A fatal case of COVID‐19 breakthrough infection due to the delta variant

COVID‐19 infections that occur at least 2 weeks after complete vaccination are known as breakthrough infections. Herein, we report a clinical case resembling breakthrough infection that was correlated with a higher score of COVID‐19 pneumonia on chest computed tomography (CT) in a patient who resulted positive for the delta variant and who died during the hospitalization.     

Ruled out of preeclampsia‐like syndrome due to COVID‐19: A case study

Coronavirus disease (COVID‐19) is an infectious disease. In this study, we report a 28‐year‐old pregnant woman who had a postpartum seizure with a background of HELLP syndrome and a proven COVID‐19 infection. Her child survived, and at 12‐week postpartum, all maternal COVID‐19–related symptoms vanished, and she was cured.     

Influences of the lncRNA TUG1‐miRNA‐34a‐5p network on fibroblast‐like synoviocytes (FLSs) dysfunction in rheumatoid arthritis through targeting the lactate dehydrogenase A (LDHA)

BackgroundRheumatoid arthritis (RA) is a systemic and chronic inflammatory disease. The cellular glucose metabolism of fibroblast‐like synoviocytes (FLSs) of RA has been revealed to be essential to the pathogenesis and development of RA. To date, the precise roles and molecular mechanisms of long noncoding RNA TUG1 in RA have not been elucidated.MethodsTUG1 and miR‐34a‐5p were detected by qRT‐PCR. Interactions between lncRNA‐miRNA and miRNA‐mRNA were validated by RNA pull‐down assay and luciferase assay. The glucose metabolism was evaluated by glucose uptake and extracellular acidification rate (ECAR). Cell viability was determined by MTT assay and Annexin V assay.ResultsTUG1 expression was significantly upregulated in synovial fibroblast‐like synoviocytes (FLSs) compared with normal FLSs. Functional assays uncovered that silence of TUG1 suppressed FLSs‐RA invasion, migration, glucose metabolism, and increased apoptosis. Bioinformatics analysis indicated that TUG1 interacted with miR‐34a‐5p. RNA pull‐down assay and luciferase assay validated that TUG1 sponged miR‐34a‐5p in FLSs‐RA. Overexpression of miR‐34a‐5p effectively inhibited glucose metabolism of FLSs‐RA. Furthermore, the glucose metabolism of FLSs‐RA was significantly elevated compared with normal FLSs. The glucose metabolism enzyme, LDHA, was directly targeted by miR‐34a‐5p in FLSs. Rescue experiments validated that the miR‐34a‐5p‐inhibited glucose metabolism of FLSs‐RA was through targeting LDHA. Finally, we showed restoration of miR‐34a‐5p in TUG1‐overexpressing FLSs‐RA successfully overcame the TUG1‐promoted glucose metabolism and apoptosis resistance via targeting LDHA.ConclusionThe present study uncovered critical roles and molecular mechanisms underlying the TUG1‐mediated glucose metabolism and apoptosis of FLSs‐RA through modulating the miR‐34a‐5p‐LDHA pathway in fibroblast‐like synoviocytes of rheumatoid arthritis.     

COVID‐19 vaccine‐induced vasculitis in a patient with sarcoidosis: A case report

A 55‐year‐old lady with a nine‐year history of controlled sarcoidosis developed vasculitis after Sinopharm COVID‐19 vaccine (BBIBP‐ CorV). She was ultimately diagnosed with mononeuritis multiplex based on EMG‐NCV findings and administered methylprednisolone and cyclophosphamide pulse therapy for 5 days, and then continue with prednisolone and a monthly pulse of cyclophosphamide.     

Leser‐Trélat syndrome secondary to non‐small‐cell lung carcinoma

The syndrome of Leser‐Trélat (LT) is a rare paraneoplastic syndrome. However, patients presenting with the sign of Leser‐Trélat should be considered to harbor an occult malignancy or a progressive tumor disease until “proven” otherwise. Herein, we present two cases of non‐small‐cell lung carcinoma associated with LT syndrome.     

Cutaneous ulcers in association with sprue‐like enteropathy secondary to Losartan

Losartan is an angiotensin II receptor blocker (ARB) which may cause severe sprue‐like enteropathy (SLE) with skin manifestation. Clinicians should be informed of this side effect and its reversibility after cessation of the drug.     

A novel heterozygous HTRA1 mutation in an Asian family with CADASIL‐like disease

Background HTRA1 gene mutations are related to the pathogenesis of cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL). However, heterozygous HTRA1 mutations at specific sites can also lead to rare autosomal dominant cerebral artery disease (CADASIL‐like disease). To date, 28 heterozygous mutations in the HTRA1 gene have been reported to be related to CADASIL‐like diseases. Only one case of this disease was caused by a heterozygous mutation of c.497G>T in exon 2 of the HTRA1 gene.MethodsIn this case, we report on an Asian family with CADASIL‐like disease caused by a heterozygous mutation of c.497G>T in exon 2 of the HTRA1 gene. The clinical and imaging characteristics of the proband were summarized, and gene mutations were verified by whole‐exome sequencing (WES) and direct Sanger sequencing.ResultsThe result of the gene sequencing showed a heterozygous missense mutation at the c.497G>T locus of the HTRA1 gene in the proband of one sick family member, resulting in a change in amino acid (p.arg166leu).ConclusionThis is the first reported pathogenic mutation at the c.497G>T locus of the HTRA1 gene in an Asian population. It provides an important theoretical basis for the specific gene‐based diagnosis and treatment of CADASIL‐like diseases.     

miR‐125a‐5p promotes gastric cancer growth and invasion by regulating the Hippo pathway

ObjectiveThis study was carried out to explore the potential involvement of miR‐125a‐5p in the oncogenic effects of EphA2, TAZ, and TEAD2 and the activity of the Hippo signaling pathway in gastric cancer progression.MethodsIn vitro transfection of miR‐125a‐5p mimics or inhibitors, qRT‐PCR, colony formation assays, and cell invasion assays were used to assess the effect of miR‐125a‐5p on the growth and invasion in gastric cancer (GC). Male nude mice bearing tumors derived from human GC cells were used for evaluating the effects of miR‐125a‐5p on tumor growth. Luciferase reporter assay, immunofluorescence, immunohistochemistry, qRT‐PCR, and immunoblotting were performed to explore the role of miR‐125a‐5p in the epithelial‐mesenchymal transition (EMT) and association among miR‐125a‐5p, EphA2, TAZ, and TEAD2 in GC cells.ResultsMiR‐125a‐5p enhanced GC cell viability and invasion in vitro, whereas inhibition of miR‐125a‐5p using a specific inhibitor and antagomir suppressed cancer cell invasion and tumor growth. Moreover, inhibition of miR‐125a‐5p reversed EMT in vitro. miR‐125a‐5p upregulated the expression of EphA2, TAZ, and TEAD2, promoted TAZ nuclear translocation, and induced changes in the activity of the Hippo pathway by enhancing the expression of TAZ target genes. Finally, miR‐125a‐5p was overexpressed in late‐stage GCs, and positive correlations were observed with its targets EphA2, TAZ, and TEAD2.ConclusionmiR‐125a‐5p can promote GC growth and invasion by upregulating the expression of EphA2, TAZ, and TEAD2.     

Perampanel markedly improved clinical seizures in a patient with a Rett‐like phenotype and 960‐kb deletion on chromosome 9q34.11 including the STXBP1

Intractable epilepsy was successfully controlled using perampanel, an α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionic acid‐type glutamate receptor antagonist, in a 27‐year‐old woman who presented with a Rett syndrome‐like phenotype and novel 960‐kb deletion involving syntaxin‐binding protein 1 on chromosome 9q34.11. Perampanel may be an effective antiepileptic drug for intractable epilepsy associated with STXBP1 mutations.     

Subcutaneous panniculitis‐like T‐cell lymphoma in a young girl presenting with periorbital edema and fever: A case report

Subcutaneous panniculitis‐like T‐cell lymphoma is a rare and highly malignant extra‐nodal lymphoma. It has a wide range of clinical presentations (such as periorbital swelling as in our case) and should be considered in the differential diagnosis of systemic lupus erythematosus, especially in children.     

Rapid progression of myelofibrosis in polycythemia vera patient carrying SRSF2 c.284C>A p.(Pro95His) and unique ASXL1 splice site c.1720‐2A>G variant

BackgroundThe prognosis in polycythemia vera (PV) is comparatively favorable, but individual myelofibrosis/leukemic progression risk is heterogeneous. About a quarter of patients progress to the fibrotic phase after 20 years.MethodsMultiplex PCR, allele‐specific qPCR, high‐resolution melt analysis, and Sanger sequencing were used to detect BCR‐ABL, JAK2, ASXL1, SRSF2, U2AF1, and IDH1/2 variants.ResultsHerein, we present a PV patient with rapid progression to secondary myelofibrosis probably due to the coexistence of homozygous JAK2 V617F mutation, SRSF2 c.284C>A p.(Pro95His) and splice site variant of ASXL1 c.1720‐2A>G. The detected ASXL1 variant was first described in Bohring–Opitz syndrome and has not been reported in hematological malignancies so far. In the presented case, the ASXL1 VAF was stable (50%) during the 4‐year follow‐up, despite an evident increase in the JAK2 V617F VAF. Family history revealed cerebral palsy in the patient''s grandson; however, germline character of the ASXL1 variant was excluded.ConclusionThe biological consequences of the variant acquisition by hematopoietic stem cells (HSC) seem to be similar to other mutations of ASXL1 responsible for the truncation of ASXL1 protein, formation of hyperactive ASXL1–BAP1 (BRCA1‐associated protein‐1) complexes, and finally, the promotion of aberrant myeloid differentiation of HSC. Our report supports the hypothesis that ASXL1 alteration cooperates with JAK2 V617F leading to biased lineage skewing, favoring erythroid and megakaryocytic differentiation, accelerating the progression of PV to the fibrotic phase.     

HAGLROS knockdown restrained cell proliferation,migration and invasion and facilitated apoptosis in laryngeal cancer via miR‐138‐5p/CLN5 axis

BackgroundThis work investigated the role of HAGLROS in laryngeal cancer (LC).MethodsHAGLROS expression in the head and neck squamous cell carcinoma (HNSC), target miRNAs of HAGLROS, target mRNAs of miR‐138‐5p, and the binding sites of HAGLROS and miR‐138‐5p or CLN5 and miR‐138‐5p were predicted through bioinformatics. HAGLROS, miR‐138‐5p, CLN5, Bcl‐2, and Bax levels were detected by qRT–PCR and Western blot. The biological functions of LC cells were assessed through CCK‐8, colony formation assays, transwell assay, and flow cytometry assay. The targeting relationship between HAGLROS and miR‐138‐5p or CLN5 and miR‐138‐5p was confirmed by dual luciferase gene reporter analysis.ResultsHAGLROS was upregulated in LC. HAGLROS‐specific small interfering RNA (Si‐HAGLROS) inhibited the viability, proliferation, migration, and invasion while increased the apoptosis in LC cells. MiR‐138‐5p was a target of HAGLROS and the miR‐138‐5p inhibitor reversed the effects of si‐HAGLROS on LC cells. CLN5 was a target of miR‐138‐5p. MiR‐138‐5p inhibitor raised the viability, migration and invasion, and Bcl‐2 expression while declined Bax expression in LC cells, with si‐CLN5 performing the opposite effects and reversing the effects of miR‐138‐5p inhibitor.ConclusionSilenced HAGLROS restrained the LC cells'' abilities to proliferate, migrate, and invade as well as facilitated apoptosis in LC via miR‐138‐5p/CLN5 axis.     

Insulin‐like growth factor‐1 positively associated with bone formation markers and creatine kinase in adults with general physical activity

BackgroundThe Insulin‐like growth factor‐1 (IGF‐1) is primarily synthesized by hepatocytes in a growth hormone (GH)‐dependent manner, it is also produced by bone and muscle. The effects of exercise on the associations between IGF‐1 levels and bone turnover markers (BTM) were found in the previous studies. However, the associations between the levels of IGF‐1 and BTM, liver function tests, and skeletal muscle markers in adults with general physical activity were not clear.MethodsNinety‐four participants were recruited from healthy survey. Blood samples were collected to analyze the levels of IGF‐1, total protein (TP), albumin (Alb), total bilirubin (T‐Bil), direct bilirubin (D‐Bil), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), bone alkaline phosphatase (BALP), lactate dehydrogenase (LDH), creatine kinase (CK), creatinine (CRTN), and glucose. Urine samples were collected to analyze the CRTN and deoxypyridinoline (Dpd) levels.ResultsThe positively significant associations were found between the IGF‐1 levels and the levels of ALP, BALP, and CK, respectively. No significant associations were found between the IGF‐1 levels and the levels of TP, Alb, A/G, T‐Bil, D‐Bil, AST, ALT, LDH, glucose, urinary CRTN, urinary Dpd, and Dpd/CRTN ratios, respectively.ConclusionThe serum IGF‐1 levels associated with the levels of skeletal muscle and bone formation markers (BFM), not the bone resorption markers under general physical activity in the healthy adults. The physician needs to consider the effects of bone formation and skeletal muscle markers on the IGF‐1 levels in the management of IGF‐1‐related disorders.     

miR‐30b‐5p up‐regulation related to the dismal prognosis for patients with renal cell cancer

The diagnosis of renal cell carcinoma (RCC) is often made late since there is no early symptom, which thus results in dismal patient prognosis. As a result, new biomarkers are urgently needed and efforts should be made to identify their functions in predicting RCC prognosis. microRNAs (miRNAs) are a class of small noncoding RNAs that are about 20‐22 nucleotides in length, and they have been demonstrated to function as prognostic markers in numerous tumors. This study aimed to assess the role of miR‐30b‐5p in predicting the prognosis of RCC postoperatively. In this study, RNA was extracted from 284 formalin‐fixed and paraffin‐embedded kidney cancer tissue samples. After cDNA synthesis, real‐time quantitative PCR (RT‐qPCR) was adopted for detecting the relative miR‐30b‐5p level. Then, the Kaplan‐Meier method, Cox regression analysis, and the receiver operating characteristic curve analysis were applied in analyzing the miR‐30b‐5p effect on the prognosis for patients. Our findings indicated that, following adjustment for age, gender, tumor stage, and tumor size, patients with low miR‐30b‐5p expression had remarkably longer overall survival. Thus, the miR‐30b‐5p level might be related to RCC prognosis.     

Neurodegenerative disorder and diffuse brain calcifications due to FARSB mutation in two siblings

Pathogenic mutations in the FARSB gene are associated with neurodevelopmental disorder involving the brain, liver, and lungs. We report genetic analysis of a family including two affected members with this disorder, which revealed a homozygous pathogenic missense variant, FARSB: {"type":"entrez-nucleotide","attrs":{"text":"NM_005687.4","term_id":"743405629","term_text":"NM_005687.4"}}NM_005687.4:c.853G > A:p.E285K in both affected patients. The parents were heterozygous for this variant.     

Multifocal periapical cemental dysplasia in periodontal Ehlers–Danlos syndrome combined with leukoencephalopathy in the mutation of c.890G > a,G297D [pEDS]

Periodontal Ehlers‐Danlos syndrome (pEDS) is a rare disorder caused by heterozygous mutations in complement 1 subunit genes C1R and C1S. To date, 148 cases have been described in the literature.We describe a case of a suspected de novo‐mutation of pEDS with generalized Periapical cemental dysplasia (PCD) and cerebral leukoencephalopathy.     

Lower level of IL‐28A as a predictive index of the artificial liver support system in effective treatment of patients with HBV‐ACLF

BackgroundHBV‐related acute‐on‐chronic liver failure (HBV‐ACLF) is the most common type of liver failure with high mortality. Artificial liver support system (ALSS) is an important mean to reduce the mortality of HBV‐ACLF but lacking index to assess its effectiveness. The cytokines are closely related to the prognosis of HBV‐ACLF patients with ALSS treatment, however, which is not fully understood.MethodsOne hundred forty‐two patients with HBV‐ACLF and 25 healthy donors were enrolled. The cytokine profile of peripheral blood was determined in the patients before and after ALSS treatment, and their relationship with effectiveness of ALSS treatment in HBV‐ACLF was analyzed.ResultsSerum IL‐28A levels were markedly lower in ALSS‐effective patients than those in non‐effective patients pre‐ALSS treatment. Similarly, serum IL‐6 was significantly lower in ALSS‐effective patients. Furthermore, for patients with effective treatment, serum IL‐28A levels were positively related with IL‐6 levels post‐ALSS (r = 0.2413, p = 0.0383). The ROC curve analysis showed that serum levels of IL‐28A (AUC = 0.6959 when alone or 0.8795 when combined with total bilirubin, platelet count and INR, both p < 0.0001) and IL‐6 (AUC = 0.6704, p = 0.0005) were useful indices for separating effective from non‐effective ALSS treatment of HBV‐ACLF patients. Multivariate logistic regression analysis demonstrated that lower level of IL‐28A was independently associated with higher effective rate of ALSS treatments.ConclusionsLower level of IL‐28A is a predictive biomarker for ALSS in effective treatment of HBV‐ACLF patients and IL‐28A may be potential target for the treatment of HBV‐ACLF.     

Circ_0000463 contributes to the progression and glutamine metabolism of non‐small‐cell lung cancer by targeting miR‐924/SLC1A5 signaling

BackgroundCircular RNAs (circRNAs) have shown pivotal regulatory roles in the pathology of non‐small cell lung cancer (NSCLC). However, the role of circ_0000463 in NSCLC progression and its associated molecular mechanism remain to be illustrated.MethodsCell proliferation ability was analyzed by colony formation assay and 5‐ethynyl‐2’‐deoxyuridine (EdU) assay. Cell migration and invasion abilities were assessed by scratch test and transwell invasion assay. Flow cytometry was employed to analyze cell apoptotic rate. The interaction between microRNA‐924 (miR‐924) and circ_0000463 or solute carrier family 1 member 5 (SLC1A5) was confirmed by dual‐luciferase reporter assay and RNA immunoprecipitation (RIP) assay. The uptake of glutamine and the production of glutamate and α‐ketoglutarate were analyzed using their corresponding kits. Xenograft model in vivo was established to analyze the role of circ_0000463 in tumor growth.ResultsCirc_0000463 expression was elevated in NSCLC tissues and cell lines. Circ_0000463 knockdown suppressed the proliferation, migration, and invasion and promoted the apoptosis of NSCLC cells. Circ_0000463 acted as a molecular sponge for miR‐924, and circ_0000463 interference‐mediated anti‐tumor effects were largely reversed by the silence of miR‐924 in NSCLC cells. miR‐924 interacted with the 3’ untranslated region (3’UTR) of SLC1A5, and SLC1A5 overexpression largely overturned miR‐924 overexpression‐mediated anti‐tumor effects in NSCLC cells. Moreover, circ_0000463 absence suppressed the glutamine metabolism of NSCLC cells by targeting miR‐924/SLC1A5 axis. Circ_0000463 knockdown suppressed xenograft tumor growth in vivo.ConclusionCirc_0000463 absence suppressed the malignant behaviors and glutamine metabolism of NSCLC cells through mediating miR‐924/SLC1A5 axis.     

Lung abscess due to Streptococcus intermedius associated with SARS CoV‐2 infection in pregnancy: Unusual presentation and complication of a commensal bacteria during pregnancy

Streptococcus intermedius is a commensal bacterium reported in a few cases as the causative agent of brain and lung abscesses, pneumonia, and endocarditis. Lung abscesses due to Streptococcus intermedius are rare, especially in pregnancy. We describe the first case of lung abscess due to Streptococcus intermedius in a pregnant woman.