Echinococcosis is a common zoonotic disease in livestock; the type with the highest incidence is cystic echinococcosis (CE). In clinical management, patients with CE of the liver in which the cyst wall is calcified have been found to have better prognoses than those without calcification. In this study, we collected calcified and uncalcified cyst wall tissue from patients with hepatic CE and observed significant changes in the expression of 2336 messenger ribonucleic acids (mRNAs), 178 long noncoding RNAs (lncRNAs), 210 microRNAs (miRNAs), and 33 circular RNAs (circRNAs) using high-throughput sequencing (HTS). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of differentially expressed RNAs (DERNAs: DEmRNAs, DElncRNAs, DEmiRNAs, and DEcircRNAs) were performed to explore these RNAs’ potential biological functions and signaling pathways. Ultimately, the results of hematoxylin and eosin (H&E) and terminal deoxynucleotidyl transferase deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL) staining confirmed the correlation between calcification and apoptosis of the cyst wall. In summary, this study was an initial exploration of the molecular-biological mechanism underlying spontaneous calcification of the hydatid cyst wall, and it provides a theoretical basis for exploring new targets for drug treatment in CE.

BACKGROUND: Previous investigations have shown that local application of nanoparticles presenting the carbohydrate moiety galactose-a-1,3-galactose (α-gal epitopes) enhance wound healing by activating the complement system and recruiting pro-healing macrophages to the injury site. Our companion in vitro paper suggest α-gal epitopes can similarly recruit and polarize human microglia toward a pro-healing phenotype. In this continuation study, we investigate the in vivo implications of α-gal nanoparticle administration directly to the injured spinal cord. METHODS: α-Gal knock-out (KO) mice subjected to spinal cord crush were injected either with saline (control) or with α-gal nanoparticles immediately following injury. Animals were assessed longitudinally with neurobehavioral and histological endpoints. RESULTS: Mice injected with α-gal nanoparticles showed increased recruitment of anti-inflammatory macrophages to the injection site in conjunction with increased production of anti-inflammatory markers and a reduction in apoptosis. Further, the treated group showed increased axonal infiltration into the lesion, a reduction in reactive astrocyte populations and increased angiogenesis. These results translated into improved sensorimotor metrics versus the control group. CONCLUSIONS Application of α-gal nanoparticles after spinal cord injury (SCI) induces a pro-healing inflammatory response resulting in neuroprotection, improved axonal ingrowth into the lesion and enhanced sensorimotor recovery. The data shows α-gal nanoparticles may be a promising avenue for further study in CNS trauma.GRAPHICAL ABSTRACT Putative mechanism of therapeutic action by α-gal nanoparticles. A. Nanoparticles injected into the injured cord bind to anti-Gal antibodies leaked from ruptured capillaries. The binding of anti-Gal to α-gal epitopes on the α-gal nanoparticles activates the complement system to release complement cleavage chemotactic peptides such as C5a, C3a that recruit macrophages and microglia. These recruited cells bind to the anti-Gal coated α-gal nanoparticles and are further polarized into the M2 state. B. Recruited M2 macrophages and microglia secrete neuroprotective and prohealing factors to promote tissue repair, neovascularization and axonal regeneration (C.).

Platelets are reprogrammed by cancer via a process called education, which favors cancer development. The transcriptional profile of tumor-educated platelets (TEPs) is skewed and therefore practicable for cancer detection. This intercontinental, hospital-based, diagnostic study included 761 treatment-naïve inpatients with histologically confirmed adnexal masses and 167 healthy controls from nine medical centers (China, n = 3; Netherlands, n = 5; Poland, n = 1) between September 2016 and May 2019. The main outcomes were the performance of TEPs and their combination with CA125 in two Chinese (VC1 and VC2) and the European (VC3) validation cohorts collectively and independently. Exploratory outcome was the value of TEPs in public pan-cancer platelet transcriptome datasets. The AUCs for TEPs in the combined validation cohort, VC1, VC2, and VC3 were 0.918 (95% CI 0.889-0.948), 0.923 (0.855-0.990), 0.918 (0.872-0.963), and 0.887 (0.813-0.960), respectively. Combination of TEPs and CA125 demonstrated an AUC of 0.922 (0.889-0.955) in the combined validation cohort; 0.955 (0.912-0.997) in VC1; 0.939 (0.901-0.977) in VC2; 0.917 (0.824-1.000) in VC3. For subgroup analysis, TEPs exhibited an AUC of 0.858, 0.859, and 0.920 to detect early-stage, borderline, non-epithelial diseases and 0.899 to discriminate ovarian cancer from endometriosis. TEPs had robustness, compatibility, and universality for preoperative diagnosis of ovarian cancer since it withstood validations in populations of different ethnicities, heterogeneous histological subtypes, and early-stage ovarian cancer. However, these observations warrant prospective validations in a larger population before clinical utilities.
Humans ; Female ; Blood Platelets/pathology* ; Biomarkers, Tumor/genetics* ; Ovarian Neoplasms/pathology* ; China

Elevated fibroblast growth factor 23 (FGF23) in X-linked hypophosphatemia (XLH) results in rickets and phosphate wasting, manifesting by severe bone and dental abnormalities. Burosumab, a FGF23-neutralizing antibody, an alternative to conventional treatment (phosphorus and active vitamin D analogs), showed significant improvement in the long bone phenotype. Here, we examined whether FGF23 antibody (FGF23-mAb) also improved the dentoalveolar features associated with XLH. Four-week-old male Hyp mice were injected weekly with 4 or 16 mg·kg^-1 of FGF23-mAb for 2 months and compared to wild-type (WT) and vehicle (PBS) treated Hyp mice (n = 3-7 mice). Micro-CT analyses showed that both doses of FGF23-mAb restored dentin/cementum volume and corrected the enlarged pulp volume in Hyp mice, the higher concentration resulting in a rescue similar to WT levels. FGF23-mAb treatment also improved alveolar bone volume fraction and mineral density compared to vehicle-treated ones. Histology revealed improved mineralization of the dentoalveolar tissues, with a decreased amount of osteoid, predentin and cementoid. Better periodontal ligament attachment was also observed, evidenced by restoration of the acellular cementum. These preclinical data were consistent with the retrospective analysis of two patients with XLH showing that burosumab treatment improved oral features. Taken together, our data show that the dentoalveolar tissues are greatly improved by FGF23-mAb treatment, heralding its benefit in clinics for dental abnormalities.
Humans ; Male ; Mice ; Animals ; Familial Hypophosphatemic Rickets/pathology* ; Fibroblast Growth Factor-23 ; Retrospective Studies ; Fibroblast Growth Factors/metabolism* ; Bone and Bones/metabolism* ; Phosphates/therapeutic use*

Objective: To investigate the clinicopathological features, immunophenotype and prognosis of nuclear protein in testis (NUT) midline carcinoma. Methods: Twenty-four resection cases of NUT midline carcinoma diagnosed at the Department of Pathology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China from January 2018 to September 2022, were collected, and retrospectively analyzed for their clinicopathological characteristics. Relevant literature was reviewed. Results: All 24 cases of NUT midline carcinoma occurred in the chest or head and neck, including 14 men and 10 women, with a median age of 40 years. Histological examination showed that the tumors were poorly differentiated, with solid nested or sheet-like arrangement, small to medium-sized cells, sparse cytoplasm and coarse granular chromatin, including 5 cases with abrupt squamous epithelial differentiation. Immunohistochemistry showed that all 24 cases were positive for NUT protein, while 16 cases were p63 positive, 19 cases were p40 positive, 15 out of 18 cases were CK5/6 positive. Follow-up data were obtained for 21 patients (follow-up time range, 1-21 months), of which 11 survived, 10 died, and 3 were lost to follow-up. Conclusions: NUT midline carcinoma is a rare and highly aggressive malignancy with unique histological, immunophenotypic and molecular features. It has a poor prognosis.
Male ; Humans ; Female ; Adult ; Neoplasm Proteins/genetics* ; Nuclear Proteins/genetics* ; Retrospective Studies ; Carcinoma/surgery* ; Testicular Neoplasms

Humans ; Lymphoma, B-Cell

OBJECTIVE: To investigate the effect of Echinococcus multilocularis infection on Tim3 expression and its co-expression with immune checkpoint molecules 2B4 and LAG3 in spleen natural killer (NK) cells of mice. METHODS: C57BL/6 mice, each weighing (20 ± 2) g, were randomly divided into a high-dose infection group (15 mice), a low-dose infection group (13 mice), and a control group (11 mice). Mice in the high- and low-dose infection groups were inoculated with 2 000 and 50 Echinococcus multilocularis protoscolices via the hepatic portal vein, while animals in the control group was injected with an equivalent amount of physiological saline via the hepatic portal vein. Mouse spleen cells were harvested 12 and 24 weeks post-infection, and Tim3 expression and its co-expression with 2B4 and LAG3 in NK cells were detected using flow cytometry. RESULTS: There were significant differences in the proportions of Tim3 expression (F = 13.559, P < 0.001) and Tim3 and 2B4 co-expression (F = 12.465, P < 0.001) in mouse spleen NK cells among groups 12 weeks post-infection with E. multilocularis, and the proportion of Tim3 expression was significantly higher in mouse spleen NK cells in the low-dose infection group [(23.84 ± 2.28)%] than in the high-dose infection group [(15.72 ± 3.67)%] and the control group [(16.14 ± 3.83)%] (both P values < 0.01), while the proportion of Tim3 and 2B4 co-expression was significantly higher in mouse spleen NK cells in the low-dose infection group [(22.20 ± 2.13)%] than in the high-dose infection group [(14.17 ± 3.81)%] and the control group [(15.20 ± 3.77)%] (both P values < 0.01). There were significant differences in the proportions of Tim3 expression (F = 5.243, P < 0.05) and Tim3 and 2B4 co-expression (F = 4.659, P < 0.05) in mouse spleen NK cells among groups 24 weeks post-infection with E. multilocularis infection, and the proportions of Tim3 expression and Tim3 and 2B4 co-expression were significantly lower in mouse spleen NK cells in the high-dose infection group [(20.55 ± 7.04)% and (20.98 ± 7.12)%] than in the control group [(31.38 ± 3.19)% and (31.25 ± 3.06)%] (both P values < 0.05), and there were no significantly difference between the proportions of Tim3 expression and Tim3 and 2B4 co-expression in splenic NK cells in the low-dose infection group [(26.80 ± 6.47)% and (26.48 ± 6.48)%] and the control group (both P > 0.05). There were no significant differences in the proportions of Tim3 and LAG3 co-expression in mouse spleen NK cells among groups 12 (F = 2.283, P > 0.05) and 24 weeks post-infection (F = 0.375, P > 0.05). In the low-dose infection group, there were no significant differences in the proportions of Tim3 expression or Tim3 and 2B4 co-expression in mouse spleen NK cells 12 (t = -1.137, P > 0.05) or 24 weeks post-infection (t = -1.658, P > 0.05), and the proportion of Tim3 and LAG3 co-expression increased in mouse spleen NK cells 24 weeks post-infection relative to 12 weeks post-infection (t = -5.261, P < 0.01). In the highdose infection group, there was no significant difference in the proportion of Tim3 expression in mouse spleen NK cells 12 and 24 weeks post-infection (t = -1.546, P > 0.05); however, the proportions of Tim3 co-expression with 2B4 and LAG3 increased in mouse splenic NK cells 24 weeks post-infection relative to 12 weeks post-infection (t = -2.425 and -4.745, both P values < 0.05). CONCLUSIONS The Tim3 expression and Tim3 co-expression with LAG3 and 2B4 on spleen NK cells is affected by doses of E. multilocularis infection and disease stages, and present different phenotypes during the course of alveolar echinococcosis. NK cells tend to form an immunosuppressive phenotype with the progression of E. multilocularis infection, which facilitates immune escape and chronic parasitism of E. multilocularis.
Animals ; Mice ; Hepatitis A Virus Cellular Receptor 2/genetics* ; Killer Cells, Natural ; Mice, Inbred C57BL ; Spleen

Humans ; Pilot Projects ; Prospective Studies ; Pulmonary Emphysema/surgery* ; Lung/surgery* ; Emphysema ; Perfusion ; Tomography, Emission-Computed ; Tomography ; Tomography, Emission-Computed, Single-Photon ; Pneumonectomy ; Bronchoscopy/methods*

Nonpharmaceutical interventions (NPIs) have been commonly deployed to prevent and control the spread of the coronavirus disease 2019 (COVID-19), resulting in a worldwide decline in influenza prevalence. However, the influenza risk in China warrants cautious assessment. We conducted a cross-sectional, seroepidemiological study in Shandong Province, Northern China in mid-2021. Hemagglutination inhibition was performed to test antibodies against four influenza vaccine strains. A combination of descriptive and meta-analyses was adopted to compare the seroprevalence of influenza antibodies before and during the COVID-19 pandemic. The overall seroprevalence values against A/H1N1pdm09, A/H3N2, B/Victoria, and B/Yamagata were 17.8% (95% CI 16.2%-19.5%), 23.5% (95% CI 21.7%-25.4%), 7.6% (95% CI 6.6%-8.7%), and 15.0 (95% CI 13.5%-16.5%), respectively, in the study period. The overall vaccination rate was extremely low (2.6%). Our results revealed that antibody titers in vaccinated participants were significantly higher than those in unvaccinated individuals (P < 0.001). Notably, the meta-analysis showed that antibodies against A/H1N1pdm09 and A/H3N2 were significantly low in adults after the COVID-19 pandemic (P < 0.01). Increasing vaccination rates and maintaining NPIs are recommended to prevent an elevated influenza risk in China.

Congenital heart surgery (CHS) is technically demanding, and its training is extremely complex and challenging. Training of the surgeon’s technical skills has relied on a preceptorship format in which the trainees are gradually exposed to patients in the operating room under the close tutelage of senior staff surgeons. Training in the operating room is an inefficient process and the concept of a learning curve is no longer acceptable in terms of patient outcomes. The benefits of surgical simulation in training of congenital heart surgeons are well known and appreciated. However, adequate surgical simulation models and equipment for training have been scarce until the recent development of three-dimensionally (3D) printed models. Using comprehensive 3D printing and silicone-molding techniques, realistic simulation training models for most congenital heart surgical procedures have been produced. Newly developed silicone-molded models allow efficient CHS training in a stressfree environment with instantaneous feedback from the proctors and avoids risk to patients. The time has arrived when all congenital heart surgeons should consider surgical simulation training before progressing to real-life operating in a similar fashion to the aviation industry where all pilots are required to complete simulation training before flying a real aircraft. It is argued here that simulation training is not an option anymore but should be a mandatory component of CHS training.