[Chronic kidney disease in community: Current state for screening and management].

OBJECTIVE: To understand the current state and problem of screening and management of chronic kidney disease (CKD) in the community, and to explore the improving strategies. METHODS: We established a community-CKD integrated data science platform based on medical information from 79 community health centers, in Xicheng District, Beijing. Patients who referred to 79 community health centers from 21 June 2015 to 20 November 2021 were retrospectively included in this study using the CKD data platform. The monitoring of the indicator of kidney injury, risk factor control, medicine use and device configuration in community were assessed in the study. RESULTS: In the study, 70.6% of the population were identified with high risk of CKD in the total 374 498 individuals who referred to the community health centers. Hypertension (62.3%), coronary heart disease (43.3%) and diabetes (30.4%) were the most common risk factors in high-risk CKD population. Only 17.2% of the patients with high risk of CKD were screened for kidney injury including at least one serum creatine (Scr) or albuminuria test, among which 10 992 (24.2%) individuals were defined as CKD. 22.7% (11 338/49 908) of the total patients with kidney screening in community were defined as CKD, of whom, 42.6% and 46.1% were identified by estimated glomerular filtration rate (eGFR) < 60 mL/(min·1.73 m2) and abnormalities of urinary proteins, respectively. The overall CKD detection rate in the community was 5.2% (19 299/374 498), and the miss-diagnosis rate of CKD was 38.1%. Of the 79 community health centers, 13 (16.5%) were equipped with ACR testing device, and eGFR was reported directly in 66 (83.5%) centers. Altogether 60.3% and 99.7% of the community CKD patients achieved glucose control and blood pressure control, respectively, and 59.3% of the CKD patients who had proteinuria was treated with renin-angiotensin-aldosterone system (RAAS) inhibitors. CONCLUSION: High-risk CKD population account for a substantial proportion of patients who refer to the community. Early screening, prevention and management of CKD in the community are of great importance to improve the prognosis and decrease the burden of CKD. It's essential to establish a screening and monitoring system, strengthen standardized management and clinician training for improving the ability of CKD management in the community.

[Reversal effect of peptide-modified chitosan tetramethylpyrazine nanoparticles on multidrug resistance in tumor cells].

To prepare peptide-modified chitosan tetramethylprazine nanoparticles(FGF-CS-TMP-NPS) and investigate its reversal effect on multidrug resistance in tumor cells. The pEGF-CS-TMP-NPs were prepared by ion crosslinking method, and their physicochemical properties were investigated. Western blot was used to detect the expression levels of epidermal growth factor receptor(EGFR)(MCF-7, MCF-7/ADR, K562 and K562/ADR) and drug-resistant related protein P-gp. MCF-7/ADR and K562/ADR were selected as cell models. The cytotoxicity of pEGF-CS-TMP-NPs, the multiple of cell resistance to adriamycin, the reversal resistance index of pEGF-CS-TMP-NPs to doxorubicin and the sensitization of pEGF-CS-TMP-NPs to doxorubicin were detected by MTT assay. After MCF-7/ADR and K562/ADR were treated with pEGF-CS-TMP-NPs, the expression changes of P-gp were detected by Western blot. The encapsulation efficiency and drug loading of pEGF-CS-TMP-NPs were 37.66%± 0.53% and 3.25%± 0.34% respectively in HPLC. The nanoparticles showed an average particle size of(150.50±9.3) nm, polymer dispersity index of(0.059±0.007) and Zeta potential of(19.30±2.02) mV as detected by laser particle size analyzer. The nanoparticles were spherical and well dispersed under transmission electron microscope. Western blot results showed that EGFR was positively expressed in MCF-7 and MCF-7/ADR cells, while negatively expressed in K562 and K562/ADR cells. P-gp was highly expressed in MCF-7/ADR and K562/ADR, while negatively expressed in MCF-7 and K562. pEGF-CS-TMP-NPs had a weak effect on MCF-7/ADR and K562/ADR. The adriamycin resistance of MCF-7/ADR cells was 108.36 times, and that of K562/ADR cells was more than 100 times. When IC_(85) of pEGF-CS-TMP-NPs was used as the administration concentration, the reversion index of MCF-7/ADR and K562/ADR cells was 3.68 and 1.87, respectively. pEGF-CS-TMP-NPs could enhance the sensitivity of adriamycin to MCF-7/ADR cells in a positive correlation with the concentration, and the sensitivity was significantly higher than that of K562/ADR cells. Western blot results showed that the expression level of P-gp in MCF-7/ADR cells decreased significantly after treatment with pEGF-CS-TMP-NPs, while the expression level of P-gp in K562/ADR cells did not change significantly. Experimental results show that pEGF-CS-TMP-NPs have an active targeting effect on MCF-7/ADR cells with high EGFR expression, and can effectively reverse the multidrug resistance of MCF-7/ADR cells. Active targeting effect is related to the peptides modification of nanoparticles, and the mechanism of reversing tumor MDR may be achieved by down-regulating the expression level of P-gp.

Automated real-time detection of drug-resistant Mycobacterium tuberculosis on a lab-on-a-disc by Recombinase Polymerase Amplification.

With the emergence of multi- and extensive-drug (MDR/XDR) resistant Mycobacterium tuberculosis (M. tb), tuberculosis (TB) persists as one of the world's leading causes of death. Recently, isothermal DNA amplification methods received much attention due to their ease of translation onto portable point-of-care (POC) devices for TB diagnosis. In this study, we aimed to devise a simple yet robust detection method for M. tb. Amongst the numerous up-and-coming isothermal techniques, Recombinase Polymerase Amplification (RPA) was chosen for a real-time detection of TB with or without MDR. In our platform, real-time RPA (RT-RPA) was integrated on a lab-on-a-disc (LOAD) with on-board power to maintain temperature for DNA amplification. Sputa collected from healthy volunteers were spiked with respective target M. tb samples for testing. A limit of detection of 102 colony-forming unit per millilitre in 15 min was achieved, making early detection and differentiation of M. tb strains highly feasible in extreme POC settings. Our RT-RPA LOAD platform has also been successfully applied in the differentiation of MDR-TB from H37Ra, an attenuated TB strain. In summary, a quantitative RT-RPA on LOAD assay with a high level of sensitivity was developed as a foundation for further developments in medical bedside and POC diagnostics.

[Clinical characteristics of abdominal solitary fibrous tumor: an analysis of 18 cases].

Objective: To summarize the clinical manifestations, pathological features, diagnosis, and treatment of abdominal solitary fibrous tumor (SFT). Methods: The data of clinical manifestations, pathological features, diagnosis, and treatment of 18 patients with abdominal SFT admitted to Department of General Surgery, Peking Union Medical College Hospital between January 2000 and December 2016 were retrospectively reviewed. Results: Abdominal mass was first presented in 14 patients. The blood routine, liver, kidney, and coagulation function were normal in all the patients. Tumor markers were abnormal in 4 cases. Most SFT showed hypoechoic mass with regular shape under ultrasound. CT findings differed among the cases. All the 18 patients underwent surgical treatment, and the diagnosis was proved by the postoperative histopathology. SFT differed in general morphology. The positive rate of Ki-67, smooth muscle actin (SMA), CD34, and S-100 was high under immunohistochemistry. Conclusions: Early diagnosis of abdominal SFT is difficult, leading to a low preoperative diagnosis rate. Complete removal of the tumor is the only reliable method of radical treatment.

Transient Neonatal Zinc Deficiency Caused by a Novel Mutation in the SLC30A2 Gene.

This is a case report of a 4-month-old full-term, fully breastfed boy who presented with a persistent periorificial and groin rash associated with poor weight gain and irritability. His serum zinc level was low. The mother's breast milk zinc level was found to be low despite her serum zinc levels being normal, confirming the diagnosis of transient neonatal zinc deficiency. Mutational analysis revealed a novel mutation in the mother's SLC30A2 gene, which encodes a zinc transporter expressed in mammary gland epithelial cells.

High-density linkage mapping aided by transcriptomics documents ZW sex determination system in the Chinese mitten crab Eriocheir sinensis.

The sex determination system in crabs is believed to be XY-XX from karyotypy, but centromeres could not be identified in some chromosomes and their morphology is not completely clear. Using quantitative trait locus mapping of the gender phenotype, we revealed a ZW-ZZ sex determination system in Eriocheir sinensis and presented a high-density linkage map covering ~98.5% of the genome, with 73 linkage groups corresponding to the haploid chromosome number. All sex-linked markers in the family we used were located on a single linkage group, LG60, and sex linkage was confirmed by genome-wide association studies (GWAS). Forty-six markers detected by GWAS were heterozygous and segregated only in the female parent. The female LG60 was thus the putative W chromosome, with the homologous male LG60 as the Z chromosome. The putative Z and W sex chromosomes were identical in size and carried many homologous loci. Sex ratio (5:1) skewing towards females in induced triploids using unrelated animals also supported a ZW-ZZ system. Transcriptome data were used to search for candidate sex-determining loci, but only one LG60 gene was identified as an ankyrin-2 gene. Double sex- and mab3-related transcription factor 1 (Dmrt1), a Z-linked gene in birds, was located on a putative autosome. With complete genome sequencing and transcriptomic data, more genes on putative sex chromosomes will be characterised, thus leading towards a comprehensive understanding of the sex determination and differentiation mechanisms of E. sinensis, and decapod crustaceans in general.

Pediatric meningiomas an aggressive subset: a clinicopathological and immunohistochemical study.

BACKGROUND: Meningiomas are uncommon neoplasms in the pediatric age group and differ in various aspects from their adult counterparts. They account for 0.4-4.6% of all primary brain tumors. AIMS: To retrospectively analyze the clinicopathological and immunohistochemical features of pediatric meningiomas. MATERIALS AND METHODS: Meningiomas in patients under 18 years of age diagnosed between January 2001 to December 2011 were analyzed retrospectively. The hematoxylin and eosin stained sections and Ki 67 labelling index (LI) were reviewed for all the cases Results: The pediatric meningiomas accounted for 1.52% of total meningiomas (15/983). The mean age at presentation was 12 years with male to female ratio of 1.5:1. The presenting symptoms were headache, seizures, and motor deficits. The histology included 9 cases (60%) of atypical meningioma (WHO grade II) followed by 4 cases (26.67%) of WHO grade-I and 2 cases (13.33%) of anaplastic meningioma (WHO grade III). Five cases had a recurrence. Ki67 LI ranged from 0.5% to 1.5% in grade I, 0.5% to 15% in grade II and 13% to 24% in grade III meningiomas. CONCLUSION: Meningiomas are rare in children and show a male preponderance. There was a higher incidence of atypical and anaplastic meningiomas in pediatric population.

FGF receptor genes and breast cancer susceptibility: results from the Breast Cancer Association Consortium.

BACKGROUND: Breast cancer is one of the most common malignancies in women. Genome-wide association studies have identified FGFR2 as a breast cancer susceptibility gene. Common variation in other fibroblast growth factor (FGF) receptors might also modify risk. We tested this hypothesis by studying genotyped single-nucleotide polymorphisms (SNPs) and imputed SNPs in FGFR1, FGFR3, FGFR4 and FGFRL1 in the Breast Cancer Association Consortium. METHODS: Data were combined from 49 studies, including 53 835 cases and 50 156 controls, of which 89 050 (46 450 cases and 42 600 controls) were of European ancestry, 12 893 (6269 cases and 6624 controls) of Asian and 2048 (1116 cases and 932 controls) of African ancestry. Associations with risk of breast cancer, overall and by disease sub-type, were assessed using unconditional logistic regression. RESULTS: Little evidence of association with breast cancer risk was observed for SNPs in the FGF receptor genes. The strongest evidence in European women was for rs743682 in FGFR3; the estimated per-allele odds ratio was 1.05 (95% confidence interval=1.02-1.09, P=0.0020), which is substantially lower than that observed for SNPs in FGFR2. CONCLUSION: Our results suggest that common variants in the other FGF receptors are not associated with risk of breast cancer to the degree observed for FGFR2.

Detection of seizure onset in childhood absence epilepsy.

OBJECTIVE: This study aims to detect the seizure onset, in childhood absence epilepsy, as early as possible. Indeed, interfering with absence seizures with sensory simulation has been shown to be possible on the condition that the stimulation occurs soon enough after the seizure onset. METHODS: We present four variations (two supervised, two unsupervised) of an algorithm designed to detect the onset of absence seizures from 4 scalp electrodes, and compare their performance with that of a state-of-the-art algorithm. We exploit the characteristic shape of spike-wave discharges to detect the seizure onset. Their performance is assessed on clinical electroencephalograms from 63 patients with confirmed childhood absence epilepsy. RESULTS: The proposed approaches succeed in early detection of the seizure onset, contrary to the classical detection algorithm. Indeed, the results clearly show the superiority of the proposed methods for small delays of detection, under 750 ms from the onset. CONCLUSION: The performance of the proposed unsupervised methods is equivalent to that of the supervised ones. The use of only four electrodes makes the pipeline suitable to be embedded in a wearable device. SIGNIFICANCE: The proposed pipelines perform early detection of absence seizures, which constitutes a prerequisite for a closed-loop system.

Lupus nephritis: a 15-year multi-centre experience in the UK.

OBJECTIVES: Our aim was to audit the outcome of lupus nephritis (LN) at three East Midlands centres. METHODS: We undertook a retrospective review of all biopsy-proven LN types III-V 1995-2010. RESULTS: In total, 61 patients with LN were identified, with a median follow-up of 68 months. LN was present at the time of systemic lupus erythematosus (SLE) diagnosis in 20 patients. The median time from SLE diagnosis to the first LN episode was 5.3 years. Some 35 patients received IV cyclophosphamide and 17 received mycophenolate mofetil (MMF) as induction therapy; 81.8% of those treated with cyclophosphamide and 81.3% with MMF had at least 'improved' according to the ACR-response criteria 6 months from induction; 33.3% and 37.5%, respectively, had a 'complete' response. MMF and azathioprine were the most frequently used maintenance therapy. We found that 32.8% experienced a flare after a mean post-induction time of 3.5 years, irrespective of the maintenance therapy used, and 43.8% of partial responders flared compared with 4.8% of complete responders. End-stage renal failure developed in 8.2%. CONCLUSIONS: Overall, outcomes (response, flare-rate, end-stage renal failure) were comparable with European clinical studies. Partial responders are more likely to flare compared with complete responders. The results highlight that LN can occur, and flare, after many years of SLE, emphasizing the importance of continued vigilance for LN in all patients.

Antibiotic-resistant Propionibacterium acnes among acne patients in a regional skin centre in Hong Kong.

BACKGROUND: There has been no study on antibiotic-resistant Propionibacterium acnes in Hong Kong. OBJECTIVE: We investigated the prevalence and pattern of antibiotic-resistant P. acnes and to identify any associated factors for harbouring the resistant strains. METHODS: Culture and sensitivity testing of P. acnes to commonly used antibiotics were performed. Resistance to tetracycline was defined at a minimal inhibitory concentration (MIC) of 2 µg/mL or more; erythromycin at an MIC of 0.5 µg/mL or more; clindamycin at an MIC of 0.25 µg/mL or more according to EUCAST. For breakpoints of doxycycline and minocycline, those with an MIC of 1 µg/mL or more were defined as resistant strains. RESULTS: Among the 111 specimens collected from 111 patients, 86 strains of P. acnes were recovered, one from each specimen. Twenty-five specimens had no growth. Forty-seven (54.8%) strains were found to be resistant to one or more antibiotics. Forty-six (53.5%), 18 (20.9%), 14 (16.3%), 14(16.3%) and 14 (16.3%) strains were resistant to clindamycin (CL), erythromycin (EM), tetracycline (TET), doxycycline (DOX) and minocycline (MR) respectively. Ten strains (11.6%) had cross resistance between the MLS antibiotics (erythromycin or clindamycin), one strain (1.2%) had cross resistance among the cyclines and 14 strains (16.4%) had cross resistance between the MLS and cycline antibiotics. Binary logistic regression showed an association between MLS antibiotic resistance with an increased age whereas cycline resistance was associated with the duration of treatment. CONCLUSION: Antibiotic-resistant P. acnes is prevalent in Hong Kong. Dermatologists should be more vigilant in prescribing antibiotics for acne patients.

Analysis of differential gene expression during floral bud abortion in radish (Raphanus sativus L.).

Radish floral bud abortion (FBA) is an adverse biological phenomenon that occurs during reproduction. Although FBA occurs frequently, its mechanism remains unknown. To elucidate the molecular mechanism underlying FBA, we detected gene expression differences between aborted and normal buds of radish using cDNA-amplified fragment length polymorphism (AFLP) and real-time polymerase chain reaction (real-time PCR). A total of 221 differentially expressed transcript-derived fragments (TDFs) were detected by 256 cDNA-AFLP primer combinations, of which 114 were upregulated and 107 were downregulated in the aborted buds. A total of 54 TDFs were cloned and sequenced. A BLAST search revealed that all TDFs have homologous sequences and 29 of these corresponded to known genes, whose functions were mainly related to metabolism, stimulus response, transcriptional regulation, and transportation. Expressions of 6 TDFs with different functions were further analyzed by real-time PCR yielding expression profiling results consistent with the cDNA-AFLP analysis. Our results indicated that radish FBA is related to abnormalities in various physiological and biochemical plant processes.

Recommendations for the use of next-generation sequencing in patients with metastatic cancer in the Asia-Pacific region: a report from the APODDC working group.

INTRODUCTION: Next-generation sequencing (NGS) diagnostics have shown clinical utility in predicting survival benefits in patients with certain cancer types who are undergoing targeted drug therapies. Currently, there are no guidelines or recommendations for the use of NGS in patients with metastatic cancer from an Asian perspective. In this article, we present the Asia-Pacific Oncology Drug Development Consortium (APODDC) recommendations for the clinical use of NGS in metastatic cancers. METHODS: The APODDC set up a group of experts in the field of clinical cancer genomics to (i) understand the current NGS landscape for metastatic cancers in the Asia-Pacific (APAC) region; (ii) discuss key challenges in the adoption of NGS testing in clinical practice; and (iii) adapt/modify the European Society for Medical Oncology guidelines for local use. Nine cancer types [breast cancer (BC), gastric cancer (GC), nasopharyngeal cancer (NPC), ovarian cancer (OC), prostate cancer, lung cancer, and colorectal cancer (CRC) as well as cholangiocarcinoma and hepatocellular carcinoma (HCC)] were identified, and the applicability of NGS was evaluated in daily practice and/or clinical research. Asian ethnicity, accessibility of NGS testing, reimbursement, and socioeconomic and local practice characteristics were taken into consideration. RESULTS: The APODDC recommends NGS testing in metastatic non-small-cell lung cancer (NSCLC). Routine NGS testing is not recommended in metastatic BC, GC, and NPC as well as cholangiocarcinoma and HCC. The group suggested that patients with epithelial OC may be offered germline and/or somatic genetic testing for BReast CAncer gene 1 (BRCA1), BRCA2, and other OC susceptibility genes. Access to poly (ADP-ribose) polymerase inhibitors is required for NGS to be of clinical utility in prostate cancer. Allele-specific PCR or a small-panel multiplex-gene NGS was suggested to identify key alterations in CRC. CONCLUSION: This document offers practical guidance on the clinical utility of NGS in specific cancer indications from an Asian perspective.

Evaluation of PCR for the diagnosis of dermatophytes in nail specimens from patients with suspected onychomycosis.

BACKGROUND: Conventional methods for detecting fungi in nail specimens are either nonspecific (microscopy) or insensitive (culture). Recently, PCR has been used to improve sensitivity in detecting the causative fungi in nail specimens from patients with suspected onychomycosis. AIM: To compare the detection rates of PCR with those of microscopy (with potassium hydroxide; KOH) and culture for dermatophytes in nail specimens from patients with suspected onychomycosis. METHODS: In total, 120 patients with clinically suspected onychomycosis were recruited, and using a topoisomerase II-based PCR, we compared the detection rate of dermatophytes for the three methods. RESULTS: KOH microscopy, culture and PCR respectively yielded positive rates of 35 (29.2%), 12 (10%) and 48 (40%), and negative rates of 85 (70.8%), 108 (90%) and 72 (60%). Two culture-positive specimens were not detected by PCR, but PCR picked up 38 specimens missed by culture. Of the 35 specimens that were microscopy-positive, 12 grew dermatophytes and 23 nondermatophytes. CONCLUSIONS: This study demonstrates that PCR has a higher positive and lower negative rate for detection of dermatophytes compared with KOH microscopy or culture. We suggest that PCR should be used as a complementary method for confirmation of clinically suspected dermatophytic onychomycosis.

Spatial frequency domain imaging technology based on Fourier single-pixel imaging.

SIGNIFICANCE: Optical properties (absorption coefficient and scattering coefficient) of tissue are the most critical parameters for disease diagnosis-based optical method. In recent years, researchers proposed spatial frequency domain imaging (SFDI) to quantitatively map tissue optical properties in a broad field of contactless imaging. To solve the limitations in wavebands unsuitable for silicon-based sensor technology, a compressed sensing (CS) algorithm is used to reproduce the original signal by a single-pixel detectors. Currently, the existing single-pixel SFDI method mainly uses a random sampling policy to extract and recover signals in the acquisition stage. However, these methods are memory-hungry and time-consuming, and they cannot generate discernible results under low sampling rate. Explorations on high performance and efficiency single-pixel SFDI are of great significance for clinical application. AIM: Fourier single-pixel imaging can reconstruct signals with less time and space costs and has fewer reconstruction errors. We focus on an SFDI algorithm based on Fourier single-pixel imaging and propose our Fourier single-pixel image-based spatial frequency domain imaging method (FSI-SFDI). APPROACH: First, we use Fourier single-pixel imaging algorithm to collect and compress signals and SFDI algorithm to generate optical parameters. Given the basis that the main energy of general image signals is concentrated in the range of low frequency of Fourier frequency domain, our FSI-SFDI uses a circular-sampling scheme to sample data points in the low-frequency region. Then, we reconstruct the image details from these points by optimization-based inverse-FFT method. RESULTS: Our algorithm is tested on simulated data. Results show that the root mean square error (RMSE) of optical parameters is lower than 5% when the data reduction is 92%, and it can generate discernible optical parameter image with low sampling rate. We can observe that our FSI-SFDI primarily recovers the optical properties while keeping the RMSE under the upper bound of 4.5% when we use an image with 512 × 512 resolution as the example for calculation and analysis. Not only that but also our algorithm consumes less space and time for an image with 256 × 256 resolution, the signal reconstruction takes only 1.65 ms, and requires less RAM memory. Compared to CS-SFDI method, our FSI-SFDI can reduce the required number of measurements through optimizing algorithm. CONCLUSIONS: Moreover, FSI-SFDI is capable of recovering high-quality resolvable images with lower sampling rate, higher-resolution images with less memory and time consumed than previous CS-SFDI method, which is very promising for clinical data collection and medical analysis.

Immunosuppressive polyketides from mantis-associated Daldinia eschscholzii.

Polyketides with unknown architectures are highly desired for the discovery of new drugs and agrochemicals. Here, the mantis-associated Daldinia eschscholzii, a fungus known to produce immunosuppressants dalesconols A and B, was found to simultaneously generate four novel skeletons capable of shaping the unusual chemistry of the fungal polyketides, of which seven were structurally unique and substantially immunosuppressive. In particular, the scaled-up fermentation of the microbe enabled the structural characterization of minor or "transitional" intermediate polyketides that allowed the reasonable recognition of the four biosynthetic pathways initiated by condensations of four, five, six and eight acetate units, respectively. Furthermore, the decarbonylation reaction of triketone, as in the case of daeschol A, was described for the first time, in addition to the structural correction of sporothrin C and nodulone. The work provided a set of novel immunosuppressive molecules that are of significance to drug discovery.

The 50% and 95% effective doses of desflurane for removal of the classic laryngeal mask airway in spontaneously breathing anaesthetised adults.

The 50% and 95% effective doses of desflurane for removal of the classic laryngeal mask airway after suction of the upper airway, in anaesthetised spontaneously breathing adult patients, are not known. To determine these, we studied 38 healthy patients, aged between 18 and 44 years. The target desflurane concentration in each individual patient was determined by the Dixon up-and-down method. When the predetermined target end-tidal desflurane concentration reached steady state, we kept a constant end-expiratory partial pressure between the alveolus and the brain for 10 min before attempting to remove the classic laryngeal mask airway after suctioning the upper airway. The initial desflurane target concentration was set at 6% and up-down desflurane increments were 0.1%. This continued until there were at least six crossover pairs. From the probit analysis, the 50% effective dose of desflurane was 5.29% (95% CI 5.132-5.379%) and the 95% effective dose was 5.55% (95% CI 5.429-6.394%).