Serum inflammatory markers in children with Mycoplasma pneumoniae pneumonia and their predictive value for mycoplasma severity.

BACKGROUND: Mycoplasma pneumoniae pneumonia (MPP) significantly impacts pediatric health, necessitating markers for early severe disease identification. AIM: To investigate the correlation between serum inflammatory marker and the severity of MPP in children. METHODS: A prospective study was carried out from January 2023 to November 2023. A total of 160 children with MPP who underwent treatment were selected: 80 had severe MPP and 80 had mild MPP. Clinical and laboratory data were collected at the time of hospital admission and during hospitalization. Receiver operating characteristic curves were utilized to assess the diagnostic and prognostic for severe MPP. RESULTS: Fever duration and length of hospitalization in pediatric patients with severe MPP exceeded those with mild MPP. The incidence of pleural effusion, lung consolidation, and bronchopneumonia on imaging was markedly elevated in the severe MPP cohort compared to the mild MPP cohort. In contrast to the mild cohort, there was a notable increase in C-reactive protein (CRP), procalcitonin (PCT), erythrocyte sedimentation rate, lactic dehydrogenase, D-dimer, and inflammatory cytokines [interleukin (IL)-6, IL-8, IL-10 and tumor necrosis factor (TNF)-α] in the severe MPP group were significantly higher. CONCLUSION: Serum inflammatory markers (CRP, PCT, IL-6, D-dimer, IL-10 and TNF-α) were considered as predictors in children with severe MPP.

Internal limiting membrane peeling combined with silicone oil or air tamponade for highly myopic foveoschisis.

AIM: To compare the efficacy of pars plana vitrectomy (PPV) combined with internal limiting membrane (ILM) and silicone oil or sterile air tamponade for the treatment of myopic foveoschisis (MF) in highly myopic eyes. METHODS: This retrospective study included 48 myopic eyes of 40 patients with MF and axial lengths (ALs) ranging from 26-32 mm treated between January 2020 and January 2022. All patients were underwent PPV combined with ILM peeling followed by sterile air or silicone oil tamponade and followed up at least 12mo. Based on the features on spectral-domain optical coherence tomography (SD-OCT), the eyes were divided into the MF-only group (Group A, n=15 eyes), MF with central foveal detachment group (Group B, n=20 eyes), and MF with lamellar macular hole group (Group C, n=13 eyes). According to AL, eyes were further divided into three groups: Group D (26.01-28.00 mm, n=12 eyes), Group E (28.01-30.00 mm, n=26 eyes), and Group F (30.01-32.00 mm, n=10 eyes). The best-corrected visual acuity (BCVA), central foveal thickness (CFT), and complications were recorded. RESULTS: The patients included 16 males and 24 females with the mean age of 56±9.82y. The BCVA and CFT improved in all groups after surgery (P<0.01), while there was no significant difference of the CFT in Group A, B, and C postoperatively (P>0.05). The intergroup differences of BCVA and CFT postoperatively were statistically significant in Group D, E, and F. Twenty eyes were injected with sterile air, and 28 eyes were injected with silicone oil for tamponade based on the AL. However, there was no statistically significant difference among Groups D, E, and F in terms of the results of sterile air or silicone oil tamponade. The mean recovery time was 5.9mo for MF patients subjected to silicone oil tamponade and 7.7mo for patients subjected to sterile air tamponade, and the difference was not statistically significant. CONCLUSION: PPV and ILM peeling combined with silicone oil or sterile air tamponade can achieve good results for MF in highly myopic eyes with ALs≤32 mm.

Diagnostic Value of Nutritional Risk Index and Other Indices for Predicting Sarcopenia in the Middle-Aged and Elderly Population of China Without Cancer: A ROC Curve Analysis.

Background: Emerging evidence suggests that systemic inflammatory and nutritional biomarkers, along with derived indices, could serve as predictors for sarcopenia in cancer population. This study aimed to compare these predictors, focusing on the nutritional risk index (NRI) and evaluate its diagnostic value, for sarcopenic patients without cancer. Methods: This cross-sectional retrospective study included 1674 participants. Sarcopenia is defined by skeletal muscle mass index (SMI). Laboratory data reflected the values of systemic inflammatory and nutritional biomarkers, from which the derived indices were calculated. Multiple logistic regression analysis, ROC curve analysis, and the Youden index were utilized to assess the association between these markers and sarcopenia and determine the cutoff value for predicting sarcopenia. Results: Among all participants (1110 men and 564 women, mean age 61.97 ± 9.83 years), 398 individuals were diagnosed with sarcopenia, indicating a prevalence of 23.78% in China's middle-aged and elderly population without cancer. Logistic regression analysis revealed significant associations between all biomarkers and derived indices with sarcopenia. Following adjustment for potential confounders, lower NRI values were significantly associated with a higher incidence of sarcopenia. For sarcopenia diagnosis, the area under the curve (AUC) for NRI was 0.769 ([95% CI, 0.742, 0.796], P < 0.001), with a cutoff value of 106.016, sensitivity of 75.6% and specificity of 66.1%. NRI demonstrated greater predictive advantage for sarcopenia incidence in men compared to women. Conclusion: A lower NRI value was associated with a higher prevalence of sarcopenia. NRI shows promise for early, rapid, and effective sarcopenia screening, particularly in China's middle-aged and elderly male population without cancer.

XELOX (capecitabine plus oxaliplatin) plus bevacizumab (anti-VEGF-A antibody) with or without adoptive cell immunotherapy in the treatment of patients with previously untreated metastatic colorectal cancer: a multicenter, open-label, randomized, controlled, phase 3 trial.

Fluoropyrimidine-based combination chemotherapy plus targeted therapy is the standard initial treatment for unresectable metastatic colorectal cancer (mCRC), but the prognosis remains poor. This phase 3 trial (ClinicalTrials.gov: NCT03950154) assessed the efficacy and adverse events (AEs) of the combination of PD-1 blockade-activated DC-CIK (PD1-T) cells with XELOX plus bevacizumab as a first-line therapy in patients with mCRC. A total of 202 participants were enrolled and randomly assigned in a 1:1 ratio to receive either first-line XELOX plus bevacizumab (the control group, n = 102) or the same regimen plus autologous PD1-T cell immunotherapy (the immunotherapy group, n = 100) every 21 days for up to 6 cycles, followed by maintenance treatment with capecitabine and bevacizumab. The main endpoint of the trial was progression-free survival (PFS). The median follow-up was 19.5 months. Median PFS was 14.8 months (95% CI, 11.6-18.0) for the immunotherapy group compared with 9.9 months (8.0-11.8) for the control group (hazard ratio [HR], 0.60 [95% CI, 0.40-0.88]; p = 0.009). Median overall survival (OS) was not reached for the immunotherapy group and 25.6 months (95% CI, 18.3-32.8) for the control group (HR, 0.57 [95% CI, 0.33-0.98]; p = 0.043). Grade 3 or higher AEs occurred in 20.0% of patients in the immunotherapy group and 23.5% in the control groups, with no toxicity-associated deaths reported. The addition of PD1-T cells to first-line XELOX plus bevacizumab demonstrates significant clinical improvement of PFS and OS with well tolerability in patients with previously untreated mCRC.

A WeChat-based nursing intervention program improves the postoperative rehabilitation of breast cancer patients: results from a randomized controlled trial.

Background: In postoperative setting, breast cancer (BC) patients can experience adverse effects, including fatigue, sleep disorders, and pain, which substantially affect their health-related quality of life (HRQoL). This study sought to assess the effectiveness of a WeChat-based multimodal nursing program (WCBMNP) that was specifically designed for the rehabilitation of women following BC surgery. Methods: BC patients were randomly, single-blinded allocated to either the intervention (n=62) or control (n=63) cohorts. Over a period of 6 months (24 weeks), the intervention cohort received a WCBMNP in addition to routine nursing care, while the control cohort received routine nursing care only. To evaluate patients' fear of cancer recurrence (FCR), their overall fear score was assessed using the Japanese version of the Concerns About Recurrence Scale (CARS-J) for primary outcome. The initial outcome (HRQoL) and secondary results, such as fatigue, sleep, and pain, were examined using the Functional Assessment of Cancer Therapy-Breast (FACT-B, version 4.0) and Nursing Rating Scale (NRS), respectively. Results: Two hundred and ten participants, 85 participants were excluded. Compared to the controls (n=63), the intervention cohort (n=62) showed statistically significant improvements in their CARS-J scores. The intervention cohort aggregate scores on the FACT-B improved significantly but were affected by the compounding influences of cohort dynamics, temporal progression, and their interaction. Similar improvements were observed in the social/family and functional well-being domains. Emotional well-being was improved based on the effects of time and group-time interaction. In the intervention cohort, the "BC-specific subscale for additional concerns" was affected by group and time, whereas physical well-being was only affected by time. Conversely, there were no statistically significant changes in the variables of fatigue, sleep, and pain. Conclusions: The WCBMNP reduced FCR and significantly increased the HRQoL of female patients with BC postoperatively. The WCBMNP could be implemented as a postoperative rehabilitation intervention in this patient population to improve outcomes. Trial Registration: Chinese Clinical Trial Registry (ChiCTR2400081557).

Successful Outcome of a Patient with Concomitant Pancreatic and Renal Carcinoma Receiving Secoisolariciresinol Diglucoside Therapy Alone: A Case Report.

Introduction: Pancreatic cancer (PC) is among the deadliest malignancies. Kidney cancer (KC) is a common malignancy globally. Chemo- or radio-therapies are not very effective to control PC or KC, and overdoses often cause severe site reactions to the patients. As a result, novel treatment strategies with high efficacy but without toxic side effects are urgently desired. Secoisolariciresinol diglucoside (SDG) belongs to plant lignans with potential anticancer activities, but clinical evidence is not available in PC or KC treatment. Patient Concerns: We report a rare case of an 83-year-old female patient with pancreatic and kidney occupying lesions that lacked the conditions to receive surgery or chemo- or radiotherapy. Diagnosis: Pancreatic and kidney cancers. Interventions: We gave dietary SDG to the patient as the only therapeutics. Outcomes: SDG effectively halted progression of both PC and KC. All clinical manifestations, including bad insomnia, loss of appetite, stomach symptoms, and skin itching over the whole body, all disappeared. The initial massive macroscopic hematuria became microscopic and infrequent, and other laboratory results also gradually returned to normal. Most of the cancer biomarkers, initially high such as CEA, CA199, CA724, CA125, came down rapidly, among which CA199 changed most radically. This patient has had progression-free survival of one year so far. Conclusion: These results demonstrate the potent inhibitory effects of SDG on PC and KC of this patient and provide promising novel therapeutics for refractory malignant tumors.

Polypyridyl ruthenium complexes with benzothiazole moiety as membrane disruptors and anti-resistance agents for Staphylococcus aureus.

Developing new antimicrobials to combat drug-resistant bacterial infections is necessary due to the increasing problem of bacterial resistance. In this study, four metallic ruthenium complexes modified with benzothiazoles were designed, synthesized and subjected to bio-evaluated. Among them, Ru-2 displayed remarkable inhibitory activity against Staphylococcus aureus (S. aureus) with a minimum inhibitory concentration (MIC) of 1.56 µg/mL. Additionally, it showcased low hemolytic toxicity (HC50 > 200 µg/mL) and the ability to effectively eradicate S. aureus without fostering drug resistance. Further investigation into the antibacterial mechanism suggested that Ru-2 may target the phospholipid component of S. aureus, leading to the disruption of the bacterial cell membrane and subsequent leakage of cell contents (nucleic acid, protein, and ONPG), ultimately resulting in the death of the bacterial cell. In vivo studies, both the G. mellonella larvae and the mouse skin infection models were conducted, indicated that Ru-2 could potentially serve as a viable candidate for the treatment of S. aureus infection. It exhibited no toxic or side effects on normal tissues. The results suggest that benzothiazole-modified ruthenium complexes may have potential as membrane-active antimicrobials against drug-resistant bacterial infections.

Exploiting the CD200-CD200R immune checkpoint axis in multiple myeloma to enhance CAR T-cell therapy.

ABSTRACT: Patients with multiple myeloma (MM) treated with B-cell maturation antigen (BCMA)-specific chimeric antigen receptor (CAR) T cells usually relapse with BCMA+ disease, indicative of CAR T-cell suppression. CD200 is an immune checkpoint that is overexpressed on aberrant plasma cells (aPCs) in MM and is an independent negative prognostic factor for survival. However, CD200 is not present on MM cell lines, a potential limitation of current preclinical models. We engineered MM cell lines to express CD200 at levels equivalent to those found on aPCs in MM and show that these are sufficient to suppress clinical-stage CAR T-cells targeting BCMA or the Tn glycoform of mucin 1 (TnMUC1), costimulated by 4-1BB and CD2, respectively. To prevent CD200-mediated suppression of CAR T cells, we compared CRISPR-Cas9-mediated knockout of the CD200 receptor (CD200RKO), to coexpression of versions of the CD200 receptor that were nonsignaling, that is, dominant negative (CD200RDN), or that leveraged the CD200 signal to provide CD28 costimulation (CD200R-CD28 switch). We found that the CD200R-CD28 switch potently enhanced the polyfunctionality of CAR T cells, and improved cytotoxicity, proliferative capacity, CAR T-cell metabolism, and performance in a chronic antigen exposure assay. CD200RDN provided modest benefits, but surprisingly, the CD200RKO was detrimental to CAR T-cell activity, adversely affecting CAR T-cell metabolism. These patterns held up in murine xenograft models of plasmacytoma, and disseminated bone marrow predominant disease. Our findings underscore the importance of CD200-mediated immune suppression in CAR T-cell therapy of MM, and highlight a promising approach to enhance such therapies by leveraging CD200 expression on aPCs to provide costimulation via a CD200R-CD28 switch.

Computational exploration of the significance of COPS6 in cancer: Functional and clinical relevance across tumor types.

BACKGROUND: The COP9 signalosome subunit 6 (COPS6) has been implicated in cancer progression, while its precise role in most types of cancer remains elusive. AIM: To investigate the functional and clinical relevance of COPS6 across various tumor types using publicly available databases. METHODS: We used R software and online analysis databases to analyze the differential expression, prognosis, mutation and related functions of COPS6 in pan-cancer. RESULTS: Differential expression analysis and survival analysis demonstrated that COPS6 was highly expressed and associated with high-risk profiles in the majority of cancer types. Possible associations between COPS6 expression level and prognostic outcomes were found using data from public databases. Mutational analysis revealed that missense mutations were the predominant type of COPS6 mutation. Additionally, positive correlations were identified between COPS6 expression level and tumor mutational burden and microsatellite instability in most types of cancer. Immune infiltration analysis demonstrated a negative correlation between COPS6 expression level and CD8+ T cell infiltration in certain types of cancer. The correlation between COPS6 expression level and cancer-associated fibroblast infiltration exhibited heterogeneity, in which a positive correlation was found in head and neck squamous cell carcinoma and tenosynovial giant cell tumor, and a negative correlation was identified in diffuse large B-cell lymphoma and thymoma. The correlation between COPS6 expression level and macrophage infiltration was closely related to macrophage type. Gene co-expression and enrichment analysis highlighted transcription elongation factor B polypeptide 2 and G protein pathway suppressor 1 were significantly and positively associated with COPS6 expression level. These genes were predominantly involved in processes, such as ubiquitin-mediated proteolysis and human immunodeficiency virus 1 infection. CONCLUSION: In conclusion, this study systematically explored the significance of COPS6 across different tumor types, providing a solid foundation for considering COPS6 as a novel biomarker in cancer research.

Interactions among acute respiratory viruses in Beijing, Chongqing, Guangzhou, and Shanghai, China, 2009-2019.

Background: A viral infection can modify the risk to subsequent viral infections via cross-protective immunity, increased immunopathology, or disease-driven behavioral change. There is limited understanding of virus-virus interactions due to lack of long-term population-level data. Methods: Our study leverages passive surveillance data of 10 human acute respiratory viruses from Beijing, Chongqing, Guangzhou, and Shanghai collected during 2009 to 2019: influenza A and B viruses; respiratory syncytial virus A and B; human parainfluenza virus (HPIV), adenovirus, metapneumovirus (HMPV), coronavirus, bocavirus (HBoV), and rhinovirus (HRV). We used a multivariate Bayesian hierarchical model to evaluate correlations in monthly prevalence of test-positive samples between virus pairs, adjusting for potential confounders. Results: Of 101,643 lab-tested patients, 33,650 tested positive for any acute respiratory virus, and 4,113 were co-infected with multiple viruses. After adjusting for intrinsic seasonality, long-term trends and multiple comparisons, Bayesian multivariate modeling found positive correlations for HPIV/HRV in all cities and for HBoV/HRV and HBoV/HMPV in three cities. Models restricted to children further revealed statistically significant associations for another ten pairs in three of the four cities. In contrast, no consistent correlation across cities was found among adults. Most virus-virus interactions exhibited substantial spatial heterogeneity. Conclusions: There was strong evidence for interactions among common respiratory viruses in highly populated urban settings. Consistent positive interactions across multiple cities were observed in viruses known to typically infect children. Future intervention programs such as development of combination vaccines may consider spatially consistent virus-virus interactions for more effective control.

Perioperative nursing care speed up recover of a male patient after bilateral endoscopic mastectomy: a case report.

Background: Gynecomastia (GYN) is mainly caused by the benign proliferation of mammary glands and adipose tissue. Currently, up to 38% of adult males have GYN. GYN can be caused by systemic diseases, obesity, endocrine disorders (such as liver cirrhosis, which impairs estrogen inactivation), malignant tumors, and medications. Surgical intervention is required after 12 months pharmacological treatment of GYN was no response who have endocrine disorder, or due to psychological and physiological factors, young patients have a higher demand for surgical intervention. Recent advances in minimally invasive endoscopic surgery, with the advantage of rapid rehabilitation, have markedly improved the surgical management of GYN. Case Description: In November 2021, we admitted a young patient with bilateral GYN whose problem began several years prior and for which he sought surgical intervention. After comprehensive evaluation and psychological consultation, he underwent surgical treatment. The present case report summarizes our experience in nursing this patient. Conclusions: Perioperative nursing care is essential in the management of patients undergoing endoscopic surgical treatment for GYN. The nursing team must be knowledgeable about the procedure, assess and manage the patient's pain, monitor vital signs, prevent infections, and provide emotional support to the patient. With proper nursing care, patients can recover smoothly and quickly after endoscopic surgical treatment of GYN.

[Remediation of Petroleum-contaminated Soil by Highly Efficient Oil-degrading Bacteria and Analysis of Its Enhancement Mechanism].

A 120-day in situ remediation of oil-contaminated soil was carried out by using highly efficient oil-degrading bacteria. The effects of bio-enhanced remediation and changes in soil physicochemical properties and enzyme activities were investigated. Combined with metagenomic sequencing and bioinformatics analysis, the strengthening mechanism was revealed. The results showed that compared with the blank control group (Ctrl), the degradation rate of total petroleum hydrocarbons in the bioremediation group (Exp-BT) was significantly increased, reaching 81.23%. During enhanced bioremediation by highly efficient oil-degrading bacteria, the pH of the soil was stable, the oxidation capacity of the system was improved, and the electrical conductivity was in the range suitable for agricultural activities. Lipase and dehydrogenase maintained high activity during repair. In addition, the analysis of the initial contaminated soil (B0), the highly efficient oil-degrading bacteria obtained from domestication (GZ), and the soil samples after bioremediation (BT) in the obtained samples showed that, at the phylum level, the total proportion of Proteobacteria and Actinobacteria increased by 17.1%. At the genus level, the abundance of Nocardioides, Achromobacter, Gordonia, and Rhodococcus increased significantly. The species and function contribution analysis of COG and KEGG proved that the above bacterial genera had important contributions to the degradation of petroleum hydrocarbons. A high abundance of petroleum hydrocarbon-related metabolic enzymes and five petroleum hydrocarbon-related degradation genes was found in the soil after remediation:alkM, tamA, rubB, ladA, and alkB. The analysis showed that the introduction of the exogenous petroleum hydrocarbon-degrading bacteria group enhanced the metabolic activity of microorganism-related enzymes and the expression of corresponding functional genes.

A surgical nursing perspective analysis of glucose variability in BCLC stage B-C hepatocellular carcinoma patients with and without T2D within 1 year of hepatectomy: a retrospective cohort study from 2016 to 2020.

Background: Previous research has reported that variability in glucose levels is associated with a variety of patient characteristics in colon cancer. However, relevant research is still lacking in relation to hepatocellular carcinoma (HCC). Methods: A total of 95 HCC patients with Barcelona Clinic Liver Cancer (BCLC) stage B-C who underwent liver resection at the Eastern Hepatobiliary Surgery Hospital and Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine were included in this study. The patients were divided into 2 groups with type 2 diabetes (T2D) and without T2D. The primary outcome variable was blood glucose variability at 1 month and within 1 year of HCC surgery. Results: In this study, the age of patients with T2D was greater than that of patients without T2D (mean age: 70.3±8.45 vs. 60.4±11.27 years, P=0.031). Compared to the patients without T2D, those with T2D had higher blood glucose measurements within 1 month (33 vs. 7) and 1 year (46.5 vs. 22.5, P<0.001) of surgery. The T2D patients and non-T2D patients did not differ in terms of chemotherapy medication or other characteristics. Among the 95 patients with BCLC stage B-C HCC, those with T2D had higher variability in glucose levels (P<0.001) than those without T2D within 1 month of surgery [standard deviation (SD) =46.43 mg/dL, coefficient of variation (CV) =23.5% vs. SD =21.56 mg/dL, CV =13.21%], and within 1 year of surgery (SD =42.49 mg/dL, CV =26.14% vs. SD =20.45 mg/dL, CV =17.36%). A correlation was found between a lower body mass index and higher variability in glucose levels within 1 month of surgery among patients with T2D [SD (r=-0.431, P<0.05) and CV (r=-0.464, P<0.01)]. A higher preoperative blood glucose level in T2D patients was correlated with a higher blood glucose variability within 1 year of surgery (r=0.435, P<0.01). Variability in glucose levels was weakly correlated with the demographic and clinical characteristics of patients who do not have T2D. Conclusions: HCC patients with T2D in BCLC stage B-C showed greater variability in glucose levels within 1 month and 1 year of surgery. Preoperative hyperglycemia, insulin use, and a lower cumulative dose of steroids were clinical features correlated with a higher variability in glucose levels in T2D patients.

Prevalence and risk factors for dementia in the Tibetan region: A population-based cross-sectional study.

BACKGROUND: As China's population ages, the nationwide prevalence of dementia is increasing. However, the epidemiology of dementia among the Tibetan population remains unclear. OBJECTIVE: A cross-sectional study was conducted involving 9116 participants aged >50 years in the Tibetan population to investigate the risk factors and prevalence of dementia among this population. Permanent residents of the region were invited to participate, and the response rate was 90.7 %. METHODS: The participants underwent neuropsychological testing and clinical assessments, from which physical measurements (e.g., body mass index, blood pressure), demographic information (e.g., gender, age), and lifestyle details (e.g., family living arrangement, smoking, alcohol arrangement) were recorded. Dementia diagnoses were made using the standard consensus diagnostic criteria. The risk factors of dementia were identified using stepwise multiple logistic regression. RESULTS: The average age of the participants was 63.71 (standard deviation = 9.36), and there were 44.86 % males. The prevalence of dementia was 4.66 %. The multivariate logistic regression analysis revealed that older age, unmarried status, lower education level, obesity, hypertension, diabetes, coronary heart disease, cerebral vascular disease, and HAPC were independently and positively associated with dementia (P < 0.05). However, no association was found between the frequency of religious activities and the prevalence of dementia in this population (P > 0.05). CONCLUSIONS: There exist a number of contributory risk factors for dementia in the Tibetan population, with variations associated with high altitude, religious activities (i.e., scripture turning, chanting, spinning Buddhist beads, and bowing), and dietary habits. These findings suggest that social activities, such as religious activities, are protective factors for dementia.

Combination of cataract surgery with intravitreal injection of dexamethasone intravitreal implant (Ozurdex) for uveitis-induced cataract.

AIM: To evaluate the long-term results of patients with chronic uveitis-induced cataract by phacoemulsification with IOL implantation and intravitreal injection of dexamethasone (DEX) intravitreal implant (Ozurdex). METHODS: The study included 32 eyes of 26 patients treated with DEX implant due to chronic uveitis-induced cataract and followed up for at least a year. Best-corrected visual acuity (BCVA), intraocular pressure (IOP), anterior chamber reaction, central macular thickness (CMT), intraoperative and postoperative complications and uveitis recurrence were analyzed retrospectively. RESULTS: A successful surgery was performed in all patients. The average follow-up period was 12mo. The female/male ratio was 13/13. Mean age was 45.65±3.83y (range 26 to 65y). Etiologically, rheumatic arthritis occurred in 6 patients (18.75%), ankylosing spondylitis in 4 (12.50%), HLA-B27 associated uveitis in 3 (9.38%), Vogt-Koyanagi-Harada-associated uveitis in 4 (12.50%) , Behcet's disease in 2 (6.25%), and 7 (21.88%) suffered from unknown diseases. All 32 eyes had varying degrees of improvement at 12mo after surgery, with 2 eyes showing BCVA of 0.1 or below (6.25%), 6 having 0.1-0.5 (18.75%), 18 of 0.5-1.0 (56.25%), and 6 of 1.0 or above (18.75%). No cases with increased IOP were observed. The values of mean CMT was increased at day 1, decreased at 1, 3mo after surgery and increased at 6, 12mo after surgery. No severe uveitis reactions, such as fibrinous exudates in the anterior chamber and exudative membrane formation on the anterior surface of the IOL, were observed after surgery. CONCLUSION: The present studies show that intravitreal injection of Ozudex during cataract operation can provide a new option for the clinical treatment of uveitis-induced cataract.

Digital image analysis of erythroblastic islands in myelodysplastic syndromes.

INTRODUCTION: Myelodysplastic syndromes (MDS) encompass a diverse group of myeloid neoplasms for which the diagnosis of low-grade subtypes remains challenging. Erythroblastic islands (EBIs) are highly organized units of erythroid proliferation, differentiation, and enucleation. EBI disruption is frequently observed and is believed to be one of the early changes in MDS. METHODS: In this study, we digitally analyzed bone marrow biopsies dual stained with alpha-hemoglobin stabilizing protein (AHSP) and CD163 to quantitatively study features of EBIs in MDS, among MDS subtypes, as well as those in normal marrows and marrows with other causes of anemia. RESULTS: EBIs in MDS specimens were smaller in size and higher in density compared to both normal and non-MDS anemia specimens. Increased CD163 expression within the EBIs is observed in both MDS and other causes of anemia. A combination of increased EBI density and CD163 expression is seen in association with MDS with high-risk cytogenetics and multiple adverse mutations. CONCLUSION: As a proof-of-concept study, we show that EBI features can be relatively easily quantified with AHSP/CD163 dual immunohistochemistry and open-source imaging analysis software, highlighting those that are unique to MDS, and which may be prognostically relevant. Further studies of the measurable EBI features may provide valuable and novel tools to aid MDS diagnosis and prognostication in the era of digital pathology.

Up-regulation of PUM1 by miR-218-5p promotes colorectal tumor-initiating cell properties and tumorigenesis by regulating the PI3K/AKT axis.

Background: Colorectal cancer (CRC) is the third most common cancer and the fourth most common cause of cancer-related death worldwide. Advanced stage CRC, during the recent past, had a dismal prognosis and only a few available treatments. Pumilio homologous protein 1 (PUM1) is reportedly aberrant in human malignancies, including CRC. However, the role of PUM1 in the regulation of tumor-initiating cells (T-ICs) remains unknown. Methods: The levels of messenger RNAs (mRNAs) were determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunoblot analyses. Statistical analyses were performed to determine the associations between the levels of PUM1 and tumor features and patient outcomes. Whether PUM1 is a downstream target of miR-218-5p was verified by bioinformatics target gene prediction and qRT-PCR. Results: Herein, it was found that T-ICs, chemoresistance, and recurrent CRC samples all manifest increased PUM1 expression. Functional investigations have shown that PUM1 increased the self-renewal, tumorigenicity, malignant proliferation, and chemoresistance of colorectal cells. PUM1 activates the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) signaling pathway biochemically. Furthermore, it was discovered that miR-218-5p specifically targets T-ICs' PUM1 3'-untranslated region (3'-UTR). More importantly, the PUM1/PI3K/AKT axis regulates CRC cells' responses to treatment with cetuximab, and PUM1 overexpression increased cetuximab resistance. More evidence points to the possibility that low PUM1 may predict cetuximab benefits in CRC patients after analysis of the patient cohort, patient-derived tumor organoids, and patient-derived xenografts (PDXs). Conclusions: Taken together, the result of this work points to the critical function of the miR-218-5p/PUM1/PI3K/AKT regulatory circuit in regulating T-ICs characteristics and thus suggests possible therapeutic targets for CRC.

Infection and co-infection patterns of community-acquired pneumonia in patients of different ages in China from 2009 to 2020: a national surveillance study.

BACKGROUND: Severe community-acquired pneumonia (SCAP) is associated with a substantial number of hospitalisations and deaths worldwide. Infection or co-infection patterns, along with their age dependence and clinical effects are poorly understood. We aimed to explore the causal and epidemiological characteristics by age, to better describe patterns of community-acquired pneumonia (CAP) and their association with severe disease. METHODS: National surveillance of CAP was conducted through a network of hospitals in 30 provinces in China from 2009-20 inclusive. Patients with CAP were included if they had evidence of acute respiratory tract, had evidence of pneumonia by chest radiography, diagnosis of pneumonia within 24 h of hospital admission, and resided in the study catchment area. For the enrolled patients with CAP, nasopharyngeal and oral swabs were taken and tested for eight viral pathogens; and blood, urine, or expectorated sputum was tested for six bacterial pathogens. Clinical outcomes, including SCAP, were investigated with respect to age and patterns of infections or co-infections by performing binary logistic regression and multivariate analysis. FINDINGS: Between January, 2009, and December, 2020, 18 807 patients with CAP (3771 [20·05%] with SCAP) were enrolled. For both children (aged ≤5 years) and older adults (aged >60 years), a higher overall rate of viral and bacterial infections, as well as viral-bacterial co-infections were seen in patients with SCAP than in patients with non-SCAP. For adults (aged 18-60 years), however, only a higher rate of bacterial-bacterial co-infection was observed. The most frequent pathogens associated with SCAP were respiratory syncytial virus (RSV; 21·30%) and Streptococcus pneumoniae (12·61%) among children, and influenza virus (10·94%) and Pseudomonas aeruginosa (15·37%) among older adults. Positive rates of detection of most of the tested pathogens decreased during 2020 compared with the 2009-19 period, except for RSV, P aeruginosa, and Klebsiella pneumoniae. Multivariate analyses showed SCAP was significantly associated with infection with human adenovirus, human rhinovirus, K pneumoniae, or co-infection of RSV and Haemophilus influenzae or RSV and Staphylococcus aureus in children and adolescents (aged <18 years), and significantly associated with infection with P aeruginosa, K pneumoniae, or S pneumoniae, or co-infection with P aeruginosa and K pneumoniae in adults (aged ≥18 years). INTERPRETATION: Both prevalence and infection pattern of respiratory pathogens differed between patients with SCAP and patients with non-SCAP in an age-dependent manner. These findings suggest potential advantages to age-related strategies for vaccine schedules, as well as clinical diagnosis, treatment, and therapy. FUNDING: China Mega-Project on Infectious Disease Prevention and The National Natural Science Funds of China. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.