Rapid Diagnosis of Pneumocystis jirovecii Pneumonia and Respiratory Tract Colonization by Next-Generation Sequencing.

OBJECTIVES: To describe the epidemiology of Pneumocystis jirovecii pneumonia and colonization diagnosed by next-generation sequencing (NGS) and explore the usefulness of the number of P. jirovecii sequence reads for the diagnosis of P. jirovecii pneumonia. METHODS: We examined the NGS results for P. jirovecii in respiratory samples collected from patients and analysed their clinical, radiological and microbiological characteristics. RESULTS: Among 285 respiratory samples collected over a 12-month period (January to December 2022), P. jirovecii sequences were detected in 56 samples from 53 patients. Fifty (94.3%) of the 53 patients were HIV-negative. Following our case definitions, 37 (69.8%) and 16 (30.2%) of the 53 patients had P. jirovecii infection and colonization respectively. P. jirovecii infection was associated with presence of underlying disease with immunosuppression (94.6% vs 18.8%, P < 0.05), positive serum 1,3-ß-D-glucan (41.2% vs 0%, P < 0.01) and higher number of P. jirovecii sequence reads (P < 0.005). In contrast, P. jirovecii colonization was associated with the male sex (93.8% vs 54.1%, P < 0.01), another definitive infectious disease diagnosis of the respiratory tract (43.8% vs 2.7%, P < 0.001) and higher survival (100% vs 67.6%, P < 0.01). Although P. jirovecii pneumonia was associated with higher number of P. jirovecii reads in respiratory samples, only a sensitivity of 82.14% and a specificity of 68.75% could be achieved. CONCLUSION: Detection of P. jirovecii sequences in respiratory samples has to be interpreted discreetly. A combination of clinical, radiological and laboratory findings is still the most crucial in determining whether a particular case is genuine P. jirovecii pneumonia.

Post-COVID-19 Pandemic Rebound of Macrolide-Resistant Mycoplasma pneumoniae Infection: A Descriptive Study.

The rebound characteristics of respiratory infections after lifting pandemic control measures were uncertain. From January to November 2023, patients presenting at a teaching hospital were tested for common respiratory viruses and Mycoplasma pneumoniae using a combination of antigen, nucleic acid amplification, and targeted next-generation sequencing (tNGS) tests. The number and rate of positive tests per month, clinical and microbiological characteristics were analyzed. A rapid rebound of SARS-CoV-2 was followed by a slower rebound of M. pneumoniae, with an interval of 5 months between their peaks. The hospitalization rate was higher, with infections caused by respiratory viruses compared to M. pneumoniae. Though the pediatric hospitalization rate of respiratory viruses (66.1%) was higher than that of M. pneumoniae (34.0%), the 4094 cases of M. pneumoniae within 6 months posed a huge burden on healthcare services. Multivariate analysis revealed that M. pneumoniae-infected adults had more fatigue, comorbidities, and higher serum C-reactive protein, whereas children had a higher incidence of other respiratory pathogens detected by tNGS or pathogen-specific PCR, fever, and were more likely to be female. A total of 85% of M. pneumoniae-positive specimens had mutations detected at the 23rRNA gene, with 99.7% showing A2063G mutation. Days to defervescence were longer in those not treated by effective antibiotics and those requiring a change in antibiotic treatment. A delayed but significant rebound of M. pneumoniae was observed after the complete relaxation of pandemic control measures. No unusual, unexplained, or unresponsive cases of respiratory infections which warrant further investigation were identified.

Can the use of azithromycin during labour reduce the incidence of infection among puerperae and newborns? A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: This systematic review and meta-analysis investigated whether the use of azithromycin during labour or caesarean section reduces the incidence of sepsis and infection among mothers and newborns. DATA SOURCES: We independently searched the PubMed, Web of Science, Cochrane Library and EMBASE databases for relevant studies published before February, 2024. METHODS: We included RCTs that evaluated the effect of prenatal oral or intravenous azithromycin or placebo on intrapartum or postpartum infection incidence. We included studies evaluating women who had vaginal births as well as caesarean sections. Studies reporting maternal and neonatal infections were included in the current analysis. Review Manager 5.4 was used to analyse 6 randomized clinical trials involving 44,448 mothers and 44,820 newborns. The risk of bias of each included study was assessed using the criteria outlined in the Cochrane Handbook for Systematic Reviews of Interventions.Primary outcomes included the incidence of maternal sepsis and all-cause mortality and neonatal sepsis and all-cause mortality; secondary outcomes included maternal (endometritis, wound and surgical site infections, chorioamnionitis, and urinary tract infections) and neonatal outcomes (infections of the eyes, ears and skin). A random-effects model was used to test for overall effects and heterogeneity. RESULTS: The pooled odds ratios (ORs) were as follows: 0.65 for maternal sepsis (95% CI, 0.55-0.77; I2, 0%; P < .00001); 0.62 for endometritis (95% CI, 0.52-0.74; I2, 2%; P < .00001); and 0.43 for maternal wound or surgical site infection (95% CI, 0.24-0.78; P < .005); however, there was great heterogeneity among the studies (I2, 75%). The pooled OR for pyelonephritis and urinary tract infections was 0.3 (95% CI, 0.17-0.52; I2, 0%; P < .0001), and that for neonatal skin infections was 0.48 (95% CI, 0.35-0.65; I2, 0%, P < .00001). There was no significant difference in maternal all-cause mortality or incidence of chorioamnionitis between the two groups. No significant differences were observed in the incidence of neonatal sepsis or suspected sepsis, all-cause mortality, or infections of the eyes or ears. CONCLUSION: In this meta-analysis, azithromycin use during labour reduced the incidence of maternal sepsis, endometritis, incisional infections and urinary tract infections but did not reduce the incidence of neonatal-associated infections, except for neonatal skin infections. These findings indicate that azithromycin may be potentially beneficial for maternal postpartum infections, but its effect on neonatal prognosis remains unclear. Azithromycin should be used antenatally only if the clinical indication is clear and the potential benefits outweigh the harms.

Identification and validation of anoikis-related lncRNAs for prognostic significance and immune microenvironment characterization in ovarian cancer.

Anoikis, a form of apoptotic cell death resulting from inadequate cell-matrix interactions, has been implicated in tumor progression by regulating tumor angiogenesis and metastasis. However, the potential roles of anoikis-related long non-coding RNAs (arlncRNAs) in the tumor microenvironment are not well understood. In this study, five candidate lncRNAs were screened through least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analysis based on differentially expressed lncRNAs associated with anoikis-related genes (ARGs) from TCGA and GSE40595 datasets. The prognostic accuracy of the risk model was evaluated using Kaplan-Meier survival analysis and receiver operating characteristic (ROC) curves. Furthermore, Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene set enrichment analysis (GSEA) analyses revealed significant differences in immune-related hallmarks and signal transduction pathways between the high-risk and low-risk groups. Additionally, immune infiltrate analysis showed significant differences in the distribution of macrophages M2, follicular T helper cells, plasma cells, and neutrophils between the two risk groups. Lastly, silencing the expression of PRR34_AS1 and SPAG5_AS1 significantly increased anoikis-induced cell death in ovarian cancer cells. In conclusion, our study constructed a risk model that can predict clinicopathological features, tumor microenvironment characteristics, and prognosis of ovarian cancer patients. The immune-related pathways identified in this study may offer new treatment strategies for ovarian cancer.

[Investigation of Antigen and Gene Frequency of Kell(K) and Rh(D) Blood Groups in Xinjiang].

OBJECTIVE: To investigate the phenotypes and gene frequencies of Kell blood group system K antigen and Rh blood group system D antigen in Xinjiang, and summarize and understand the distribution of Kell(K) blood type and Rh(D) blood type in this area. METHODS: A total of 12 840 patients who met the inclusion criteria during physical examination and treatment in our hospital and 18 medical institutions in our district from January 1, 2019 to December 31, 2019 were collected for identification of Kell blood group system K antigen and Rh blood group System D antigen, and the distribution of K and D blood groups in different regions, genders and nationalities were investigated and statistically analyzed. RESULTS: The proportion of K positive in the samples was 1.39%, the highest was 1.91% in southern Xinjiang, and the lowest was 1.03% in northern Xinjiang(P<0.01). The proportion of Rh(D) negative samples was 2.75% and the gene frequency was 16.64%. The proportion of Rh(D) negative samples was 4.03% and the gene frequency was 20.10% in southern Xinjiang, followed by eastern Xinjiang and the lowest in northern Xinjiang (P<0.01). The frequency of K antigen in Uygur nationality was the highest, reaching 2.16%, Kirgiz 1.54%, and the distribution trend of D/d antigen was similar to that of K antigen. Among women, the K positive frequency of Kazak nationality was slightly higher than that of Mongolian nationality. The highest proportion of K positive in Uygur women was 2.38%, which was higher than that in Uygur men (1.86%). The frequency of d phenotype in Kazak women was 3.15%, which was higher than that in Kirgiz （2.89%） (P<0.01). CONCLUSION: The distributions of Kell(K) and Rh(D) blood groups in northern and southern Xinjiang and eastern Xinjiang had its own unique characteristics and differences. There are significant differences in blood group distribution among different ethnic groups and gender groups. In the future, k antigen detection can be included to further improve the investigation on the distribution of Kell blood group system in this region.

Hsa_circ_0007321 regulates Zika virus replication through miR-492/NFKBID/NF-κB signaling pathway.

IMPORTANCE: Over the past decade, increasing evidence has shown that circular RNAs (circRNAs) play important regulatory roles in viral infection and host antiviral responses. However, reports on the role of circRNAs in Zika virus (ZIKV) infection are limited. In this study, we identified 45 differentially expressed circRNAs in ZIKV-infected A549 cells by RNA sequencing. We clarified that a downregulated circRNA, hsa_circ_0007321, regulates ZIKV replication through targeting of miR-492 and the downstream gene NFKBID. NFKBID is a negative regulator of nuclear factor-κB (NF-κB), and we found that inhibition of the NF-κB pathway promotes ZIKV replication. Therefore, this finding that hsa_circ_0007321 exerts its regulatory role on ZIKV replication through the miR-492/NFKBID/NF-κB signaling pathway has implications for the development of strategies to suppress ZIKV and possibly other viral infections.

miR-124 delivered by BM-MSCs-derived exosomes targets MCT1 of tumor-infiltrating Treg cells and improves ovarian cancer immunotherapy.

Metabolic rewiring of tumor cells leads to an enrichment of lactate in the tumor microenvironment (TME). This lactate-rich environment of solid tumors has been reported to support tumor-infiltrating regulatory T (Treg) cells. Therefore, agents that modify the lactate metabolism of Treg cells have therapeutic potential. Monocarboxylate transporter 1 (MCT1), which Treg cells predominantly express, plays an essential role in the metabolism of tumor-infiltrating Treg cells. In this study, we show that miR-124 directly targets MCT1 and reduces lactate uptake, eventually impairing the immune-suppressive capacity of Treg cells. Particularly, exosomal miR-124 derived from bone marrow mesenchymal stromal cells (BM-MSCs) slows tumor growth and increases response to PD-1 blockade therapy. These data indicate a potential treatment strategy for improving immune checkpoint blockade therapy using miR-124-carried BM-MSCs-derived exosomes.

Analysis of single-cell sequencing results of an elderly patient with myeloid leukemia reveals high expression of multiple oncogenes in monocytes and hematopoietic stem cells.

OBJECTIVE: Older patients with acute myeloid leukemia (AML) face a higher risk of death. This study analyzed the gene sequencing results of an elderly AML patient to provide new ideas for treatment. METHODS: This study performed single-cell RNA sequencing (scRNA-seq) bioinformatics analysis of blood cells in the peripheral blood and bone marrow of a 64-year-old AML-M5 patient before chemotherapy. The differentially expressed genes (DEGs) were identified, and functional enrichment analyses were performed. RESULTS: A total of 7990 and 123 DEGs were identified in monocytes and hematopoietic stem cells (HSCs), respectively. Among the top 40 DEGs analyzed, MYB showed high expression in peripheral blood monocytes, while 13 other tumor-related genes exhibited high expression in monocytes in the bone marrow. Peripheral blood and bone marrow HSCs had 6 and 12 highly expressed tumor-related genes respectively, including MCL1, JUN, and JUNB. These genes may form a interconnected network contributing to the progression and heterogeneity of AML, which can have an impact on patient treatment and prognosis. CONCLUSIONS: In conclusion, when treating elderly AML patients, it is important to consider their individual characteristics in order to optimize treatment strategies.

Mitophagy Activation Targeting PINK1 Is an Effective Treatment to Inhibit Zika Virus Replication.

Mitophagy is a selective degradation mechanism that maintains mitochondrial homeostasis by eliminating damaged mitochondria. Many viruses manipulate mitophagy to promote their infection, but its role in Zika virus (ZIKV) is unclear. In this study, we investigated the effect of mitophagy activation on ZIKV replication by the mitochondrial uncoupling agent niclosamide. Our results demonstrate that niclosamide-induced mitophagy inhibits ZIKV replication by eliminating fragmented mitochondria, both in vitro and in a mouse model of ZIKV-induced necrosis. Niclosamide induces autophosphorylation of PTEN-induced putative kinase 1 (PINK1), leading to the recruitment of PRKN/Parkin to the outer mitochondrial membrane and subsequent phosphorylation of ubiquitin. Knockdown of PINK1 promotes ZIKV infection and rescues the anti-ZIKV effect of mitophagy activation, confirming the role of ubiquitin-dependent mitophagy in limiting ZIKV replication. These findings demonstrate the role of mitophagy in the host response in limiting ZIKV replication and identify PINK1 as a potential therapeutic target in ZIKV infection.

Whipple's disease presenting as weight gain and constipation in a Chinese woman.

BACKGROUND: Whipple's disease is a chronic infection due to Tropheryma whipplei, commonly reported in the Caucasian but not in the Chinese population. CASE PRESENTATION: A 52-year-old female with good past health, was diagnosed with Whipple's disease, presenting with constipation, unintentional weight gain, and fleeting polyarthralgia. Investigations prior to admission showed raised CA125 and computed tomography of the abdomen showed multiple retroperitoneal mesenteric lymphadenopathies. Extensive investigations performed on secondary causes of weight gain were unrevealing. Subsequent PET-CT scan revealed generalized lymphadenopathy involving the left deep cervical, supraclavicular, and retroperitoneal mesenteric area. Excisional biopsy of the left supraclavicular lymph node was performed, with histology showing infiltrations of Periodic acid-Schiff positive foamy macrophages. T. whipplei DNA was detected in her serum, saliva, stool, and lymph node by PCR targeting the 16S ribosomal RNA gene. She was started on intravenous ceftriaxone, and then stepped down to oral antibiotics for a total of 44 months. The recurrence of fever after 12 days of ceftriaxone raised the suspicion of Immune Reconstitution Inflammatory Syndrome (IRIS). Serial imaging showed a gradual reduction in the size of retroperitoneal lymphadenopathies. Literature review on Whipple's disease in the Chinese population identified 13 reports of detectable T. whipplei DNA in clinical specimens. The majority of the cases were pneumonia, followed by culture-negative endocarditis, encephalitis, and skin and soft tissue infection. However, most patients with pneumonia were diagnosed based on next generation sequencing alone, with the resolution of pulmonary infiltrates without adequate duration of antibiotics, suggesting the possibility of colonization instead of infection. The recommendation of long-term doxycycline suppression after treatment may be supported by the slow response of retroperitoneal lymphadenopathies to antibiotics in our patient. CONCLUSIONS: Unintentional weight gain and constipation could be atypical presentations of Whipple's disease. It is a rare disease in the Chinese population despite the advancement of molecular techniques in the diagnosis of infections. A prolonged course of antibiotics may be required due to slow clinical response as documented by serial imaging in our case. The possibility of IRIS should be considered in patients with breakthrough fever during treatment of Whipple's disease.

Cutaneous Mycobacterium szulgai infection in a patient with Cushing's syndrome: a case report and literature review.

BACKGROUND: Opportunistic infection is an under-recognized complication of Cushing's syndrome, with infection due to atypical mycobacterium rarely reported. Mycobacterium szulgai commonly presents as pulmonary infection, with cutaneous infection seldom reported in the literature. CASE PRESENTATION: 48-year-old man with a newly-diagnosed Cushing's syndrome secondary to adrenal adenoma presented with a subcutaneous mass on the dorsum of his right hand, was diagnosed with cutaneous Mycobacterium szulgai infection. The most likely source of the infection was through minor unnoticed trauma and inoculation from a foreign body. The patient's Cushing's syndrome, high serum cortisol levels and secondary immune suppression facilitated mycobacterial replication and infection. The patient was successfully treated with adrenalectomy, surgical debridement of cutaneous lesion, and a combination of rifampicin, levofloxacin, clarithromycin, and ethambutol for 6 months. There were no signs of relapse one year after cessation of anti-mycobacterial treatment. A literature review on cutaneous M. szulgai infection to further characterize the clinical characteristics of this condition, identified 17 cases of cutaneous M. szulgai infection in the English literature. Cutaneous M. szulgai infections with subsequent disease dissemination are commonly reported in immunocompromised hosts (10/17, 58.8%), as well as in immunocompetent patients with a history of breached skin integrity, such as invasive medical procedures or trauma. The right upper extremity is the most commonly involved site. Cutaneous M. szulgai infection is well controlled with a combination of anti-mycobacterial therapy and surgical debridement. Disseminated infections required a longer duration of therapy than localized cutaneous infections. Surgical debridement may shorten the duration of antibiotics. CONCLUSIONS: Cutaneous M. szulgai infection is a rare complication of adrenal Cushing's syndrome. Further studies are needed to provide evidence-based guidelines on the best combination of anti-mycobacterial and surgical therapy for managing this rare infective complication.

Study on the Mechanism of Qing-Fei-Shen-Shi Decoction on Asthma Based on Integrated 16S rRNA Sequencing and Untargeted Metabolomics.

Qing-Fei-Shen-Shi decoction (QFSS) consists of Prunus armeniaca L., Gypsum Fibrosum, Smilax glabra Roxb., Coix lacryma-jobi L., Benincasa hispida (Thunb.) Cogn., Plantago asiatica L., Pyrrosia lingua (Thunb.) Farw., Houttuynia cordata Thunb., Fritillaria thunbergii Miq., Cicadae Periostracum, and Glycyrrhizae Radix Et Rhizoma Praeparata Cum Melle. QFSS shows significant clinical efficacy in the treatment of asthma. However, the specific mechanism of QFSS on asthma remains unclear. Recently, multiomics techniques are widely used in elucidating the mechanisms of Chinese herbal formulas. The use of multiomics techniques can better illuminate the multicomponents and multitargets of Chinese herbal formulas. In this study, ovalbumin (OVA) was first employed to induce an asthmatic mouse model, followed by a gavage of QFSS. First, we evaluated the therapeutic effects of QFSS on the asthmatic model mice. Second, we investigated the mechanism of QFSS in treating asthma by using an integrated 16S rRNA sequencing technology and untargeted metabolomics. Our results showed that QFSS treatment ameliorated asthma in mice. In addition, QFSS treatment affected the relative abundances of gut microbiota including Lactobacillus, Dubosiella, Lachnospiraceae_NK4A136_group, and Helicobacter. Untargeted metabolomics results showed that QFSS treatment regulated the metabolites such as 2-(acetylamino)-3-[4-(acetylamino) phenyl] acrylic acid, D-raffinose, LysoPC (15 : 1), methyl 10-undecenoate, PE (18 : 1/20 : 4), and D-glucose6-phosphate. These metabolites are associated with arginine and proline metabolism, arginine biosynthesis, pyrimidine metabolism, and glycerophospholipid metabolism. Correlation analysis indicated that arginine and proline metabolism and pyrimidine metabolism metabolic pathways were identified as the common metabolic pathways of 16s rRNA sequencing and untargeted metabolomics. In conclusion, our results showed that QFSS could ameliorate asthma in mice. The possible mechanism of QFSS on asthma may be associated with regulating the gut microbiota and arginine and proline metabolism and pyrimidine metabolism. Our study may be useful for researchers to study the integrative mechanisms of Chinese herbal formulas based on modulating gut microbiota and metabolism.

Analysis of Data on Fludarabine, Cyclophosphamide, and Rituximab Chemoimmunotherapy for Chronic Lymphocytic Leukemia Shows High Patient Heterogeneity and the Need for More Consideration of Individualized Treatment.

Methods: Data from single-cell RNA sequencing (RNA-seq) of CLL patients were obtained from the Gene Expression Omnibus database. The R package was utilized to analyze the data, and the relation of results was predicted via the GeneMANIA website. The information of 7 samples covered three stages: observation stage, pretreatment by CIT with rituximab, fludarabine, and cyclophosphamide (pre-CIT), and post-CIT. The differentially expressed genes (DEGs) were identified, and functional enrichment analyses were performed. B cell subpopulations and pseudotime trajectories analysis was conducted. Results: A total of 70,659 DEGs were identified. Each patient's DEGs presented their own characteristics, with low similarity. Therefore, it is difficult to identify potential hub genes. Similarly, pathway enrichment analysis showed significant tumor heterogeneity among CLL patients. Analysis of relapsed post-CIT compared to the observation stage suggested that the TP53 pathway should be taken seriously as it is closely related to treatment strategy and patient prognosis. Conclusions: Tumor heterogeneity may be a more common manifestation of CLL. Individualized treatment should be considered for CLL. TP53 abnormality and its regulatory factors should still be the focus of CLL diagnosis and treatment.

Resveratrol reduces lactate production and modifies the ovarian cancer immune microenvironment.

Tumor cells show deregulated metabolism leading to an enrichment of lactate in the tumor microenvironment (TME). This lactate-rich environment has been reported to impair effector T cells. However, T-regulatory cells (Tregs) show metabolic advantages in lactate-rich TME that maintain a strong suppression of effector T cells, which leads to tumor immune evasion. Therefore, the glycolytic process of tumors could represent a therapeutic target, and agents that modify the energy metabolism of tumor cells have therapeutic potential. Resveratrol is a naturally occurring polyphenol that has been confirmed to suppress tumor cells' glycolytic metabolism. In this study, we show that resveratrol induces metabolic reprogramming in ovarian cancer cells. Resveratrol increases oxidative and decreases glycolysis, in association with decreased lactate production both in vitro and in vivo. Lactate reduction in TME weakens the suppressive function of Tregs, and subsequently restores anti-tumor immunity. Significantly, combined resveratrol and PD-1 blockade promote anti-tumor efficacy. These data suggest that resveratrol's anti-tumor actions in ovarian cancer could be explained, in part, through modification of the anti-tumor immunity, and indicate a novel treatment strategy for improving immune checkpoint blockade therapy using resveratrol.

Relationship of serum copper and zinc with kidney function and urinary albumin to creatinine ratio: Cross-sectional data from the NHANES 2011-2016.

BACKGROUND & OBJECTIVE: Chronic kidney disease (CKD) is a common condition in worldwide with underlying causes. The role of trace elements such as copper and zinc in CKD is uncertain. We aimed to examine the relationship of serum copper and zinc with kidney function status and explore its possible effect modifiers in the general population. METHODS: Data from 5353 National Health and Nutrition Examination Survey (NHANES) participants from 2011 to 2016 were analyzed for the role of trace elements in the age range 18 to 80 years. The kidney outcomes were reduced estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 and increased urinary albumin-to-creatinine ratio (ACR) ≥ 30 mg/g. RESULTS: Findings showed a significant positive association between serum copper and urinary ACR (OR = 1.04, 95% CI = 1.00-1.07). Serum copper levels of 18.0 µmol/L (median) or higher (reference level <18.0 µmol/L) were significantly associated with increased urinary ACR (OR = 1.67, 95% CI = 1.21-2.31) after adjusting for confounding factors. In contrast, there was a significant inverse association between serum zinc and reduced eGFR (OR = 0.89,95% CI = 0.81-0.99). Where serum zinc level was greater than 12.3 µmol/L (median), the prevalence of reduced eGFR was lower (OR = 0.65, 95% CI = 0.16-0.60). In addition, a stratified analysis based on various risk factors found that in those individuals with serum albumin greater than 43 g/L or systolic blood pressure greater than 120 mmHg, positive correlations between serum copper and risk of increased urinary ACR was more significant. CONCLUSIONS: Our findings suggest that the reference levels of serum copper and zinc levels in healthy individuals may be different from current understanding. If further studies substantiate the same, the results will be a useful guide for designing future clinical trials and nutritional guidelines.

Case Report: First-Line Immune Checkpoint Inhibitor Plus Chemotherapy for Oral Metastasis in a Patient with Ultra High-Risk Gestational Choriocarcinoma.

Choriocarcinoma (CC) tends to metastasize early into various organs and may exhibit peculiar clinical behaviors specific to metastases. Although chemotherapy has revolutionized the survival of most patients, the mortality rate remains high in cases at ultra high-risk, which may be associated with multiple organs involvement and intolerable toxicity resulting from combination chemotherapy. Here, we illustrate a 46-year-old woman patient with oral and lung lesions whose clinical and morphological heterogeneity misled the preliminary diagnosis. According to the initial pathological report of oral squamous cell carcinomas with lung metastasis and a combined positive score = 100, she received first-line immunotherapy plus two-drug chemotherapy, which obtained a surprisingly favourable outcome. Then, CC was identified by a high level of beta human chorionic gonadotropin (ß-HCG) in serum and biopsies. DNA polymorphic analysis revealed its gestational origin, and a more aggressive standard regimen was subsequently implemented. However, the patient suffered repeated vomiting and myelosuppression, and the duration of treatment was significantly prolonged. Ultimately, she succumbed to death. The clinical course of this report helps to improve the understanding of this disease. We consider immune checkpoint inhibitors as potential first-line alternatives for ultra-high-risk CC patients, which provide a therapeutic reference for clinicians.

Diverse and atypical manifestations of Q fever in a metropolitan city hospital: Emerging role of next-generation sequencing for laboratory diagnosis of Coxiella burnetii.

Although Q fever has been widely reported in the rural areas of China, there is a paucity of data on the epidemiology and clinical characteristics of this disease in large metropolitan cities. In this study, we profile the epidemiology and clinical manifestations of Q fever from a tertiary hospital in Shenzhen, a Southern Chinese metropolitan city with a large immigrant population from other parts of China. A total of 14 patients were confirmed to have Q fever during a nine-year-and-six-month period, five of whom were retrospectively diagnosed during case review or incidentally picked up because of another research project on unexplained fever without localizing features. Some patients had the typical exposure histories and clinical features, while a few other patients had rare manifestations of Q fever, including one with heart failure and diffuse intracapillary proliferative glomerulonephritis, a patient presenting with a spontaneous bacterial peritonitis-like syndrome, and another one with concomitant Q fever and brucellosis. Using a combination of clinical manifestation, inflammatory marker levels, echocardiographic findings and serological or molecular test results, nine, three and two patients were diagnosed to have acute, chronic and convalescent Q fever, respectively. Seven, five and two patients were diagnosed to have Q fever by serological test, nested real-time PCR and next-generation sequencing respectively. Diverse and atypical manifestations are associated with Q fever. The incidence of Q fever is likely to be underestimated. Next-generation sequencing is becoming an important diagnostic modality for culture-negative infections, particularly those that the physicians fail to recognize clinically, such as Q fever.

Radix ranunculus temate saponins sensitizes ovarian cancer to Taxol via upregulation of miR-let-7b.

A common cause of treatment failure in ovarian cancer is acquired drug resistance. Therefore, effective novel drugs against chemoresistance need to be developed. MicroRNAs (miRNAs or miRs) serve key regulatory roles in tumorigenesis and chemoresistance. The objective of the present study was to explore the role of miR-let-7b in ovarian cancer chemoresistance, and to develop novel strategy for the treatment of drug-resistant ovarian cancer. For this purpose, reverse transcription-quantitative PCR was performed to evaluate the expression level of miR-let-7b in fresh ovarian cancer tissues and cell lines. miR-let-7b mimic was transfected into ovarian cancer cell lines. Functional experiments, cell apoptosis and cell viability assays were carried out to identify the tumor-suppressor function of miR-let-7b. The treatment effect of Radix ranunculus temate saponins (RRTS), one of the primary constituents extracted from the traditional Chinese medicine radix Ranunculi ternati, was identified in vitro and in vivo. The results revealed that miR-let-7b was downregulated significantly in chemoresistant ovarian cancer patients. miR-let-7b overexpression suppressed cell growth and invasion and enhanced sensitivity to Taxol of ovarian cancer cells. Furthermore, miR-let-7b levels in ovarian cancer tissue were inversely associated with collagen type III α1 chain (COL3A1) levels. COL3A1, a non-fibrillar collagen associated with chemoresistance, was targeted by miR-let-7b. RRTS showed cytotoxic effects on ovarian cancer cells through inducing miR-let-7b expression and decreasing COL3A1 expression. In addition, RRTS sensitized ovarian cancer to Taxol both in vitro and in vivo. In conclusion, the present results revealed synergistic cytotoxicity of RRTS and Taxol on against ovarian cancer cells via upregulating expression of miR-let-7b. Combination of Taxol and RRTS may be a novel treatment strategy for patients with TR ovarian cancer.