Assessment of the 2023 European Kidney Function Consortium (EKFC) equations in a Chinese adult population.

OBJECTIVES: The European Kidney Function Consortium (EKFC) developed two novel equations in 2023 for estimating glomerular filtration rate (GFR): one sex-free cystatin C-based equation (EKFCCys) and one creatinine-cystatin C combined equation (EKFCCr-Cys). This study compared their performance with the previous creatinine-based EKFC equation (EKFCCr) and commonly used Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Berlin Initiative Study (BIS) equations in Chinese adults. METHODS: A total of 2,438 Chinese adults (mean age=53.04 years) who underwent the 99mTc-DTPA renal dynamic imaging for reference GFR (rGFR) were included. Diagnostic value was evaluated using correlation coefficients, sensitivity, specificity, and area under the receiver operating characteristic curve (ROCAUC). Performance was assessed in terms of bias, precision (interquartile range of the median difference [IQR]), accuracy (percentage of estimates ±30 % of rGFR [P30], and root-mean-square error [RMSE]) across age, sex, and rGFR subgroups. Gender differences in bias and P30 were also analyzed. RESULTS: Average rGFR was 73.37 mL/min/1.73 m2. EKFC equations showed stronger correlations and larger AUCs compared to the parallel CKD-EPI equations, with EKFCCr-Cys demonstrating the greatest improvement (R=0.771, ROCAUC=0.913). Concerning bias, precision, and accuracy, EKFC equations consistently outperformed CKD-EPI equations. EKFCCr-Cys and EKFCCr performed acceptably well in the entire population and were equivalent to BIS equations in the elderly. All equations, including EKFCCys, showed similar P30 accuracy across sexes. CONCLUSIONS: EKFC equations provided a reasonable alternative for estimating GFR in the Chinese adult population. While EKFCCys did not outperform EKFCCr, EKFCCr-Cys improved the accuracy of single-marker equations.

Data mining of reference intervals for serum creatinine: an improvement in glomerular filtration rate estimating equations based on Q-values.

OBJECTIVES: Glomerular filtration rate (GFR) estimating equations based on rescaled serum creatinine (SCr/Q) have shown better performance, where Q represents the median SCr for age- and sex-specific healthy populations. However, there remains a scarcity of investigations in China to determine this value. We aimed to develop Chinese age- and sex-specific reference intervals (RIs) and Q-values for SCr and to validate the equations incorporating new Q-values. METHODS: We included 117,345 adults from five centers for establishing RIs and Q-values, and 3,692 participants with reference GFR (rGFR, 99mTc-DTPA renal dynamic imaging measurement) for validation. Appropriate age partitioning was determined using the decision tree method. Lower and upper reference limits and medians were calculated using the refineR algorithm, and Q-values were determined accordingly. We evaluated the full age spectrum (FAS) and European Kidney Function Consortium (EKFC) equations incorporating different Q-values considering bias, precision (interquartile range, IQR), and accuracy (percentage of estimates within ±20 % [P20] and ±30 % [P30] of rGFR). RESULTS: RIs for males were: 18-79 years, 55.53-92.50 µmol/L; ≥80 years, 54.41-96.43 µmol/L. RIs for females were: 18-59 years, 40.42-69.73 µmol/L; 60-79 years, 41.16-73.69 µmol/L; ≥80 years, 46.50-73.20 µmol/L. Q-values were set at 73.82 µmol/L (0.84 mg/dL) for males and 53.80 µmol/L (0.61 mg/dL) for females. After validation, we found that the adjusted equations exhibit less bias, improved precision and accuracy, and increased agreement of GFR categories. CONCLUSIONS: We determined Chinese age- and sex-specific RIs and Q-values for SCr. The adjustable Q-values provide an effective alternative to obtain valid equations for estimating GFR.

A Phase IIb, single arm, multicenter trial of sacituzumab govitecan in Chinese patients with metastatic triple-negative breast cancer who received at least two prior treatments.

Refractory or relapsing metastatic triple-negative breast cancer (mTNBC) has a poor prognosis. Sacituzumab govitecan (SG) is a novel antibody-drug conjugate, targeting human trophoblast cell-surface antigen 2 (Trop-2). This is the first report of SG's efficacy and safety in Chinese patients with mTNBC. EVER-132-001 (NCT04454437) was a multicenter, single-arm, Phase IIb study in Chinese patients with mTNBC who failed ≥2 prior chemotherapy regimens. Eligible patients received 10 mg/kg SG on Days 1 and 8 of each 21-day treatment cycle, until disease progression/unacceptable toxicity. The primary endpoint was objective response rate (ORR) assessed by the Independent Review Committee. Secondary endpoints included: duration of response (DOR), clinical benefit rate (CBR), progression-free survival (PFS), overall survival (OS) and safety. Eighty female Chinese patients (median age 47.6 years; range 24-69.9 years) received ≥1 SG dose with a median of 8 treatment cycles by the cutoff date (August 6, 2021). Median number of prior systemic cancer treatments was 4.0 (range 2.0-8.0). ORR and CBR were reported 38.8% (95% confidence interval [CI]: 28.06-50.30) and 43.8% (95% CI, 32.68-55.30) of patients, respectively. The median PFS was 5.55 months (95% CI, 4.14-N/A). SG-related Grade ≥3 treatment-emergent adverse events (TEAEs) were reported in 71.3%, the most common were neutrophil count decreased (62.5%), white blood cell count decreased (48.8%) and anemia (21.3%); 6.3% discontinued SG because of TEAEs. SG demonstrated substantial clinical activity in heavily pretreated Chinese patients with mTNBC. The observed safety profile was generally manageable.

iTRAQ-based differential proteomic analysis of high- and low-virulence strains of Spiroplasma eriocheiris.

Spiroplasma eriocheiris is one of the major pathogenic bacteria in crustaceans, featuring high infectivity, rapid transmission, and an absence of effective control strategies, resulting in significant economic losses to the aquaculture industry. Research into virulence-related factors provides an important perspective to clarify how Spiroplasma eriocheiris is pathogenic to shrimps and crabs. Therefore, in this study, isobaric tags for relative and absolute quantitation (iTRAQ) technology was utilized to undertake a differential proteomic analysis of high- and low-virulence Spiroplasma eriocheiris strains at different growth phases. A total of 868 differentially expressed proteins (DEPs) were obtained, of which 31 novel proteins were identified by proteogenomic analysis. There were 62, 61, 175, and 235 DEPs between the log phase (YD) and non-log phase (YFD) of the high-virulence strain, between the log phase (CD) and non-log phase (CFD) of the low-virulence strain, between YD and CD, and between CFD and YFD, respectively. All the DEPs were compared with virulence protein databases (MvirDB and VFDB), and 68 virulence proteins of Spiroplasma eriocheiris were identified, of which 12 were involved in a total of 21 metabolic pathways, including motility, chemotaxis, growth, metabolism and virulence of the bacteria. The results of this study form the basis for further research into the molecular mechanism of virulence and physiological differences between high- and low-virulence strains of Spiroplasma eriocheiris, and provide a scientific basis for a detailed understanding of its pathogenesis.

The hsa_circ_0000276-ceRNA regulatory network and immune infiltration in cervical cancer.

BACKGROUND: Our previous studies have confirmed that miR-154-5p can regulate pRb expression, and thus, play a tumor suppressor role in HPV16 E7-induced cervical cancer. However, its upstream molecules have not been elucidated in the progression of cervical cancer. This study aimed to explore the role of the miR-154-5p upstream molecule, hsa_circ_0000276 in cervical cancer development and its possible mechanisms of action. METHODS: We detected differences in whole transcriptome expression profiles of cervical squamous carcinoma and tissues adjacent to cervical cancer tissues from patients using microarray technology to predict circular RNAs (circRNAs) with binding sites to miR-154-5p. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to detect the expression of hsa_circ_0000276 (which had the strongest binding capacity to miR-154 and was selected as the target molecule) in cervical cancer tissues, followed by in vitro functional assays. Downstream microRNAs (miRNAs) and mRNAs of hsa_circ_0000276 were identified using transcriptome microarray data and databases, while the protein-protein interaction networks were obtained using STRING. A competing endogenous RNA (ceRNA) network centered on hsa_circ_0000276 was constructed using Cytoscape and GO and KEGG databases. Abnormal expression and prognosis of critical downstream molecules were analyzed using gene databases and molecular experiments. qRT-PCR and western blot analysis was performed to verify the expression of candidate genes. RESULTS: We identified 4,001 differentially expressed circRNAs between HPV16-positive cervical squamous carcinoma and benign cervical tissues and 760 circRNAs targeting miR-154-5p, including hsa_circ_0000276. hsa_circ_0000276 and miR-154-5p directly bound, and hsa_circ_0000276 was upregulated, in cervical precancerous lesions and cervical cancer tissues and cells. Silencing hsa_circ_0000276 inhibited G1/S transition and cell proliferation and promoted apoptosis in SiHa and CaSki cells. Bioinformatics analysis showed that the hsa_circ_0000276 ceRNA network included 17 miRNAs and seven mRNAs, and downstream molecules of hsa_circ_0000276 were upregulated in cervical cancer tissues. These downstream molecules were associated with a poor prognosis and affected cervical cancer-associated immune infiltration. Of these, expression of CD47, LDHA, PDIA3, and SLC16A1 was downregulated in sh_hsa_circ_0000276 cells. CONCLUSIONS: Our findings show that hsa_circ_0000276 exerts cancer-promoting effects in cervical cancer and is an underlying biomarker for cervical squamous cell carcinoma.

Prevalence and molecular characterization of Cryptosporidium spp. in dairy cattle in Central Inner Mongolia, Northern China.

BACKGROUND: Cryptosporidium is a gastrointestinal protozoan that widely exists in nature, it is an established zoonotic pathogen. Infected cattle are considered to be associated with cryptosporidiosis outbreaks in humans. In the present study, we aimed to assess the prevalence and species distribution of Cryptosporidium in dairy cattle in Central Inner Mongolia. METHODS: We focused on the small subunit ribosomal RNA gene (SSU rRNA) of Cryptosporidium and 60-kDa glycoprotein gene (gp60) of Cryptosporidium parvum. We collected 505 dairy cattle manure samples from 6 sampling sites in Inner Mongolia in 2021; the samples were divided into 4 groups based on age. DNA extraction, polymerase chain reaction (PCR), sequence analysis, and restriction fragment length polymorphism (RFLP) using SspI and MboII restriction endonucleases were performed. RFLP analysis was performed to determine the prevalence and species distribution of Cryptosporidium. RESULTS: SSU rRNA PCR revealed that the overall prevalence of Cryptosporidium infection was 29.90% (151/505), with a prevalence of 37.67% (55/146) and 26.74% (96/359) in diarrheal and nondiarrheal samples, respectively; these differences were significant. The overall prevalence of Cryptosporidium infection at the 6 sampling sites ranged from 0 to 47.06% and that among the 4 age groups ranged from 18.50 to 43.81%. SSU rRNA sequence analysis and RFLP analysis revealed the presence of 4 Cryptosporidium species, namely, C. bovis (44.37%), C. andersoni (35.10%), C. ryanae (21.85%), and C. parvum (11.92%), along with a mixed infection involving two or three Cryptosporidium species. Cryptosporidium bovis or C. andersoni was the most common cause of infection in the four age groups. The subtype of C. parvum was successfully identified as IIdA via gp60 analysis; all isolates were identified as the subtype IIdA19G1. CONCLUSIONS: To the best of our knowledge, this is the first report of dairy cattle infected with four Cryptosporidium species in Inner Mongolia, China, along with a mixed infection involving two or three Cryptosporidium species, with C. bovis and C. andersoni as the dominant species. Moreover, this is the first study to identify C. parvum subtype IIdA19G1 in cattle in Inner Mongolia. Our study findings provide detailed information on molecular epidemiological investigation of bovine cryptosporidiosis in Inner Mongolia, suggesting that dairy cattle in this region are at risk of transmitting cryptosporidiosis to humans.

Application of single-layer continuous duct-to-mucosa pancreaticojejunostomy with two figure-of-eight sutures in total laparoscopic pancreaticoduodenectomy.

INTRODUCTION: To investigate the application potential of single-layer continuous duct-to-mucosa pancreaticojejunostomy with two figure-of-eight sutures ("1 + 2" PJ) in total laparoscopic pancreaticoduodenectomy (TLPD). Explore the advantages of "1 + 2" PJ over the traditional double-layer interrupted duct-to-mucosa pancreaticojejunostomy (traditional PJ). METHODS: We retrospectively collected the clinical data of 184 patients who were admitted in our department from Oct 2019 to Oct 2022, including 95 cases who underwent TLPD with "1 + 2" PJ and 89 cases who underwent TLPD with traditional PJ. The pre/intra/postoperation data were analyzed and compared. RESULTS: The "1 + 2" PJ procedures were successfully performed in all the 95 cases. When compared with the traditional PJ group, there were no statistically significant variations between the pre-operative and pathological data. However, the "1 + 2" PJ group had a shorter operation time (235 (210, 300) minutes vs. 310 (270, 360) minutes in the traditional PJ group, P < 0.001), shorter pancreaticojejunostomy time (15 (10, 20) minutes vs. 50 (45, 55) minutes in the traditional PJ group, P < 0.001), lower pancreatic fistula (both grade B/C) rate (4.21% vs. 12.34% in the traditional group, P = 0.044), and abdominal infection rate (2.11% vs. 8.99% in the traditional group, P = 0.044), as well as reduced hospital stay (11 (9, 15) days vs. 13 (11, 15) days in the traditional PJ group, P = 0.013). In the "1 + 2" PJ group, the median diameter of the pancreatic duct was 3 (3, 4) mm; 82 cases (86.31%) had a normal pancreatic texture, while nine (9.47%) cases had a hard texture, and seven (7.37%) cases had a soft texture; the median intraoperative blood loss was 200 (100, 400) mL and 19 cases (20.00%) needed intraoperative transfusion; eight cases (8.4%) developed postoperative complications, including four cases (4.2%) of pancreatic fistula (including both grade B/C), one case (1.1%) of bile leakage, three cases (3.2%) of delayed gastric emptying, three cases (3.2%) of postoperative hemorrhage, two cases (2.1%) of abdominal infection, and one case (1.1%) of reoperation; the median hospital stay was 13 (8, 17) days; 25 cases were pathologically classified as pancreatic cancer, 35 cases as bile duct cancer, 23 cases as duodenal cancer, and 12 cases as ampullary cancer. CONCLUSION: Single-layer continuous duct-to-mucosa pancreaticojejunostomy with two figure-of-eight sutures is a feasible and safe procedure that can be applied in TLPD.

Prognostic significance of frailty status in patients with primary lung cancer.

Lung cancer has one of the highest morbidity and mortality rates in the world. Frailty is common in many countries and is a major cause of premature functional decline and premature death in older adults, and may affect the treatment and prognosis of lung cancer patients. To investigate the predictive value of frailty at diagnosis on all-cause mortality in lung cancer patients, this study retrospectively collected and analysed clinical information on lung cancer patients from 2015-2018. A total of 1667 patients with primary lung cancer were finally included in this study. The median follow-up time of patients was 650 (493, 1001.5) days. A total of 297(17.8%) patients had FI-LAB(the frailty index based on laboratory test) status of frail at the moment of diagnosis and the all-cause mortality rate for all patients was 61.1% (1018/1667). In a univariate model, we found a higher total all-cause mortality risk in frail patients (frail vs. robust, HR(hazard ratio) = 1.616, 95% CI(confidence interval) = 1.349,1.936), after balancing other variables combined into model 1 to model 6. The results were analyzed visually using ROC(Receiver operating characteristic) curves with nomogram and the AUC values ranged from 0.866-0.874. The final inclusion of age, TNM stage, CCI(Charlson comorbidity index) score, surgery history and chemotherapy into a multifactorial model balanced the predictive power of frailty grading on all-cause mortality. The study showed that for lung cancer patients, the higher the level of frailty at diagnosis, the higher the risk of all-cause mortality. In the context of widespread electronic medical records in hospitals, it is convenient and feasible to use FI-LAB to assess the prognosis of lung cancer patients.

Prognostic significance of frailty in hospitalized elderly patients with community-acquired pneumonia: a retrospective cohort study.

BACKGROUND: Frailty is associated with poor prognosis in a wide range of illnesses. However, its prognostic implications for older patients with community-acquired pneumonia (CAP) are not adequately addressed. METHODS: In this study, patients were classified into 3 groups according to the frailty index based on standard laboratory tests (FI-Lab) score: robust (FI-Lab < 0.2), pre-frail (FI-Lab 0.2-0.35), and frail (FI-Lab ≥ 0.35). The relationships between frailty and all-cause mortality and short-term clinical outcomes (length of stay, duration of antibiotic therapy, in-hospital mortality) were examined. RESULTS: Finally, 1164 patients were included, the median age was 75 years (interquartile range: 69, 82), and 438 patients (37.6%) were women. According to FI-Lab, 261(22.4%), 395(33.9%), and 508(43.6%) were robust, pre-frail, and frail. After adjustment for confounding variables, frailty was independently associated with prolonged antibiotic treatment (p = 0.037); pre-frailty and frailty were independently associated with longer inpatient days (p < 0.05 for both). The risk of in-hospital mortality was independently increased in frail patients (HR = 5.01, 95% CI = 1.51-16.57, p = 0.008) but not pre-frail patients (HR = 2.87, 95% CI = 0.86-9.63, p = 0.088) compared to robust patients. During a median follow-up of 33.9 months (interquartile range: 32.8 to 35.1 months), 408 (35.1%) patients died, of whom 29 (7.1%) were robust, 112 (27.5%) were pre-frail, and 267 (65.9%) were frail. Compared to robust patients, frail and pre-frail were significantly associated with increased risk for all-cause death (HR = 4.29, 95%CI: 1.78-10.35 and HR = 2.42 95%CI: 1.01-5.82, respectively). CONCLUSIONS: Frailty is common among older patients with CAP and is strongly associated with increased mortality, longer length of stay, and duration of antibiotics. A routine frail assessment at the admission of elderly patients with CAP is necessary as the first step for appropriate multidisciplinary interventions.

Different equations for estimating age-related changes of glomerular filtration rate in the healthy population.

BACKGROUND: Identifying age-related trend of estimated glomerular filtration rate (eGFR) is necessary to assess whether kidney function is healthily aging. This study aimed to investigate the application of CKD-EPI, FAS, and Xiangya equations for the aging estimation of eGFR in the healthy Chinese individuals. METHODS: A total of 36,911 healthy individuals were enrolled in this study. We grouped every ten years to observe the trend of eGFR with aging and investigated decline rate of it by general linear regression analysis in each age-groups. Agreement between equations was determined by intraclass correlation coefficient (ICC) and Bland-Altman plot. We calculated reference interval in each age-group. We further analyzed above statistical indicators in males and females. RESULTS: The eGFR by CKD-EPI, and Xiangya equation started to decline from the age of 18. Whereas eGFR by FAS equation remained stable under 40 years, then decreased more rapidly. Compared with males, the females had a higher level but a faster decline rate of eGFR with aging. Agreement analysis revealed good agreement between CKD-EPI and FAS equations (ICC 0.818-0.920). Agreement between Xiangya and CKD-EPI or FAS equations was poor to moderate in most of the population under 70 years old (ICC 0.282-0.786), but good in individuals above 70 years (ICC 0.769-0.881). CONCLUSIONS: The trend of eGFR with aging was different by CKD-EPI, FAS, and Xiangya equations in the healthy Chinese. It may be necessary to take these equations- or age-related differences into consideration when assessing kidney function in primary health care and clinical practice.

Pembrolizumab and Trastuzumab in High Tumor Mutational Burden and POLE-Mutated HER2-Positive Refractory Breast Cancer.

Metastatic breast cancer (mBC) is an incurable disease, and it is not sensitive to immunotherapy due to its low immunogenicity. Recently, inactivated DNA polymerase epsilon (POLE) mutations have been found to be associated with high tumor mutational burden (TMB), which is an effective immuno-oncology biomarker. Patients with POLE mutations with different types of cancer have properly responded to immunotherapy. We aimed to report the first case of programmed death-ligand 1 (PD-L1)-negative mBC presenting with high TMB and POLE mutations, in which a complete response to 5 cycles of chemotherapy and 1 year of pembrolizumab and trastuzumab was noted after failing several lines of HER2-targeted therapies. Our findings also suggest that biomarker-driven patient selection is highly significant for further clinical development of combination therapies via anti-HER2 plus immune-checkpoint inhibitors for HER2+ BC patients.

Associations of RBC and Serum Folate Concentrations with Cervical Intraepithelial Neoplasia and High-Risk Human Papillomavirus Genotypes in Female Chinese Adults.

BACKGROUND: Although folate status is associated with cervical carcinogenesis, it is not clear whether folate deficiency is associated with risk of cervical intraepithelial neoplasia (CIN) progression and infection with high-risk human-papillomavirus (hrHPV). OBJECTIVES: To evaluate the associations of RBC and serum folate concentrations with prevalence of CIN grades and hrHPV infection, their interactions with prevalence of CIN grades, and RBC folate with the risk of CIN1 progressing to CIN2. METHODS: Using data from the Shanxi CIN cohort of 2304 female Chinese adults, we used logistic-regression model to estimate ORs and prevalence ratios (PRs) of RBC and serum folate concentrations with prevalence of CIN grades and hrHPV infection. Categoric and spline analyses were used to evaluate the dose-response relations. We estimated the association of RBC folate with risk of CIN1 progressing to CIN2 in the nested case-control cohort. RESULTS: An inverse association was observed between increased RBC folate concentration and the odds of all CIN grades [quartile 1 (Q1) compared with Q4: OR: 2.28; 95% CI: 1.77, 2.93; Ptrend < 0.001]. Significant interaction of RBC folate and hrHPV infection was observed for prevalence of CIN2 or above (Pinteraction < 0.01). No associations were found between RBC and serum folate with PRs of hrHPV in each CIN grade. Over a median follow-up of 21.0 mo, RBC folate was associated with increased risk of CIN1 progressing to CIN2 (Q1 compared with Q4: OR: 3.86; 95% CI: 1.01, 14.76). CONCLUSIONS: Our study indicates that RBC folate concentration is associated with prevalence of CIN grades and CIN1 progression in female Chinese adults. Maintenance of normal folate status is important for reducing the risk of CIN and its progression in women with or without hrHPV infection.

Integrated analysis of mRNA and microRNA transcriptome related to immunity and autophagy in shrimp hemocytes infected with Spiroplasma eriocheiris.

In recent years, the industry in charge of the cultivation of Macrobrachium nipponense (M.nipponense) has suffered significant economic losses due to an infectious pathogen called Spiroplasma eriocheiris (S.eriocheiris). There has therefore been a need to identify the key immune and autophagy genes that respond to M.nipponense's infection with S. eriocheiris to analyze its immune response mechanism and the regulation of related microRNAs (miRNAs). In this study, the mRNA and miRNA transcriptome of M.nipponense's hemocytes were analyzed at different stages of infection. This analysis employed the second and third-generation sequencing technologies. In the mRNA transcriptome, 1656 genes were expressed in healthy and susceptible M.nipponense. 892 of these were significantly up-regulated, while 764 were down-regulated. 118 genes with significant differences in autophagy, endocytosis, lysosome, Toll, IMD, and VEGF pathways were obtained from the transcriptome. In the miRNA transcriptome, 312 miRNAs (Conserved: 112, PN-type: 18, PC-type: 182) were sequenced. 74 were significantly up-regulated, and 57 were down-regulated. There were 25 miRNAs involved in regulating the Toll and IMD pathways, 41 in endocytosis, 30 in lysosome, and 12 in the VEGF pathway. An integrated analysis of immune-related miRNAs and mRNAs showed that miRNAs with significant differences (P < 0.05) such as ame-miR-29b-3p, dpu-miR-1and PC-3p-945_4074, had corresponding regulatory relationships with 118 important immune genes such as Relish, Dorsal, Caspase-3, and NF-κB. This study obtained the key immune and autophagy-related genes and corresponding regulatory miRNAs in M. nipponense's hemocytes in response to an infection by S.eriocheiris. The results can provide vital data that further reveals the defense mechanism of M.nipponense's immune system against S.eriocheiris. It can also help further comprehension and interpretation of M.nipponense's resistance mechanism to the invading S.eriocheiris, and provide molecular research information for the realization of host-directed therapies (HDT) for M.nipponense.

Thyroid function and age-related decline in kidney function in older Chinese adults: a cross-sectional study.

BACKGROUND: Thyroid function may be a factor affecting kidney function in the general population. Kidney and thyroid function vary with age; therefore, the association between thyroid function and decreased kidney function in older adults may be different from that in younger adults and remains controversial. This study aimed to estimate the association between normal-range thyroid function and age-related decline in kidney function in older Chinese adults. METHODS: A total of 15,653 adults, of whom 23.2% (N = 3624) were older adults (age≧65 years), were collected at the Health Management Center of the First Affiliated Hospital of Nanjing Medical University from January 2018 to January 2020. Basic demographic information was collected by a physician-administered questionnaire. The estimated glomerular filtration rate (eGFR) was calculated using the CKD-EPI formula. Trends in thyroid function with age were shown by means of free triiodothyronine (FT3), free thyroxine (FT4), and thyroid-stimulating hormone (TSH) in subgroups every ten years. The association between kidney function and thyroid function was estimated by multiple linear regression using ß value and by multivariable logistic regression models using odds ratios (OR) after adjusting for age, gender, body mass index, and serum urine acid. RESULTS: In the older population, TSH tended to increase with age and FT3 tended to decrease, whereas FT4 was relatively stable. eGFR decreased significantly with increasing TSH (ß = -0.081) and decreasing FT3 (ß = 0.083) concentrations. Compared with those in the lowest quartile of FT3 (3.10-4.47 pmol/L), the prevalence of eGFR < 75 ml/min/1.73m2 decreased significantly by 22.0% for those with FT3 of 4.47-4.81 pmol/L, 27.6% for those with FT3 of 4.82-5.20 pmol/L, and 34.9% for those with FT3 of 5.21-6.8 pmol/L in older individuals (P for trend < .001). The OR was 1.315 (P: 0.025) in subjects with high-normal TSH, using low-normal TSH as a reference. The prevalence of reduced kidney function was not significantly associated with FT4 within the reference range. Similar results were found in association between the prevalence of eGFR < 60 ml/min/1.73m2 and thyroid function. CONCLUSIONS: This study demonstrated a significant association between kidney function and thyroid function, particularly FT3, in the older population. Clinicians may need to pay more attention to the assessment and follow-up of kidney function in older individuals with low-normal FT3 and high-normal TSH.

Interleukin-19 Aggravates Pulmonary Fibrosis via Activating Fibroblast through TGF-ß/Smad Pathway.

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial pneumonia disease with no cure. Communication between injured cells is triggered and maintained by a complicated network of cytokines and their receptors. IL-19 is supported by increasing evidences for a deleterious role in respiratory diseases. However, its potential role in lung fibrosis has never been explored. Methods: Bioinformatic, immunohistochemistry and western blot analysis were used to assess the expression of IL-19 in human and mouse fibrosis lung tissues. CCK-8, transwell and flow cytometry assay were utilized to analyze the effect of IL-19 on biological behaviors of lung fibroblasts. Histopathology was used to elucidate profibrotic effect of IL-19 in vivo. Results: IL-19 was upregulated in fibrosis lung tissues. IL-19 promoted lung fibroblasts proliferation and invasion, inhibited cell apoptosis, and induced differentiation of fibroblasts to the myofibroblast phenotype, which could be revised by LY2109761, a TGF-ß/Smad signaling pathway inhibitor. Furthermore, we found that IL-19 aggravated lung fibrosis in murine bleomycin-induced lung fibrosis. Conclusions: Our results imply the profibrotic role for IL-19 through direct effects on lung fibroblasts and the potential of targeting IL-19 for therapeutic intervention in pulmonary fibrosis.

Prognostic validity of the American joint committee on cancer eighth edition staging system for well-differentiated pancreatic neuroendocrine tumors.

BACKGROUND: The American Joint Committee on Cancer (AJCC) made improvements for staging pancreatic neuroendocrine tumors (pNETs) in its 8th Edition; however, multicenter studies were not included. METHODS: We collected multicenter datasets (n = 1,086, between 2004 and 2018) to validate the value of AJCC 8 and other coexisting staging systems through univariate and multivariate analysis for well-differentiated (G1/G2) pNETs. RESULTS: Compared to other coexisting staging systems, AJCC 7 only included 12 (1.1%) patients with stage III tumors. Patients with European Neuroendocrine Tumor Society (ENETS) stage IIB disease had a higher risk of death than patients with stage IIIA (hazard ratio [HR]: 4.376 vs. 4.322). For the modified ENETS staging system, patients with stage IIB disease had a higher risk of death than patients with stage III (HR: 6.078 vs. 5.341). According to AJCC 8, the proportions of patients with stage I, II, III, and IV were 25.7%, 40.3%, 23.6%, and 10.4%, respectively. As the stage advanced, the median survival time decreased (NA, 144.7, 100.8, 72.0 months, respectively), and the risk of death increased (HR: II = 3.145, III = 5.925, and IV = 8.762). CONCLUSION: These findings suggest that AJCC 8 had a more reasonable proportional distribution and the risk of death was better correlated with disease stage.

Nab-paclitaxel-based regimens with docetaxel-based regimens as neoadjuvant treatment for early breast cancer.

Background Nanoparticle albumin-bound paclitaxel (nab-PTX) and docetaxel (DOC) both demonstrated favorable efficacy as neoadjuvant therapy in breast cancer. We retrospectively evaluated the efficacy and safety of nab-PTX-based chemotherapy (nPBC) and DOC-based chemotherapy (DBC) as neoadjuvant therapy in patients with breast cancer. Methods Breast cancer patients who received neoadjuvant nPBC or DBC and underwent surgery from January 2018 to June 2020 were consecutively analyzed. Pathologic complete response (pCR) was defined as no residual invasive cells in the breast and axillary nodes (ypT0/is ypN0) after surgery. The pCR, clinical complete response (cCR), and safety profiles were assessed in the two groups. Results A total of 104 breast cancer patients were included in this study. Fourty one patients received nPBC, and 63 patients received DBC The pCR was 34.1% in the nPBC group and 12.7% in the DBC group. Additionally, the cCR was 36.6% in the nPBC group and 15.9% in the DBC group. Peripheral sensory neuropathy was more common in the nPBC group, while hematologic toxicity was observed more frequently in the DBC group. Conclusions This study presented antitumor activity of nPBC and DBC in patients with early breast cancer receiving neoadjuvant treatment in a real-world setting. Further prospective research is warranted to confirm the results and to develop biomarkers for better patient selection.

YAP manipulates proliferation via PTEN/AKT/mTOR-mediated autophagy in lung adenocarcinomas.

BACKGROUND: Autophagy is a double-edged sword during the initiation and progression of multiple tumors. The Hippo pathway effector YAP has been proved to be involved in autophagy processes. The present study aimed to investigate how YAP regulates cell proliferation via autophagy in lung adenocarcinomas (LUAD). METHODS: Data of LUAD chip GSE43458 was obtained from Gene Expression Omnibus (GEO). RT-qPCR and Western blot were performed to assess YAP expression in LUAD cell lines. CCK-8 assay, xenograft tumor model, immunochemistry and GFP-mRFP-LC3 fusion proteins were utilized to evaluate the effect of YAP on autophagy of LUAD cells in vitro and in vivo. Autophagy inhibitor treatment and rescue experiments were carried out to elucidate the mechanism by which YAP manipulates autophagy in LUAD cells. RESULTS: YAP was significantly overexpressed in samples of LUAD patients and its expression level is related to 5-year survival. YAP manipulated the proliferation and autophagy in A549 and H1299 LUAD cells. YAP could induce activation of Akt/mTOR signaling pathway via suppressing PTEN in a Hippo-pathway-dependent manner. 3-Methyladenine impeded autophagy flux and promoted the proliferation in vitro and in vivo. CONCLUSIONS: Hippo pathway critical transcriptional coactivators YAP manipulates the proliferation of lung adenocarcinoma, which is regulated by PTEN/AKT/mTOR autophagic signaling.

Integrated transcriptome analysis of immune-related mRNAs and microRNAs in Macrobrachium rosenbergii infected with Spiroplasma eriocheiris.

Macrobrachium rosenbergii (M. rosenbergii), is a major aquaculture species in China and Southeast Asia. However, infection with Spiroplasma eriocheiris (S. eriocheiris) has caused huge economic losses to the cultivation of M. rosenbergii. Currently, there are few reports on the immune response mechanism of M. rosenbergii that are infected with S. eriocheiris. To clarify the immune response mechanism of M. rosenbergii infected with S. eriocheiris, the key immune genes which respond to the infection with the pathogen and the regulation of related microRNAs (miRNAs) on them were identified. In this study, the mRNA and miRNA transcriptome of hepatopancreas of M. rosenbergii at different infection stages were analyzed using high-throughput sequencing and qRT-PCR. In the mRNA transcriptome, 27,703 and 33,402 genes were expressed in healthy and susceptible M. rosenbergii, respectively. By digital gene-expression profiling analysis, 23,929 and 24,325 genes were expressed, and 223 and 373 genes were significantly up-regulated and down-regulated, respectively. A total of 145 key genes related to Toll, IMD, JAK/STAT and MAPK were excavated from the transcriptome. In the miRNA transcriptome, 549 miRNAs (Conserved: 41, PN-type: 83, PC-type: 425) were sequenced, of which 87 were significantly up-regulated and 23 were significantly down-regulated. Among the related immune pathways, there are 259 miRNAs involved in the regulation of target genes in the Toll and IMD pathways, 231 JAK/STAT pathways and 122 MAPK pathways. qRT-PCR differential detection of immune-related miRNAs and mRNAs showed that 22 miRNAs with significant differences (P < 0.05) such as mro-miR-100, PC-mro-3p-27 and PN-mro-miR-316 had corresponding regulatory relationships with 22 important immune genes such as TLR2, TLR3, TLR4, TLR5, MyD88, Pelle and Relish in different stages after infection. In this study, the immune genes and related regulatory miRNAs of M. rosenbergii in response to S. eriocheiris infection were obtained. The results can provide basic data to further reveal the immune defense mechanism of M. rosenbergii against S. eriocheiris infection.

Biological features and clinical outcome in infant neuroblastoma: a multicenter experience in Beijing.

Neuroblastoma (NB) is the most common extracranial solid tumor in childhood, with 37% of patients diagnosed during infancy. This study is aimed at evaluating the survival outcome in infants diagnosed with neuroblastoma. This was a retrospective cohort study including patients under the age of 12 months with neuroblastoma from four tertiary referral centers in Beijing, China (Beijing Children's Hospital, Beijing Tongren Hospital, Peking University First Hospital, and Capital Institute of Pediatrics). Two hundred and forty-seven infants with neuroblastoma were included (male = 132 and female = 115). 91.1% (n = 225) patients were classified as having low-risk or intermediate-risk disease and 8.9% (n = 22) as having high-risk disease. The most common metastatic site is distant lymph node (n=89, 36.0%), followed by liver (n=57, 23.1%), bone (n=42, 17.0%), bone marrow (n=37, 15.0%), soft tissue (n=25, 10%), and central nervous system (n=4, 1.6%). MYCN amplification was present in 9.9% of tumor samples, chromosome 1p or 11q aberration in 14%. Treatment involved surgery alone in 9.7% of patients (n=24, all with low-risk disease), surgery followed by adjuvant chemotherapy in 50.2% (n=124), neoadjuvant chemotherapy followed by surgery in 40.1% (n=97), and chemotherapy alone in 0.8% (n=2). 4.9% (n=12) patients died, and the major cause of death is disease progression. Three-year event-free and overall survival were 91.6%±2.1% and 97.4%±1.1%, respectively, in patients with low- or intermediate-risk disease, and 58.7%±11.5% and 63.6%±11.2%, respectively, in those with high-risk disease.Conclusions: Infants with neuroblastoma achieve a reasonable clinical outcome when treated with surgery with or without chemotherapy using a risk-stratified approach in China. Such information will facilitate counseling, therapeutic decision-making, and development of adapted standard-of-care guidelines for future patients in the country. What is Known: • NB is a disease of infancy; 37% of patients are diagnosed as infants. • Most children younger than 12 months of age have a good prognosis even in the presence of metastatic disease. What is New: • Infants with neuroblastoma achieve reasonable clinical outcome when treated with surgery with or without chemotherapy using a risk-stratified approach in China. • CNS metastasis in infants with neuroblastoma is very rare at diagnosis and had a worse prognosis than those without metastasis.