X-Paste improves wound healing in diabetes via NF-E2-related factor/HO-1 signaling pathway.

BACKGROUND: Diabetic foot ulcers (DFU), as severe complications of diabetes mellitus (DM), significantly compromise patient health and carry risks of amputation and mortality. AIM: To offer new insights into the occurrence and development of DFU, focusing on the therapeutic mechanisms of X-Paste (XP) of wound healing in diabetic mice. METHODS: Employing traditional Chinese medicine ointment preparation methods, XP combines various medicinal ingredients. High-performance liquid chromatography (HPLC) identified XP's main components. Using streptozotocin (STZ)-induced diabetic, we aimed to investigate whether XP participated in the process of diabetic wound healing. RNA-sequencing analyzed gene expression differences between XP-treated and control groups. Molecular docking clarified XP's treatment mechanisms for diabetic wound healing. Human umbilical vein endothelial cells (HUVECs) were used to investigate the effects of Andrographolide (Andro) on cell viability, reactive oxygen species generation, apoptosis, proliferation, and metastasis in vitro following exposure to high glucose (HG), while NF-E2-related factor-2 (Nrf2) knockdown elucidated Andro's molecular mechanisms. RESULTS: XP notably enhanced wound healing in mice, expediting the healing process. RNA-sequencing revealed Nrf2 upregulation in DM tissues following XP treatment. HPLC identified 21 primary XP components, with Andro exhibiting strong Nrf2 binding. Andro mitigated HG-induced HUVECs proliferation, metastasis, angiogenic injury, and inflammation inhibition. Andro alleviates HG-induced HUVECs damage through Nrf2/HO-1 pathway activation, with Nrf2 knockdown reducing Andro's proliferative and endothelial protective effects. CONCLUSION: XP significantly promotes wound healing in STZ-induced diabetic models. As XP's key component, Andro activates the Nrf2/HO-1 signaling pathway, enhancing cell proliferation, tubule formation, and inflammation reduction.

Haplotype-resolved assembly of auto-polyploid genomes via combining Hi-C and gametic data.

Haplotype-resolved genome assembly plays a crucial role in understanding allele-specific functions. However, obtaining haplotype-resolved assembly for auto-polyploid genomes remains challenging. Existing methods can be classified into reference-based phasing, assembly-based phasing, and gamete binning. Nevertheless, there is a lack of cost-effective and efficient methods for haplotyping auto-polyploid genomes. In this study, we propose a novel phasing algorithm called PolyGH, which combines Hi-C and gametic data. We conducted experiments on tetraploid potato cultivars and divided the method into three steps. Firstly, gametic data was utilized to bin non-collapsed contigs, followed by merging adjacent fragments of the same type within the same contig. Secondly, accurate Hi-C signals related to differential genomic regions were acquired using unique k-mers. Finally, collapsed fragments were assigned to haplotigs based on combined Hi-C and gametic signals. Comparing PolyGH with Hi-C-based and gametic data-based methods, we found that PolyGH exhibited superior performance in haplotyping auto-polyploid genomes when integrating both data types. This approach has the potential to enhance haplotype-resolved assembly for auto-polyploid genomes.

Experience in the treatment of long-gap esophageal atresia by intraluminal esophageal stretching elongation.

Objective: To summarize the experience with intraluminal esophageal stretching elongation (ILESE) in the successful treatment of long-gap esophageal atresia (LGEA) at a single center. Methods: Clinical data of 68 neonates who underwent LGEA between February 2015 and January 2022 were retrospectively analyzed. Four patients died of multiple associated severe malformations and did not undergo ILESE. Esophageal anastomosis was successfully performed in 60 cases (93.75%) and failed in 4 cases (6.25%) treated with ILESE. The ILESE techniques, esophageal reconstruction, results, postoperative complications, and follow-up treatment were analyzed. Results: The beginning time of performing ILESE preoperation was 53.4 ± 39.4 days after birth, and the age of esophageal reconstruction was 122.2 ± 70.3 days after birth in 60 cases. The gap length of proximal and distal esophageal segments which were evaluated the first time at admission was 4.8 ± 1.3 vertebral bodies, whereas the gap before anastomosis was -0.46 ± 0.90 vertebral bodies. Among the patients with esophageal primary-anastomosis, 55 received thoracoscopic surgery, and 5 underwent thoracotomy in the early stage. Of the 60 children with ILESE, 58 underwent end-to-end esophagostomy, of which 17 cases were combined with circular esophagotomy (livaditis), and 2 cases of esophageal lengthening were combined with the reversal of the ligulate loop of the proximal esophagus (flap). Overall, 59 cases were cured (98.3%), and 1 patient died of respiratory failure postoperatively. All patients were followed up for 7-96 months. Postoperative anastomotic leakage occurred in 16 patients (27.6%), all of whom were successfully treated conservatively. Anastomotic stenosis occurred in 49 cases (83.1%), all of which were successfully managed by non-surgical treatment, including 12.7 ± 9.3 times of esophageal balloon dilatation and 2 cases of stent dilatation. Gastroesophageal reflux occurred in 44 patients (74.6%), including associated or acquired esophageal hiatal hernia in 22 patients, and Nissen fundoplication was performed in 17 patients. Conclusions: ILESE is an effective method for prolonging the proximal and distal esophagus of the LGEA to reconstruct esophageal continuity using its esophageal tissue, with an efficacy rate of 93.75%. Postoperative anastomotic stricture and gastroesophageal reflux are common and require long-term, standardized follow-up and treatment.

Alternative splice variants of the mitochondrial fission protein DNM1L/Drp1 regulate mitochondrial dynamics and tumor progression in ovarian cancer.

Aberrant mitochondrial fission/fusion dynamics have been reported in cancer cells. While post translational modifications are known regulators of the mitochondrial fission/fusion machinery, we show that alternative splice variants of the fission protein Drp1 (DNM1L) have specific and unique roles in cancer, adding to the complexity of mitochondrial fission/fusion regulation in tumor cells. Ovarian cancer specimens express an alternative splice transcript variant of Drp1 lacking exon 16 of the variable domain, and high expression of this splice variant relative to other transcripts is associated with poor patient outcome. Unlike the full-length variant, expression of Drp1 lacking exon 16 leads to decreased association of Drp1 to mitochondrial fission sites, more fused mitochondrial networks, enhanced respiration, and TCA cycle metabolites, and is associated with a more metastatic phenotype in vitro and in vivo. These pro-tumorigenic effects can also be inhibited by specific siRNA-mediated inhibition of the endogenously expressed transcript lacking exon 16. Moreover, lack of exon 16 abrogates mitochondrial fission in response to pro-apoptotic stimuli and leads to decreased sensitivity to chemotherapeutics. These data emphasize the significance of the pathophysiological consequences of Drp1 alternative splicing and divergent functions of Drp1 splice variants, and strongly warrant consideration of Drp1 splicing in future studies.

Comparison of Hi-C-Based Scaffolding Tools on Plant Genomes.

De novo genome assembly holds paramount significance in the field of genomics. Scaffolding, as a pivotal component within the genome assembly process, is instrumental in determining the orientation and arrangement of contigs, ultimately facilitating the generation of a chromosome-level assembly. Scaffolding is contingent on supplementary linkage information, including paired-end reads, bionano, physical mapping, genetic mapping, and Hi-C (an abbreviation for High-throughput Chromosome Conformation Capture). In recent years, Hi-C has emerged as the predominant source of linkage information in scaffolding, attributed to its capacity to offer long-range signals, leading to the development of numerous Hi-C-based scaffolding tools. However, to the best of our knowledge, there has been a paucity of comprehensive studies assessing and comparing the efficacy of these tools. In order to address this gap, we meticulously selected six tools, namely LACHESIS, pin_hic, YaHS, SALSA2, 3d-DNA, and ALLHiC, and conducted a comparative analysis of their performance across haploid, diploid, and polyploid genomes. This endeavor has yielded valuable insights in advancing the field of genome scaffolding research.

Nasal Tip Cutaneous Metastasis of Hepatocellular Carcinoma: A Case Report.

Background: Cutaneous metastasis is rare in clinical practice, especially that from primary hepatocellular carcinoma (HCC), which is even rarer. Case Presentation: This report describes a male patient with HCC with cutaneous metastases to the nasal tip. The patient developed a raised nodule at the nasal tip 5 years after surgery for HCC, with surface ulceration and crusting and no obvious symptoms. Abdominal computed tomography (CT) showed an obvious mass in the liver. The skin lesions on the nasal tip were confirmed to be cutaneous metastasis of HCC by histopathological and immunohistochemical examinations. Conclusion: The incidence of cutaneous metastasis of HCC is extremely low, and nasal tip cutaneous metastasis of HCC has no specific clinical manifestations; therefore, it needs to be distinguished from rosacea rhinophyma, fungal and atypical mycobacterial infections, tumours of vascular origin, and tumours of skin appendages that occur in the nasal tip and is prone to misdiagnosis and missed diagnosis, thus requiring clinical dermatologists and otolaryngologists to be aware of such metastasis.

A multicenter prospective study on the management of hepatoblastoma in children: a report from the Chinese Children's Cancer Group.

BACKGROUND: This study aimed to identify survival risk factors in Chinese children with hepatoblastoma (HB) and assess the effectiveness of the new treatment protocol proposed by the Chinese Children's Cancer Group (CCCG) in 2016. METHODS: A multicenter, prospective study that included 399 patients with HB from January 2015 to June 2020 was conducted. Patient demographics, treatment protocols, and other related information were collected. Cox regression models and Kaplan-Meier curve methods were used. RESULTS: The 4-year event-free survival (EFS) and overall survival (OS) were 76.9 and 93.5%, respectively. The 4-year EFS rates for the very-low-risk, low-risk, intermediate-risk, and high-risk groups were 100%, 91.6%, 81.7%, and 51.0%, respectively. The 4-year OS was 100%, 97.3%, 94.4%, and 86.8%, respectively. Cox regression analysis found that age, tumor rupture (R +), and extrahepatic tumor extension (E +) were independent prognostic factors. A total of 299 patients had complete remission, and 19 relapsed. Patients with declining alpha-fetoprotein (AFP) > 75% after the first two cycles of neoadjuvant chemotherapy had a better EFS and OS than those ≤ 75%. CONCLUSIONS: The survival outcome of HB children has dramatically improved since the implementation of CCCG-HB-2016 therapy. Age ≥ 8 years, R + , and E + were independent risk factors for prognosis. Patients with a declining AFP > 75% after the first two cycles of neoadjuvant chemotherapy had better EFS and OS.

Histopathology of Ganglion Cells in the Proximal Resected Bowel Correlates With the Clinical Outcome in Hirschsprung Disease: A Pilot Study.

INTRODUCTION: Intraoperative leveling biopsy by identifying ganglion cells is crucial to determine surgical margin during surgery for Hirschsprung disease (HSCR). The anastomosis should be performed at least 5 cm proximal to the ganglionic segment to prevent transition zone pull-through. However, the length of the transition zone could be much longer than expected and the histological evaluation of the entire circumference of the proximal margin is recommended, which is time-consuming and not applicable for leveling biopsy. We found that the histopathologic features of ganglion cells varied in the examined bowel specimens and demonstrated a pattern similar to immature and degenerated neuron cells. We assumed that the histopathologic features of ganglion cells in the proximal resected bowel were associated with the clinical outcome and might guide the leveling biopsy. In this study, we described a histopathologic grade of ganglion cells based on the degree of maturity and degeneration. We assessed the correlation between the histopathological grade of ganglion cells in the proximal surgical margin and clinical outcome. METHODS: Three hundred fifty seven patients with HSCR treated between 2013 and 2020 were included. The ganglion cells were divided into six grades based on the histopathologic features in frozen sections. Medical records and detailed histopathologic results of intraoperative frozen sections were reviewed. Follow-up data were collected to evaluate clinical outcomes. The pediatric incontinence and constipation scoring system was used to predict bowel function. RESULTS: The histopathologic results of proximal resected bowel from 357 HSCR patients were presented as follows: Grade I in 52 patients (14.6%), Grade II in 186 patients (52.1%), Grade III in 107 patients (30.0%), and Grade IV in 12 patients (3.4%). The median follow-up time was 46.8 mo (13.0-97.6 mo). The histopathologic grade of ganglion cells from the proximal resected margin was significantly related to postoperative constipation problems and the incidence of Hirschsprung-associated enterocolitis. The results from the pediatric incontinence and constipation scoring system indicated a positive correlation between better postoperative bowel function and lower histopathologic grade of ganglion cells. CONCLUSIONS: This pilot study showed an association between the histopathologic features of ganglion cells in the proximal surgical margin and the clinical outcome. It may provide additional information for intraoperative pathologic consultation in leveling biopsy to prevent insufficient resection of the affected colon. A prospective study is warranted to validate these findings before clinical application.

TREM2 as a Potential Immune-Related Biomarker of Prognosis in Patients with Skin Cutaneous Melanoma Microenvironment.

Background: The skin cutaneous melanoma (SKCM) is a devastating form of skin cancer triggered by genetic and environmental factors, and the incidence of SKCM has rapidly increased in recent years. Immune infiltration of the tumor microenvironment is positively associated with overall survival in many tumors. Triggering receptor expressed on myeloid cells 2 (TREM2) is a transmembrane receptor of the immunoglobulin superfamily and a crucial signaling hub for multiple pathological pathways that mediate immunity. Although numerous evidences suggest a crucial role for TREM2 in tumorigenesis of some tumors, no systematic SKCM analysis of TREM2 is available. Mehods. The relationship between TREM2 expression and diagnostic and prognostic value of SKCM patients via using The Cancer Genome Atlas (TCGA) data. The expression level of TREM2 and clinical characteristic correlation in SKCM patients were assessed by the Wilcoxon rank sum test. The cox regression methods, Kaplan-Meier (KM), and log-rank test were used to assess the impact of TREM2 expression on the overall survival (OS). Furthermore, the Gene Set Enrichment Analysis (GSEA) and TIMER were performed to evaluate the enrichment pathways and potential functions and quantify the immune cell infiltration level for TREM2 expression. Results: The TREM2 in SKCM sample expression levels was significantly higher than in normal tissues. Moreover, this expression level of TREM2 was also associated with the BMI of SKCM patients. KM overall survival analysis and OS curve displayed that a high-level TREM2 expression was significantly correlated with a better SKCM prognosis of patients as compared with a low level of TREM2 expression. The GSEA analysis also revealed that TREM2 was associated with immune functions, such as neutrophil activation. Conclusion: TREM2 played a crucial role in SKCM, which might be a prognostic biomarker and correlated with immune infifiltrates in SKCM patients.

Single-cell RNA sequencing combined with whole exome sequencing reveals the landscape of the immune pathogenic response to chronic mucocutaneous candidiasis with STAT1 GOF mutation.

Chronic mucocutaneous candidiasis (CMC) is characterized by recurrent or persistent infections with Candida of the skin, nails, and mucous membranes (e.g., mouth, esophagus, and vagina). Compared with that of other infectious diseases, the immune pathogenic mechanism of CMC is still poorly understood. We identified a signal transducer and activator of transcription 1 gain-of-function (c.Y289C) mutation in a CMC patient. Single-cell transcriptional profiling on peripheral blood mononuclear cells from this patient revealed decreases in immature B cells and monocytes. Further analysis revealed several differentially expressed genes related to immune regulation, including RGS1, TNFAIP3, S100A8/A9, and CTSS. In our review of the literature on signal transducer and activator of transcription 1 gain-of-function (c.Y289C) mutations, we identified seven cases in total. The median age of onset for CMC (n=4, data lacking for three cases) was 10.5 years (range: birth to 11 years), with an average onset age of 8 years. There were no reports linking tumors to the c.Y289C mutation, and the incidence of pre-existing clinical disease in patients with the c.Y289C mutation was similar to previous data.

Clinical guideline for the diagnosis and treatment of cutaneous warts (2022).

AIM: Cutaneous warts caused by human papillomavirus are benign proliferative lesions that occur at any ages in human lives. Updated, comprehensive and systematic evidence-based guidelines to guide clinical practice are urgently needed. METHODS: We collaborated with multidisciplinary experts to formulate this guideline based on evidences of already published literature, focusing on 13 clinical questions elected by a panel of experts. We adopted Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to form classification of recommendations as well as the improved Delphi method to retain respective recommendations with a consensus degree of over 80%. RESULTS: Our guideline covered aspects of the diagnosis and treatment of cutaneous warts such as diagnostic gold standard, transmission routes, laboratory tests, treatment principle, clinical cure criterion, definitions, and treatments of common warts, flat warts, plantar warts, condyloma acuminatum, and epidermodysplasia verruciformis. Recommendations about special population such as children and pregnant women are also listed. In total, 49 recommendations have been obtained. CONCLUSIONS: It is a comprehensive and systematic evidence-based guideline and we hope this guideline could systematically and effectively guide the clinical practice of cutaneous warts and improve the overall levels of medical services.

Comparative analysis of galactomannan lateral flow assay, galactomannan enzyme immunoassay and BAL culture for diagnosis of COVID-19-associated pulmonary aspergillosis.

BACKGROUND: Galactomannan Enzyme Immunoassay (GM-EIA) is proved to be a cornerstone in the diagnosis of COVID-19-associated pulmonary aspergillosis (CAPA), its use is limited in middle and low-income countries, where the application of simple and rapid test, including Galactomannan Lateral Flow Assay (GM-LFA), is highly appreciated. Despite such merits, limited studies directly compared GM-LFA with GM-EIA. Herein we compared the diagnostic features of GM-LFA, GM-EIA and bronchoalveolar lavage (BAL) culture for CAPA diagnosis in Iran, a developing country. MATERIALS/METHODS: Diagnostic performances of GM-LFA and GM-EIA in BAL (GM indexes ≥1) and serum (GM indexes >0.5), i.e. sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) and areas under the curve (AUC), were evaluated using BAL (n = 105) and serum (n = 101) samples from mechanically ventilated COVID-19 patients in intensive care units. Patients were classified based on the presence of host factors, radiological findings and mycological evidences according to 2020 ECMM/ISHAM consensus criteria for CAPA diagnosis. RESULTS: The Aspergillus GM-LFA for serum and BAL samples showed a sensitivity of 56.3% and 60.6%, specificity of 94.2% and 88.9%, PPV of 81.8% and 71.4%, NPV of 82.3% and 83.1%, when compared with BAL culture, respectively. GM-EIA showed sensitivities of 46.9% and 54.5%, specificities of 100% and 91.7%, PPVs of 100% and 75%, NPVs of 80.2% and 81.5% for serum and BAL samples, respectively. CONCLUSION: Our study found GM-LFA as a reliable simple and rapid diagnostic tool, which could circumvent the shortcomings of culture and GM-EIA and be pivotal in timely initiation of antifungal treatment.

Efficacy of Combined Phacoemulsification and Goniosynechialysis in Primary Angle Closure Disease With Different Degrees of Peripheral Anterior Synechiae.

PRCIS: Phacoemulsification and goniosynechialysis (Phaco-GSL) was equally effective in the treatment of primary angle-closure disease (PACD) with preoperative peripheral anterior synechiae (PAS) <180 degrees and larger than 180 degrees. Patients with a larger preoperative PAS range required more range of mechanical separation intraoperatively and displayed more recurrence of PAS (re-PAS) range postoperatively. PURPOSE: To evaluate the long-term efficacy of combined phaco-GSL in PACD with different extent of PAS. PATIENTS AND METHODS: A retrospective study was conducted on 67 patients (79 eyes) who received phaco-GSL. The patients were divided into 2 groups according to the extent of PAS (group A: PAS ≤180 degrees; group B: PAS >180 degrees). Changes in intraocular pressure (IOP), the number of anti-glaucoma drugs, intraoperative mechanical separation of PAS and range of re-PAS during the last follow-up ≥12 months were analyzed. RESULTS: At baseline, eyes in group B presented with higher IOP and more anti-glaucoma drugs usage ( P =0.008 and 0.004). The PAS range, IOP, number of anti-glaucoma medication were reduced both in 2 groups at the final visit. The range of mechanical separation intraoperatively and re-PAS postoperatively were both larger in group B ( P =0.002 and <0.001). The postoperative re-PAS range was positively correlated with the range of mechanical separation ( R2 =0.17). The complete success rates at 12, 24, 36, and 48 months were 86.8%, 71.1%, 71.1%, and 71.1% in group A; and 80.5%, 74.6%, 69.9%, and 69.9% in group B. The qualified success rates were 100%, 96.6%, 92.0%, and 92.0% in group A; and 100%, 89.5%, 85.1%, and 85.1% in group B. CONCLUSION: Phaco-GSL for the treatment of PACD showed equally effective IOP control regardless of the extent of preoperative PAS.

Functionalization of Nanomaterials for Skin Cancer Theranostics.

Skin cancer has drawn attention for the increasing incident rates and high morbidity worldwide. Timely diagnosis and efficient treatment are of paramount importance for prompt and effective therapy. Thus, the development of novel skin cancer diagnosis and treatment strategies is of great significance for both fundamental research and clinical practice. Recently, the emerging field of nanotechnology has profoundly impact on early diagnosis and better treatment planning of skin cancer. In this review, we will discuss the current encouraging advances in functional nanomaterials for skin cancer theranostics. Challenges in the field and safety concerns of nanomaterials will also be discussed.

HuR-dependent SOD2 protein synthesis is an early adaptation to anchorage-independence.

During metastasis cancer cells must adapt to survive loss of anchorage and evade anoikis. An important pro-survival adaptation is the ability of metastatic tumor cells to increase their antioxidant capacity and restore cellular redox balance. Although much is known about the transcriptional regulation of antioxidant enzymes in response to stress, how cells acutely adapt to alter antioxidant enzyme levels is less well understood. Using ovarian cancer cells as a model, we demonstrate that an increase in mitochondrial superoxide dismutase SOD2 protein expression is a very early event initiated in response to detachment, an important step during metastasis that has been associated with increased oxidative stress. SOD2 protein synthesis is rapidly induced within 0.5-2 h of matrix detachment, and polyribosome profiling demonstrates an increase in the number of ribosomes bound to SOD2 mRNA, indicating an increase in SOD2 mRNA translation in response to anchorage-independence. Mechanistically, we find that anchorage-independence induces cytosolic accumulation of the RNA binding protein HuR/ELAVL1 and promotes HuR binding to SOD2 mRNA. Using HuR siRNA-mediated knockdown, we show that the presence of HuR is necessary for the increase in SOD2 mRNA association with the heavy polyribosome fraction and consequent nascent SOD2 protein synthesis in anchorage-independence. Cellular detachment also activates the stress-response mitogen-activated kinase p38, which is necessary for HuR-SOD2 mRNA interactions and induction of SOD2 protein output. These findings illustrate a novel translational regulatory mechanism of SOD2 by which ovarian cancer cells rapidly increase their mitochondrial antioxidant capacity as an acute stress response to anchorage-independence.

Multi-kingdom microbiota analyses identify bacterial-fungal interactions and biomarkers of colorectal cancer across cohorts.

Despite recent progress in our understanding of the association between the gut microbiome and colorectal cancer (CRC), multi-kingdom gut microbiome dysbiosis in CRC across cohorts is unexplored. We investigated four-kingdom microbiota alterations using CRC metagenomic datasets of 1,368 samples from 8 distinct geographical cohorts. Integrated analysis identified 20 archaeal, 27 bacterial, 20 fungal and 21 viral species for each single-kingdom diagnostic model. However, our data revealed superior diagnostic accuracy for models constructed with multi-kingdom markers, in particular the addition of fungal species. Specifically, 16 multi-kingdom markers including 11 bacterial, 4 fungal and 1 archaeal feature, achieved good performance in diagnosing patients with CRC (area under the receiver operating characteristic curve (AUROC) = 0.83) and maintained accuracy across 3 independent cohorts. Coabundance analysis of the ecological network revealed associations between bacterial and fungal species, such as Talaromyces islandicus and Clostridium saccharobutylicum. Using metagenome shotgun sequencing data, the predictive power of the microbial functional potential was explored and elevated D-amino acid metabolism and butanoate metabolism were observed in CRC. Interestingly, the diagnostic model based on functional EggNOG genes achieved high accuracy (AUROC = 0.86). Collectively, our findings uncovered CRC-associated microbiota common across cohorts and demonstrate the applicability of multi-kingdom and functional markers as CRC diagnostic tools and, potentially, as therapeutic targets for the treatment of CRC.

Prediction of hospital discharge outcome from changes in cerebrospinal fluid/serum albumin quotient and cerebrospinal fluid lactate dehydrogenase in patients with cryptococcal meningitis.

Aim: This study aims to provide reliable prognostic factors for patients with cryptococcal meningitis (CM). Patients & methods: Clinical characteristics and laboratory findings of CM patients were retrospectively reviewed. Results: Sixty-three patients with CM were enrolled and 38/63 were confirmed to be HIV serology positive. Among clinical characteristics, headache, nausea and/or vomiting, and fever were the most common symptoms. Among cerebrospinal fluid (CSF) parameters, changes in leukocyte count, lactate dehydrogenase and chloride were significantly associated with the outcome. An increased CSF/serum albumin quotient (QAlb) was indicative of an unfavorable outcome in HIV-negative patients. Conclusion: CSF lactate dehydrogenase and QAlb may improve the prediction of outcomes in patients with CM.

Investigation of the Emerging Nosocomial Wickerhamomyces anomalus Infections at a Chinese Tertiary Teaching Hospital and a Systemic Review: Clinical Manifestations, Risk Factors, Treatment, Outcomes, and Anti-fungal Susceptibility.

Wickerhamomyces anomalus is an emerging pathogen, which has been associated with clonal outbreaks and poor clinical outcomes. Despite being an important emerging yeasts species, our understanding concerning the microbiological and clinical characteristics of infections due to this species is limited. Herein, we are reporting a retrospective analysis of fungemia patients with W. anomalus from a 2,100-bed hospital in Shanghai during 2014-2016. Moreover, we conducted an extensive literature review to gain a deeper clinical and microbiological insights. Detailed clinical data were recorded. Antifungal susceptibility testing (AFST) followed CLSI M27-A3, and isolates were identified using MALDI-TOF MS. In total, 13 patients were identified with a mortality rate of 38.5% (5/13). Central venous catheter (CVC), broad-spectrum antibiotic therapy, total parenteral nutrition (TPN), surgery, and mechanical ventilation were the most frequently observed risk factors. Eight patients (61.5%) experienced mixed bacterial/Candida bloodstream infections, and four patients developed mixed candidemia (MC). W. anomalus isolates showed high minimum inhibitory concentrations (MICs) against all azoles tested and flucytosine, while AMB showed the highest in vitro activity. Azoles were used for 84.6% (11/13) of the cases, while 36.4% (4/11) of them died. When combining with the AFST data and the literature review, our study highlights the poor efficacy of azoles and optimal efficacy of AMB and LAMB against infections caused by W. anomalus. In conclusion, our study highlights the emerging threat of W. anomalus affecting both neonates and adults. Furthermore, our results advocate the use of AMB formulations rather than azoles among patients infected with W. anomalus. Future studies are warranted to reach a definitive consensus regarding the utility of echinocandins among such patients.

The Change in the Neutrophil/Lymphocyte Ratio Predicts the Prognosis of Patients with Cryptococcal Meningitis.

PURPOSE: The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been studied in many diseases. However, their roles in cryptococcal meningitis (CM) are unclear. The purpose of this article was to analyse the roles of the PLR and NLR in CM patients during treatment. METHODS: 139 newly diagnosed CM patients were enrolled. We divided patients into two groups: the successful group (n = 121) and the failure group (n = 18) based on the prognosis of patients. Then, we analyzed changes in clinical data of two groups, which were measured at the time of admission, after 2 weeks and 4 weeks in the hospital. Then the patients were divided into HIV group (n = 26) and non-HIV group (n = 113) to determine whether HIV status had an impact on the prognosis and clinical data of patients. RESULTS: Most patients were male living in rural areas; headache was the most common symptom before admission. In the subgroup analysis based on HIV status, there were significantly fewer patients with HIV (26 individuals) than without HIV (113 individuals), and 40.7% non-HIV CM patients had no underlying diseases. There was no significant difference in prognosis (p = 0.746), lymphocytes (p = 0.109) or neutrophils (p = 0.269) between patients with and without HIV. A mixed-effect model indicated that there was no difference (p = 0.171) in PLR between successful group and failure group. However, the change of NLR was statistically significant (p = 0.004 < 0.05) between successful group and failure group. CONCLUSION: An increase in the NLR during treatment may be used as an indicator of treatment failure.

Comparative Study of Thoracoscopic and Modified Small Incision Repair for Congenital Diaphragmatic Eventration in Children.

Background: Thoracoscopic diaphragmatic plication has gained popularity in the treatment of congenital diaphragmatic eventration (CDE), but the therapeutic effect and prognosis have rarely been compared with nonendoscopic surgery. Materials and Methods: The medical records of 77 children who had received treatment for CDE in our institution from September 2006 to January 2019 were retrospectively analyzed. According to the repair approach, the children were divided into a thoracoscopic plication group and a modified small incision plication group. The perioperative characteristics and follow-up details after diaphragm plication were compared between the two groups. Results: Among 77 children with CDE, 44 cases were in the thoracoscopic plication group and 33 cases were in the modified small incision plication group. All the cases of CDE were unilateral, with 13 cases on the left side and 64 cases on the right side. There were no differences in the preoperative characteristics between the two groups. The modified small incision plication group had a higher bleeding volume (P = .000) and a greater proportion of patients needing chest drainage (P = .000), whereas the differences in the total and postoperative hospital stays (P = .088, P = .247, respectively) did not significantly differ between the two groups. There were no differences in postoperative improvement in the location of the diaphragm between the two groups or between the right and left lesions (P = .438, P = .677, respectively). The total follow-up time was 2-11 years. No recurrence was reported during this period in either of the groups, but the incidence of postoperative thoracic deformities was higher in the modified small incision plication group (P = .013). Conclusions: Compared with the modified small incision plication, thoracoscopic plication has the advantages of smaller blood loss, a low percentage of intrathoracic drainage tube usage, and no occurrence of thoracic deformities.