Case report: Disseminated mucormycosis misdiagnosed as malignancy developed from allergic bronchopulmonary mycosis caused by Rhizopus microsporus following SARS-CoV-2 infection in a woman.

Mucormycosis has become more prevalent during the COVID-19 pandemic and is associated with a high mortality rate. However, concurrent host allergic reactions, invasive pulmonary mucormycosis, and disseminated mucormycosis are rarely reported. Herein, we describe a case of disseminated mucormycosis initially misdiagnosed as a malignancy that developed from allergic bronchopulmonary mycosis caused by Rhizopus microsporus in a woman with post-SARS-CoV-2 infection. The previously healthy patient presented with a sizeable mass in the right middle lobe and multiple lesions across the lungs, brain, spleen, kidneys, pancreas, and subcutaneous tissue 6 months after SARS-CoV-2 infection, mimicking an extensive metastatic malignancy. Eosinophilia, elevated total plasma immunoglobulin E, and significant eosinophilic lung tissue infiltration were observed. Rhizopus microsporus was isolated from subcutaneous tissue, and hyphae were detected in the lung tissue. Sequential amphotericin B liposomes followed by isavuconazole antifungal therapy combined with systemic corticosteroids improved symptoms, significantly reduced the sizes of pulmonary lesions, and reduced eosinophil count. However, it failed to halt the overall progression of the disease, and the patient died. The absence of asthma-like symptoms and delayed recognition of invasive fungal infection signs contributed to poorer outcomes, highlighting the need for a thorough post-COVID-19 follow-up.

Injectable conductive hydrogel remodeling microenvironment and mimicking neuroelectric signal transmission after spinal cord injury.

Severe spinal cord injury (SCI) leads to dysregulated neuroinflammation and cell apoptosis, resulting in axonal die-back and the loss of neuroelectric signal transmission. While biocompatible hydrogels are commonly used in SCI repair, they lack the capacity to support neuroelectric transmission. To overcome this limitation, we developed an injectable silk fibroin/ionic liquid (SFMA@IL) conductive hydrogel to assist neuroelectric signal transmission after SCI in this study. The hydrogel can form rapidly in situ under ultraviolet (UV) light. The mechanical supporting and neuro-regenerating properties are provided by silk fibroin (SF), while the conductive capability is provided by the designed ionic liquid (IL). SFMA@IL showed attractive features for SCI repair, such as anti-swelling, conductivity, and injectability. In vivo, SFMA@IL hydrogel used in rats with complete transection injuries was found to remodel the microenvironment, reduce inflammation, and facilitate neuro-fiber outgrowth. The hydrogel also led to a notable decrease in cell apoptosis and the achievement of scar-free wound healing, which saved 45.6 ± 10.8 % of spinal cord tissue in SFMA@IL grafting. Electrophysiological studies in rats with complete transection SCI confirmed SFMA@IL's ability to support sensory neuroelectric transmission, providing strong evidence for its signal transmission function. These findings provide new insights for the development of effective SCI treatments.

The molecular feature of abnormal fetal neuromuscular development after maternal use of telbivudine or tenofovir during pregnancy in rodent model.

AIMS: Maternal treatment with nucleoside analogues such as telbivudine (LdT) and tenofovir disoproxil fumarate (TDF) has been applied worldwide. However, administration of LdT or TDF during pregnancy may affect the fetal neuromuscular development. We conducted the current study to investigate the histological pathology and transcriptomic changes pertaining to the neuromuscular system of the newborn exposed to LdT or TDF during pregnancy in rodent model. MAIN METHODS: Pregnant C57/BL6 mice were randomly divided into three arms and administered either with LdT solution (0.1 ml, 78 mg/kg/d), TDF solution (0.1 ml, 39 mg/kg/d) or normal saline solution (0.1 ml). Pups in each arm were weighed and sacrificed after birth. Both sides of quadriceps femoris muscle of the newborn were obtained. The histological observation was conducted under light microscope. The transcriptional profiling was analyzed with RNA sequencing (RNA seq). KEY FINDINGS: Four types of morphological abnormalities of the newborn neuromuscular system, being clusters of rhabdomyoblasts, skeletal muscle fibrosis, rhabdomyolysis and necrosis and immature muscle fiber bundles, were noted in both LdT group and TDF group. Moreover, both groups showed significantly decreased gross cross-sectional area of muscle fiber and significantly increased percentage of muscle lesion area. RNA seq identified a total of 164 differentially expressed genes (DEGs) essential to fetal neuromuscular development. These DEGs were involved in calcium regulation, phospholipid activity, muscle cell development, the functioning of mitochondria/endoplasmic reticulum/lysosome/cytoskeleton, the regulation of arachidonic acid and the development of nervous system. SIGNIFICANCE: Our findings suggest maternal administration of LdT or TDF lead to abnormal neuromuscular development in offspring mice. Further study should be encouraged to investigate the down-stream signaling pathways.

Case Report: Complete pathological remission of human chorionic gonadotrophin-producing gallbladder carcinoma with multiple liver metastases after treatment with chemotherapy plus an immune checkpoint inhibitor.

Background: Gallbladder carcinoma (GBC) producing human chorionic gonadotrophin (HCG) is an extremely rare and highly invasive tumor with a poor prognosis. This unfavorable clinical outcome is partly due to the aggressive nature of the tumor and its insensitivity to chemotherapy. Case presentation: We herein report a case of primary GBC producing HCG with liver metastases in a 58-year-old woman. The patient presented with a markedly elevated ß-HCG level and a mass in the gallbladder with multiple liver metastases. A definitive diagnosis was obtained after a needle biopsy of the liver metastases, showing poorly differentiated carcinoma with large-scale necrosis and strong positivity of immunostaining for HCG in tumor cells. The patient received chemotherapy (gemcitabine plus capecitabine) combined with carrellizumab, an immune checkpoint inhibitor (ICI). Pathological complete response was achieved after eight courses of combined therapy, which was confirmed by pathological analysis of resected specimens. After surgery, two courses of chemotherapy plus ICIs were adopted again. Complete response remained for approximately 1 year up to the present. Tumor tissue was collected to perform immunostaining of PD-L1, whole-exome sequencing, and RNA-seq. Low-TMB (1.51 mut/Mb), MSS, and high PD-L1 expression (TPS ≥ 50%) were observed in the tumor. Besides, the dominant types of infiltrating immune cells were macrophage and CD4+ T cells. Compared to other gallbladder adenocarcinoma without HCG, the proportion of M1 macrophage was at a higher level and the gene sets of MYC targets v1 and PI3K/AKT/mTOR signaling were highly expressed in our case. To the best of our knowledge, this is the first case report of complete remission of HCG-producing gallbladder carcinoma with liver metastases after chemotherapy combined with an immune checkpoint inhibitor. Furthermore, this is also the first report that described the tumor genetic feature and tumor immune microenvironment atlas of HCG-producing GBC. Conclusion: chemotherapy plus an immune checkpoint inhibitor may provide a potentially curative option for gallbladder carcinoma with HCG production.

Retrorectal mucinous adenocarcinoma arising from a tailgut cyst: A case report and review of literature.

BACKGROUND: Tailgut cysts are defined as congenital cysts that develop in the rectosacral space from the residue of the primitive tail. As a congenital disease, caudal cysts are very rare, and their canceration is even rarer, which makes the disease prone to misdiagnosis and delayed treatment. We describe a case of caudal cyst with adenocarcinogenesis and summarize in detail the characteristics of cases with analytical value reported since 1990. CASE SUMMARY: A 35-year-old woman found a mass in her lower abdomen 2 mo ago. She was asymptomatic at that time and was not treated because of the coronavirus disease 2019 pandemic. Two weeks ago, the patient developed abdominal distension and right waist discomfort and came to our hospital. Except for the high level of serum carcinoembryonic antigen, the medical history and laboratory tests were not remarkable. Magnetic resonance imaging showed a well-defined, slightly lobulated cystic-solid mass with a straight diameter of approximately 10 cm × 9 cm in the presacral space, slightly high signal intensity on T2-weighted imaging, and moderate signal intensity on T1-weighted imaging. The mass was completely removed by laparoscopic surgery. Histopathological examination showed that the lesion was an intestinal mucinous adenocarcinoma, and the multidisciplinary team decided to implement postoperative chemotherapy. The patient recovered well, the tumor marker levels returned to normal, and tumor-free survival has been achieved thus far. CONCLUSION: The case and literature summary can help clinicians and researchers develop appropriate examination and therapeutic methods for diagnosis and treatment of this rare disease.

A photo-triggering double cross-linked adhesive, antibacterial, and biocompatible hydrogel for wound healing.

Full-thickness wounds, lacking the epidermis and entire dermis and extending into subcutaneous fat, represent a common treatment challenge. Due to the loss of adnexal structures as a source of keratinocytes, full-thickness wounds healing can only be achieved by re-epithelialization from the wound edge and contraction. Here, we developed a hydrogel composed of chitosan methacrylate (CSMA) and o-nitrosobenzaldehyde-modified gelatin (GelNB) for promoting full-thickness wound healing. The CSMA/GelNB (CM/GN) hydrogels exhibited superior mechanical and adhesive properties than that of pure CSMA hydrogel. In vivo experiments confirmed that CM/GN could promote wound healing by generating more hair follicles and mutual blood vessels, high fibroblasts density, and thicker granulation tissue thickness. In addition, reduced secretions of tumor necrosis factor-α (TNF-α) and enhanced secretions of vascular endothelial growth factor (VEGF) could be observed in regenerated tissues after CM/GN treatment. These results suggested that CM/GN hydrogels could be promising candidates to promote wound healing.

Surgically treated rare intestinal bleeding due to submucosal hematoma in a patient on oral anticoagulant therapy: A case report.

RATIONALE: Bleeding in the gastrointestinal tract is a common complication of oral anticoagulant therapy (AT), and it usually appears as mucosal erosion or ulcer; however, intestinal submucosal hematoma (ISH) is an uncommon cause of hemorrhage. PATIENT CONCERNS: This report presents the case of a 70-year-old woman with acute hematochezia induced by AT. She underwent computed tomography and endoscopy. DIAGNOSES: Colon submucosal hematoma. INTERVENTIONS: Conservative treatment had no effect, and the patient underwent emergency surgery. OUTCOMES: Surgical resection showed hemorrhage and necrosis in the left colon, and the patient recovered 24 hours after surgery and continued AT. LESSONS: The present case indicates that the ISH should be kept in mind as a complication of AT. It can be managed conservatively in some stable patients, but emergency surgery may be needed in some serious situations.

Efficacy and safety of mTOR inhibitor therapy in patients with early-stage autosomal dominant polycystic kidney disease: a meta-analysis of randomized controlled trials.

BACKGROUND: The objective of this study was to conduct a meta-analysis of randomized controlled trials (RCTs) to present a profound review and an objective appraisal of the efficacy and safety of the mammalian target of rapamycin (mTOR) inhibitor therapy in patients with autosomal dominant polycystic kidney disease (ADPKD). METHODS: RCTs involving the mTOR inhibitor therapy in patients with ADPKD are included. The data of studies and major outcomes include changes in patients' glomerular filtration rate (GFR), urinary protein, total kidney volume (TKV), cyst volume, parenchymal volume, and lipid profile and the frequency of adverse events. Review Manager 5.0 for meta-analysis was used in this study. RESULTS: Up to January 31, 2011, 4 RCTs (with a total of 564 patients) were included. The mTOR inhibitor therapy group had smaller TKV than the control group [weighted mean difference (WMD) of TKV after treatment: -318.45, P = 0.04]. The mTOR inhibitor treatment does not necessarily slow down the aggravation of renal function in patients with ADPKD (WMD of GFR after therapy: 5.55, P < 0.01; at 6-month analyses = -0.97, P = 0.56). Side effects could occur during the mTOR inhibitor therapy, but the severities can be controlled by the appropriate use of drug. CONCLUSIONS: Based on the current limited clinical trials, this study suggests that short-duration mTOR inhibitor therapy is relatively safe to slow down the increase in kidney volume in patients with early-stage ADPKD, but it has limited impact on slowing down the decrease in GFR.

Urinary proteome analysis by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry with magnetic beads for identifying the pathologic presentation of clinical early IgA nephropathy.

IgA nephropathy is the most common type of chronic glomerulonephritis which leads eventually to end-stage renal disease (ESRD). The duration of clinical early stage IgA nephropathy to ESRD varies a lot. The pathologic presentation may have detrimental effect on outcome. But the renal biopsy is a high-risk invasive operation not able to be accepted by all patients. In this study, we tried to find biomarkers in urine as a non-invasive approach to diagnose different pathologic presentations of clinical early stage IgA nephropathy. A total of 56 patients with IgA nephropathy were included in this study, with 23 patients having severe pathologic presentation and the other 33 having mild ones. The control group consisted of 14 normal subjects. The urinary proteomic spectra from those three groups were generated by Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) with weak cationic exchange magnetic beads. The total experiment data was handled by the Zhejiang University ProteinChip Data Analysis System. We found that the urine protein/peptide spectra patterns could be established to distinguish severe IgA nephropathy from the mild IgA nephropathy group and the normal group. Several potential biomarkers were found and the diagnostic system could distinguish between severe IgA nephropathy from the mild IgA nephropathy with a sensitivity of 90.48% and specificity of 96.77%. We conclude that, using MALDI-TOF-MS with magnetic beads to detect urine proteomic patterns shows great potential in identifying early IgA nephropathy with different pathologic prognosis.