and OA are recommended. The guideline also introduces emerging therapies, such as interleukin-1 inhibitors and selective urate transport inhibitors, as potential treatment options for refractory cases. The update offers a comprehensive, patient-centered approach to managing gout, particularly in individuals with associated comorbidities. Multidisciplinary collaboration and emerging new treatments and evidence ensure the optimization of the recommendations.

Objective:To investigate the association between estimated cumulative low-density lipoprotein cholesterol (LDL-C) exposure and the severity of coronary artery disease and long-term adverse cardiovascular and cerebrovascular events (MACCE) in patients with acute coronary syndrome (ACS).Methods:The subjects were from the PROMISE study. This study was a prospective cohort study led by Fuwai Hospital, Chinese Academy of Medical Sciences, with participation from eight regional tertiary hospitals as sub-centers, and enrolled 18 701 patients with confirmed coronary heart disease between January 2015 and May 2019. Among them, 8 429 patients with ACS were included in this study. The estimated cumulative LDL-C exposure was calculated by multiplying LDL-C by age. Participants were then divided into four groups based on quartiles. Baseline data and coronary angiography data were collected, and participants were followed for 2 years. The primary endpoint was MACCE, which was composed of all-cause death, cardiac death, myocardial infarction, revascularization, and stroke. Spearman correlation analysis was used to estimate the correlation between cumulative LDL-C exposure and the severity of coronary artery disease. The differences in MACCE among the four groups were compared, and multivariate Cox regression was used to divide the estimated cumulative exposure LDL-C into two groups, three groups, and four groups to analyze its relationship with MACCE.Results:The 8 429 ACS patients included in the study had an age of (60.9±11.4) years, with 1 951(23.1%) females. Spearman correlation analysis revealed that estimated cumulative LDL-C exposure was positively associated with the preoperative SYNTAX score, three-vessel lesions disease, left main disease, and the number of target lesions (correlation coefficients r=0.14, 0.10, 0.04 and 0.03, respectively, with all P<0.05). The 2-year follow-up results indicated that the incidence rates of MACCE, all-cause death, cardiac death, myocardial infarction, and stroke in ACS patients grouped by different levels of estimated cumulative LDL-C exposure were statistically significant (all P<0.05). The results of the Cox multivariate regression analysis showed that when the estimated cumulative LDL-C exposure was treated as a continuous variable and analyzed in two, three, and four groups, with the lowest group as the reference, the risk of MACCE occurrence in the high-value group increased by 21% (95% CI 1.08-1.37, P=0.002), 24% (95% CI 1.07-1.43, P=0.004), and 21% (95% CI 1.02-1.43, P=0.025) respectively. Conclusions:A positive correlation was found between estimated cumulative LDL-C exposure and severity of coronary artery disease. High estimated cumulative LDL-C exposure level is a risk factor for MACCE in ACS patients within 2 years.

Rare diseases are a collective term for diseases with extremely low prevalence and incidence rates.Up to now,China has released two lists identifying a total of 207 rare diseases.Given that most rare diseases do not have drugs with corresponding indications,physicians frequently resort to using off-label drugs when treating patients with rare diseases.However,there is currently no systematic guideline or expert consensus for the use of off-label medications in China.To comprehensively collect existing evidence of off-label drug use for rare diseases,fully analyze and evaluate the rationality of off-label drug use for rare diseases,and standardize the management of off-label drug use for rare diseases,the Rare Disease Branch of Beijing Medical Association,Chinese Pharmaceutical Association,Beijing Pharmaceutical Association,and the School of Public Health,Peking University have jointly initiated the drafting of the Expert Consensus on Off-label Use of Drugs for Rare Diseases.This consensus refer to the WHO Handbook for Guideline Development,the Guidelines for Developing/Revising Clinical Diagnostic and Treatment Guidelines in China(2022 Edition),the AGREE Ⅱ and the STAR tools.This protocol outlines the background and purpose of consensus,as well as the comprehensive framework for consensus development,encompassing panel formation,clinical issue identification,evidence retrieval,data extraction,and evidence-based recommendation formulation.

Objective:To conduct a scoping review of studies on decision aids for lung cancer screening and provide a reference for the development of such tools in China.Methods:In accordance with the methodology of scoping reviews, a comprehensive search was performed across PubMed, Web of Science, Embase, Cochrane Library, China Biology Medicine disc, China National Knowledge Infrastructure, Wanfang Data, and VIP from inception to November 1, 2024. The included literature was summarized and analyzed.Results:A total of 18 studies were included. The decision aids for lung cancer screening mainly addressed elements such as information support and guidance, analysis of pros and cons related to screening decisions, clarification of values and preferences, and communication support during decision-making. Outcome indicators included cognitive and behavioral aspects, values and preferences, decision outcomes, acceptability and feasibility of the tools. The application effects showed improvements in participants' knowledge about lung cancer screening, screening behaviors, reduced decisional conflict and regret, and increased satisfaction with decision-making. Participants showed a high level of acceptance of these tools.Conclusions:Current research on lung cancer screening decision aids is predominantly conducted in other countries and demonstrates positive effects. In the future, China can draw on these experiences to develop decision aids suitable for the Chinese population, with the aim of reducing decisional conflict and improving decision quality.

Objective To analyze the effects of irbesartan(IBN)regulating the stromal cell-derived factor-1(SDF-1)/CXC chemokine receptor 4(CXCR4)pathway on proliferation,migration,and radiosensitivity of lung cancer cells.Methods Human lung cancer A549 cells were randomly divided into the A549 group(without treatment),radiation group(4 Gy X-ray radiation),IBN group(1 μmol/L IBN treatment for 24 hours),IBN+radiation group(1 μmol/L IBN treatment for 24 hours+4 Gy X-ray radiation),pcDNA3.1 group(transfected with pcDNA3.1+1 μmol/L IBN treatment for 24 hours+4 Gy X-ray radiation),and SDF-1 group(transfected with pcDNA3.1 SDF-1+1 μmol/L IBN treatment for 24 hours+4 Gy X-ray radiation).The cell viability,colony formation,apoptosis,and migration of each group were observed.The leakage rate of lactate dehydrogenase(LDH)and Ang Ⅱ levels in cells were detected.Immunofluorescence method was applied to analyze the number of γH2AX focal points of cells in each group.Western blot was applied to detect the expression of proliferation and apoptosis related proteins and SDF-1/CXCR4 pathway related proteins.Results Both radiation and IBN treatment inhibited the proliferation and migration of A549 cells,promoted cell apoptosis,upregulated the number of γH2AX focal points and LDH leakage rate,upregulated the expression of Caspase-3,Bax,and Caspase-7,and downregulated the level of Ang Ⅱand expression of SDF-1,CXCR4,Bcl-2 and PCNA(P<0.05).The combined treatment of radiation and IBN further enhanced the changes of the above indicators(P<0.05).And SDF-1 treat-ment effectively reversed the effects of radiation and IBN treatment on the changes of the above indicators(P<0.05).Conclusion IBN can limit proliferation and migration of lung cancer cells,and increase radiosensitivity by inhibiting the SDF-1/CXCR4 pathway.

Objective:To evaluate the efficacy and safety of Nimotuzumab combined with concurrent chemoradiotherapy in elderly women with locally advanced cervical cancer.Methods:A retrospective analysis was conducted among elderly patients with cervical cancer who received nimotuzumab combined with concurrent chemoradiotherapy in the gynecology department of Beijing Hospital from November 2018 to March 2023.Efficacy assessments included the objective response rate(ORR), recurrence rates after 1-3 years of follow-up, and comparisons of the levels of squamous cell carcinoma antigen(SCC), carcino-embryonic antigen(CEA), and carbohydrate antigen 125(CA125)before and after treatment.Adverse reactions were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events(NCI-CTCAE)version 5.0.Results:A total of 47 elderly patients aged 60 years and older with stage ⅠB3-Ⅳa cervical cancer were included, with ages ranging from 60 to 76 years[mean age: (65.8±4.3) years; median age: 65(62, 70) years].The patients were divided into three age groups: 60-64 years(21 cases), 65-69 years(14 cases), and ≥70 years(12 cases).After treatment, SCC and CEA levels significantly decreased compared to pre-treatment levels, with statistically significant differences ( W=5.281 and 2.607, respectively; both P<0.05).However, there was no significant difference in CA125 levels before and after treatment( W=1.591, P=0.112).Among the 47 patients, 3 did not undergo post-treatment imaging examinations.Efficacy evaluation results were collected from 44 patients, including 21 cases of complete response(CR)(47.7%), 21 cases of partial response(PR)(47.7%), 1 case of stable disease(SD)(2.3%), and 1 case of progressive disease(PD)(2.3%).The ORR was 95.5%(42/44), and the diseae control rate was 97.7%(43/44).There were statistically significant differences in efficacy among different age groups(Fisher's exact test P=0.015).During the treatment process, a total of 36 patients experienced grade 3 or higher adverse reactions during treatment.Among them, 14 cases(29.8%)with grade 3 or higher acute hematological adverse reactions, 11 cases(23.4%)with grade 3 or higher acute gastrointestinal reactions, and 6 cases(12.8%)with grade 3 or higher acute urinary symptoms.Additionally, 2 cases of radiation cystitis and 3 cases of radiation proctitis were reported.There was no statistically significant difference in recurrence rates among different age groups(Fisher's exact test P=0.292).The highest recurrence rate among elderly patients was observed at the 2-3 year follow-up. Conclusions:For elderly patients with good organ function status, standard concurrent chemoradiotherapy combined with nimotuzumab may be an effective treatment for locally advanced cervical cancer.

Objective To investigate the effects and mechanisms of ubiquitin-associated domain-containing protein 2(UBAC2)mediated by m6A methylation modification on the invasion and migration abilities of colorectal cancer cells.Methods The GEPIA2.0 database was utilized to analyze the expression differences of UBAC2 mRNA between colorectal cancer tissues and adjacent normal tissues,as well as its expression in colorectal cancer tissues at different stages.The correlation between Wilms tumor 1-associated protein(WTAP)and UBAC2 expression was analyzed.The Kaplan-Meier plotter online tool was applied to analyze the correlation between UBAC2 and the overall survival rate of colorectal cancer patients.The RMVar and SRAMP databases were employed to predict potential m6A methylation modification sites in the UBAC2 gene.Quantitative real-time PCR(qRT-PCR)and Western blotting were performed to detect the expression levels of UBAC2 mRNA and protein in colorectal cancer cell lines.For UBAC2 knockdown experiments,SW480 cells were divided into control group(no treatment),sh-NC group(transfected with sh-NC negative control plasmid),and sh-UBAC2 group(transfected with sh-UBAC2 plasmid).For WTAP knockdown experiments,groups included control group(no treatment),si-NC group(transfected with negative control siRNA),and si-WTAP group(transfected with WTAP-targeting siRNA).For UBAC2 overexpression experiments,groups were control group(no treatment),si-WTAP group(transfected with pcDNA3.1 empty plasmid),and si-WTAP+OE-UBAC2 group(transfected with UBAC2 overexpression plasmid pcDNA3.1-UBAC2).Western blotting was used to detect the protein expression levels of UBAC2,WTAP,E-cadherin,N-cadherin,and Vimentin;qRT-PCR was applied to detect the expression level of UBAC2 mRNA;Transwell assays were conducted to assess cell invasion and migration abilities.MeRIP-qPCR was employed to detect the m6A methylation modification of UBAC2 mRNA;RIP-qPCR experiments were conducted to verify the binding of WTAP to UBAC2 mRNA.In nude mouse colorectal cancer lung metastasis experiments,groups included LV-sh-NC group(tail vein injection of SW480 cells stably infected with LV-sh-NC)and LV-sh-UBAC2 group(tail vein injection of SW480 cells stably infected with LV-sh-UBAC2).After 42 d of tumor-implantation in nude mice,lung tissues were harvested:the number of lung nodules observed by hematoxylin/eosin(HE)staining,and the expression level of Luc2 mRNA detected by qRT-PCR.Results GEPIA2.0 database analysis revealed that the expression level of UBAC2 mRNA in colorectal cancer tissues was significantly higher than that in adjacent normal tissues,and it gradually increased with the progression of tumor stage(P<0.05).The expression levels of UBAC2 mRNA and protein in multiple colorectal cancer cell lines were significantly higher than those in normal colonic epithelial cells(P<0.05).Compared with sh-NC group,sh-UBAC2 group showed significantly increased E-cadherin protein expression,significantly decreased N-cadherin and Vimentin protein expression,and significantly reduced number of invaded and migrated SW480 cells(P<0.05).GEPIA2.0 database analysis results indicated a positive correlation between WTAP and UBAC2 expression(r=0.24,P<0.001).Compared with si-NC group,si-WTAP group showed significantly decreased expression levels of WTAP and UBAC2 mRNA and protein in SW480 cells(P<0.05).MeRIP-qPCR results demonstrated that the m6A modification level of UBAC2 mRNA in si-WTAP group was significantly lower than that in si-NC group(P<0.05).RIP-qPCR further confirmed that WTAP could bind to UBAC2 mRNA.Compared with control group,si-WTAP group showed significantly increased E-cadherin protein expression and significantly decreased N-cadherin and Vimentin protein expression in SW480 cells(P<0.05);compared with si-WTAP group,si-WTAP+OE-UBAC2 group showed significantly decreased E-cadherin protein expression and significantly increased N-cadherin and Vimentin protein expression in SW480 cells(P<0.05).The number of lung nodules in LV-sh-UBAC2 group was significantly fewer than that in LV-sh-NC group,and the expression level of Luc2 mRNA in lung tissues was significantly lower than that in LV-sh-NC group(P<0.05).Conclusion UBAC2 mediated by m6A methylation modification can regulate the epithelial-mesenchymal transition(EMT)process in colorectal cancer cells,thereby affecting the invasion and migration abilities of colorectal cancer cells.

OBJECTIVE: To investigate the association of various polycyclic aromatic hydrocarbon (PAH) metabolites with diverse subtypes of cardiovascular disease (CVD) risk. METHODS: A novel predicting risk of cardiovascular disease EVENTs PREVENT equation was used to estimate the 10-year diverse subtypes of CVD risk, and their associations with PAH metabolites were analyzed using multiple logistic regression models, the weighted quantile sum (WQS) model, the quantile g-computation (qgcomp) model, and a stratified analysis of subgroups. RESULTS: For this study, six thousand seven hundred and forty-five participants were selected, and significant positive associations were observed between PAHs, naphthalene (NAP), and fluorene (FLU), and the risks of total CVD, atherosclerotic cardiovascular disease (ASCVD), and heart failure (HF). NAP and FLU were the primary contributors to the effects of PAH mixtures, and their associations with total CVD, ASCVD, and HF risk were significant in younger participants (30 ≤ age < 50 years); however, the associations of phenanthrene (PHEN) with ASCVD, HF, coronary heart disease (CHD), and stroke were dominant in aging participants (age ≥ 50 years). Notably, pyrene (PYR) was negatively associated with the risk of ASCVD, HF, CHD, and stroke. Similarly, negative associations of PYR with the four CVD subtypes were noticeable in aging participants. CONCLUSION Different PAHs metabolites had different impacts on each CVD subtype among different age groups. Notably, the protective effects of PYR on ASCVD, HF, CHD, and stroke were noticeable in aging individuals.
Humans ; Cardiovascular Diseases/chemically induced* ; Middle Aged ; Polycyclic Aromatic Hydrocarbons/metabolism* ; Male ; Female ; Adult ; Aged ; Risk Factors ; China/epidemiology*