Clinical and metagenomic characteristics of lymphadenopathy related to fever of unknown origin in children.

BACKGROUND: Diagnosis of fever of unknown origin remains challenge for pediatricians. Lymphadenopathy is a separate entity that mainly originates from infection or malignancy. METHODS: 168 patients with FUO accompanied by lymphadenectasis were reviewed. 33 lymph node tissue samples were examined by mNGS. Differences in clinical characteristics were compared among different disease groups. The value of mNGS in diagnosing and improving the clinical situation was assessed. RESULTS: Multivariate analysis revealed that hepatosplenomegaly and LDH levels were associated with infectious diseases. Arthralgia was correlated with non-infectious inflammatory diseases. Weight loss and a node located in supraclavicular region may indicate neoplastic diseases. mNGS-positive rate was 60.60%, higher than that obtained with traditional methods. Treatment for 3/4 patients was adjusted according to the pathogen detected by mNGS, and antibiotics uses was discontinued or degraded in over 1/2 of the patients according to mNGS results. CONCLUSIONS: Clinical characteristics of children with lymphadenopathy related to FUO have limited diagnostic value for distinguishing different kinds of diseases, while mNGS of lymph node tissue serves as a useful tool for identifying infectious diseases, especially those caused by rare pathogens. mNGS results can lead to not only adjustments in targeted treatment but also further confirmation of underlying diseases. IMPACT STATEMENT: 1. The clinical features of children with FUO and lymphadenopathy differ according to disease group,although multivariate analysis indicated little diagnostic value for these features. 2. mNGS on lymph node tissue from children with FUO may serve as a efficient tool for distinguishing infectious diseases from other diseases. This is especially useful when a diagnosis cannot be determined with traditional methods. 3. mNGS targeted treatment can be administered in a timely manner and some underlying diseases can be indicated.

Evaluation of the efficiency and drivers of complemented cropland in Southwest China over the past 30 years from the perspective of cropland abandonment.

Complemented croplands are a crucial component of cropland resources and play a significant role in ensuring national food security. In recent decades, to counter the loss of prime farmland caused by urban construction, the Chinese government introduced a requisition-compensation balance policy, leading to the substantial expansion of new croplands. Therefore, there is an urgent need to determine whether these complemented croplands can be effectively used. Taking Southwest China as a case study, we used high-precision long-term land-use data from 1990 to 2020 to reveal the dynamics of complemented cropland utilization, evaluate the efficiency of complemented cropland utilization from the perspective of abandoned farmland, and identify the factors driving complemented cropland use efficiency based on more than 13 million land parcels. The results showed that: (1) From 1990 to 2020, complemented cropland amounted to approximately 1170.07 × 104 hm2, accounting for 32.67% of the total arable land area in 1990. The potential grain production capacity of these complemented croplands was significantly lower than that of base croplands. (2) The abandonment of complemented croplands was more serious than that of base croplands, and 47.03% of the complemented croplands experienced abandonment at least once during the study period, and the average efficiency of the complemented croplands was 75.61%. (3) The labor population ratio, elevation, and land parcel size played pivotal roles in influencing the complemented cropland utilization efficiency; however, there was substantial variation among the different provinces. Labor replacement, overcoming farming difficulties brought by mountainous terrain, and improving farmers' income are the keys to alleviating cropland abandonment in mountainous areas and improving cropland utilization efficiency. This study provides novel insights into the efficiency assessment and exploration of the mechanisms driving complemented croplands and can provide references for cropland management.

Fluorescent aptasensor based on the MNPs-CRISPR/Cas12a-TdT for the determination of nasopharyngeal carcinoma-derived exosomes.

A fluorescence aptasensor based on taking the advantage of the combination of magnetic nanoparticles (MNPs), terminal deoxynucleotidyl transferase (TdT), and CRISPR/Cas12a was developed for the determination of nasopharyngeal carcinoma (NPC)-derived exosomes. The MNPs can eliminate background interference due to their magnetic separation capability. TdT can form an ultra-long polynucleotide tail which can bind with multiple crRNA, generating a signal amplification effect. The trans-cleavage activity of CRISPR/Cas12a can be specifically triggered via the crRNA binding with DNA, resulting in the bi-labeled DNA reporter with fluorophore and quencher being cleaved. The excitation wavelength of the fluorescence spectra was 490 nm. Fluorescence spectra with emission wavelengths ranging from 511 to 600 nm were collected. Under the optimization condition, the fabricated fluorescence aptasensor for NPC-derived exosome determination exhibited excellent sensitivity and specificity, with the linear range between 500 to 5 × 104 particles mL-1 and the limit of detection of 100 particles mL-1. It can be used for the determination of NPC-derived exosomes in clinical samples, which has a considerable clinical potential and prospect.

Diagnostic Performance of Metagenomic Next-Generation Sequencing in Pediatric Patients: A Retrospective Study in a Large Children's Medical Center.

BACKGROUND: Metagenomic next-generation sequencing (mNGS) has the potential to become a complementary, if not essential, test in some clinical settings. However, the clinical application of mNGS in a large population of children with various types of infectious diseases (IDs) has not been previously evaluated. METHODS: From April 2019 to April 2021, 640 samples were collected at a single pediatric hospital and classified as ID [479 (74.8%)], non-ID [NID; 156 (24.4%)], and unknown cases [5 (0.8%)], according to the final clinical diagnosis. We compared the diagnostic performance in pathogen detection between mNGS and standard reference tests. RESULTS: According to final clinical diagnosis, the sensitivity and specificity of mNGS were 75.0% (95% CI: 70.8%-79.2%) and 59.0% (95% CI: 51.3%-66.7%), respectively. For distinguishing ID from NID, the sensitivity of mNGS was approximately 45.0% higher than that of standard tests (75.0% vs 30.0%; P < 0.001). For fungal detection, mNGS showed positive results in 93.0% of cases, compared to 43.7% for standard tests (P < 0.001). Diagnostic information was increased in respiratory system samples through the addition of meta-transcriptomic sequencing. Further analysis also showed that the read counts in sequencing data were highly correlated with clinical diagnosis, regardless of whether infection was by single or multiple pathogens (Kendall's tau b = 0.484, P < 0.001). CONCLUSIONS: For pediatric patients in critical condition with suspected infection, mNGS tests can provide valuable diagnostic information to resolve negative or inconclusive routine test results, differentiate ID from NID cases, and facilitate accurate and effective clinical therapeutic decision-making.

Impact of viral coinfection and macrolide-resistant mycoplasma infection in children with refractory Mycoplasma pneumoniae pneumonia.

BACKGROUND: Cases of refractory Mycoplasma pneumoniae pneumonia have been increasing recently; however, whether viral coinfection or macrolide-resistant M. infection contribute to the development of refractory M. pneumoniae pneumonia remains unclear. This study aimed to investigate the impacts of viral coinfection and macrolide-resistant M. pneumoniae infection on M. pneumoniae pneumonia in hospitalized children and build a model to predict a severe disease course. METHODS: Nasopharyngeal swabs or sputum specimens were collected from patients with community-acquired pneumonia meeting our protocol who were admitted to Shanghai Children's Medical Center from December 1, 2016, to May 31, 2019. The specimens were tested with the FilmArray Respiratory Panel, a multiplex polymerase chain reaction assay that detects 16 viruses, Bordetella pertussis, M. pneumoniae, and Chlamydophila pneumoniae. Univariate and multivariate logistic regression models were used to identify the risk factors for adenovirus coinfection and macrolide-resistant mycoplasma infection. RESULTS: Among the 107 M. pneumoniae pneumonia patients, the coinfection rate was 56.07%, and 60 (60/107, 56.07%) patients were infected by drug-resistant M. pneumoniae. Adenovirus was the most prevalent coinfecting organism, accounting for 22.43% (24/107). The classification tree confirmed that viral coinfection was more common in patients younger than 3 years old. Adenovirus coinfection and drug-resistant M. pneumoniae infection occurred more commonly in patients with refractory M. pneumoniae pneumonia (P = 0.019; P = 0.001). A prediction model including wheezing, lung consolidation and extrapulmonary complications was used to predict adenovirus coinfection. The area under the receiver operating characteristic curve of the prediction model was 0.795 (95% CI 0.679-0.893, P < 0.001). A prolonged fever duration after the application of macrolides for 48 h was found more commonly in patients infected by drug-resistant M. pneumoniae (P = 0.002). A fever duration longer than 7 days was an independent risk factor for drug-resistant Mycoplasma infection (OR = 3.500, 95% CI = 1.310-9.353, P = 0.012). CONCLUSIONS: The occurrence of refractory M. pneumoniae pneumonia is associated with adenovirus coinfection and infection by drug-resistant M. pneumoniae. A prediction model combining wheezing, extrapulmonary complications and lung consolidation can be used to predict adenovirus coinfection in children with M. pneumoniae pneumonia. A prolonged fever duration indicates drug-resistant M. pneumoniae infection, and a reasonable change in antibiotics is necessary.

Metformin reverses the drug resistance of cisplatin in irradiated CNE-1 human nasopharyngeal carcinoma cells through PECAM-1 mediated MRPs down-regulation.

Objective: To explore a way to reverse the drug resistance for irradiated CNE-1 human nasopharyngeal carcinoma cells and try to develop a new high efficacy with low toxicity therapeutic approach. Methods: 300 Gy irradiated the CNE-1 human nasopharyngeal carcinoma cells, and then treated with single-agent cisplatin or metformin, or combination of both drugs. MTT assay and FCM were applied to detect cell viability and apoptosis. Western blot and RT-PCR were used to characterize the protein and mRNA expression after various drug administrations. Results: The results presented single-agent metformin was capable of arresting the tumor growth and inducing apoptosis in irradiated CNE-1 cells and also demonstrated a synergy effect with cisplatin. Furthermore, metformin down-regulates the PECAM-1 expression, which could regulate Multi-drug Resistance-associate Proteins (MRPs) expression leading to cisplatin resistance of irradiated CNE-1 cells. A pan-MRP inhibitor, probenecid, can resecure cisplatin resistance leading by radiation. Conclusions: Metformin, due to its independent effects on PECAM-1, had a unique anti-proliferative effect on irradiated CNE-1 cells. It would be a new therapeutic option to conquer cisplatin resistance for advanced NPC patients after radiotherapy.

The Semantic Integration Between Two Subliminally Perceived Words Simultaneously Presented at Different Locations.

In the present study, we showed evidence of an integration between two unconscious semantic representations. In experiment 1, two masked Chinese words of the same or different categories ("orange apple" or "grape hammer") were simultaneously presented in the prime, followed by two Chinese words also of same or different categories in the target. We examined possible prime/target visual feature priming, semantic category priming and motor response priming effects. Moreover, two ISI intervals (53, 163 ms) between the prime and the target words were used to examine the positive and negative priming. The results revealed a negative motor response priming and a positive semantic category priming effect independent of the ISI when the target words were of the same category. Experiment 2 eliminated an alternative interpretation of the effect based on different number of category words changed across the prime and the target. Experiment 3 eliminated a potential confound of unequal numbers of trials for motor congruent and incongruent conditions in Experiment 1. Overall, these results indicated an integration between the meanings of the two subliminally perceived words in the prime. The difference between simultaneous and sequential presentations, and the reason why positive priming was not observed when the interval between the prime and the target was short were discussed in the context of unconscious semantic integration.

Rosmarinic Acid Derivatives' Inhibition of Glycogen Synthase Kinase-3ß Is the Pharmacological Basis of Kangen-Karyu in Alzheimer's Disease.

Inhibition of glycogen synthase kinase 3ß (GSK-3ß) is considered to be the central therapeutic approach against Alzheimer's disease (AD). In the present study, boiled water extracts of the Kangen-karyu (KK) herbal mixture and its constituents were screened for GSK-3ß inhibitory activity. KK is used in traditional Kampo and Chinese medicines for improving cognitive function. The GSK-3ß inhibition potential was evaluated by using the Kinase-Glo luminescent kinase assay platform. Furthermore, enzyme kinetics and in silico modeling were performed by using AutoDockTools to demonstrate the mechanism of enzyme inhibition. KK extract significantly inhibited GSK-3ß in a concentration-dependent manner (IC50: 17.05 ± 1.14 µg/mL) when compared with the reference drug luteolin (IC50: 2.18 ± 0.13 µM). Among the six components of KK, extracts of Cyperi Rhizoma and Salviae Miltiorrhizae Radix significantly inhibited GSK-3ß with IC50 values of 20.68 ± 2.50 and 7.77 ± 1.38 µg/mL, respectively. Among the constituents of the roots of S. miltiorrhiza water extract, rosmarinic acid, magnesium lithospermate B, salvianolic acid A, salvianolic acid B, and salvianolic acid C inhibited GSK-3ß with IC50 values ranging from 6.97 to 135.5 µM. Salvianolic acid B was found to be an ATP-competitive inhibitor of GSK-3ß and showed the lowest IC50 value (6.97 ± 0.96 µM). In silico modeling suggested a mechanism of action by which the hydrophobic, π⁻cation, and hydrophilic interactions of salvianolic acid B at ATP and substrate sites are critical for the observed GSK-3ß inhibition. Therefore, one of the mechanisms of action of KK against AD may be the inhibition of GSK-3ß and one of the active components of KK is the root of S. miltiorrhiza and its constituents: rosmarinic acid, magnesium lithospermate B, and salvianolic acids A, B, and C. Our results demonstrate the pharmacological basis for the use of KK against AD.

Structure⁻Activity Relationship of the Tyrosinase Inhibitors Kuwanon G, Mulberrofuran G, and Albanol B from Morus Species: A Kinetics and Molecular Docking Study.

Kuwanon G (KG) and benzofuran flavonoids such as mulberrofuran G (MG) and albanol B (AB) isolated from Morus sp. are reported to exhibit anti-Alzheimer's disease, anti-inflammatory, fungicidal, anti-cancer, anti-bacterial, and anti-tyrosinase properties. We investigated the inhibition of mono- and diphenolase activity of mushroom tyrosinase by KG, MG, and AB. KG and MG displayed acceptable inhibition activity compared to kojic acid. AB did not show any activity up to 350 µM. MG displayed six-fold higher inhibition of l-tyrosine oxidation (IC50 = 6.35 ± 0.45 µM) compared to kojic acid (IC50 = 36.0 µM). Kinetic studies revealed that KG and MG inhibited monophenolase activity of tyrosinase in a competitive manner. Docking simulations of KG and MG demonstrated favorable binding energies with amino acid residues of the active sites of tyrosinase. Our investigation of the structure-activity relationship of the fused benzofuran flavonoids (MG vs. AB) implicated the methyl cyclohexene ring moiety in tyrosinase inhibition. The enzyme substrate and relative structural analyses demonstrated that KG and MG from Morus sp. could be useful natural tyrosinase inhibitors in foods or cosmetics.

[Early postnatal application of glucocorticoids for preventing bronchopulmonary dysplasia in preterm infants: a Meta analysis].

OBJECTIVE: To study the clinical effect and safety of early postnatal application of glucocorticoids in the prevention of bronchopulmonary dysplasia (BPD) in preterm infants. METHODS: The databases including PubMed, Cochrane Library, Embase, CNKI, Wanfang Data, and VIP were comprehensively searched for articles on early postnatal application of glucocorticoids in the prevention of BPD in preterm infants published up to June 2016. Review Manager 5.3 was used for the Meta analysis of 16 randomized controlled trials (RCTs) that met the inclusion criteria. RESULTS: A total of 2 962 participants were enrolled in the 16 RCTs, with 1 486 patients in the trial group and 1 476 in the control group. The Meta analysis showed that early postnatal application of glucocorticoids reduced the incidence rate of BPD at a corrected gestational age of 36 weeks (OR=0.73, 95%CI: 0.61-0.87, P=0.0004), but there was an increase in the risk of hyperglycemia (OR=1.61, 95%CI: 1.24-2.09, P=0.0003), hypertension (OR=1.63, 95%CI: 1.11-2.38, P=0.01), and intestinal perforation (OR=1.51, 95%CI: 1.12-2.04, P=0.007). CONCLUSIONS: At present, it is not recommended to use glucocorticoids to prevent BPD in preterm infants. Its advantages and disadvantages need further studies, with special focuses on the adverse effects of hyperglycemia, hypertension, and intestinal perforation.

Autophagy induction contributes to GDC-0349 resistance in head and neck squamous cell carcinoma (HNSCC) cells.

Dysregulation of mammalian target of rapamycin (mTOR) signaling contributes to head and neck squamous cell carcinoma (HNSCC) tumorigenesis and progression. In the current study, we tested the anti-HNSCC cell activity by GDC-0349, a selective ATP-competitive inhibitor of mTOR. We showed that GDC-0349 inhibited proliferation of established and primary human HNSCC cells bearing high-level of p-AKT/p-S6K. Further, it induced caspase-dependent apoptosis in the HNSCC cells. GDC-0349 blocked mTORC1 and mTORC2 activation, yet it simultaneously induced autophagy activation in HNSCC cells. The latter was evidenced by induction of LC3B-II, Beclin-1 and Autophagy-related (ATG)-7, as well as downregulation of p62. Autophagy inhibitors (3-methyladenine and bafilomycin A1) or ATG-7 siRNA dramatically potentiated GDC-0349's cytotoxicity against HNSCC cells. Intriguingly, we showed that ceramide (C14), a pro-apoptotic sphingolipid, also induced ATG-7 degradation, and sensitized HNSCC cells to GDC-0349. Collectively, the preclinical study provided evidences to support GDC-0349 as a promising anti-HNSCC agent. GDC-0349 sensitization may be achieved via autophagy inhibition.

The anti-esophageal cancer cell activity by a novel tyrosine/phosphoinositide kinase inhibitor PP121.

Here we explored the potential effect of PP121, a novel dual inhibitor of tyrosine and phosphoinositide kinases, against human esophageal cancer cells. We showed that PP121 exerted potent cytotoxic effect in primary (patient-derived) and established (Eca-109, TE-1 and TE-3 lines) esophageal cancer cells, possibly through activating caspase-3-dependnent apoptosis. PP121 was, however, non-cytotoxic to the normal human esophageal epithelial cells (EECs). At the molecular level, we showed that PP121 blocked Akt-mTOR (mammalian target of rapamycin) activation in esophageal cancer cells, which was restored by introducing a constitutively-active Akt (CA-Akt). Yet, CA-Akt only partly inhibited cytotoxicity by PP121 in Eca-109 cells. Importantly, we showed that PP121 inhibited nuclear factor kappa B (NFκB) signaling activation in esophageal cancer cells, which appeared independent of Akt-mTOR blockage. In vivo, oral administration of PP121 remarkably inhibited Eca-109 xenograft growth in nude mice, and significantly improved mice survival. Further, the immunohistochemistry (IHC) and Western blot assays analyzing xenografted tumors showed that PP121 inhibited Akt-mTOR and NFκB activations in vivo. Together, we demonstrate that PP121 potently inhibits esophageal cancer cells in vitro and in vivo, possibly through concurrently inhibiting Akt-mTOR and NFκB signalings.

[Analysis of XRD spectral characteristics of soil clay mineral in two typical cultivated soils].

The present paper took black soil and chernozem, the typical cultivated soil in major grain producing area of Northeast, as the study object, and determinated the soil particle composition characteristics of two cultivated soils under the same climate and location. Then XRD was used to study the composition and difference of clay mineral in two kinds of soil and the evolutionary mechanism was explored. The results showed that the two kinds of soil particles were composed mainly of the sand, followed by clay and silt. When the particle accumulation rate reached 50%, the central particle size was in the 15-130 microm interval. Except for black soil profile of Shengli Xiang, the content of clay showed converse sequence to the central particle in two soils. Clay accumulated under upper layer (18.82%) in black soil profile while under caliche layer (17.41%) in chernozem profile. Clay content was the least in parent material horizon except in black profile of Quanyanling. Analysis of clay XRD atlas showed that the difference lied in not only the strength of diffraction peak, but also in the mineral composition. The main contents of black soil and chernozem were both 2 : 1 clay, the composition of black soil was smectite/illite mixed layer-illite-vermiculite and that of chernozem was S/I mixture-illite-montmorillonite, and both of them contained little kaolinite, chlorite, quartz and other primary mineral. This paper used XRD to determine the characteristics of clay minerals comprehensively, and analyzed two kinds of typical cultivated soil comparatively, and it was a new perspective of soil minerals study.

Deficiency of Secreted Phosphoprotein 1 Alleviates Hyperoxia-induced Bronchopulmonary Dysplasia in Neonatal Mice.

Bronchopulmonary dysplasia (BPD) is a common chronic lung disorder characterized by impaired proximal airway and bronchoalveolar development in premature births. Secreted phosphoprotein 1 (SPP1) is involved in lung development and lung injury events, while its role was not explored in BPD. For establishing the in vivo models of BPD, a mouse model of hyperoxia-induced lung injury was generated by exposing neonatal mice to hyperoxia for 7 days after birth. Alveolar myofibroblasts (AMYFs) were treated with hyperoxia to establish the in vitro models of BPD. Based on the scRNA-seq analysis of lungs of mice housed under normoxia or hyperoxia conditions, mouse macrophages and fibroblasts were main different cell clusters between the two groups, and differentially expressed genes in fibroblasts were screened. Further GO and KEGG enrichment analysis revealed that these differentially expressed genes were mainly enriched in the pathways related to cell proliferation, apoptosis as well as the PI3K-AKT and ERK/MAPK pathways. SPP1 was found up-regulated in the lung tissues of hyperoxia mice. We also demonstrated the up-regulation of SPP1 in the BPD patients, the mouse model of hyperoxia-induced lung injury, and hyperoxia-induced cells. SPP1 deficiency was revealed to reduce the hyperoxia-induced apoptosis, oxidative stress and inflammation and increase the viability of AMYFs. In the mouse model of hyperoxia induced lung injury, SPP1 deficiency was demonstrated to reverse the hyperoxia-induced alveolar growth disruption, oxidative stress and inflammation. Overall, SPP1 exacerbates BPD progression in vitro and in vivo by regulating oxidative stress and inflammatory response via the PI3K-AKT and ERK/MAPK pathways, which might provide novel therapeutic target for BPD therapy.

Superhydrophobic foam combined with biomass-derived TENG based on upcycled coconut husk for efficient oil-water separation.

The ocean ecological environments are seriously affected by oil spilling and plastic-debris, preventing and significantly reducing marine pollution via using biocomposite production from natural fiber reinforcement is a more friendly way to deal with marine oil pollution. Herein, we upcycled coir-coconut into lignin and coconut shell into spherical TENG by a combination of dip-dry and chemical treatment and used the SiO2 nanoparticles together with cellulose nanofibrils to prepare serial sugar-templated, anisotropic and hybrid foams. The as-prepared lignin/SiO2 porous sponge (LSPS) with a hierarchical porous morphology and uniformly dispersed nanoparticles structure benefits from the advantages of biomass-based additives, which presents reversible large-strain deformation (50%) and high compressive strength (11.42 kpa). Notably, the LSPS was significantly more hydrophobic (WCA ≈150°) than pure silicone-based foams, and its selective absorbability can separate oil from water under continuous pumping. Meanwhile, the coconut husk was also upcycled as a spherical TENG shell by a combination of the nanofiber-enhanced polymer spherical oscillator (CESO), which possessed high triboelectric properties (Uoc = 272 V, Isc = 14.5 µA, Q = 70 nC) and was comparable to the plastic shell TENG at low frequency (1.6 Hz). The monolithic foam structure developed using this clean synthetic strategy holds considerable promise for new applications in sustainable petroleum contamination remediation.

Correction: Immunoassay-aptasensor for the determination of tumor-derived exosomes based on the combination of magnetic nanoparticles and hybridization chain reaction.

[This corrects the article DOI: 10.1039/D0RA10159A.].

Diabetes and two kinds of primary tumors in a patient with thalassemia: a case report and literature review.

Background: Thalassemia is a group of common genetic hematologic disorders characterized by deficient synthesis of the hemoglobin chain. Due to effective blood transfusion and optimization of chelate therapy, the survival of thalassemia patients and their overall quality of life have improved noticeably in the past few decades. As a consequence, the longer life expectancy has led to the manifestation of several concomitant morbidities, including heart disease, infections, cirrhosis, endocrine abnormalities, various malignancies, and so on. In this context, the probability and updated literature about some malignancy cases in patients with thalassemia build new scenarios for the next few years. We describe the first report of a thalassemic patient developing diabetes and head and neck cancer and try to summarize the possible predisposing factors and mechanisms behind their phenomenon. Case presentation: The current case report describes a 50-year-old Asian man who has been diagnosed with thalassemia since childhood. In early 2017, he was also diagnosed with diabetes and started on insulin-hypoglycemic treatment. The patient was then diagnosed with primary non-keratinizing undifferentiated carcinoma of the nasopharynx in late February 2013. A biopsy of the left tongue revealed squamous cell carcinoma (SCC) in late March 2019. Conclusions: We report the first case of a thalassemic patient developing diabetes and squamous cell carcinoma of the head and neck and discuss the possibility of a link between the three diseases. This specific case should alert physicians to the possibility of endocrinopathy and malignancy in thalassemic patients.

Developing a novel framework to re-examine half a century of compound drought and heatwave events in mainland China.

Compound drought and heatwave events (CDHEs) are more devastating than single drought or heatwave events and have gained widespread attention. However, previous studies have not investigated the impacts of the precipitation attenuation effect (PAE) (i.e., the effect of previous precipitation on the dryness and wetness of the current system is attenuated) and event merging (EM) (i.e., merging two CDHEs with short intervals into a single event). Moreover, few studies have assessed short-term CDHEs within monthly scales and their variation characteristics under different background temperatures. Here we propose a novel framework for assessing CDHEs on a daily scale and considering the PAE and EM. We applied this framework to mainland China and investigated the spatiotemporal variation of the CDHE indicators (spatial extent (CDHEspa), frequency (CDHEfre), duration (CHHEdur), and severity (CDHEsev)) from 1968 to 2019. The results suggested that ignoring the PAE and EM led to significant changes in the spatial distribution and magnitude of the CDHE indicators. Daily-scale assessments allowed for monitoring the detailed evolution of CDHEs and facilitated the timely development of mitigation measures. Mainland China experienced frequent CDHEs from 1968 to 2019 (except for the southwestern part of Northwest China (NWC) and the western part of Southwest China (SWC)), whereas, hotspot areas of CDHEdur and CDHEsev had a patchy distribution in different geographical subregions. The CDHE indicators were higher in the warmer 1994-2019 period than in the colder 1968-1993 period, but the rate of increase of the indicators was lower or there was a downward trend. Overall, CDHEs in mainland China have been in a state of remarkable continuous strengthening over the past half a century. This study provides a new quantitative analysis approach for CDHEs.

[One case of adult Kawasaki disease].

Kawasaki disease is far more frequent in children than in adults. The pathogenesis of Kawasaki disease is unknown, but it involves changes to the coronary artery and other diverse clinical manifestations. There are currently no specific laboratory diagnostic indexes, and especially since the disease is rare in adults, so it is extremely easy to misdiagnose or to overlook entirely. Our retrospective analysis of an diagnosis of and treatment for Kawasaki disease in an adult provides a guide to clinical doctors in terms of understanding Kawasaki disease, early diagnosis of it, and improved prognosis.

Analysis of Human Geography Space Based on Geographic Information System in the Context of Rural Revitalization.

Nowadays, it is proposed "Firmly implement the rural revitalization strategy", and rural revitalization has risen to the level of national-level strategy. Human geography is to respond to the cultural effects produced by various residents with similar living habits together. As a spatial science, GIS, with its unique spatial viewpoint and spatial thinking, reveals the spatial distribution characteristics and dynamic change laws of various things and phenomena from spatial interconnections and interactions. From the spatial objects studied by GIS, this paper puts forward thoughts on the new directions of GIS development: expanding from Earth space to cosmic space, it is necessary to build coordinate system and cosmic geospatial information system, lunar geospatial information system, etc.; extending from outdoor space to indoor space, it is necessary to develop indoor geospatial information system and expand to underwater space and underground space; from macro to micro space, we can develop sports geospatial information system for games, human geospatial information system for life and health management, etc.; facing the era of big data, we can develop theories and methods of spatial analysis of big data and contribute to the development of big data science. Thus, the way of constructing GIS based on human geospatial analysis can be built in the context of the era of rural revitalization. The purpose of the research in this paper is mainly to show the role of GIS in the construction of human geography space. Through GIS means, it can better gather some villages in human geography, have a better form of expression, and can better construct a spatial information system.