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Objective: Symptoms are significant kind of phenotypes for managing and controlling of the burst of acute infectious diseases, such as COVID-19. Although patterns of symptom clusters and time series have been considered the high potential prediction factors for the prognosis of patients, the elaborated subtypes and their progression patterns based on symptom phenotypes related to the prognosis of COVID-19 patients still need be detected. This study aims to investigate patient subtypes and their progression patterns with distinct features of outcome and prognosis., Methods: This study included a total of 14,139 longitudinal electronic medical records (EMRs) obtained from four hospitals in Hubei Province, China, involving 2,683 individuals in the early stage of COVID-19 pandemic. A deep representation learning model was developed to help acquire the symptom profiles of patients. K-means clustering algorithm is used to divide them into distinct subtypes. Subsequently, symptom progression patterns were identified by considering the subtypes associated with patients upon admission and discharge. Furthermore, we used Fisher's test to identify significant clinical entities for each subtype., Results: Three distinct patient subtypes exhibiting specific symptoms and prognosis have been identified. Particularly, Subtype 0 includes 44.2% of the whole and is characterized by poor appetite, fatigue and sleep disorders; Subtype 1 includes 25.6% cases and is characterized by confusion, cough with bloody sputum, encopresis and urinary incontinence; Subtype 2 includes 30.2% cases and is characterized by dry cough and rhinorrhea. These three subtypes demonstrate significant disparities in prognosis, with the mortality rates of 4.72%, 8.59%, and 0.25% respectively. Furthermore, symptom cluster progression patterns showed that patients with Subtype 0 who manifest dark yellow urine, chest pain, etc. in the admission stage exhibit an elevated risk of transforming into the more severe subtypes with poor outcome, whereas those presenting with nausea and vomiting tend to incline towards entering the milder subtype., Conclusion: This study has proposed a clinical meaningful approach by utilizing the deep representation learning and real-world EMR data containing symptom phenotypes to identify the COVID-19 subtypes and their progression patterns. The results would be potentially useful to help improve the precise stratification and management of acute infectious diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The coronavirus disease 2019 (COVID-19) pandemic has caused health concerns worldwide since December 2019. From the beginning of infection, patients will progress through different symptom stages, such as fever, dyspnea or even death. Identifying disease progression and predicting patient outcome at an early stage helps target treatment and resource allocation. However, there is no clear COVID-19 stage definition, and few studies have addressed characterizing COVID-19 progression, making the need for this study evident., Methods: We proposed a temporal deep learning method, based on a time-aware long short-term memory (T-LSTM) neural network and used an online open dataset, including blood samples of 485 patients from Wuhan, China, to train the model. Our method can grasp the dynamic relations in irregularly sampled time series, which is ignored by existing works. Specifically, our method predicted the outcome of COVID-19 patients by considering both the biomarkers and the irregular time intervals. Then, we used the patient representations, extracted from T-LSTM units, to subtype the patient stages and describe the disease progression of COVID-19., Results: Using our method, the accuracy of the outcome of prediction results was more than 90% at 12 days and 98, 95 and 93% at 3, 6, and 9 days, respectively. Most importantly, we found 4 stages of COVID-19 progression with different patient statuses and mortality risks. We ranked 40 biomarkers related to disease and gave the reference values of them for each stage. Top 5 is Lymph, LDH, hs-CRP, Indirect Bilirubin, Creatinine. Besides, we have found 3 complications - myocardial injury, liver function injury and renal function injury. Predicting which of the 4 stages the patient is currently in can help doctors better assess and cure the patient., Conclusions: To combat the COVID-19 epidemic, this paper aims to help clinicians better assess and treat infected patients, provide relevant researchers with potential disease progression patterns, and enable more effective use of medical resources. Our method predicted patient outcomes with high accuracy and identified a four-stage disease progression. We hope that the obtained results and patterns will aid in fighting the disease.

Background Drug treatment was recommended for stage 1 hypertensive patients (blood pressure of 130-139 / 80-89 millimetres of mercury (mmHg)) with high cardiovascular disease (CVD) risk in the 2017 Hypertension Clinical Practice Guidelines, 2018 Chinese guidelines and 2021 World Health Organization guidelines, but not in other guidelines. However, evidence on the cost-effectiveness of drug treatment among young and middle-aged patients remains scarce. This study aimed to compare the cost-effectiveness of drug treatment vs. nondrug treatment for stage 1 hypertensive patients aged <60 years with high CVD risk. Methods A microsimulation model projected quality-adjusted life years (QALYs), health care costs, and incremental cost-effectiveness ratios for drug treatment from a societal perspective. Transition probabilities were estimated from the Kailuan study with a sample size of 34 093 patients aged <60 years with high CVD risk. Costs and health utilities were obtained from the Kailuan study, national statistics reports and published literature. Results Over a 15-year time horizon, the model predicted that drug treatment generated QALY of 9.36 and was associated with expected costs of 3735 US dollars ($) compared with 9.07 and $3923 produced by non-drug treatment among stage 1 hypertensive patients, resulting in a cost-saving for drug treatment. At a willingness-to-pay threshold of $10439/QALY (one gross domestic product (GDP) per capita in 2020), drug treatment had a 99.99% probability of being cost-effective for 10 000 samples of probabilistic sensitivity analysis. Sensitivity analyses by different values of transition probability, cost, utility and discount rate did not appreciably change the results. Shortening the time horizon to the average follow-up period of eight years resulted in ICER of $189/QALY for drug treatment (<1 × GDP/QALY). Conclusions Our results suggested that drug treatment was a dominant strategy for stage 1 hypertensive patients aged <60 years with high CVD risk in China, which may provide evidence for policymakers and clinicians when weighing the pros and cons of drug treatment for young and middle-aged stage 1 hypertensive patients. [ABSTRACT FROM AUTHOR]

Background: Traumatic brain injury is a kind of injury caused by external violence on the head. Its danger is not limited to life rescue in the early stage of the disease. Moreover, the subsequent inflammatory reaction and the change in its oxidative stress level will cause secondary myocardial injury. The purpose of this study is to explore the myocardial protective effect of ozone autohemotherapy (OA) in the progression of acute traumatic brain injury (TBI). Methods: Forty patients with acute TBI were recruited and divided into The treatment group (Group OA, n = 18) and the Control group (Group C, n = 19). Patients in Group OA received OA before surgery and on the 1st and 2nd postoperative days, while patients in Group C underwent autologous blood transfusion. Venous blood was collected from all patients before (T0) and after 7 days (T1) days of surgery for measurement of cardiac troponin T (cTnT) and amino-terminal pro-B-type natriuretic peptide (NT-proBNP). At T0 and T1, transthoracic cardiac ultrasound was performed to measure left ventricular ejection fraction (LVEF), tricuspid annular plane systolic excursion (TAPSE), and venous blood was sampled to determine the contents of superoxide dismutase (SOD) and malondialdehyde (MDA). NIH Stroke Scale (NIHSS) and Glasgow Coma Scale (GCS) scores were calculated, and other clinical indexes were recorded. Results: (1) The levels of cTnT at T1 were significantly higher as compared with that at T0 in both groups (p < 0.01). Compared with Group C, a remarkable decline in the content of NT-proBNP was found in Group OA at T1 (p = 0.021). (2) The LVEF (p = 0.002) and serum SOD (p = 0.015) at T1 were significantly increased in Group OA as compared with those in Group C. (3) The length of Intensive Care Unit and hospitalization time for patients in Group OA was distinctly shorter than that for patients in Group C (p = 0.021, p = 0.015, respectively). Conclusion: Perioperative OA treatment can alleviate the secondary myocardial injury during the disease course of TBI, which might be associated with its myocardial protective effect against oxidative stress. Trial registration: This study was approved by the Ethical Committee of Changzhou NO.2 People's Hospital. The protocol was registered prospectively with the Chinese Clinical Trial Registry (ChiCTR2000029612) on February 02, 2020. [ABSTRACT FROM AUTHOR]

During the period of Twelfth Five - Year Plan for National Economic and Social Development, clinical study on cerebrovascular disease in China has made great progress. The results of antiplatelet treatment in patients with high - risk non - disabling cerebrovascular events, standardized secondary prevention of ischemic stroke, epidemiological survey of asymptomatic ischemic stroke in community population, cross-sectional survey on traditional Chinese medicine for treating ischemic stroke, the impact of blood glucose on prognosis of acute ischemic stroke, ischemic stroke combined with chronic kidney disease and cerebral microbleeds, biomarkers of ischemic cerebrovascular diseases, mitochondrial encephalomyopathy with lactic academia and stroke - like episodes (MELAS) and encephalatrophy, perioperative management of blood pressure in intracerebral hemorrhage, vascular structural abnormality - related intracerebral hemorrhage score (VSARICHS), and epidemiological survey of cerebrovascular disease in China have been published in many important journals. This paper reviewed these studies and made a brief introduction. [ABSTRACT FROM AUTHOR]

Glioma shows diffuse infiltrative growth in the brain parenchyma. Even following the principle of "maximum safe resection", the residual tumor cells are resistant to adjuvant chemoradiotherapy and continue to invase and migrate in the brain tissue. This is the main reason for the recurrence of glioma and the dissemination in the central nervous system (CNS). As a result, understanding the mode of glioma invasion and migration can provide a new method for the treatment of glioma. This paper reviews our research findings of the invasion and migration of glioma during the period of Twelfth Five-Year Plan for National Economic and Social Development. [ABSTRACT FROM AUTHOR]

In this paper, a discrete mathematical model is formulated to describe tuberculosis (TB) progression from latent infection to active disease. The data of national TB epidemiology surveys in China are taken to estimate the TB progression rate for children aged 0–14 years. The progression rate obtained in this paper gives a detailed and better estimate of TB progression rate among children. [ABSTRACT FROM PUBLISHER]

Anthracnose, caused by Colletotrichum siamense, is a destructive disease of Pachira glabra in southern China. Early and proper monitoring and quantification of C. siamense is of importance for disease control. A calmodulin (CAL) gene-based TaqMan real-time PCR assay was developed for efficient detection and quantification of C. siamense, which reliably detected as low as 5 pg of genomic DNA and 12.8 fg (5800 copies) of target DNA. This method could specifically recognize all tested C. siamense isolates, while no amplification was observed in other closely related Colletotrichum species. The assay could still detect C. siamense in plant mixes, of which only 0.01% of the tissue was infected. A dynamic change in the amount of C. siamense population was observed during infection, suggesting that this real-time PCR assay can be used to monitor the fungal growth progression in the whole disease process. Moreover, the method enabled the detection of C. siamense in naturally infected and symptomless leaves of P. glabra trees in fields. Taken together, this specific TaqMan real-time PCR provides a rapid and accurate method for detection and quantification of C. siamense colonization in P. glabra, and will be useful for prediction of the disease to reduce the epidemic risk. [ABSTRACT FROM AUTHOR]

Background: Studies on antiretroviral therapy (ART) in children living with HIV (CLHIV) are limited due to the small population and low accession rate of ART. Methods: All 0-14-year-old CLHIV admitted to the Ganzhou Center for Disease Control and Prevention from January 2006 to June 2023 were included retrospectively. The information of treatment regimens, disease progression, and laboratory tests of the patients under ART were used to explore the outcomes and impacts of long-term ART. The normality of all the data was tested by the Shapiro-Wilk test. Results: From 2006 to 2023, 18 CLHIV were reported in Ganzhou. Among them, 11 received ART and were followed up for 60.0 ± 48.4 months. After receiving ART, the median viral load of them decreased from 89,600 copies/ml to 22 copies/ml (P = 0.007), the median CD4+ T cell count increased from 380.7 cells/µL to 661.9 cells/µL (P = 0.028), and the median CD8+ T cell count decreased from 1065.8 cells/µL to 983.3 cells/µL (P = 0.584). The laboratory test results regarding liver function, renal function, blood cell count, and glucolipid metabolism tended to be within normal reference ranges, and the mean height-for-age z-score and weight-for-age z-score increased. However, all the three CLHIV who received cotrimoxazole developed pneumocystis carinii pneumonia, upper respiratory infection, skin lesions, bacterial pneumonia and/or thrush; the mean body-mass-index-for-age z-score decreased from 0.52 to -0.63. Conclusion: For CLHIV, ART could effectively inhibit the replication of HIV and improve the immune function of patients. More studies that focus on ART in CLHIV are urgently needed. [ABSTRACT FROM AUTHOR]

Background: Axial spondyloarthritis (axSpA) is a chronic inflammatory rheumatic disease predominantly affecting the axial skeleton. We aimed to describe the clinical characteristics of patients with non-radiographic axSpA (nr-axSpA) in China and compare the differences between adult- and juvenile-onset cases. Methods: A cross-sectional study was conducted using data from 776 patients with nr-axSpA in the Clinical Characteristic and Outcome in Chinese Axial Spondyloarthritis (COCAS) study cohort. Patients were divided into two groups including the adult-onset group (n = 662) and the juvenile-onset group (n = 114) according to age at disease onset. Baseline demographics and clinical characteristics were compared between patients with adult-onset and juvenile-onset nr-axSpA. Results: Overall, the male-to-female ratio was 1.26:1, the prevalence of HLA-B27 positivity was 72.2%, and the median age at disease onset of nr-axSpA was 22 years. Nearly 75% of nr-axSpA patients had peripheral arthritis in the disease course, and the prevalence of extra-articular manifestations was 10.4%. The juvenile-onset group contained a higher proportion of men (66.7% vs. 53.9%, P = 0.011) and a longer baseline disease duration (4.0 [4.0] vs. 1.6 [3.5], P < 0.001) than the adult-onset group. A family history of spondyloarthritis was more frequent in the juvenile-onset group than in the adult-onset group (23.7% vs. 15.4%, P = 0.028), but no significant difference in the prevalence of HLA-B27 positivity was observed between the two groups (P = 0.537). Regarding initial symptoms, peripheral arthritis occurred more often in patients with juvenile-onset nr-axSpA, whereas patients with adult-onset nr-axSpA presented more frequently with axial involvement. The prevalence of inflammatory back pain (IBP) was higher in the adult-onset group than in the juvenile-onset group (85.0% vs. 75.4%, P = 0.010), whereas the juvenile-onset group showed a higher prevalence of peripheral arthritis and enthesitis than the adult-onset group (67.5% vs. 48.5%, P < 0.001; 35.1% vs. 23.3%, P = 0.007, respectively). Conclusions: Compared with adult-onset nr-axSpA, juvenile-onset nr-axSpA was more common in men and those with a family history of spondyloarthritis. Juvenile-onset nr-axSpA presents with a "peripheral predominant" mode at disease onset and a higher frequency of peripheral arthritis and enthesitis during the disease course. [ABSTRACT FROM AUTHOR]

Background: Fear of disease progression (FoP) is among the most prevalent and major psychological burdens breast cancer patients encounter. Excessive FoP may result in serious adverse effects for patients. FoP in breast cancer patients has gained attention recently; however, its prevalence in China is unknown. Objectives: This meta-analysis and systematic review aimed to assess the overall FoP among Chinese breast cancer patients to make recommendations for treatment and care. Methods: Systematic search databases included PubMed, EMbase, The Cohrane Library, Web of Science, CINAHL, PsycINFO and 4 Chinese databases (Wan Fang Data, CBM, VIP and CNKI). The retrieval time ranged from the database's establishment to March 20, 2023. After two researchers independently evaluated the literature, retrieved information, and assessed the risk of bias for the included literature, Stata 15.1 software was used to conduct a meta-analysis. Results: A total of 37 moderate or high-quality studies involving 9,689 breast cancer patients were included. Meta-analysis showed that the pooled mean score of FoP for Chinese breast cancer patients was 33.84 [95% CI (31.91, 35.77)], prediction interval (21.57 ~ 46.11). The subgroup study found that FoP levels varied among breast cancer patients of different regions, ages, educational levels, marital statuses, residences, illness stages, and disease statuses. Conclusion: Breast cancer patients have higher FoP scores. Healthcare workers should be concerned. We expect that more relevant research will be undertaken and more effective interventions will be developed. Patients can manage their illness and improve their quality of life by reducing their fears. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier: PROSPERO CRD42023408914. [ABSTRACT FROM AUTHOR]

During the outbreak of a disease caused by a pathogen with unknown characteristics, the uncertainty of its progression parameters can be reduced by devising methods that, based on rational assumptions, exploit available information to provide actionable insights. In this study, performed a few (~6) weeks into the outbreak of COVID-19 (caused by SARS-CoV-2), one of the most important disease parameters, the average time-to-recovery, was calculated using data publicly available on the internet (daily reported cases of confirmed infections, deaths, and recoveries), and fed into an algorithm that matches confirmed cases with deaths and recoveries. Unmatched cases were adjusted based on the matched cases calculation. The mean time-to-recovery, calculated from all globally reported cases, was found to be 18.01 days (SD 3.31 days) for the matched cases and 18.29 days (SD 2.73 days) taking into consideration the adjusted unmatched cases as well. The proposed method used limited data and provided experimental results in the same region as clinical studies published several months later. This indicates that the proposed method, combined with expert knowledge and informed calculated assumptions, could provide a meaningful calculated average time-to-recovery figure, which can be used as an evidence-based estimation to support containment and mitigation policy decisions, even at the very early stages of an outbreak. [ABSTRACT FROM AUTHOR]

Background: The HTLV-1 prevalence in China varies geographically, while HTLV-2 infection has rarely been found so far. Proviral load is one of the determining factors of pathogenesis and progression of HTLV-1 related diseases. However, neither molecular assays nor commercial kits are available for HTLV-1 diagnosis in China. The objective of the present study was to develop and validate a TaqMan qPCR assay for HTLV-1 proviral load quantification. Results: A plasmid containing both the HTLV-1 of interest and a fragment of the RNase P (RPPH1) gene was constructed and used to establish the standard curves. The assay has a wide dynamic range (2.5 × 108 copies/reaction ~ 25 copies/reaction) and sensitive to 1 copy for HTLV-1 and RPPH1. The limit of detection for Hut102 cell concentration was 0.0218% (95% confidence interval 0.0179–0.0298%). The assay gave coefficient of variation (CV) for both the HTLV-1 and RPPH1 Ct values. All of the HTLV-1 sero-negative samples and MOT cell line (infected with HTLV-2) amplified only the RPPH1 gene by our method, presenting 100% specificity. 85 Samples confirmed positive or indeterminate by LIA were performed by established qPCR assay and WB. 90.0% (27/30) of LIA-HTLV-1-positive, 33% (2/6) of LIA-untypeable and 2% (1/49) of LIA-indeterminate samples were defined as qPCR-positive. The median PVL of LIA-positive samples (n = 27, 1.780 copies/100 cells) was much higher than that of LIA-untypeable and (n = 2, 0.271 copies/100 cells) indeterminate samples (n = 1, 0.017 copies/ 100 cells). Additionally, compared to WB, the duplex qPCR verified more positive samples, demonstrating a better sensitivity. Conclusion: The duplex qPCR developed here with high sensitivity, good specificity and reproducibility could accurately and quantitatively detect the HTLV-1 PVLs, which can be used to confirm the initial reactive samples for an improved cost/benefit ratio as well as to monitor the clinical progression and efficacy of therapy in patients with HTLV-1 related disease. [ABSTRACT FROM AUTHOR]

Simple Summary: Afatinib has been approved for patients with lung cancer carrying uncommon epidermal growth factor receptor gene (EGFR) mutations. Dacomitinib, another second-generation inhibitor, has also shown promising potential for these mutations. This is the first and largest comparative study on second-generation inhibitors in patients with uncommon EGFR mutations to date. We found that dacomitinib demonstrated a more favorable activity with manageable toxicity compared with afatinib, which provided more evidence for dacomitinib application in this setting. (1) Background: Afatinib has been approved for patients with non-small cell lung cancer (NSCLC) carrying major uncommon epidermal growth factor receptor gene (EGFR) mutations. Dacomitinib, another second-generation tyrosine kinase inhibitor, has also shown promising potential for uncommon EGFR mutations. However, no comparative study has been conducted. (2) Methods: Two cohorts were employed: the AFANDA cohort, an ambispective cohort including 121 patients with uncommon EGFR mutations admitted to two tertiary hospitals in China, and an external validation afatinib cohort (ex-AC), extracted from the Afatinib Uncommon EGFR Mutations Database (N = 1140). The AFANDA cohort was divided into an afatinib cohort (AC) and a dacomitinib cohort (DC) for internal exploration. Objective response rate (ORR), progression-free survival (PFS), and adverse events (AEs) were assessed for comparison. Progression patterns and resistance mechanisms were explored. (3) Results: In total, 286 patients with advanced NSCLC carrying uncommon EGFR mutations treated with afatinib or dacomitinib were enrolled, including 79 in the AFANDA cohort (44 in the DC, 35 in the AC) and 207 in the ex-AC. In internal exploration, the ORR of the DC was significantly higher than that of the AC (60.5 vs. 26.7%, p = 0.008), but there was no significant difference in median PFS between the DC and the AC (12.0 months vs. 10.0 months, p = 0.305). Multivariate analysis confirmed an independent favorable effect of dacomitinib on PFS (hazard ratio (HR), 1.909; p = 0.047). In external validation, multivariate analysis confirmed the independent prognostic role of dacomitinib in PFS (HR, 1.953; p = 0.029). Propensity score matching analysis confirmed the superiority of dacomitinib over afatinib in terms of PFS in both univariate and multivariate analyses. Toxicity profiling analysis suggested more G1 (p = 0.006), but fewer G3 (p = 0.036) AEs in the DC than in the AC. Progression patterns revealed that the incidence of intracranial progression in the AC was significantly higher than that in the DC (50 vs. 21.1%, p = 0.002). Drug resistance analysis indicated no significant difference in the occurrence of T790M between the AC and the DC (11.8 vs. 15.4%, p = 0.772). (4) Conclusions: Compared with afatinib, dacomitinib demonstrated a more favorable activity with manageable toxicity and different progression patterns in patients with NSCLC carrying uncommon EGFR mutations. [ABSTRACT FROM AUTHOR]

Simple Summary: Inflammation has been recognized as one of the hallmarks of cancers. PYCARD, the adaptor protein of inflammasomes, plays an important role in pyroptosis and apoptosis. However, the function of PYCARD remains unclear in human cancers. Here, we systematically performed a comprehensive analysis of PYCARD expression and its relationship with immunotherapy response and prognosis. We found significant differences in PYCARD expression between tumor and normal tissue, particularly in clear cell renal cell carcinoma. We also found that PYCARD was an unfavorable prognostic factor and was confirmed by external validation cohorts. Exploration of the profound mechanisms of PYCARD might help to identify new therapeutic targets and improve the efficacy of immunotherapy. PYCARD is a protein engaged in inflammation, pyroptosis, and apoptosis. However, the function of PYCARD in human cancers remains unclear. The objective of our study was to explore PYCARD expression and prognostic value in human cancers. Public databases were used to assess PYCARD expression and prognostic value. The TISIDB database was used to explore the associations between PYCARD expression and different immune subtypes. The correlations between PYCARD expression and ICP genes, MMR genes, MSI, and TMB were also investigated. The immunotherapy response was assessed using the TIDE database. Single-cell RNA databases evaluated the PYCARD expression of immune cells. External datasets and immunohistochemical staining were conducted to validate PYCARD expression and prognostic value. The results showed that PYCARD expression varied in several cancers and was associated with prognosis, immune-related genes, published biomarkers, and immunotherapy response. Of note, PYCARD expression was upregulated in renal cancers with high diagnostic ability. Upregulation of PYCARD was correlated with worse prognosis in KIRC and external validation cohorts. In conclusion, PYCARD demonstrated strong correlations with prognosis, immune response, and disease progression in pan-cancer analysis. In ccRCC, PYCARD might serve as a biomarker for diagnosis and therapeutic target-boosting immunotherapy response. [ABSTRACT FROM AUTHOR]

Simple Summary: TCIRG1, also known as V-ATPase-a3, is critical for cellular metabolism, membrane transport, and intracellular signaling through its dependent acidification. In earlier research, TCIRG1 was found to be dysregulated in several cancers and to accelerate the growth of various malignancies. The molecular mechanisms behind TCIRG1 and its possible role in the development of clear cell renal cell carcinoma are still poorly understood. Our research is the first to thoroughly examine TCIRG1's function in clear cell renal cell carcinoma prognosis, immunity, and treatment. The validity that TCIRG1 can accelerate the development of renal clear cell carcinoma was also confirmed in this work by using certain testable experiments. This establishes the theoretical framework for our future investigation into the occurrence and progression of clear cell renal cell carcinoma. Background: TCIRG1, also known as V-ATPase-a3, is critical for cellular life activities through its dependent acidification. Prior to the present research, its relationship with prognostic and tumor immunity in clear cell renal cell carcinoma (ccRCC) had not yet been investigated. Methods: We assessed TCIRG1 expression in normal and tumor tissues using data from TCGA, GEO, GTEX, and IHC. We also analyzed the relationship between TCIRG1 and somatic mutations, TMB, DNA methylation, cancer stemness, and immune infiltration. We evaluated the relevance of TCIRG1 to immunotherapy and potential drugs. Finally, we explored the effect of TCIRG1 knockdown on tumor cells. Results: TCIRG1 was overexpressed in tumor tissue and predicted a significantly unfavorable clinical outcome. High TCIRG1 expression may be associated with fewer PBRM1 and more BAP1 mutations and may reduce DNA methylation, thus leading to a poor prognosis. TCIRG1 was strongly associated with CD8+ T-cell, Treg, and CD4+ T-cell infiltration. Moreover, TCIRG1 was positively correlated with TIDE scores and many drug sensitivities. Finally, experiments showed that the knockdown of TCIRG1 inhibited the migration of ccRCC cells. Conclusions: TCIRG1 may have great potential in identifying prognostic and immunomodulatory mechanisms in tumor patients and may provide a new therapeutic strategy for ccRCC. [ABSTRACT FROM AUTHOR]

Background. The possible role and detailed mechanisms of Tumor-associated macrophages (TAMs) in laryngeal squamous cell carcinoma (LSCC) have not been revealed. Methods. The expressions of typical markers were evaluated by qRT-PCR. In macrophages cocultured with TU212 cells, CD163, and CD206 protein expressions were detected by western blot analysis; IL-10 and IL-12 expressions were detected by ELISA assay. Exosomes isolated from TU212 cells were characterized by TEM analysis. As for the TU212 cells cocultured with macrophages processed with HOK or TU212 cells derived exosomes, their viability, migration, and invasion were assessed by CCK-8 assay, wounding healing, and Transwell assays, respectively. Results. In this study, macrophages processed with exosomes from human TU212 cells notably advanced LSCC cell viability, migration, and invasion. miR-1246 inhibitor suppressed the M2 polarization of macrophages. Macrophages transfected with miR-1246 inhibitor suppressed LSCC cell viability, migration, and invasion. Conclusion. In summary, our data implied that the exosomal, miR-1246 of LSCC, induced polarization of M2 type macrophages and promoted the progression of LSCC. This trial is registered with 2020-13. [ABSTRACT FROM AUTHOR]

Objective. The aim of the study is to observe the difference in progression between type 1 and type 2 Bietti crystalline dystrophy (BCD) using multimodal imaging. Methods. A retrospective clinical study was performed with six BCD patients who underwent multimodal imaging twice in Hebei Provincial Eye Hospital from October 2015 to December 2020. Multimodal imaging includes color fundus photography, fundus autofluorescence (AF), infrared autofluorescence (IRAF), fundus fluorescein angiography (FFA), and spectral domain optical coherence tomography (SD-OCT). The fundus lesion progression difference was observed in 3 patients with type 1 BCD and 3 patients with type 2 BCD. Results. In type 1 BCD, the range of hypoautofluorescence (hypo-AF), hypoinfrared autofluorescence (hypo-IRAF), and hypofluorescence in the posterior pole was enlarged, and FFA showed that the lesions in the posterior pole and periphery extended to the middle periphery. SD-OCT revealed retinal and choroidal thinning, progressive loss of the outer nuclear layer and ellipsoid zone, and reduction of the choroid macrovascular diameter. In type 2 BCD, the range of hypo-AF was enlarged, but there was no significant change in the macula area. The uniform hypo-IRAF in the posterior pole showed no significant change. FFA showed no significant change with the progression of the disease in the macula area and the hypofluorescence around it expanded. SD-OCT revealed no obvious change in the macula area. Conclusions. The retinal choroid atrophy in the macula area of type 1 BCD continued to worsen, and the choroid great vessels became narrower. The macular lesions of type 2 BCD can remain unchanged for a long time. [ABSTRACT FROM AUTHOR]

Background. Chronic sinusitis (CRS) was a chronic inflammation that originated in the nasal mucosa and affected the health of most people around the world. Chronic rhinosinusitis with nasal polyps (CRSwNP) was one kind of chronic sinusitis. Emerging research had suggested that long noncoding RNAs (lncRNAs) played vital parts in inflammatories and inflammation development. Methods. We acquired GEO data to analyze the differential expression between the miRNA, immune genes, TF, and lncRNA data in CRSWNP and the corresponding control tissues. Bioinformatic analysis by coexpression of endogenous RNA network and competitive way enrichment, analysis, and forecasting functions of these noncoding RNA. The different pathway expressions in CRSwNP patients were confirmed using GSVA to analyze the differentially expressed immune genes and TF data sets in CRSwNP patients. The differential immune gene and transcription factor data set in CRSwNP perform functional notes and protein-protein interaction (PPI) network structure. We predicted the potential genes and RNAs related to CRSWNP by constructing a ceRNA network. In addition, we also used 19 hub immune genes to predict the potential drugs of CRSWNP. lncRNA biomarkers in CRSwNP were identified by lncRNAs LASSO regression. The CIBERSORT algorithm was used to contrast the divergence in immune infiltrations between CRSwNP and usual inferior turbinate organizations in 22 immunocyte subgroups. Results. We identified a total of 48 miRNAs, 304 lncRNAs, 92 TFs, and 525 immune genes as CRSwNP-specific RNAs. GO and KEGG pathways both analyzed differentially expressed immune genes and transcription factor data sets. We predicted the potential genes GNG7, TUSC8, LINC01198, and has-miR-6776-5p by constructing ceRNA and PPI networks. At the same time, we found that the above genes were involved in two important pathways: chemokine signal path and PI3K/AKT signal path. In addition, we predicted 5 small molecule drugs to treat CRSwNP by analyzing 19 central immune genes, namely, danazol, ikarugamycin, semustine, cefamandole, and molindone. Finally, we identified 5 biomarkers in CRSwNP, namely, LINC01198, LINC01094, LINC01798, LINC01829, and LINC01320. Conclusions. We had identified CRSwNP-related miRNAs, lncRNAs, TFs, and immune genes, which may be making use of latent therapeutic target for CRSwNP. At the same time, we identified 5 lncRNA biomarkers in CRSwNP. The results of this study showed that LINC01198 promoted the progression of CRSwNPs through spongy miR-6776-5p. Our studies provide a new way for further analyses of the pathogenesis of CRSwNP. [ABSTRACT FROM AUTHOR]

Background: Programmed death 1 (PD-1) inhibitors—tislelizumab, toripalimab, camrelizumab, and sintilimab—are used for advanced urothelial carcinoma (UC) in China. To date, the efficacy and adverse events (AEs) of these PD-1 inhibitors have been poorly reported for advanced UC. Methods: We reviewed 118 patients treated with PD-1 inhibitors for advanced UC from July 2019 to October 2021 at Yantai Yuhuangding Hospital. Patient data were obtained from hospital records and telephone follow-ups. The safety and efficacy of PD-1 inhibitors were assessed by RESIST and Common Terminology Criteria for Adverse Events (version 4.0), respectively. Results: During a median follow-up period of 6 months, 112 patients (95%) experienced AEs; of these, 104 (88%) were grade 1–2 AEs, and 60 (51%) were grade 3–4 AEs. The most common AE was anemia, and no patients died as a result of treatment. A subanalysis according to treatment method (PD-1 inhibitor vs. PD-1 inhibitor plus chemotherapy) was performed. The incidence of grade 1–2 AEs was not different between the groups (85% vs. 94%), but combination therapy significantly increased grade 3–4 AEs (32% vs. 89%). Monotherapy and combination therapy also did not differ with regard to immune-related AEs of grades 1–2 (13% vs. 22%) or grades 3–4 (1% vs. 6%). In efficacy, complete response was not observed, but 33 patients (28%) had partial response, 30 (25%) had stable disease, and 47 had progressive disease (40%). The overall response and disease control rates were 28% and 53%, respectively. The preliminary efficacy of disease control was better with combination therapy versus monotherapy (78 vs. 43%). Conclusion: PD-1 inhibitors show promising tolerance and efficacy in advanced UC. PD-1 inhibitors combined with chemotherapy offered better disease control but had more grade 3–4 AEs. The clinical use of combination therapy warrants caution. [ABSTRACT FROM AUTHOR]

Recently, circular RNAs have been shown to function as critical regulators of many human cancers. However, the circRNA mechanism in laryngeal squamous cell carcinoma (LSCC) remains elusive. Recent investigations using bioinformatics analysis revealed high expression of hsa_circ_0023305 in LSCC tissues compared to normal tissues. Furthermore, we discovered that hsa_circ_0023305 expression level was positively correlated to tumor/node/metastasis (TNM) stage as well as lymph node metastasis in LSCC. Moreover, higher hsa_circ_0023305 levels were correlated to poorer LSCC patient outcomes. Knockdown of hsa_circ_0023305 significantly inhibited LSCC cell proliferation, invasion, and migration abilities. Our team validated that hsa_circ_0023305 functioned as a miR-218-5p sponge from a mechanistic perspective, targeting the melastatin-related transient receptor potential 7 (TRPM7) in LSCC cells. TRPM7 regulates a nonselective cation channel and promotes cancer proliferation and metastasis. Our data demonstrated that miR-218-5p was downregulated in LSCC and that miR-218-5p upregulation repressed LSCC proliferation and invasion both in vivo and in vitro. Additionally, we found that hsa_circ_0023305-mediated upregulation of TRPM7 inhibited miR-218-5p and contributed to LSCC migration, proliferation, and invasion. In summary, these data propose a new mechanism by which the hsa_circ_0023305/miR-218-5p/TRPM7 network enhances LSCC progression. [ABSTRACT FROM AUTHOR]

This article interrogates the mainstream healthcare narrative that frames human immunodeficiency virus (HIV) as a chronic disease, and triangulates it with the lived experiences of people with HIV in Singapore. It also examines how HIV patients reconstruct their identities after the diagnosis of HIV. Four HIV patients (two males and two females) were interviewed in depth by an experienced medical social worker. Findings revealed that even as the illness trajectory of HIV has shifted from a terminal condition to a chronic one, living with HIV continues to be fraught with difficulty as society, especially in the Asian context, perceives HIV with much fear and disapproval. The participants had an overwhelming sense of shame when they were initially diagnosed with HIV and they had to reconstruct a liveable identity by containing the shroud of shame, reinforcing their normative identities and constructing new ones. These strategies help them to keep their shame at bay. This paper also unpacks nuanced insights of shame experienced by Chinese HIV patients in an Asian city dominated by Confucian values. [ABSTRACT FROM AUTHOR]

The aim is to analyze the clinical outcomes of patients with extramedullary plasmacytoma (EMP) and review the characteristics of this disease. We retrospectively reviewed the clinical data of a cohort of 22 patients diagnosed with EMP between 1983 and 2017. Baseline characteristics and progression data were collected to calculate the incidence of progression to multiple myeloma (MM) and to analyze survival rates and outcomes. Previous major cohort studies were reviewed and compared with this study. Extramedullary plasmacytomas were located in the head and neck in 17 (77%) of the 22 patients. The median time between onset and diagnosis was 7 months, and the median age at diagnosis was 52.5 years (range 15-72 years). Extramedullary plasmacytoma occurred more frequently in men with an approximate ratio of 2.1:1. The majority of patients underwent surgery (13/22, 59.1%) and half received radiation (11/22, 50%). A small proportion of patients received chemotherapy (2/22, 9.1%). There was a median follow-up time of 98.5 months. The 5-year overall survival, progression-free survival, and MM-free survival rates were 84.2%, 67.3% and 75.9%, respectively. Complete resection without major functional damage is a promising option that can favorably improve prognosis in patients with resectable disease. Patients with regional lymph node metastasis or positive immunoelectrophoresis results require more aggressive treatment and may have poorer prognosis. [ABSTRACT FROM AUTHOR]

Objective. To investigate the association between myopia progression and school entrance age among Chinese schoolchildren and to suggest a more appropriate school age. Methods. 1,463 children aged six to nine years from Wenzhou, China, were examined and followed up for two and a half consecutive years. Their noncycloplegic refraction was measured twice each year by using an automatic refractometer; axial length (AL) and corneal radius of curvature (CRC) were tested annually by using the IOLMaster for 2.5 years. The questionnaires were completed by the children to collect detailed information regarding risk factors. Here, myopia is defined as a spherical equivalent less than −1.0D. Results. The changes in spherical equivalent (SE) of 7-year-old children in grade 1 and grade 2 were −0.45D and -0.56D, while changes in AL were 0.59 mm and 0.62 mm, respectively. The SE changes of 8-year-old children in grade 2 and grade 3 were −0.54D and −0.75D; meanwhile, the AL changes were 0.57 mm and 0.61 mm, respectively. Significant statistical differences were observed in ocular biological structure parameters, except for corneal radius of curvature (CRC) or anterior chamber depth (ACD), among children with the same age in different grades during this study. The prevalence of myopia was also significantly higher in higher grades for children with same age. Conclusions. Myopia is related to children's school entrance age. Children who start school in an earlier age are more likely to suffer from myopia, and the progression of myopia can be considerably faster. Therefore, it is recommended to enter school after the age of 7. [ABSTRACT FROM AUTHOR]

Background: This study is aimed at reviewing the published literature on the prognostic role of serum procalcitonin (PCT) in COVID-19 cases. Data retrieval: We systematically reviewed the literature available on PubMed, MEDLINE, LitCovid NLM, and WHO: to assess the utility of PCT in prognosis of coronavirus disease. Scrutiny for eligible studies comprising articles that have evaluated the prognostic utility of PCT and data compilation was undertaken by two separate investigators. Original articles in human subjects reporting the prognostic role of PCT in adult COVID-19 patients were included. The Quality in Prognosis Studies (QUIPS) tool was utilized to assess the strength of evidence. Results were reported as narrative syntheses. Results: Out of the total 426 citations, 52 articles passed through screening. The quality of evidence and methodology of included studies was overall acceptable. The total sample size of the studies comprised of 15,296 COVID-19-positive subjects. Majority of the studies were from China, i.e., 40 (77%). The PCT cut-off utilized was 0.05 ng/mL by 18 (35%) studies, followed by 0.5 ng/mL by 9 (17.5%). Eighty five percent (n = 44) studies reported statistically significant association (p value < 0.05) between PCT and severity. Conclusion: Procalcitonin appears as a promising prognostic biomarker of COVID-19 progression in conjunction with the clinical context. [ABSTRACT FROM AUTHOR]

Background: Chronic obstructive pulmonary disease (COPD) is an important risk factor for developing lung cancer. Aged citrus peel (chenpi) has been used as a dietary supplement for respiratory diseases in China. Objective: To explore the mechanism and candidate compounds of chenpi preventing COPD and its progression to lung cancer. Methods: The active components and potential targets of chenpi were retrieved from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. Disease-associated targets of COPD and lung cancer were collected in the Gene Cards and TTD database. The component-target network and PPI network were constructed using the Cytoscape 3.8.0 software. David database was used for GO and KEGG enrichment analysis. The main active components were verified by using the autodock Vina 1.1.2 software. Mouse lung cancer with COPD was induced by cigarette smoking (CS) combined with urethane injection to confirm preventing the effect of hesperetin (the candidate compound of chenpi) on COPD progression to lung cancer and its underlying mechanisms. Results: The network analysis revealed that the key active components of chenpi (nobiletin, naringenin, hesperetin) regulate five core targets (AKT1, TP53, IL6, VEGFA, MMP9). In addition, 103 potential pathways of chenpi were identified. Chenpi can prevent COPD and its progression to lung cancer by getting involved in the PI3K-Akt signaling pathway and MAPK signaling pathway. Molecular docking indicated that hesperetin had better binding activity for core targets. In mouse lung cancer with COPD, treatment with hesperetin dose-dependently improved not only lung tissue injury in COPD but also carcinoma lesions in lung cancer. Meanwhile, hesperetin could suppress the protein expression of AKT1, IL6, VEGFA, MMP9 and up-regulate the protein expression of TP53, and thus reduced the risk of COPD progression to lung cancer. Conclusion: Hesperetin is a candidate compound of chenpi that helps in preventing COPD and its progression to lung cancer by regulating AKT1, IL6, VEGFA, MMP9 and TP53. [ABSTRACT FROM AUTHOR]

Background. Since the first reports of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in December 2019 in Wuhan, China, the virus has spread to other parts of China and across the world. Although a few studies have assessed the clinical course of coronavirus disease 2019 (COVID-19), the changes in clinical characteristics during disease progression remain unclear. Methods. We retrospectively analyzed the clinical characteristics of 62 patients who died from COVID-19 at the Central Hospital of Wuhan between January 26 and February 17, 2020. We compared the clinical features on admission and at the last follow-up before death. Results. Of the 62 patients with COVID-19, 41 (66%) patients were male, and 21 (34%) were female. The median age was 72 years (interquartile range (IQR), 54-88), and 45 (72.5%) patients had preexisting conditions. The median time from symptom onset to the first visit at the clinic was three days, while the median time from symptom onset to death was 18.5 days. During disease progression, the amounts of arterial gases worsened, and liver, renal, and heart dysfunction was observed. Due to the cytokine storm, infection-related biomarkers, including lactic acid, C-reactive protein, and interleukine-6, gradually worsened during hospitalization. Conclusion. Our findings suggest that during hospitalization, many COVID-19 patients experienced multiple organ dysfunction and cytokine storm. The time from symptom onset to death was only 18.5 days, highlighting the disease's rapid progression. The better understanding of the clinical changes during disease progression might provide further insight into the COVID-19 pathophysiology. [ABSTRACT FROM AUTHOR]

Background: We aimed to validate a simple Comprehensive Geriatric Assessment (CGA) in older adults with diffuse large B‐cell lymphoma (DLBCL) in China and to evaluate the tolerability and efficacy of CGA‐driven therapy. Materials and Methods: In total, 78 patients with DLBCL aged ≥60 years were evaluated using CGA with the following parameters: age ≥ 80 years, activities of daily living (ADL), instrumental ADL, and modified cumulative illness rating score for geriatrics. Patients were grouped as fit, unfit, or frail. Patients classified as fit received standard‐dose rituximab plus CHOP, whereas patients in the latter two groups received reduced‐dose or reduced‐agent therapy. The overall response rate (ORR), overall survival (OS), progression‐free survival (PFS), and toxicities in the three groups were evaluated. Results: According to the CGA, 45 (57.5%) patients were classified as fit, 5 (6.4%) as unfit, and 28 (35.9%) as frail. The ORR was 82.1% (64/78) among all the patients, including 55 patients (70.6%) who achieved complete response and 9 patients (11.5%) who achieved partial response. In the fit and unfit + frail groups, it achieved 97.8% and 60.6%, respectively. In total, 26 (33.3%) patients (10/45 [22.2%] fit and 16/33 [48.5%] unfit + frail) showed disease progression or recurrence. The median follow‐up time was 18 months (range, 5–62). The 3‐year OS and PFS rates were 82% and 58%, respectively. There were no treatment‐related deaths. Conclusion: A simple CGA in older adults with DLBCL may be an effective tool for guiding therapeutic strategies in China. Implications for Practice: Diffuse large B‐cell lymphoma (DLBCL) is the most common malignant lymphoma in older adults. The simple tool, Comprehensive Geriatric Assessment (CGA), is proved to be an effective method to identify older adults with DLBCL who are suitable for standard‐dose R‐CHOP regimen therapy. This is the first prospective trial in China to evaluate the tolerability and efficacy of CGA‐driven therapy for older adults with DLBCL, and the result showed that this simple CGA may be an effective tool for guiding therapeutic strategies. Clinicians should take into account geriatric assessment results when recommending chemotherapy. This article evaluates the tolerability and efficacy of Comprehensive Geriatric Assessment‐driven therapy in China. [ABSTRACT FROM AUTHOR]

Purpose. To compare the patterns of relative peripheral refractions of myopic children who were currently on atropine treatment for myopia control and myopic children who did not use atropine. Methods. Chinese children (n = 209) aged 7 to 12 years participated in the study, 106 used atropine and 103 did not. Participants were also classified into three groups: emmetropes (SE: +0.50 to −0.50 D), low myopes (SE: −0.50 to −3.00 D), and moderate myopes (SE: −3.00 to −6.00 D). The central and peripheral refractions along the horizontal meridians (for both nasal and temporal fields) were measured in 10-degree steps to 30 degrees. Results. There were no statistically significant differences in spherical equivalent and astigmatism of the three refractive groups in either the nasal or temporal retina. The atropine group showed a significant relative myopia in the temporal 30° field in spherical equivalent compared to the emmetropic group (t49 = 3.36, P = 0.02). In eyes with low myopia, the atropine group had significant relative myopia in the nasal 30° and temporal 30° fields (t118 = 2.59, P = 0.01 ; t118 = 2.06, P = 0.04), and it is also observed at 20° and 30° of the nasal field for the moderate myopic group (t36 = 2.37, P = 0.02 ; t2.84 = 2.84, P = 0.01). Conclusion. Significant differences in relative peripheral refraction were found between the atropine group and its controls. The findings suggested that the eyes that received atropine may have a less prolate shape and thus explain why using atropine is effective in controlling myopia progression. [ABSTRACT FROM AUTHOR]

Background. To explore the effect of atropine 0.01% on accommodation functions and pupil size for safely and effectively controlling myopia in Chinese children. Methods. This was a single-center randomized clinical trial. 63 participants with myopia of at least −0.50 D and astigmatism of ≤−2.50 D were enrolled and randomized to receive atropine 0.01% once nightly with regular single-vision lenses or to wear regular single-vision lenses, in an allocation ratio of 3 : 2. Primary outcomes included changes of accommodation functions, pupil diameter, distant and near best-corrected visual acuity (BCVA), near stereoacuity, and intraocular pressure (IOP). Secondary outcome was myopic progression at 6 months. Results. 61 participants completed the follow-up. Compared with the control group, the atropine-treated children showed a statistically significant increase in pupil diameter after 6 months (0.7 ± 0.7 vs. 0.1 ± 0.5 mm, P = 0.01). Despite the enlarged pupil, routine vision-related activities were not affected. The mean changes in accommodative functions, BCVA, near stereoacuity, and IOP, did not differ significantly between the groups. At 6 months, participants in the control group showed greater myopia progression than those in the atropine group (spherical equivalent: −0.60 ± 0.43 vs.−0.30 ± 0.42 D, P < 0.001 ; axial length: 0.35 ± 0.20 vs. 0.24 ± 0.16 mm, P = 0.001). Conclusions. Atropine 0.01% eye drops significantly increased pupil diameter less than one mm, but it did not affect accommodative functions, BCVA, near stereoacuity, and IOP. Combined with its reducing myopia progression, atropine 0.01% can be used as a safe and effective treatment for myopia in Chinese children. [ABSTRACT FROM AUTHOR]

Melanoma is a human skin malignant tumor with high invasion and poor prognosis. The limited understanding of genomic alterations in melanomas in China impedes the diagnosis and therapeutic strategy selection. We conducted comprehensive genomic profiling of melanomas from 39 primary and metastatic formalin-fixed paraffin-embedded (FFPE) samples from 27 patients in China based on an NGS panel of 223 genes. No significant difference in gene alterations was found between primary and metastasis melanomas. The status of germline mutation, CNV, and somatic mutation in our cohort was quite different from that reported in Western populations. We further delineated the mutation patterns of 4 molecular subgroups (BRAF, RAS, NF1, and Triple-WT) of melanoma in our cohort. BRAF mutations were more frequently identified in melanomas without chromic sun-induced damage (non-CSD), while RAS mutations were more likely observed in acral melanomas. NF1 and Triple-WT subgroups were unbiased between melanomas arising in non-CSD and acral skin. BRAF, RAS, and NF1 mutations were significantly associated with lymph node metastasis or presence of ulceration, implying that these cancer driver genes were independent prognostic factors. In summary, our results suggest that mutational profiles of malignant melanomas in China are significantly different from Western countries, and both gene mutation and amplification play an important role in the development and progression of melanomas. [ABSTRACT FROM AUTHOR]

Background: The impact of HIV-1 subtype (CRF01_AE and non-CRF01_AE) on HIV-1 DNA levels in HIV-1 chronically infected patients with suppressive antiretroviral therapy (ART) remains poorly understood. To evaluate the correlation of HIV-1 subtype with DNA level, and identify baseline predictors of HIV-1 DNA decay.Methods: ART-naïve HIV-1-infected patients from two large multi-center studies in China were classified into CRF01_AE and non-CRF01_AE subtype groups. Peripheral blood samples were collected at baseline and week 12, 24, 48 and 96 after ART initiation and total HIV-1 DNA levels were quantified by real-time PCR. HIV-1 DNA levels at week 96 were categorized into high, moderate, and low levels, reflecting HIV-1 DNA ≥ 3, 2-3, ≤ 2 log10 copies/106 PBMCs, respectively, and the corresponding proportion of CRF01_AE and non-CRF01_AE subtype were compared. The baseline predictors of low HIV-1 total DNA levels (≤ 2 log10 copies/106 PBMCs) at week 96 were evaluated using a logistic regression model.Results: Compared to the non-CRF01_AE subtypes (n = 185), patients with CRF01_AE subtype (n = 188) harboured a higher level of HIV-1 DNA (median: 3.19 vs. 2.95 log10 copies/106 PBMCs, P < 0.001) prior to treatment. After 96 weeks of ART, HIV-1 DNA levels remained higher in the CRF01_AE subtype group (median: 2.63 vs. 2.39 log10 copies/106 PBMCs, P = 0.002). There was no significant difference in the proportion of patients achieving high (22.3% vs. 14.6%, P = 0.054), moderate (59.6% vs. 60.5%, P = 0.849) and low levels (18.1% vs 24.9%, P = 0.111) between CRF01_AE and non-CRF01_AE groups. In the multivariable analysis, baseline HIV-1 DNA level and CD4+ T cell count but not the subtype were independent risk factors for achieving HIV-1 DNA level ≤ 2 log10 copies/106 PBMCs.Conclusion: HIV-1 CRF01_AE subtype is neither correlated with HIV-1 DNA reservoir decline nor a prognostic factor for achieving lower HIV-1 DNA levels (≤ 2 log10 copies/106 PBMCs) after ART. However, higher HIV-1 DNA level in HIV-1 CRF01_AE patients should be aroused much attention and strengthen surveillance during ART. [ABSTRACT FROM AUTHOR]

Background: Previous studies have documented the therapeutic value of computed tomography (CT)‐guided percutaneous microwave ablation (MWA) for early‐stage non‐small cell lung cancer (NSCLC). However, few studies have focused on patients aged 80 years and older. This retrospective study aimed to evaluate the safety and clinical outcomes of CT‐guided percutaneous MWA in patients aged 80 years and older with early‐stage peripheral NSCLC. Methods: A retrospective analysis of 63 patients aged 80 years and older with cT1a‐2bN0M0 peripheral NSCLC who underwent CT‐guided percutaneous MWA was performed between January 2008 and January 2018 at 11 hospitals in Shandong Province, China. Results: The median follow‐up time was 21.0 months. The overall median survival time was 50 months. The cancer‐specific median survival time was not reached in five years. The one‐, two‐, three‐, four‐, and five‐year overall survival rates were 97.1%, 92.6%, 63.4%, 54.4%, and 32.6%, respectively. The one‐, two‐, and three‐year cancer‐specific survival (CSS) rates were 97.9%, 97.9%, and 69.4%, respectively. The four‐ and five‐year CSS rates were not achieved. A total of 14 patients (22.2%) had local progression. The one‐, two‐, three‐, four‐, and five‐year local control rates were 88.8%, 78.8%, 70.3%, 63.9%, and 63.9%, respectively. The mortality rate was 0% within 30 days after the procedure. Major complications included pneumothorax requiring drainage (21.1%), pulmonary infection (4.2%), and pleural effusions requiring drainage (2.8%). Conclusions: CT‐guided percutaneous MWA is a safe and effective modality for treating patients aged 80 years and older with early‐stage peripheral NSCLC. [ABSTRACT FROM AUTHOR]

The CAPTRA‐Lung study (NCT03334864) is a prospective observational study that will capture real‐world data of patients with advanced or metastatic non‐small cell lung cancer (NSCLC) across China. The study aims to complement the results from current therapeutic regimens to improve the standard of diagnosis and treatment, evaluate the effectiveness and safety of systemic therapy, and determine the factors influencing the outcomes and responses to treatment. From January 2018 to December 2023, eligible patients with advanced or metastatic NSCLC who are receiving treatment and participating in follow‐up at 16 institutions in China, will be enrolled. The demographic, clinical, laboratory, and treatment characteristics and responses to treatment will be recorded in a case report form and transcribed into an electronic data capture system. Overall survival, progression‐free survival, overall response rate, and incidence of adverse events will be calculated from the time of initial enrolment until progression evaluated by physicians, last contact, date of death, or analysis cutoff date, respectively. Based on the disease characteristics and treatment strategies, four sub‐cohorts will also be established. This study cohort could serve as a pool of patients with advanced or metastatic NSCLC to support further research. [ABSTRACT FROM AUTHOR]

Background: Chronic periodontitis is a multifactorial polygenetic disease with an increasing number of associated factors that have been identified over recent decades. Longitudinal epidemiologic studies have demonstrated that the risk factors were related to the progression of the disease. A traditional multivariate regression model was used to find risk factors associated with chronic periodontitis. However, the approach requirement of standard statistical procedures demands individual independence. Multilevel modelling (MLM) data analysis has widely been used in recent years, regarding thorough hierarchical structuring of the data, decomposing the error terms into different levels, and providing a new analytic method and framework for solving this problem. The purpose of our study is to investigate the relationship of clinical periodontal index and the risk factors in chronic periodontitis through MLM analysis and to identify high-risk individuals in the clinical setting.Methods: Fifty-four patients with moderate to severe periodontitis were included. They were treated by means of non-surgical periodontal therapy, and then made follow-up visits regularly at 3, 6, and 12 months after therapy. Each patient answered a questionnaire survey and underwent measurement of clinical periodontal parameters.Results: Compared with baseline, probing depth (PD) and clinical attachment loss (CAL) improved significantly after non-surgical periodontal therapy with regular follow-up visits at 3, 6, and 12 months after therapy. The null model and variance component models with no independent variables included were initially obtained to investigate the variance of the PD and CAL reductions across all three levels, and they showed a statistically significant difference (P < 0.001), thus establishing that MLM data analysis was necessary. Site-level had effects on PD and CAL reduction; those variables could explain 77-78% of PD reduction and 70-80% of CAL reduction at 3, 6, and 12 months. Other levels only explain 20-30% of PD and CAL reductions. Site-level had the greatest effect on PD and CAL reduction.Conclusions: Non-surgical periodontal therapy with regular follow-up visits had a remarkable curative effect. All three levels had a substantial influence on the reduction of PD and CAL. Site-level had the largest effect on PD and CAL reductions. [ABSTRACT FROM AUTHOR]

Background: No systemic evaluation of asthma control in Jilin Province has been reported. Asthma control might provide the basis for asthma management in this region. A multicenter hospital-based cross-sectional study was performed to investigate the asthma control and related factors for severe asthma exacerbations in patients with moderate or severe asthma in Jilin Province, China.Methods: The study enrolled 1546 patients in five grade one general hospitals from January to December 2013. Asthma medication, patient self-management, asthma control test (ACT) scores and frequency of severe asthma exacerbations during the follow-up (12 months) were collected via a follow-up questionnaire.Results: In the study, 889 patients provided a complete follow-up questionnaire. Severe asthma exacerbations occurred in 54.89 % of patients. ACT score ≤15, asthma medication ≤ 3 months, severe asthma, income level lower than average Per Capita Disposable Income (PCDI) and a lower educational level were risk factors of a severe exacerbation.Conclusions: Poor adherence to asthma medication, poor asthma symptom control, lower income, a low educational level might be possible reasons for the high incidence of severe asthma exacerbations and poor asthma control in Jilin Province of China. [ABSTRACT FROM AUTHOR]

There is considerable variability between individuals in susceptibility to infection by human immunodeficiency virus (HIV). Many social, clinical and genetic factors are known to contribute to the likelihood of HIV transmission, but there is little consensus on the relative importance and potential interaction of these factors. Additionally, recent studies of several variants in chemokine receptors have identified alleles that may be predictive of HIV transmission and disease progression; however the strengths and directions of the associations of these genetic markers with HIV transmission have markedly varied between studies. To better identify factors that predict HIV transmission in a Chinese population, 180 cohabiting serodiscordant couples were enrolled for study by the Henan Center for Disease Prevention and Control, and transmission and progression of HIV infection were regularly measured. We found that anti-retroviral therapy, education level, and condom use were the most significant factors in determining likelihood of HIV transmission in this study. We also assessed ten variants in three genes (CXCL12, CCR2, and CCR5) that have been shown to influence HIV transmission. We found two tightly linked variants in CCR2 and CCR5, rs1799864 and rs1800024, have a significant positive association with transmission as recessive models (OR>10, P value=0.011). Mixed effects models showed that these genetic variants both retained significance when assessed with either treatment or condom use. These markers of transmission susceptibility may therefore serve to help stratify individuals by risk for HIV transmission. [ABSTRACT FROM AUTHOR]

Background A total of 453 laboratory-confirmed cases of human infected with avian influenza A (H7N9) virus (including 175 deaths) have been reported by WHO till October 2,2014, of which 30.68% (139/453) of the cases were identified from Zhejiang Province. We describe the largest reported cluster of virologically confirmed H7N9 cases, comprised by a fatal Index case and two mild secondary cases. Methods A retrospective epidemiological investigation was conducted in January of 2014. Three confirmed cases, their close contacts, and relevant environments samples were tested by realtime reverse transcriptase-polymerase chain reaction (RT-PCR), viral culture, and sequencing. Serum samples from contacts and cases were tested by haemagglutination inhibition (HI) assay. Results The cluster was comprised of the Index case, a 49-year-old farmer with type II diabetes, who lived with his daughter (Case 2, aged 24) and wife (Case 3, aged 43) and his son-in-law (H7N9 negative). The Index case and Case 3 worked daily in a live bird market. Onset of illness in Index case occurred in January 13, 2014 and subsequently, he died of multi-organ failure on January 20. Case 2 presented with mild symptoms on January 20 following frequent unprotected bed-side care of the Index case between January 14 to 19, and exposed to live bird market on January 17. Case 3 became unwell on January 23 after providing bedside care to the Index case on January 17 to 18, and following the contact with Case 2 during January 21 to 22 at the funeral of the Index case. The two secondary cases were discharged on February 2 and 5 separately after early treatment with antiviral medication. Four virus strains were isolated and genome analyses showed 99.6 ~ 100% genetic homology, with two amino mutations (V192I in NS and V280A in NP). 42% (11/26) of environmental samples collected in January were H7N9 positive. Twenty-five close contacts remained well and were negative for H7N9 infection by RT-PCR and HI assay. Conclusions In the present study, we reported that the Index case was infected from a live bird market while the two secondary cases were infected by the Index case during unprotected exposure. This family cluster is, therefore, compatible with non-sustained person-to-person transmission of avian influenza A/H7N9. [ABSTRACT FROM AUTHOR]

An increase in the incidence of hand, foot and mouth disease (HFMD) cases has been observed in the Hunan province of mainland China since 2009 with a particularly higher level of severe cases in 2010–2012. Intestinal viruses of the picornaviridae family are responsible for the human syndrome associated with HFMD with enterovirus 71 (EV71) and Coxsackievirus A16 (Cox A16) being the most common causative strains. HFMD cases associated with EV71 are generally more severe with an increased association of morbidity and mortality. In this study, the etiology surveillance data of HFMD cases in Hunan province from March 2010 to October 2012 were analyzed to determine if there is a statistically relevant linear correlation exists between the detection rate of EV71 in mild cases and the proportion of severe cases among all HFMD patients. As the cases progressed from mild to severe to fatal, the likelihood of EV71 detection increased (25.78%, 52.20% and 84.18%, respectively). For all cases in the timeframe evaluated in this study, the presence of virus was detected in 63.21% of cases; among cases showing positivity for virus, EV71 infection accounted for 50.14%. These results provide evidence to support the observed higher morbidity and mortality associated with this outbreak and emphasizes the importance of early detection in order to implement necessary prevention measures to mitigate disease progression. [ABSTRACT FROM AUTHOR]

Background: To retrospectively review the incidence, treatment efficacy, we followed up newly diagnosed chronic myelogenous leukemia (CML) patients residing in Shanghai during 2001-2006. Methods: All eligible cases were reviewed with the data of efficacy responses as well as overall survival (OS) and progression-free survival (PFS) time. Results: A total of 615 cases entered the study. CML mainly afflicted those aged 40-60 years old and was slightly more frequent in males than females. More than 85% of the patients were in chronic phase (CP) when diagnosed. All patients were divided into four groups based on the main regimens - hydroxyurea, interferon alpha (IFN-a), imatinib, and hemopoietic stem cell transplantation (HSCT). With the median follow-up of 18 months, imatinib treatment induced 92.2% complete hematologic responses, and 64.3% complete cytogenetic responses among CML-CP patients. Overall the therapeutic efficacy in the imatinib group was higher than that in the hydroxyurea or IFN-α group. Meanwhile, in the imatinib group, all response rates of patients in CP were significantly greater than that in accelerated or blastic crisis phase. The patients treated with imatinib also showed the most promising results regarding OS and PFS. Patients receiving HSCT decreased markedly in number with the introduction of imatinib. Conclusions: The number of new patients arising in Shanghai increased from 2001 to 2006. There were still patients receiving hydroxyurea and IFN-α. As the first-line regime for CML, imatinib was less administered in Shanghai before, but has received considerable development and great responses since 2003. [ABSTRACT FROM AUTHOR]

Background: It remains controversial how HCV coinfection influences the disease progression during HIV-1 infection. This study aims to define the influence of HCV infection on the replication of HIV-1 and the disease progression in HIV-infected former plasma donors (FPDs) naïve to ART. Methodology/Principal Findings: 168 HIV-1-infected FPDs were enrolled into a cohort study from Anhui province in central China, and thereafter monitored at month 3, 9, 15, 21 and 33. Fresh whole blood samples were used for CD4+ T-cell counting. Their plasma samples were collected and stored for quantification of HIV-1 viral loads and for determination of HCV and Toxoplasma. Out of 168 HIV-infected FBDs, 11.9% (20 cases), 80.4% (135 cases) and 7.7% (13 cases) were infected with HIV-1 alone, HIV-1/HCV and HIV/HCV/Toxoplasma, respectively. During the 33-month follow-up, only 35% (7 out of 20 cases) HIV-1 mono-infected subjects remained their CD4+ T-cell counts above 200 cells/μl and retained on the cohort study, which was significantly lower than 56% (75 out of 135 cases) for HIV/HCV group and 69% (9 out of 13 cases) for HIV/HCV/ Toxoplasma group (p<0.05). CD4+ T cells in HIV mono infection group were consistently lower than that in HIV/HCV group (p = 0.04, 0.18, 0.03 and 0.04 for baseline, month 9, month 21 and month 33 visit, respectively). In accordance with those observations, HIV viral loads in HIV mono-infection group were consistently higher than that in HIV/HCV group though statistical significances were only reached at baseline (p = 0.04). Conclusions/Significance: These data indicated HCV coinfection with HIV-1 is associated with the slower disease progression at the very late stage when comparing with HIV-1 mono-infection. The coinfection of Toxoplasma with HIV and HCV did not exert additional influence on the disease progression. It will be highly interesting to further explore the underlying mechanism for this observation in the future. [ABSTRACT FROM AUTHOR]

Background: A novel coronavirus (SARS-CoV-2)-induced pneumonia (COVID-19) emerged in December 2019 in China, spreading worldwide. The aim of the present investigation was to evaluate the immunological response and the clinical subset of peripheral lymphocyte subset alteration in COVID-19 infection. Methods: the study was conducted on four different clinical groups (n = 4; total n = 138). Each individual was assigned to different groups based on specific criteria evaluated at the admission such as fever, dyspnea, arterial blood gas analysis (ABG), oral-nasopharyngeal swab/RT-PCR, and thoracic CT-scan. Treatment was performed only after blood samples were collected from each patient (PP and PP) at day 1. The blood samples were analyzed and tested the same day (CBC and Flowcytometry). The positive–positive group (PP n = 45; F = 18/ M = 27; median age = 62.33), comprised individuals affected by COVID-19 who showed fever, dyspnea (ABG = pO2 < 60), confirmed positive by oral-nasopharyngeal swab/RT-PCR and with CT-scan showing ground-glass opacities. The negative–positive (NP; n = 37; F = 11/M = 26; median age = 75.94) or "COVID-like" group comprised individuals with fever and dyspnea (ABG = pO2 < 60), who tested negative to nasopharyngeal swab/RT-PCR, with CT-scans showing ground-glass opacities in the lungs. The negative–affected group (NA; n = 40; F = 14/M = 26; median age = 58.5) included individuals negative to COVID-19 (RT-PCR) but affected by different chronic respiratory diseases (the CT-scans didn't show ground-glass opacities). Finally, the negative–negative group (NN; n = 16; F = 14/M = 2) included healthy patients (NN; n = 16; median age = 42.62). Data and findings were collected and compared. Results: Lymphocytes (%) cells showed a decline in COVID-19 patients. The subsets showed a significant association with the inflammatory status in COVID-19, especially with regard to increased neutrophils, T-killer, T-active, T-suppressor, and T-CD8+CD38+ in individuals belong to the either COVID-19 and Covid-like NP group. Conclusions: Peripheral lymphocyte subset alteration was associated with the clinical characteristics and progression of COVID-19. The level of sub-set cells T-lymphocytes (either high or low) and B-lymphocytes could be used as an independent predictor for COVID-19 severity and treatment efficacy. [ABSTRACT FROM AUTHOR]

Background: Myasthenia gravis (MG) is the most common disorder of neuromuscular transmission, and it is typified by fluctuating degrees and variable combinations of weakness in the ocular, bulbar, limb, and respiratory muscles. Under rare circumstances, MG can be accompanied by Addison's disease. Case presentation: Here, we reported the case of a 57-year-old Chinese woman with MG. She experienced progressive muscle weakness for 1 week. MG with acute exacerbation was initially suspected. However, further biochemistry tests found mild hyperkalemia (5.6 mEq/L) and a lower renal potassium excretion rate. Consequently, low aldosterone action was highly suspected. Further findings included a suppressed cortisol level, a higher adrenocorticotropic hormone concentration, and 21-hydroxylase antibody positivity, supporting a diagnosis of primary adrenal insufficiency due to autoimmune adrenalitis. Conclusion: We successfully demonstrated that adrenal insufficiency could be diagnosed, due to the presence of hyperkalemia. This case suggested a need for clinicians to consider the possible coincidence of adrenal insufficiency in a patient with MG and hyperkalemia. Early hormone supplementation should be begun. [ABSTRACT FROM AUTHOR]

Background: Chronic kidney disease (CKD) leads to end-stage renal failure and cardiovascular events. An attribute to these progressions is abnormalities in inflammation, which can be evaluated using the neutrophil-to-lymphocyte ratio (NLR). We aimed to investigate the association of NLR with the progression of end stage of renal disease (ESRD), cardiovascular disease (CVD) and all-cause mortality in Chinese patients with stages 1-4 CKD.Methods: Patients with stages 1-4 CKD (18-74 years of age) were recruited at 39 centers in 28 cities across 22 provinces in China since 2011. A total of 938 patients with complete NLR and other relevant clinical variables were included in the current analysis. Cox regression analysis was used to estimate the association between NLR and the outcomes including ESRD, CVD events or all-cause mortality.Results: Baseline NLR was related to age, hypertension, serum triglycerides, total serum cholesterol, CVD history, urine albumin to creatinine ratio (ACR), chronic kidney disease-mineral and bone disorder (CKD-MBD), hyperlipidemia rate, diabetes, and estimated glomerular filtration rate (eGFR). The study duration was 4.55 years (IQR 3.52-5.28). Cox regression analysis revealed an association of NLR and the risk of ESRD only in patients with stage 4 CKD. We did not observe any significant associations between abnormal NLR and the risk of either CVD or all-cause mortality in CKD patients in general and CKD patients grouped according to the disease stages in particular.Conclusion: Our results suggest that NLR is associated with the risk of ESRD in Chinese patients with stage 4 CKD. NLR can be used in risk assessment for ESRD among patients with advanced CKD; this application is appealing considering NLR being a routine test. Trial registration ClinicalTrials.gov Identifier NCT03041987. Registered January 1, 2012. (retrospectively registered) ( https://www.clinicaltrials.gov/ct2/show/NCT03041987?term=Chinese+Cohort+Study+of+Chronic+Kidney+Disease+%28C-STRIDE%29&rank=1 ). [ABSTRACT FROM AUTHOR]

Objectives: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths globally. In China, sorafenib and oxaliplatin plus infusional-fluorouracil/leucovorin (FOLFOX4) are approved for the systemic treatment of advanced HCC. This study compared the cost-effectiveness of these therapies from a healthcare system perspective and a patient perspectives. Methods: A Markov model was constructed using overall and progression-free survival rates and adverse event (AE) rate from two randomized controlled studies of advanced HCC patients from Asia: EACH for FOLFOX4 and ORIENTAL for sorafenib. The patients in the Markov model were followed until death, the length of each Markov cycle was 1 month, and the survival was adjusted for quality-adjusted life years (QALYs). Direct medical costs included costs of therapies, AE treatment, general ward and tests. Costs were derived from published sources, interviews with oncologists and hospital data from China. One-way and probabilistic sensitivity analyses (PSA) were performed to test the robustness of the results. Results: From the healthcare system perspective, FOLFOX4 dominated sorafenib with lower therapy costs (FOLFOX4: US$ 6972; sorafenib: US$ 12,289), lower direct medical costs (FOLFOX4: US$ 8428; sorafenib: US$ 12,798), and higher QALYs (FOLFOX4: 0.42; sorafenib: 0.38) per patient. This result was robust according to comprehensive one-way sensitivity analyses. According to the PSA, at the cost-effectiveness threshold for China (3 × GDP, US$ 22,073), FOLFOX4 should be chosen in 63.9% of simulations. From the patient perspective, FOLFOX4 also dominated sorafenib. Conclusions: The study results indicate that FOLFOX4 dominates sorafenib because it appears to provide higher effectiveness with significantly lower costs in treating Chinese advanced HCC patients. [ABSTRACT FROM AUTHOR]

Background: To determine the one-year incidence and progression rates of myopia and its association with baseline ocular biometric parameters in school-based samples of children and adolescents in China.Methods: Two thousand four hundred thirty two grade 1 and 2346 grade 7 students living in the southwest part of China participated in the baseline survey. After 1 year, 2310 (95.0%) grade 1 and 2191 (93.4%) grade 7 students attended the follow-up examination. Refractive error was measured after cycloplegia using the same autorefractor and by the same optometrists in the baseline and follow-up examination. Myopia was defined as spherical equivalent of less than - 0.50 diopter.Results: The overall one-year incidence of myopia was 33.6% (95% confidence interval [CI]: 31.7-35.5) among grade 1 students and 54.0% (95% CI: 51.5-56.5) for grade 7 students. The one-year myopia progression rate was - 0.97 D (95% CI: -1.22 to - 0.71) in grade 1 students and - 1.02 D (95% CI: -1.07 to - 0.96) in grade 7 students. Per mm increase in baseline axial lengths increased the risk of myopia onset by 28% among grade 1 students and 22% among grade 7 students after 1 year. The incidence rates of myopia were found to be higher in grade 7 students with thinner premyopic lenses.Conclusions: The incidence and progression rates of myopia were very high in Chinese children and adolescents in recent years. Premyopic eyes were characterized with longer axial lengths and thinner lenses. These data had considerable implications for formulating myopia prevention strategies in China. [ABSTRACT FROM AUTHOR]