s u m m a r yBackground: The ongoing outbreak of COVID-19 pneumonia is globally concerning. We aimed to investigate the clinical and CT features in the pregnant women and children with this disease, which have not been well reported. Methods: Clinical and CT data of 59 patients with COVID-19 from January 27 to February 14, 2020 were retrospectively reviewed, including 14 laboratory-confirmed non-pregnant adults, 16 laboratory-confirmed and 25 clinically-diagnosed pregnant women, and 4 laboratory-confirmed children. The clinical and CT features were analyzed and compared. Findings: Compared with the non-pregnant adults group ( n = 14), initial normal body temperature (9 [56%] and 16 [64%]), leukocytosis (8 [50%] and 9 [36%]) and elevated neutrophil ratio (14 [88%] and 20 [80%]), and lymphopenia (9 [56%] and 16 [64%]) were more common in the laboratory-confirmed ( n = 16) and clinically-diagnosed ( n = 25) pregnant groups. Totally 614 lesions were detected with predominantly peripheral and bilateral distributions in 54 (98%) and 37 (67%) patients, respectively. Pure ground-glass opacity (GGO) was the predominant presence in 94/131 (72%) lesions for the non-pregnant adults. Mixed consolidation and complete consolidation were more common in the laboratory-confirmed (70/161 [43%]) and clinically-diagnosed (153/322 [48%]) pregnant groups than 37/131 (28%) in the non-pregnant adults ( P = 0 ·007, P < 0 ·001). GGO with reticulation was less common in 9/161 (6%) and 16/322 (5%) lesions for the two pregnant groups than 24/131 (18%) for the non-pregnant adults ( P = 0 ·001, P < 0 ·001). The pulmonary involvement in children with COVID-19 was mild with a focal GGO or consolidation. Twentythree patients underwent follow-up CT, revealing progression in 9/13 (69%) at 3 days whereas improvement in 8/10 (80%) at 6-9 days after initial CT scans. Interpretation: Atypical clinical findings of pregnant women with COVID-19 could increase the difficulty in initial identification. Consolidation was more common in the pregnant groups. The clinically-diagnosed cases were vulnerable to more pulmonary involvement. CT was the modality of choice for early detection, severity assessment, and timely therapeutic effects evaluation for the cases with epidemic and clinical features of COVID-19 with or without laboratory confirmation. The exposure history and clinical symptoms were more helpful for screening in children versus chest CT.

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Toxoplasma gondii has been suggested as an important opportunistic pathogen in immunocompromised patients. We conducted a global meta-analysis to assess the prevalence and odds ratios (ORs) of T. gondii infection in immunocompromised individuals. Electronic databases were reviewed for T. gondii infection in HIV/AIDS patients, cancer patients, and transplant recipients, and meta-analyses were conducted to calculate overall estimated prevalence and ORs using random or fixed-effects models. Totally, 72 eligible studies were included. The estimated pooled prevalence of T. gondii infection in immunocompromised patients and the control was 35.9 and 24.7% (p < 0.001), with an OR of 2.24, i.e., 42.1 and 32.0% for HIV/AIDS patients and the control (p < 0.05), 26.0 and 12.1% for cancer patients and the control (p < 0.001), and 42.1 and 34.5% for transplant recipients and the control (p > 0.05), whose estimated pooled ORs were 1.92 (95% CI, 1.44–2.55), 2.89 (95% CI, 2.36–3.55), and 1.51 (95% CI, 1.16–1.95), respectively. This study is the first to demonstrate that the immunocompromised patients are associated with higher odds of T. gondii infection, and appropriate prevention and control measures are highly recommended for these susceptible populations.

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Chemotherapy and radiotherapy predominantly improve the clinical outcomes of patients with human papillomavirus (HPV)-related head and neck squamous cell carcinoma (HNSCC). Whether this superiority goes on when treated with immune checkpoint inhibitors is still unclear. This study sought to determine the predictive value and potential mechanisms of HPV status for the treatment of programmed cell death 1 (PD-1)/ligand 1(PD-L1) inhibitors. We conducted an integrated analysis of the relationships between HPV status and PD-L1, tumor mutation burden (TMB) and inflammation-related immune cells and molecules, based on the analysis of repository databases and resected HNSCC specimens. The pooled analysis of overall survival (OS) and objective response rate (ORR) suggested that HPV-positive patients benefited more from PD-1/PD-L1 inhibitors than HPV-negative patients (OS: hazard ratio (HR) = 0.71, p = 0.02; ORR: 21.9% vs 14.1%, odds ratio (OR) = 1.79, p = 0.01). Analysis of public databases and resected HNSCC specimens revealed that HPV status was independent of PD-L1 expression and TMB in HNSCC. However, HPV infection significantly increased T-cell infiltration, immune effector cell activation and the diversity of T-cell receptors. Notably, HPV-positivity correlated with increased immune cytolytic activity and a T-cell-inflamed gene expression profile. This work provides evidence that HPV status can be used to predict the effectiveness of PD-1 inhibitors in HNSCC, independently of PD-L1 expression and TMB, and probably results from an inflamed immune microenvironment induced by HPV infection.

Nestin defines a novel tendon stem/progenitor cell subpopulation with high tenogenesis potential.

As tendon stem/progenitor cells were reported to be rare in tendon tissues, tendons as vulnerable targets of sports injury possess poor self-repair capability. Human ESCs (hESCs) represent a promising approach to tendon regeneration. But their teno-lineage differentiation strategy has yet to be defined. Here, we report that force combined with the tendon-specific transcription factor scleraxis synergistically promoted commitment of hESCs to tenocyte for functional tissue regeneration. Force and scleraxis can independently induce tendon differentiation. However, force alone concomitantly activated osteogenesis, while scleraxis alone was not sufficient to commit, but augment tendon differentiation. Scleraxis synergistically augmented the efficacy of force on teno-lineage differentiation and inhibited the osteo-lineage differentiation by antagonized BMP signaling cascade. The findings not only demonstrated a novel strategy of directing hESC differentiation to tenocyte for functional tendon regeneration, but also offered insights into understanding the network of force, scleraxis and bmp2 controlling tendon-lineage differentiation.

Background: Diarrhea caused by opportunistic intestinal protozoa is a common problem in HIV infection. We aimed to establish the prevalence of Cryptosporidium, misrosporidia, and Isospora in HIV-infected people using a systematic review and meta-analysis, which is central to developing public policy and clinical services. Methods: We searched PubMed, ScienceDirect, Google Scholar, Embase, Chinese Web of Knowledge, Wanfang, and Chongqing VIP databases for studies reporting Cryptosporidium, microsporidia, or Isospora infection in HIV-infected people. We extracted the numbers of people with HIV and protozoa infection, and estimated the pooled prevalence of parasite infection by a random effects model. Results: Our research identified 131 studies that reported Cryptosporidium, microsporidia, and Isospora infection in HIV-infected people. We estimated the pooled prevalence to be 14.0% (3283/43,218; 95% CI: 13.0-15.0%) for Cryptosporidium, 11.8% (1090/18,006; 95% CI: 10.1-13.4%) for microsporidia, and 2.5% (788/105,922; 95% CI: 2.1-2.9%) for Isospora. A low prevalence of microsporidia and Isospora infection was found in high-income countries, and a high prevalence of Cryptosporidium and Isospora infection was found in sub-Saharan Africa. We also detected a high prevalence of Cryptosporidium, microsporidia, and Isospora infection in patients with diarrhea. Sensitivity analysis showed that three studies significantly affect the prevalence of Isospora, which was adjusted to 5.0% (469/8570; 95% CI: 4.1-5.9%) by excluding these studies. Conclusions: Our findings suggest that HIV-infected people have a high prevalence of Cryptosporidium, microsporidia, and Isospora infection in low-income countries and patients with diarrhea, especially in sub-Saharan Africa, reinforcing the importance of routine surveillance for opportunistic intestinal protozoa in HIV-infected people.