mNGS helped diagnose scrub typhus-associated HLH in children: a report of two cases.

Background: Scrub typhus, caused by the Orientia tsutsugamushi (Ot), is a widespread vector-borne disease transmitted by chigger mites. Hemophagocytic lymphohistiocytosis (HLH) is considered to be one of the potentially severe complications. The diagnosis of scrub typhus-associated HLH may be overlooked due to the non-specific clinical characteristics and the absence of pathognomonic eschar. Case presentation: We obtained clinical data from two patients in the South of Sichuan, China. The first case involved a 6-year-old girl who exhibited an unexplained fever and was initially diagnosed with sepsis, HLH, and pulmonary infection. The other patient presented a more severe condition characterized by multiple organ dysfunction and was initially diagnosed with septic shock, sepsis, HLH, acute kidney injury (AKI), and pulmonary infection. At first, a specific examination for scrub typhus was not performed due to the absence of a characteristic eschar. Conventional peripheral blood cultures yielded negative results in both patients, and neither of them responded to routine antibiotics. Fortunately, the causative pathogen Orientia tsutsugamushi (Ot) was detected in the plasma samples of both patients using metagenomics next-generation sequencing (mNGS) and further confirmed by polymerase chain reaction. Subsequently, they both were treated with doxycycline and recovered quickly. Conclusion: The unbiased mNGS provided a clinically actionable diagnosis for an uncommon pathogen-associated infectious disease that had previously evaded conventional diagnostic approaches.

A primary pediatric acute myelomonocytic leukemia with t(3;21)(q26;q22): A case report.

RATIONALE: The rare t(3;21)(q26;q22) translocation results in gene fusion and generates multiple fusion transcripts, which are typically associated with therapy-related myelodysplastic syndrome, acute myeloid leukemia, and chronic myelogenous leukemia. Here, we report a rare case of de novo acute myelomonocytic leukemia in a young child with t(3;21)(q26;q22). PATIENT CONCERNS: A 2-and-a-half-year-old female patient presented with abdominal pain, cough, paleness, and fever for 3 weeks, without any history of malignant diseases. DIAGNOSES: Chest computed tomography revealed pneumonia. Bone marrow smear confirmed acute myelomonocytic leukemia. Cytogenetic analysis and Sanger sequencing identified RUNX1-MECOM and RUNX1-RPL22 fusion genes as a result of t(3;21)(q26;q22). INTERVENTIONS: The patient received 3 courses of chemotherapy, but bone marrow smear examination showed no remission. According to the wishes of the patient family, the allogeneic hematopoietic stem cell transplantation (Allo-HSCT) was chosen. OUTCOMES: The patient did not experience any adverse reactions after Allo-HSCT. The red blood cells and platelets increased without transfusion. The pneumonia recovered after antibiotic treatment. LESSONS: The patient recovered well after Allo-HSCT. Therefore, for patients with RUNX1-MECOM and RUNX1-RPL22 fusion genes, transplantation may be a good choice when chemotherapy is not effective.

Precautions against COVID-19 reduce respiratory virus infections among children in Southwest China.

Acute respiratory tract infections pose a serious threat to the health of children worldwide, with viral infections representing a major etiology of this type of disease. Protective measures such as mask-wearing, social distancing, and hand hygiene can be effective in curbing the spread of severe acute respiratory syndrome coronavirus 2. These precautions may also have an impact on the spread of other respiratory viruses. In this study, we retrospectively compared the respiratory virus infections of children in Southwest China before and after the outbreak of COVID-19. Nasopharyngeal swabs were collected from 1578 patients under 14 years old with acute respiratory tract infection symptoms before and after COVID-19 pandemic. Nine common respiratory viruses including human bocavirus, human rhinoviruses, human coronaviruses, human adenoviruses, human metapneumovirus, respiratory syncytial virus, influenza A virus, influenza B virus, and parainfluenza virus were measured by advanced fragment analysis. The respiratory virus infection rates among children of all ages and genders in Southwest China under the precautions against COVID-19 pandemic were significantly lower than that of the same period before the pandemic. Our findings indicate that public health measures implemented during the COVID-19 pandemic, including strict mask-wearing, social distancing, and hand hygiene, may be effective in preventing the transmission of other respiratory viruses in children, thereby controlling the spread of infections.

Analysis of Ureaplasma urealyticum, Chlamydia trachomatis, Mycoplasma genitalium and Neisseria gonorrhoeae infections among obstetrics and gynecological outpatients in southwest China: a retrospective study.

BACKGROUND: The aim of this study was to analyze the present situation of Ureaplasma urealyticum (UU), Chlamydia trachomatis (CT), Mycoplasma genitalium (MG) and Neisseria gonorrhoeae (NG) infections among obstetrics and gynecological outpatients in southwest China. METHODS: A total of 3225 urogenital swabs were included in this study. All swabs were tested by RNA-based simultaneous amplification and testing (SAT) methods. Routine analysis of leucorrhea smear and drug susceptibility were performed in UU positive patients. RESULTS: Of these 3225 outpatients, the positive rate was 27.07% for UU, 4.99% for CT, 3.10% for MG, and 0.09% for NG. UU, CT, and MG infections were more common in women of reproductive age (aged 25-34 years), while NG infection was more prominent in women aged 30-34 years and over 40 years. Overall, the infection rate of UU was significantly higher than that of the other three infections, and UU also played a major role even in the mixed infections. 65.07% of the UU positive patients had negative results on routine leucorrhea smear analysis, and the remaining patients may have bacterial vaginitis (15.79%), fungal vaginitis (11.48%), trichomonas vaginitis (0.96%) or other vaginal inflammation (6.70%). We have observed that maternal UU infection can lead to low birth weight, neonatal pneumonia, and premature delivery. The results of the drug susceptibility test of UU showed a higher sensitivity to pristinamycin, doxycycline, tetracycline, clarithromycin, and josamycin (100%, 97.0%, 96.4%, 95.9%, and 95.3%, respectively), and lower sensitivity to ciprofloxacin and ofloxacin (2.4% and 4.7% respectively). CONCLUSIONS: This study could contribute to a better understanding of the current epidemiological features of UU, CT, MG, and NG among obstetrics and gynecological outpatients in southwest China, and thus facilitate to development of the more effective intervention, prevention, and treatment of reproductive tract infection.

Multisite Pseudomonas aeruginosa Infections Detected by Metagenomic Next-Generation Sequencing in a Child with Aplastic Anemia: A Case Report.

Microbial cultivation is the current gold standard for the clinical diagnosis of bacterial infections. However, this method sometimes produces false negative results. We present a case study of multisite Pseudomonas aeruginosa infections detected by metagenomic next-generation sequencing in a child with aplastic anemia, highlighting the rapid and accurate advantages of this technique.

Low expression of NTF3 is associated with unfavorable prognosis in hepatocellular carcinoma.

Neurotrophin 3 (NTF3) is a member of the nerve growth factor (NGF) family involved in cancer progression, including medulloblastoma and breast cancer. However, the expression and prognostic value of NTF3 has not been reported in human hepatocellular carcinoma (HCC). Here, we first performed an mRNA expression analysis of the NTF family using the TCGA database and found that NTF3 was significantly downregulated in patients with HCC. Low expression of NTF3 in various HCC cohorts from the GEO database was frequently identified. Consistently, NTF3 protein level was also decreased in HCC tissues as compared with controls. Moreover, survival analysis showed that low NTF3 expression correlated with shorter overall survival (OS) and disease-free survival (DFS) in HCC patients. In addition, there was a positive correlation between the mRNA expression of NTF3 and TrkC in HCC specimens. Generally, these results revealed that low expression of NTF3 predicted an unfavorable clinical outcome. NTF3 may be a diagnostic and prognostic marker in HCC.

Prevalence of food allergen and aeroallergen sensitization among children in Sichuan province.

Food allergen and aeroallergen sensitization are common allergic diseases worldwide, with widely varying estimates of prevalence in children. Our study investigated the characteristics of ingestion and inhalation allergy among children from Sichuan province in Southwest China, so as to get public awareness of these disorders.A total of 1722 children between 0 and 14 years' old were enrolled in this study. They were outpatients in the West China Second University Hospital during June 2019 to September 2019. Serum specific IgE specific to 10 types of food allergen and 10 types of aeroallergen were estimated. Nutrition indicators were tested by electrochemical luminescence.59.70% children were allergic to at least 1 allergen, comprising 24.90% to aeroallergen and 38.81% to food allergen, respectively, whereas 36.28% children were allergic to both aeroallergen and food allergen. Milk was the most common food allergen, and egg came in second place. With regard to aeroallergen, house dust mite held the maximum proportion (65.02%), whereas dust mite followed behind. Inhalation allergy was more commonly seen in boys than girls. Bronchitis was the most common symptom of both allergies. In addition, the highest incidence age for children to be sensitive to food allergen and aeroallergen were 0∼2 years' old and 3∼5 years' old, respectively. It is worth mentioning that there was no significant difference in nutritional status between children with or without allergic diseases.Our findings reveal that milk, egg, house dust mite, and dust mite are the most common allergens among children in Sichuan province. Boys are more susceptible to aeroallergen than girls. Furthermore, the prevalence of ingestion and inhalation allergy varies from different age groups, and has no correlation with nutritional status. In brief, the analysis of the pattern of food allergen and aeroallergen sensitization is invaluable to effective diagnosis and treatment of allergic diseases.

Long noncoding RNA SNHG12 modulated by human papillomavirus 16 E6/E7 promotes cervical cancer progression via ERK/Slug pathway.

Recently, long noncoding RNA SNHG12 has been reported to be dysregulated in various types of cancer. This study investigated its biological function and the underlying molecular mechanism in cervical squamous cell carcinoma (CSCC). We found that SNHG12 was significantly overexpressed in CSCC tissues. Further evidence showed that human papillomavirus (HPV) type 16 E6 and E7 might regulate the expression level of SNHG12 by modulating transcription factor c-Myc. Functional experiments suggested that SNHG12 knockdown dramatically repressed CSCC cells proliferation, migration, and invasion while induced apoptosis in vitro as well as suppressed tumor growth in vivo. In addition, SNHG12 could facilitate epithelial-mesenchymal transition through ERK/Slug/E-cadherin pathway at least in part. Our findings highlight SNHG12 functions as an oncogenic long noncoding RNA in malignant phenotype and tumorigenesis of CSCC, which implicate it may be a potential target for CSCC treatment.

Human papillomavirus 16 E7 oncoprotein alters the expression profiles of circular RNAs in Caski cells.

Cervical cancer is one of the most common cancer in female worldwide. The expression of high-risk human papillomavirus E7 oncogene is necessary for the maintenance of malignant phenotypes and transformation. Accumulating studies of this protein has been explored in cervical cancer, however, there are fewer studies on how E7 expression affects the expression of global circular RNA. CircRNA, a promising biomarker and even therapeutic target, has become a star molecular in research after miRNA and long non-coding RNA. Our aim of this study was to investigate the global circRNA levels modulated by HPV E7 expression and identified the potential consequences for mechanism studies. Here we investigated the expression profiles of circRNAs by transfecting E7 siRNA in Caski cells with high-throughput microarray technology. In total, we identified 526 dysregulated circRNAs with fold change ≥2 or≤0.5, and p< 0.05. Among them, 352 were up-regulated and 174 were down-regulated. In addition, 8 selected circRNAs confirmed using qRT-PCR was in line with the results of microarray analysis. Furthermore, bioinformatic analyses indicated that differently expressed circRNAs might implicate in the mTOR signaling pathway, proline metabolism and glutathione metabolism. In conclusion, this study showed the expression profiles of circRNAs regulated by HPV16 E7 in cervical cancer cells and provides novel insights into the new potential candidates for future mechanism studies.

Myosin 1b promotes cell proliferation, migration, and invasion in cervical cancer.

OBJECTIVE: Recent evidence suggests an important role of Myosin 1b (Myo1b) in the progression of several cancers, including prostate cancer and head and neck squamous cell carcinoma (HNSCC). However, the contribution of Myo1b to cervical cancer (CC) remains elusive. METHODS: Quantitative reverse transcription polymerase chain reaction (qRT-PCR), immunohistochemistry and western blotting assays were used to confirm the expression of Myo1b in CC tissues compared with matched non-tumor tissues and CC cells, and analyze its clinical significance. In vitro, RNA interference (siRNA or shRNA) was used to investigate the biological function and underlying mechanism of Myo1b in cervical carcinogenesis. Furthermore, tumor growth was evaluated in vivo using a xenogenous subcutaneously implant model. RESULTS: Here, for the first time we reported that Myo1b expression was significantly increased in human CC, compared to cervical intraepithelial neoplasia (CIN) and normal cervical tissues and that the upregulation of Myo1b was significantly correlated with FIGO Stage, HPV infection, lymph node metastasis and pathological grade. In vitro, knockdown of Myo1b significantly suppressed proliferation, migration, and invasion of CaSki and SiHa cells, and markedly decreased the MMP1/MMP9 activities. Also, silencing the expression of Myo1b dramatically repressed tumor growth in a mouse xenograft model. Further investigations showed that HPV16 E6 or E7 could enhance the expression of Myo1b via upregulating c-MYC. CONCLUSION: Taken together, our data suggested a potential role of Myo1b in cervical carcinogenesis and tumor progression and provided novel insights into the mechanism of how this factor promotes cell proliferation, migration, and invasion in CC cells.

High expression of TMEM40 is associated with the malignant behavior and tumorigenesis in bladder cancer.

BACKGROUND: Bladder cancer (BCa) is one of the most common cancers in the urinary system among the world. Previous studies suggested that TMEM40 expression level was significantly associated with clinicopathological parameters including histological grade, clinical stage and pT status of bladder cancer. However, the molecular mechanism of TMEM40 in BCa remains poorly understood. METHODS: Real-time quantitative RT-PCR (qRT-PCR) and western blot (WB) were used to examine the expression levels of TMEM40 in BCa tissues, paired non-cancer tissues and cell lines. A series of experiments, including CCK-8, wound healing, flow cytometry, transwell and EdU assays were performed to assess the effects of TMEM40 on cell proliferation, cell cycle and apoptosis, migration and invasion. In addition, tumor growth was evaluated in vivo using a xenogenous subcutaneously implant model. All statistical analyses were executed by using the SPSS 20.0 software. All experimental data from three independent experiments were analyzed by Student's t test and results were expressed as mean ± standard deviation. RESULTS: In this study, we identified the role of TMEM40 in the tumorigenesis of bladder cancer and found that it was upregulated in bladder cancer tissues and cell lines, compared with their normal counterparts. The results demonstrated that effective silence of TMEM40 expression suppressed cell proliferation, blocked G1-to-S cell cycle transition, and inhibited cell migration and invasion in human bladder 5637 and EJ cell lines. Consistently, in vivo data showed that TMEM40 silencing could dramatically decreased tumor growth. Further study revealed that TMEM40 knockdown resulted in accumulation of p53 and p21 protein and decrease of c-MYC and cyclin D1 protein. CONCLUSION: These data suggest that TMEM40 represents a potential oncogene, which exert a crucial role in the proliferation and apoptosis via the p53 signaling pathway in BCa, thus probably serve as a novel candidate biomarker and a potential therapeutic target for patients with BCa.