Few studies have evaluated the global burden of chronic kidney disease (CKD) in adolescents and young adults (AYAs). Methods: Age-standardized rates of incidence (ASIR), mortality (ASMR), and disability-adjusted life-years (ASDR) were used to describe the CKD burden in AYAs. The estimated annual percentage changes (EAPCs) were calculated to evaluate the temporal trends from 1990 to 2019. Risk factors were calculated by population attributable fractions. Results: In 2019, the ASIR, ASMR, and ASDR of CKD in AYAs were 32.21 (95% uncertainty interval [UI], 23.73–40.81) per 100,000, 2.86 (2.61–3.11) per 100,000 and 236.85 (209.03–268.91) per 100,000, respectively. The ASIR was higher among females than males, whereas the ASMR was higher among males than females in 2019. From 1990 to 2019, significant increases in ASIR were found for CKD (EAPC, 0.98%; 95% confidence interval [CI], 0.95%–1.01%), although the ASMR had decreased (EAPC, –0.40%; 95% CI, –0.56% to –0.24%). The largest increase in ASIR was observed in countries with a middle sociodemographic index (SDI) (EAPC, 1.30%; 95% CI, 1.28%–1.33%), while the largest increase in ASMR was observed in high SDI. Globally, the proportional contribution of risk factors for CKD mortality varied across regions, with the highest proportions of high fasting plasma glucose being 14.04% in low SDI, compared with 24.01% in high SDI. Conclusion: CKD is a growing global health problem in AYAs, especially in countries with a middle SDI. Targeted measures are needed to address the rising burden of CKD in AYAs, focusing on prevention, early diagnosis, and reducing disparities.

Objective:To investigate the effects of different surgical approaches on the efficacy and safety of patients with primary central nervous system lymphoma(PCNSL).Methods:The clinical data of 130 PCNSL patients admitted to The First Affiliated Hospital of University of Science and Tecnology of China between July 2012 and May 2023 were retrospectively analyzed.Patients were assigned into resection and biopsy groups according to the surgical approach.The safety and efficacy of the two groups were compared,including the objective re-sponse rate(ORR),overall survival(OS),and progression-free survival(PFS)after chemotherapy.Results:ORR and 2-year OS and PFS rates of the resection group were not significantly different from those of the biopsy group(ORR:63.2%vs.62.8%;2-year OS rate:68.6%vs.73.7%;2-year PFS rate:35.2%vs.40.7%,all P>0.05).The incidence of postoperative complications was significantly higher in the resection group than in the biopsy group(29.3%vs.11.4%,P=0.04).The difference in the length of hospitalization between the two groups was not statistic-ally significant.Treatment of the biopsy group was less expensive(P<0.01).Conclusions:In patients with PCNSL,biopsy and resection had comparable efficacy;however,the safety profile was better,and hospitalization was less costly in biopsy than in resection.

Objective:To solve international students' problems of learning difficulties and passive learning caused by language barriers in the process of biochemistry learning from the perspective of teachers in this specialty.Methods:Eighty international students were randomly divided into experimental group and control group. In the experimental group, the regional management mode was introduced in teaching, allowing students to speak mother tongues or English for group discussions on well-designed questions, and at the same time, classroom quizzes and stage tests were given, introducing formative evaluation to supervise students' learning and assess their learning performance. The control group received conventional teaching. The learning effects were assessed through a final exam and questionnaire survey. SPSS 25.0 was used to perform the Kruskal-Wallis H test and Nemenyi test. Results:Twenty-seven (75.00%) students believed that group discussion by region could deepen the discussion of questions; 27 (75.00%) no longer felt difficult, or even felt easy, to learn biochemistry; and nearly 90.00% of the students affirmed the formative evaluation mode, believing that it had positive effects on their learning attitude and behavior. In addition, the median exam score of the experimental group was 36.94% higher than that of the control class in the same year.Conclusions:Regional management combined with formative evaluation can promote international students' learning enthusiasm, improve their comprehensive achievement, and positively affect their learning behavior.

Endocrine-resistance remains a major challenge in estrogen receptor α positive (ERα⁺) breast cancer (BC) treatment and constitutively active somatic mutations in ERα are a common mechanism. There is an urgent need to develop novel drugs with new mode of mechanism to fight endocrine-resistance. Given aberrant ERα activity, we herein report the identification of novel covalent selective estrogen receptor degraders (cSERDs) possessing the advantages of both covalent and degradation strategies. A highly potent cSERD 29c was identified with superior anti-proliferative activity than fulvestrant against a panel of ERα⁺ breast cancer cell lines including mutant ERα. Crystal structure of ERα‒ 29c complex alongside intact mass spectrometry revealed that 29c disrupted ERα protein homeostasis through covalent targeting C530 and strong hydrophobic interaction collied on H11, thus enforcing a unique antagonist conformation and driving the ERα degradation. These significant effects of the cSERD on ERα homeostasis, unlike typical ERα degraders that occur directly via long side chains perturbing the morphology of H12, demonstrating a distinct mechanism of action (MoA). In vivo, 29c showed potent antitumor activity in MCF-7 tumor xenograft models and low toxicity. This proof-of-principle study verifies that novel cSERDs offering new opportunities for the development of innovative therapies for endocrine-resistant BC.

To explore the pharmacogenomic markers that affect the platinum-based chemotherapy response in non-small-cell lung carcinoma (NSCLC), we performed a two-cohort of genome-wide association studies (GWAS), including 34 for WES-based and 433 for microarray-based analyses, as well as two independent validation cohorts. After integrating the results of two studies, the genetic variations related to the platinum-based chemotherapy response were further determined by fine-mapping in 838 samples, and their potential functional impact were investigated by eQTL analysis and in vitro cell experiments. We found that a total of 68 variations were significant at P < 1 × 10^-3 in cohort 1 discovery stage, of which 3 SNPs were verified in 262 independent samples. A total of 541 SNPs were significant at P < 1 × 10^-4 in cohort 2 discovery stage, of which 8 SNPs were verified in 347 independent samples. Comparing the validated SNPs in two GWAS, ADCY1 gene was verified in both independent studies. The results of fine-mapping showed that the G allele carriers of ADCY1 rs2280496 and C allele carriers of rs189178649 were more likely to be resistant to platinum-based chemotherapy. In conclusion, our study found that rs2280496 and rs189178649 in ADCY1 gene were associated the sensitivity of platinum-based chemotherapy in NSCLC patients.

Objective: To identify the characteristics including clinical features and pulmonary computed tomography (CT) features of heart failure and novel coronavirus pneumonia(COVID-19). Methods: This study was a retrospective study. A total of 7 patients with Heart failure and 12 patients with COVID-19 in the Second Xiangya Hospital of Central South University between December 1, 2019 and February 15, 2020 were enrolled. The baseline clinical and imaging features of the two groups were statistically analyzed. Results: There was no significant difference in age and sex between the two groups, but the incidence of epidemiological contact history, fever or respiratory symptoms in the COVID-19 group was significantly higher than that in the heart failure group (12/12 vs. 2/7, P=0.001; 12/12 vs. 4/7, P<0.001). While the proportion of cardiovascular diseases and impaired cardiac function was significantly less than that of the heart failure group(2/12 vs.7/7, P<0.001; 0/12 vs.7/7, P<0.001). For imaging features, both groups had ground-glass opacity and thickening of interlobular septum, but the ratio of central and gradient distribution was higher in patients with heart failure than that in patients with COVID-19 (4/7 vs. 1/12, P=0.04). In heart failure group, the ratio of the expansion of small pulmonary veins was also higher (3/7 vs. 0, P=0.013), and the lung lesions can be significantly improved after effective anti-heart failure treatment. Besides, there are more disease with rounded morphology in COVID-19 (9/12 vs. 2/7, P=0.048) . Conclusions More patients with COVID-19 have epidemiological history and fever or respiratory symptoms. There are significant differences in chest CT features, such as enlargement of pulmonary veins, lesions distribution and morphology between heart failure and COVID-19.

PURPOSE: Recent evidence suggests that B cells can both promote and inhibit the development and progression of allergic disease. However, the characteristics of B cell subsets in patients with allergic rhinitis (AR) have not been well documented. This study aimed to analyze the characteristics of B cell subsets in the peripheral blood of AR patients. METHODS: Forty-seven AR patients and 54 healthy controls were enrolled in this study, and the B cell subsets in peripheral blood of all subjects were analyzed by flow cytometry. Moreover, the serum total immunoglobulin E (IgE) and IgE concentrations secreted into the cultured peripheral blood mononuclear cells (PBMCs) were measured by using enzyme-linked immunosorbent assay. RESULTS: We found the peripheral blood of AR patients contained higher percentages of memory B cells, plasma cells, and CD19+CD24hiCD27+ regulatory B cells (Bregs) than those of age-matched healthy controls (P < 0.05), while the percentages of naïve B cells and CD19+CD24hiCD38hi Bregs were significantly lower in AR patients than in healthy individuals (P < 0.05). In addition, the serum total IgE and IgE concentrations secreted into the cultured PBMCs were elevated in AR patients than in the healthy controls (P < 0.05). CONCLUSIONS: Our findings indicate that AR patients were characterized by increase in terminally differentiated memory B cells or plasma cells and decreases in CD19+CD24hiCD38hi Breg cells in the peripheral blood.
B-Lymphocyte Subsets* ; B-Lymphocytes ; B-Lymphocytes, Regulatory ; Enzyme-Linked Immunosorbent Assay ; Flow Cytometry ; Humans ; Immunoglobulin E ; Immunoglobulins ; Memory ; Plasma Cells ; Rhinitis, Allergic*

Objective To investigate the clinic significance of real-time fluorescent quantity polymerase chain reaction(RT-PCR) for detection of Mycoplasma pneumoniae(MP) DNA in patients suspected with MP infection.Methods A total of 1 402 samples,including serum,sputum,pleural fluid,nasopharyngeal swab,alveolar irrigating solution and bronchial irrigating solution,were detected for MP-DNA by using RT-PCR.Results The total positive rate all samples were 12.20%.The positive rate of serum was the lowest,which was 2.36%.The positive rates of sputum,alveolar irrigating solution and bronchial irrigating solutions were relatively high,which were 62.96%,77.08% and 88.71%,respectively.Conclusion RT-PCR could be fitted for the detection of MP-DAN in various samples,which could be effective method for the diagnosis of MP infection.

Xu XP,Xiao N);Department ofGeneral Surgery,Pingxiang People's Hospital,Pingxiang,Jiangxi 337000,China(Rong J) Objective To study the expression of vascular endothelial growth factor(VEGF),S100A4 and survivin in thyroid carcinoma and their clinical significance.Methods The expression of VEGF,S100A4 and survivin in normal thyroid tissues from 28 people and thyroid cancer tissues obtained from 73 patients were detect by immuno-histochemistry method.Results The positive rates of VEGF,S100A4 and survivin in thyroid cancer were 84.93%, 86.30% and 79.45%,which in the normal thyroid tissues were 3.57%,7.14% and 14.29%,respectively.There were significant differences between every two groups,thyroid cancer and the normal thyroid tissues,statistically(χ2 =57.08,55.28,36.26,all P =0.000).VEGF,S100A4 and survivin in the positive expression of capsular infiltration carcinoma group were 97.37%,97.74%,97.74%,which in lymph node metastasis positive group cancer rates were 97.30%,94.60%,97.30% were significantly increased compared with no capsular infiltration group (71.43%, 77.14%,62.86%,respectively)and lymph node metastasis group(72.22%,77.78%,61.11%),the differences were statistically significant(χ2 =8.96,4.37,14.63,9.58,4.77,11.34,all P <0.05);the positive expression rate of three with thyroid cancer histological grade increased.Conclusion VEGF,S100A4 and survivin are closely related to the aggressive and metastatic character of thyroid cancer.A combination of VEGF,S100A4 and survivin may be of grate significance for predicting high aggressive and metastatic character in thyroid carcinoma.

OBJECTIVETo screen tumor biomarkers in the plasma close related with hypopharyngeal carcinoma.

METHODSPooled plasma from 6 patients with hypopharyngeal carcinoma and 6 healthy individuals were collected. After removal of high-abundance plasma proteins, two-dimensional gel electrophoresis (2-DE) was performed to isolate the total proteins, and the protein spots with more than 2-fold differential expressions were detected by 2D analysis software followed by identification by MALDI-TOF/TOF mass spectrometer. Western blotting was performed to validate the expression level of α2-HS-glycoprotein.

RESULTSA total of 11 differentially expressed protein spots were selected, including 5 upregulated proteins and 6 downregulated proteins. MALDI-TOF/TOF identified the upregulated proteins in hypopharyngeal carcinoma patients as alpha-2-HS-glycoprotein and haptoglobin and downregulated ones as Ig kappa chain C region and apolipoprotein A-I. Western blotting demonstrated that α-2-HS- glycoprotein expression level was consistent with that detected by 2-DE.

CONCLUSIONPatients with hypopharyngeal carcinoma show different plasma protein profiles from healthy individuals. These differentially expressed proteins may serve as potential specific tumor biomarkers for hypopharyngeal carcinoma.

Biomarkers, Tumor ; blood ; Blood Proteins ; metabolism ; Humans ; Hypopharyngeal Neoplasms ; blood ; Male ; Middle Aged ; Proteomics ; methods