Peripheral Lymphoid Volume Expansion and Maintenance Are Controlled by Gut Microbiota via RALDH+ Dendritic Cells.

Lymphocyte homing to draining lymph nodes is critical for the initiation of immune responses. Secondary lymphoid organs of germ-free mice are underdeveloped. How gut commensal microbes remotely regulate cellularity and volume of secondary lymphoid organs remains unknown. We report here that, driven by commensal fungi, a wave of CD45(+)CD103(+)RALDH(+) cells migrates to the peripheral lymph nodes after birth. The arrival of these cells introduces high amounts of retinoic acid, mediates the neonatal to adult addressin switch on endothelial cells, and directs the homing of lymphocytes to both gut-associated lymphoid tissues and peripheral lymph nodes. In adult mice, a small number of these RALDH(+) cells might serve to maintain the volume of secondary lymphoid organs. Homing deficiency of these cells was associated with lymph node attrition in vitamin-A-deficient mice, suggesting a perpetual dependence on retinoic acid signaling for structural and functional maintenance of peripheral immune organs.

Molecular Characterization and Phylogenetic Analysis of Centipedegrass [Eremochloa ophiuroides (Munro) Hack.] Based on the Complete Chloroplast Genome Sequence.

Centipedegrass (Eremochloa ophiuroides) is an important warm-season grass plant used as a turfgrass as well as pasture grass in tropical and subtropical regions, with wide application in land surface greening and soil conservation in South China and southern United States. In this study, the complete cp genome of E. ophiuroides was assembled using high-throughput Illumina sequencing technology. The circle pseudomolecule for E. ophiuroides cp genome is 139,107 bp in length, with a quadripartite structure consisting of a large single copyregion of 82,081 bp and a small single copy region of 12,566 bp separated by a pair of inverted repeat regions of 22,230 bp each. The overall A + T content of the whole genome is 61.60%, showing an asymmetric nucleotide composition. The genome encodes a total of 131 gene species, composed of 20 duplicated genes within the IR regions and 111 unique genes comprising 77 protein-coding genes, 30 transfer RNA genes, and 4 ribosome RNA genes. The complete cp genome sequence contains 51 long repeats and 197 simple sequence repeats, and a high degree of collinearity among E. ophiuroide and other Gramineae plants was disclosed. Phylogenetic analysis showed E. ophiuroides, together with the other two Eremochloa species, is closely related to Mnesithea helferi within the subtribe Rottboelliinae. These findings will be beneficial for the classification and identification of the Eremochloa taxa, phylogenetic resolution, novel gene discovery, and functional genomic studies for the genus Eremochloa.

Fascin-1 limits myosin activity in microglia to control mechanical characterization of the injured spinal cord.

BACKGROUND: Mechanical softening of the glial scar region regulates axonal regeneration to impede neurological recovery in central nervous system (CNS) injury. Microglia, a crucial cellular component of the glial scar, facilitate neuronal survival and neurological recovery after spinal cord injury (SCI). However, the critical mechanical characterization of injured spinal cord that harmonizes neuroprotective function of microglia remains poorly understood. METHODS: Spinal cord tissue stiffness was assessed using atomic force microscopy (AFM) in a mouse model of crush injury. Pharmacological depletion of microglia using PLX5622 was used to explore the effect of microglia on mechanical characterization. Conditional knockout of Fascin-1 in microglia (Fascin-1 CKO) alone or in combination with inhibition of myosin activity was performed to delve into relevant mechanisms of microglia regulating mechanical signal. Immunofluorescence staining was performed to evaluate the related protein levels, inflammatory cells, and neuron survival after SCI. The Basso mouse scale score was calculated to assess functional recovery. RESULTS: Spinal cord tissue significantly softens after SCI. Microglia depletion or Fascin-1 knockout in microglia limits tissue softening and alters mechanical characterization, which leads to increased tissue pathology and impaired functional recovery. Mechanistically, Fascin-1 inhibits myosin activation to promote microglial migration and control mechanical characterization after SCI. CONCLUSIONS: We reveal that Fascin-1 limits myosin activity to regulate mechanical characterization after SCI, and this mechanical signal should be considered in future approaches for the treatment of CNS diseases.

Kawasaki disease coronary artery lesions prediction with monocyte-to-high-density lipoprotein ratio.

OBJECTIVE: The aim of this study was to evaluate the predictive value of the monocyte-to-high-density lipoprotein ratio (MHR) in Kawasaki disease (KD) complicated with coronary artery lesions (CALs) and to construct a nomogram prediction model. METHODS: The medical records of KD inpatients diagnosed in the Department of Pediatrics of Lanzhou University Second Hospital from May 2015 to September 2021 were retrospectively analyzed. ROC curves were applied to evaluate the predictive value of MHR in KD complicated with CALs, and logistic regression analysis was used to screen independent risk factors. We constructed a nomogram model and performed internal validation. RESULTS: A total of 568 KD patients were enrolled in the study. MHR was significantly higher in KD patients complicated with CALs and was identified as an independent risk factor for CALs (OR: 1.604, 95% CI: 1.292-1.990). The area under the ROC curve for MHR in predicting CALs was 0.661. The C-index of the nomogram model constructed by incorporating MHR was 0.725 (95% CI: 0.682-0.768), and the calibration curve revealed good agreement between the predicted and actual probabilities. CONCLUSIONS: MHR may not be suitable as a single biomarker to predict the occurrence of CALs, but the nomogram model constructed in combination with other independent risk factors had acceptable predictive performance. IMPACT: The inflammatory response plays an important role in the pathogenesis of Kawasaki disease. The monocyte-to-high-density lipoprotein ratio is a novel systemic inflammation marker. The monocyte-to-high-density lipoprotein ratio is an independent risk factor for Kawasaki disease complicated with coronary artery lesions. The nomogram established by incorporating the monocyte-to-high-density lipoprotein ratio has satisfactory predictive performance for coronary artery lesion formation.

Reference gene selection for quantitative RT-PCR in Miscanthus sacchariflorus under abiotic stress conditions.

BACKGROUND: Reference genes are necessary for quantitative real-time PCR (qRT-PCR) analysis and their stability can directly influence the accuracy of gene expression result. Miscanthus sacchariflorus, a perennial C4 grass that serves as promising biofuel plant for temperate climates, has not been explored for the identification of stable reference genes yet. MATERIALS AND METHODS: Nine potential reference genes (ACT, EF1a, FBOX, GAPDH, PP2A, SAND, TIP41, TUB and UBC) of M. sacchariflorus under different abiotic (salinity, drought and cadmium) stresses, as well as in two tissues (roots and leaves) were evaluated. The expression stability of these genes were analyzed by four commonly used software programs (geNorm, NormFinder, BestKeeper, ΔCt method and RefFinder). RESULTS: Our results found that FBOX and SAND are the most stable genes among all tested samples. FBOX and EF1a are suitable for gene expression normalization of cadmium-treated samples and salinity-treated leaves. FBOX and PP2A are appropriate reference genes for salt-stressed roots and PEG-treated leaves. The traditional reference gene ACT and GAPDH exhibited the most variable pattern, which would not be recommended for qRT-PCR analysis under different abiotic stresses. Furthermore, the expression levels of PIP2, NHX1 and MT2a under drought, salt and cadmium treatment were detected with above reference genes. CONCLUSIONS: This work identified the appropriate reference genes for qRT-PCR in M. sacchariflorus and FBOX was recommended to be effective internal control for gene expression normalization in M. sacchariflorus in response to different abiotic stresses.

Integration of the metabolome and transcriptome reveals the mechanism of resistance to low nitrogen supply in wild bermudagrass (Cynodon dactylon (L.) Pers.) roots.

BACKGROUND: Nitrogen (N) is an essential macronutrient that significantly affects turf quality. Commercial cultivars of bermudagrass (Cynodon dactylon (L.) Pers.) require large amounts of nitrogenous fertilizer. Wild bermudagrass germplasm from natural habitats with poor nutrition and diverse N distributions is an important source for low-N-tolerant cultivated bermudagrass breeding. However, the mechanisms underlying the differences in N utilization among wild germplasm resources of bermudagrass are not clear. RESULTS: To clarify the low N tolerance mechanism in wild bermudagrass germplasm, the growth, physiology, metabolome and transcriptome of two wild accessions, C291 (low-N-tolerant) and C716 (low-N-sensitive), were investigated. The results showed that root growth was less inhibited in low-N-tolerant C291 than in low-N-sensitive C716 under low N conditions; the root dry weight, soluble protein content and free amino acid content of C291 did not differ from those of the control, while those of C716 were significantly decreased. Down-regulation of N acquisition, primary N assimilation and amino acid biosynthesis was less pronounced in C291 than in C716 under low N conditions; glycolysis and the tricarboxylic acid (TCA) cycle pathway were also down-regulated, accompanied by a decrease in the biosynthesis of amino acids; strikingly, processes such as translation, biosynthesis of the structural constituent of ribosome, and the expression of individual aminoacyl-tRNA synthetase genes, most of genes associated with ribosomes related to protein synthesis were all up-regulated in C291, but down-regulated in C716. CONCLUSIONS: Overall, low-N-tolerant wild bermudagrass tolerated low N nutrition by reducing N primary assimilation and amino acid biosynthesis, while promoting the root protein synthesis process and thereby maintaining root N status and normal growth.

Physiological and transcriptomic analyses reveal the mechanisms underlying the salt tolerance of Zoysia japonica Steud.

BACKGROUND: Areas with saline soils are sparsely populated and have fragile ecosystems, which severely restricts the sustainable development of local economies. Zoysia grasses are recognized as excellent warm-season turfgrasses worldwide, with high salt tolerance and superior growth in saline-alkali soils. However, the mechanism underlying the salt tolerance of Zoysia species remains unknown. RESULTS: The phenotypic and physiological responses of two contrasting materials, Zoysia japonica Steud. Z004 (salt sensitive) and Z011 (salt tolerant) in response to salt stress were studied. The results show that Z011 was more salt tolerant than was Z004, with the former presenting greater K+/Na+ ratios in both its leaves and roots. To study the molecular mechanisms underlying salt tolerance further, we compared the transcriptomes of the two materials at different time points (0 h, 1 h, 24 h, and 72 h) and from different tissues (leaves and roots) under salt treatment. The 24-h time point and the roots might make significant contributions to the salt tolerance. Moreover, GO and KEGG analyses of different comparisons revealed that the key DEGs participating in the salt-stress response belonged to the hormone pathway, various TF families and the DUF family. CONCLUSIONS: Zoysia salt treatment transcriptome shows the 24-h and roots may make significant contributions to the salt tolerance. The auxin signal transduction family, ABA signal transduction family, WRKY TF family and bHLH TF family may be the most important families in Zoysia salt-stress regulation.

Drug resistance evolution in patients with human immunodeficiency virus-1 under long-term antiretroviral treatment-failure in Yunnan Province, China.

BACKGROUND: Understanding the prevalence and evolution of HIV-1 drug resistance (DR) and associated mutation patterns is critical to implementing free antiretroviral therapy in Yunnan, the first antiretroviral treatment location in China. Here We provide a basis for understanding the occurrence and development of HIV-1 resistance in Yunnan and a theoretical foundational for strategy to delay HIV-1 drug resistance and achieve successful individualized treatment. METHODS: Plasma samples from different cities/prefectures were collected at Yunnan Provincial Hospital of Infectious Disease from January 2010 to September 2016, and those from drug-resistant individuals were genotyped using in-house assays, 88 patients were selected for the study who had been on treatment for ≥6 months (and for whom drug resistance was then measured), and each patient had at least 3 genotype resistance tests and who were enrolled to analyze mutation and evolution of HIV resistance. RESULTS: 264 Pol sequences of 88 patients were obtained. Drug resistance levels to eight drugs increased to varying degrees with prolonged treatment. Resistance to efavirenz (EFV) and etravirine (ETR) showed the highest change, comparisons of resistant changes to second and first and to third and second agents showed altered level of drug resistance were 25 and 20 cases, 28 and 18 cases, respectively. The smallest change was Lopinavir/Ritonavir (LPV/r) present 2 and 3 cases; Resistance to lamivudine (3TC) and lopinavir/ritonavir (LPV/r) was high among patients detected thrice, whereas other drugs were distributed in all resistance levels. M184 V/I (26.14%), T69S (11.36%), and T215Y/I (10.23%) mutations were the most common in nucleoside reverse transcriptase inhibitors (NRTIs), and K103 N/R/S (21.59%), V179D/E (20.45%) in Non-NRTIs (NNRTIs). Furthermore, L10 V/F/I (6.82%), A71V (4.55%), and I54V (4.55%) mutations were common in protease inhibitors (PIs). CONCLUSIONS: We found dynamic genotypic changes in HIV-1 drug-resistance in Yunnan, with prolonged treatment, and drug resistance was inevitable. However, resistance to different drugs occurred at varying times, and mutation site emergence was the main cause. These findings enhance our understanding of evolution and regulation, and are valuable for developing HIV-1 DR prevention strategies in Yunnan.

Self-assembled alluaudite Na(2)Fe(3-x)Mn(x)(PO4)(3) micro/nanocompounds for sodium-ion battery electrodes: a new insight into their electronic and geometric structure.

A series of alluaudite Na2 Fe3-x Mnx (PO4 )3 microcompounds, which self-assembled from primary nanorods, were prepared successfully through a solvothermal method. As a promising candidate cathode for sodium-ion batteries, it is necessary to obtain a deeper understanding of the relationship between the structure and physicochemical properties of these materials. The local electronic and geometric environments were systematically investigated, for the first time, by using a combination of soft/hard X-ray absorption, IR, and Mössbauer spectroscopy. The results show that the electrochemical performance is not only associated with morphology, but also with the electronic and crystalline structure. With the introduction of manganese into the lattice, the long-range order maintains the isostructural framework and the lattice parameters expand as expected. However, for short-range order, PO4 tetrahedra and MO6 octahedra (M=Fe and Mn) become more severely distorted as a function of Mn concentration. Meanwhile, larger MnO6 octahedra will compress the space of FeO6 octahedra, which will result in stronger core/electron-electron interactions for Fe, as characterized by hard/soft X-ray absorption spectra. These slight changes in the electronic and local structures lead to different electrochemical performances with changes to the manganese content. Moreover, other physicochemical properties, such as magnetic behavior, are also confirmed to be correlated with these different electron interactions and local geometric environments.

Low prevalence of human leukocyte antigen-B*5701 in HIV-1-infected Chinese subjects: a prospective epidemiological investigation.

BACKGROUND: Human leukocyte antigen (HLA)-B*5701 is strongly associated with developing a hypersensitivity reaction to abacavir (ABC). Limited data exist on HLA-B*5701 prevalence in HIV-1-infected subjects in China. We investigated HLA-B*5701 prevalence in HIV-1-infected population including Han and non-Han ethnic groups. METHODS: A prospective multi-centre study was designed to determine status of HLA-B*5701 in HIV-1-infected adults at six sites across China. HLA-B*5701 was tested by the method of PCR-SSP. RESULTS: From six centers, 3,000 HIV-infected patients [2,452 (81.7%) Han, 548 (18.3%) Non-Han] were recruited with a mean age of 36.7 years old. The overall HLA-B*5701 prevalence was 0.86% [95% confidence interval (CI) 0.55-1.26%]. The prevalence of HLA-B*5701 among Han subjects was similar to that among non-Han subjects, which was 0.88% (95% CI 0.54-1.34%) and 0.76% (95% CI 0.19-1.93%), respectively (p value = 0.787). There were no differences in prevalence of HLA-B*5701 between subjects born in Henan, Yunnan, Shanxi, Guangdong, Hebei, Beijing and other provinces (p = 0.999). CONCLUSIONS: HLA-B*5701 prevalence is very low in HIV-infected Chinese subjects, both in the Han and Non-Han nationalities. And there are no differences among different birthplaces across China.

Homoeologous relationship of rye chromosome arms as detected with wheat PLUG markers.

Based on the similarity in gene structure between rice and wheat, the polymerase chain reaction (PCR)-based landmark unique gene (PLUG) system enabled us to design primer sets that amplify wheat genic sequences including introns. From the previously reported wheat PLUG markers, we chose 144 markers that are distributed on different chromosomes and in known chromosomal regions (bins) to obtain rye-specific PCR-based markers. We conducted PCR with the 144 primer sets and the template of the Imperial rye genomic DNA and found that 131 (91.0%) primer sets successfully amplified PCR products. Of the 131 PLUG markers, 110 (76.4%) markers showed rye-specific PCR amplification with or without restriction enzyme digestion. We assigned 79 of the 110 markers to seven rye chromosomes (1R to 7R) using seven wheat-rye (cv. Imperial) chromosome addition and substitution lines: 12 to 1R, 8 to 2R, 11 to 3R, 8 to 4R, 16 to 5R, 12 to 6R, and 12 to 7R. Furthermore, we located their positions on the short or long (L) chromosome arm, using 13 Imperial rye telosomic lines of common wheat (except for 3RL). Referring to the chromosome bin locations of the 79 PLUG markers in wheat, we deduced the syntenic relationships between rye and wheat chromosomes. We also discussed chromosomal rearrangements in the rye genome with reference to the cytologically visible chromosomal gaps.

[Analysis of HIV genotypic drug resistance among pediatric HIV/AIDS cases with virological failure after free antiretroviral therapy in Yunnan province].

OBJECTIVE: To assess the prevalence and the characteristics of HIV-1 drug-resistance in pediatric HIV/AIDS cases with virological failure after free antiretroviral therapy in Yunnan Province. METHODS: The data of clinical test and laboratory detection about free antiretroviral therapy in pediatric HIV/AIDS cases from 2005 to 2012 were collected. Then the detection of HIV genotypical drug resistance was performed for the plasmas samples whose viral load were over 1 000 copies/ml after the duration of antiretroviral therapy beyond 6 months. The prevalence and the characteristics of HIV-1 drug resistance were obtained for subsequent analysis. RESULTS: A total of 73 cases suffered virological failure among 729 cases while 53 cases exhibited the resistance for antiretroviral drugs.So the resistance ratio was 72.6% (53/73) and the general resistance ratio 7.3% (53/729). The prevalent mutations associated with drug resistance were M184V/I, K103N, T215F/Y, G190A, Y181C and K101E at the frequencies of 52.1% (38/73), 30.1% (22/73), 21.9% (16/73), 20.5% (15/73), 15.1% (11/73) and 12.3% (9/73) respectively. The percentage of resistance to NVP, 3TC, EFV, D4T, AZT and ABC was 61.6% (45/73) , 54.8% (40/73) , 47.9% (35/73) , 13.7% (10/73) , 12.3% (9/73) and 5.5% (4/73) respectively. One case developed intermediate resistance to LPV/r. CONCLUSIONS: The main causes of virological failure is drug resistance.So reducing the incidence and spread of HIV drug resistance is of vital importance in modern era of resource scarcity.

Targeting the PI3K/AKT/mTOR pathway offer a promising therapeutic strategy for cholangiocarcinoma patients with high doublecortin-like kinase 1 expression.

BACKGROUND: Cholangiocarcinoma (CCA), characterized by high heterogeneity and extreme malignancy, has a poor prognosis. Doublecortin-like kinase 1 (DCLK1) promotes a variety of malignant cancers in their progression. Targeting DCLK1 or its associated regulatory pathways can prevent the generation and deterioration of several malignancies. However, the role of DCLK1 in CCA progression and its molecular mechanisms remain unknown. Therefore, we aimed to investigate whether and how DCLK1 contributes to CCA progression. METHODS: The expression of DCLK1 in CCA patients was detected using Immunohistochemistry (IHC). We established DCLK1 knockout and DCLK1 overexpression cell lines for Colony Formation Assay and Transwell experiments to explore the tumor-promoting role of DCLK1. RT-PCR, Western blot and multiple fluorescent staining were used to assess the association between DCLK1 and epithelial-mesenchymal transition (EMT) markers. RNA sequencing and bioinformatics analysis were performed to identify the underlying mechanisms by which DCLK1 regulates CCA progression and the EMT program. RESULTS: DCLK1 was overexpressed in CCA tissues and was associated with poor prognosis. DCLK1 overexpression facilitated CCA cell invasion, migration, and proliferation, whereas DCLK1 knockdown reversed the malignant tendencies of CCA cells, which had been confirmed both in vivo and in vitro. Furthermore, we demonstrated that DCLK1 was substantially linked to the advancement of the EMT program, which included the overexpression of mesenchymal markers and the downregulation of epithelial markers. For the underlying mechanism, we proposed that the PI3K/AKT/mTOR pathway is the key process for the role of DCLK1 in tumor progression and the occurrence of the EMT program. When administered with LY294002, an inhibitor of the PI3K/AKT/mTOR pathway, the tumor's ability to proliferate, migrate, and invade was greatly suppressed, and the EMT process was generally reversed. CONCLUSIONS: DCLK1 facilitates the malignant biological behavior of CCA cells through the PI3K/AKT/mTOR pathway. In individuals with cholangiocarcinoma who express DCLK1 at high levels, inhibitors of the PI3K/AKT/mTOR signaling pathway may be an effective therapeutic approach.

Genome-Wide Identification and Characterization of the TIFY Gene Family and Their Expression Patterns in Response to MeJA and Aluminum Stress in Centipedegrass (Eremochloa ophiuroides).

The TIFY family is a group of novel plant-specific transcription factors involved in plant development, signal transduction, and responses to stress and hormones. TIFY genes have been found and functionally characterized in a number of plant species. However, there is no information about this family in warm-season grass plants. The current study identified 24 TIFY genes in Eremochloa ophiuroides, a well-known perennial warm-season grass species with a high tolerance to aluminum toxicity and good adaptability to the barren acidic soils. All of the 24 EoTIFYs were unevenly located on six out of nine chromosomes and could be classified into two subfamilies (ZIM/ZML and JAZ), consisting of 3 and 21 genes, respectively, with the JAZ subfamily being further divided into five subgroups (JAZ I to JAZ V). The amino acids of 24 EoTIFYs showed apparent differences between the two subfamilies based on the analysis of gene structures and conserved motifs. MCScanX analysis revealed the tandem duplication and segmental duplication of several EoTIFY genes occurred during E. ophiuroides genome evolution. Syntenic analyses of TIFY genes between E. ophiuroides and other five plant species (including A. thaliana, O. sativa, B. distachyon, S. biocolor, and S. italica) provided valuable clues for understanding the potential evolution of the EoTIFY family. qRT-PCR analysis revealed that EoTIFY genes exhibited different spatial expression patterns in different tissues. In addition, the expressions of EoTIFY genes were highly induced by MeJA and all of the EoTIFY family members except for EoJAZ2 displayed upregulated expression by MeJA. Ten EoTIFY genes (EoZML1, EoZML1, EoJAZ1, EoJAZ3, EoJAZ5, EoJAZ6, EoJAZ8, EoJAZ9, EoJAZ10, and EoJAZ21) were observed to be highly expressed under both exogenous MeJA treatment and aluminum stress, respectively. These results suggest that EoTIFY genes play a role in the JA-regulated pathway of plant growth and aluminum resistance as well. The results of this study laid a foundation for further understanding the function of TIFY genes in E. ophiuroides, and provided useful information for future aluminum tolerance related breeding and gene function research in warm-season grass plants.

Genome-Wide Identification and Expression Analysis of the PUB Gene Family in Zoysia japonica under Salt Stress.

The U-box protein family of ubiquitin ligases is important in the biological processes of plant growth, development, and biotic and abiotic stress responses. Plants in the genus Zoysia are recognized as excellent warm-season turfgrass species with drought, wear and salt tolerance. In this study, we conducted the genome-wide identification of plant U-box (PUB) genes in Zoysia japonica based on U-box domain searching. In total, 71 ZjPUB genes were identified, and a protein tree was constructed of AtPUBs, OsPUBs, and ZjPUBs, clustered into five groups. The gene structures, characteristics, cis-elements and protein interaction prediction network were analyzed. There were mainly ABRE, ERE, MYB and MYC cis-elements distributed in the promoter regions of ZjPUBs. ZjPUBs were predicted to interact with PDR1 and EXO70B1, related to the abscisic acid signaling pathway. To better understand the roles of ZjPUBs under salt stress, the expression levels of 18 ZjPUBs under salt stress were detected using transcriptome data and qRT-PCR analysis, revealing that 16 ZjPUBs were upregulated in the roots under salt treatment. This indicates that ZjPUBs might participate in the Z. japonica salt stress response. This research provides insight into the Z. japonica PUB gene family and may support the genetic improvement in the molecular breeding of salt-tolerant zoysiagrass varieties.

A study on the changing trend and influencing factors of hospitalization costs of schizophrenia in economically underdeveloped areas of China.

The public health problems caused by schizophrenia are becoming increasingly prominent and can place a huge economic burden on society. This study takes Gansu Province as an example to analyze the level and changing trend of the economic burden of schizophrenia inpatients in economically underdeveloped areas of China. Using a multi-stage stratified cluster sampling method, 39,054 schizophrenics from 197 medical and health institutions in Gansu Province were selected as the research objects, and their medical expenses and related medical records were obtained from the medical information system. The rank sum test and Spearman rank correlation were used for univariate analysis. Quantile regression and random forest were used to analyze the influencing factors. The results show that the average length of stay of schizophrenics in Gansu Province of China was 52.01 days, and the average hospitalization cost was USD1653.96 from 2014 to 2019. During the six years, the average hospitalization costs per time decreased from USD2136.85 to USD1401.33. The average out-of-pocket costs per time decreased from USD1238.78 to USD267.68. And the average daily hospitalization costs increased from USD38.18 to USD41.25. The main factors influencing hospitalization costs are length of stay, proportion of medications, and schizophrenic subtype. The hospitalization costs per time of schizophrenics in Gansu Province have decreased but remain at a high level compared to some other chronic non-communicable diseases. In the future, attention should be paid to improving the efficiency of medical institutions, enhancing community management, and promoting the transformation of the management model of schizophrenia.

Treatment of gorham-stout disease with bisphosphonates and total hip arthroplasty: A case report.

Background: Gorham-Stout disease (GSD) is a rare osteolytic disease with unknown etiology, varied clinical manifestations and unpredictable prognosis. This disease is characterized by progressive massive local osteolysis and resorption caused by intraosseous lymphatic vessel structure and thin-walled vascular proliferation. The diagnosis of GSD has not yet formed a uniform standard, but the combination of clinical manifestations, radiological features and unique histopathological examinations and excluding other diseases contribute to early diagnosis. Although medical therapy, radiotherapy and surgical interventions or combinations have been used for the treatment of GSD, there is currently still no recommended standardized treatment regimen. Case report: This paper presents a case of a previously healthy 70-year-old man presented with a 10-year history of severe right hip pain and progressive walking disorder of the lower limbs. Based on the patient's clear clinical presentation, unique radiological features, and histological findings, a diagnosis of GSD was made with the exclusion of other potential diseases. The patient was treated with bisphosphonates to slow the progression of the disease followed by total hip arthroplasty to help restore walking function. At the 3-year follow-up, the patient returned to normal walking and no recurrence was observed. Conclusion: Bisphosphonates combined with total hip arthroplasty may be an effective method for the treatment of severe GSD in the hip joint.

The Bidirectional Relationship between Chronic Kidney Disease and Hyperuricemia: Evidence from a Population-Based Prospective Cohort Study.

BACKGROUND: Although several studies have examined the association between chronic kidney disease (CKD) and hyperuricemia (HUA), the direction of the association remains unclear. We aimed to investigate whether there was a bidirectional association between them. METHODS: The present study was conducted in three analyses. Analysis I included 25,433 participants free of HUA at baseline to evaluate the associations between CKD and estimated glomerular filtration rate (eGFR) with incident HUA. Analysis II had 28,422 participants free of CKD at baseline to analyze the relationships between HUA and serum uric acid (sUA) with new-onset CKD. Cox proportional hazards regression models were applied to evaluate the association involved in Analysis I and II. Analysis III included 31,028 participants with complete data and further dissected the bidirectional association between sUA and eGFR using cross-lag models. RESULTS: New-onset HUA and CKD were observed in the first round of the follow-up study among 1597 and 1212 participants, respectively. A significantly higher risk of HUA was observed in individuals with CKD compared to individuals without CKD (HR = 1.58, 95% CI: 1.28-1.95). The adjusted HRs (95% CIs) of HUA were 3.56 (2.50-5.05) for the participants in the group of eGFR less than 60 mL·min-1·1.73 m-2, 1.61 (1.42-1.83) for those in the group of eGFR between 60 and 90 mL·min-1·1.73 m-2, and 1.74 (1.42-2.14) for those in the group of eGFR more than 120 mL·min-1·1.73 m-2, compared with the group of eGFR between 90 and 120 mL·min-1·1.73 m-2. A higher risk of CKD was also observed in individuals with HUA compared to individuals without HUA (HR = 1.28, 95% CI: 1.12-1.47). Compared with the first quintile of sUA, the adjusted HR (95% CI) of CKD was 1.24 (1.01-1.51) for the participants in the fourth quantile. There was a bidirectional relationship between sUA and eGFR, with the path coefficients (ρ1 = -0.024, p < 0.001) from baseline eGFR to follow-up sUA and the path coefficients (ρ2 = -0.015, p = 0.002) from baseline sUA to follow-up eGFR. CONCLUSIONS: The present study indicated that CKD and HUA were closely associated, and there was a bidirectional relationship between sUA and eGFR.

DCLK1 Suppresses Tumor-Specific Cytotoxic T Lymphocyte Function Through Recruitment of MDSCs via the CXCL1-CXCR2 Axis.

BACKGROUND & AIMS: Gastrointestinal cancer stem cell marker doublecortin-like kinase (DCLK1) is strongly associated with poor outcomes in colorectal cancer (CRC). Although DCLK1's regulatory effect on the tumor immune microenvironment has been hypothesized, its mode of action has not been shown previously in vivo, which hampers the potential intervention based on this molecule for clinical practice. METHODS: To define the immunomodulatory mechanisms of DCLK1 in vivo, we generated DCLK1-/- tumor cells by Clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9) and developed subcutaneous and intestinal orthotopic transplantation tumor models. Tumor tissues were harvested and subjected to immunofluorescence staining, flow cytometry analysis of tumor-infiltrating immune cell populations, tumor myeloid-derived suppressor cell (MDSC) sorting by isolation kit and then co-culture with spleen T cells, and RNA sequencing for transcriptomic analysis. RESULTS: We found that DCLK1-/- tumor cells lose their tumorigenicity under immune surveillance. Failed tumor establishment of DCLK1-/- was associated with an increase in infiltration of CD8+ T cells and effector CD4+ T cells, and reduced numbers of MDSCs in the tumor tissue. Furthermore, DCLK1 promoted the up-regulation of C-X-C motif ligand 1, which recruits MDSCs in CRC through chemokine C-X-C motif receptor 2. The ability of in vivo tumor growth of DCLK1-/- tumor cells was rescued by C-X-C motif ligand 1 overexpression. Collectively, we validated that DCLK1 promotes tumor growth in CRC through recruitment of T-cell-suppressive MDSCs. CONCLUSIONS: DCLK1-mediated immune suppression in tumor models allows escaping from the host's antitumor response. Because DCLK1 is one of the most common markers in gastrointestinal tumors, these results identify a precise therapeutic target for related clinical interventions.