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Rationale: Venous thrombosis remains a significant problem in modern days. Genetic factors contribute to a subset of patients with venous thrombosis. It is sometimes challenging to identify the underlying culprit in thrombophilic individuals based on traditional laboratory testing and Sanger sequencing. Patient concerns: A thrombophilic family presented with multiple venous thrombosis was examined. Diagnoses: Molecular genetic analysis revealed a pathogenic missense variant of the PROS1 gene. Based on this finding and clinical manifestations, a final diagnosis of protein S deficiency was made. Interventions: Whole exome sequencing (WES) of the proband was performed to identify disease-causing variants. Subsequently, Sanger sequencing was performed to validate the variant in the affected members. Outcomes: Using WES, we rapidly identified a proven pathogenic missense variant (c.1543C > T, p.Arg515Cys) in the sex hormone-binding globulin domain of PROS1, which was confirmed by Sanger sequencing. The decreased level and activity of protein S caused by the variant explained the phenotypes of the family. Patients received rivaroxaban as a long-term anticoagulation therapy and achieved a good prognosis. Lessons: Our study suggests WES as a rapid search strategy to identify the genetic factors underlying thrombophilic disorders. Patients with venous thrombosis caused by PROS1 mutations could receive rivaroxaban as the first choice of anticoagulation therapy.

Cholangiocarcinoma (CCA) is one of the most common malignant tumors. Although gene-targeted therapies have significantly improved the outcome of many cancers, the results are still not satisfactory for patients with CCA. Owing to the lack of an effective biomarker for guiding clinical treatment and monitoring prognosis in patients with CCA, the purpose of this study was to identify a new biomarker that could help predict the outcome of patients with CCA using bioinformatics tools. Gene expression data were collected from three publicly available datasets, comprising 263 patients with CCA and 22 healthy controls. Differentially expressed genes were obtained using the limma package (FDR 1), and the respective protein–protein interaction revealed five relevant genes in the STRING dataset (TOP2A, BUB1, RRM2, TYMS, and KIF4A). The immunohistochemistry and PCR were used to analyze the difference in KIF4A expression in CCA. Kinesin Family Member 4A (KIF4A) was the only gene significantly associated with overall patient survival (P .035), with higher KIF4A expression being associated with poor survival rates. Moreover, KIF4A was significantly correlated with the infiltration of activated memory T cells (P = .0198) and activated mast cells (P = .008) in the tumor microenvironment. Increase in KIF4A expression affected the infiltration degree of the immune cells, which may be involved in the regulation of immune tolerance by CCA cells. The results indicated that the expression of KIF4A in CCA was higher than that in paracancerous tissues. Taken together, these findings suggest that KIF4A could be a potential new biomarker in CCA for predicting the response of patients to targeted immunotherapies.

Rationale: Although vertebral osteomyelitis (VO) is commonly associated with high morbidity and high recurrence rate, effective diagnostic and prognostic biomarkers of VO are still lacking. Patients concerns: Case 1: a 60-year-old male had had upper back pain for 3 days. Case 2: a 71-year-old female presented upper back pain for 2 days. Diagnoses: Based on physical examination and findings of magnetic resonance imaging and findings by matrix-assisted laser desorption ionization-time of flight mass spectrometry, they were diagnosed with Staphylococcus aureus VO. Interventions: Using Sengenics ImmunomeTM Protein Array by analyzing autoantibodies in both VO patients, potential biomarkers of VO were explored. Outcomes: Four subjects with more than 1600 antigens screened while the results showed that 14-3-3 protein gamma, pterin-4-alpha-carbinolamine dehydratase, fructose-bisphosphate aldolase A, and keratin type II cytoskeletal 8 were highly differentially expressed among VO and controls. Relevant auto-antibody profiles were discovered after intra-group and inter-group comparison, and based on functional rationality, an adapter protein 14-3-3 protein gamma, and pterin-4-alpha-carbinolamine dehydratase that involved in tetrahydrobiopterin biosynthesis, might serve as valuable diagnostic biomarkers. Lessons: This pilot study on 4 subjects with more than 1600 antigens screened on the Sengenics Immunome protein array provided a general outlook on autoantibody biomarker profiles of VO subjects. Future large-scale trials with longer follow-up times are warranted.

Background Fungal keratitis is one of the leading causes of ocular morbidity. The prognosis of fungal keratitis is poorer than many other forms of keratitis but the research of which relatively lags behind. We conducted a bibliometric and visualized analysis in order to characterize the overall status, general trends and current foci of keratomycosis research field. Methods Literature database ranged from 1959 to 2019 was obtained from web of science core collection and analyzed by Citespace and VOSviewer software. Results A total of 1906 papers of fungal keratitis were retrieved and derived a 27,917 references document set. The number of publications increased rapidly in past 30 years. Cornea was the journal published most papers of keratomycosis. The leading countries were United States of America (USA), India and Peoples Republic of China (PRC), from where came the most productive and most cited institutions and authors. Co-cited reference analysis revealed the most cited manuscripts were concerned about epidemiology or spectrum. Lens-associated Fusarium, amphotericin B, voriconazole, corneal cross-linking, predisposing factor are some of the high frequency topics in clustered co-cited reference analysis and co-occurrence keywords analysis. Burst detection analysis of keywords showed ocular drug delivery was the new research foci. Conclusion From this study, we received an overall view to the current status, trends and hot spots of fungal keratitis research field. Visualized bibliometric analysis is an efficient way for literature learning and useful for future researchers.

Introduction Amyotrophic lateral sclerosis (ALS) is the most common cause of motor neuron disease, and effective treatment for ALS is still lacking. Transactive response (TAR) -DNA-binding protein-43 (TDP-43) is aggregated in the neurons of ALS patients. Animal studies shown TDP-43 aggregation can be attenuated by enhancing autophagy by tamoxifen. However, its beneficial effects for ALS patients remain unknown. Methods Eighteen patients with ALS without mutations in superoxide dismutase-1 (SOD-1) or fused in sarcoma (FUS) genes were randomly assigned into the tamoxifen 40 mg/day or placebo group in a double-blinded manner and all were given riluzole twice daily. Participants were followed up at 1, 3, 6, and 12 months. The primary end point was time to death or dependence on mechanical ventilation. Secondary end points were decline of the revised ALS Functional Rating Scale (ALSFRS-R) score and pulmonary function measured by forced vital capacity (FVC). Results Ten participants were randomly assigned in the treatment group with tamoxifen, 7 finished trial, 1 reach primary endpoint; while 8 participants in the placebo group, 2 finished trial and 2 reach primary end point. The proportion of participants reaching the primary end point was lower in the tamoxifen group but did not reach statistical significance. At the 1-, 3-, and 6-month follow-up, the average decline rates of the ALSFRS-R score were slower in the tamoxifen group. No significant difference was observed in FVC and ALSFRS-R score at 12 months between groups. Conclusion Tamoxifen exerted only a modest effect on attenuate progression for 6 months in this small trial. Additional larger scale studies should be necessary to confirm whether enhancing autophagy can attenuate ALS progression.

Background Hyaluronan (HA), glucosamine, and chondroitin sulfate are widely consumed as dietary supplements for the treatment of knee osteoarthritis (OA). This study aimed to explore the efficacy and safety of a dietary liquid supplement mixture containing HA, glucosamine, and chondroitin in patients with knee OA who had moderate knee pain (visual analogue scale of 4-6 points). Methods This was a short-term, randomized, double-blind, placebo-controlled study. Subjects were allocated to administer either a bottle of 20 mL supplement mixture (50 mg HA plus 750 mg glucosamine plus 250 mg chondroitin, namely A + HA) or placebo once daily for 8 weeks. Outcome measures included the Knee Injury and Osteoarthritis Outcome Score, Western Ontario and McMaster Universities Osteoarthritis Index, 36-item Short Form Survey (SF-36), Chinese version of Pittsburgh Sleep Quality Index, and incidence of adverse event were evaluated at the end of week 8. Efficacy analyses were conducted in the modified intent-to-treat population. Results Of the 80 subjects in the modified intent-to-treat population, 39 received A + HA while 41 received placebo. After 8 weeks of treatment, the A + HA group failed to demonstrate a significant symptomatic efficacy and quality of life improvement in terms of Knee Injury and Osteoarthritis Outcome Score, Western Ontario and McMaster Universities Osteoarthritis Index, SF-36, and Chinese version of Pittsburgh Sleep Quality Index as compared to the placebo group. However, the mean changes in most of the SF-36 scale scores were numerically higher in the A + HA group than in the placebo group. No treatment-related adverse event was reported in both groups. Conclusions This present study found that the combination of liquid low molecular weight HA, glucosamine, and chondroitin oral supplement did not effectively improve knee OA pain and symptoms after short-term use in knee OA patients with moderate knee pain. However, these results should be interpreted with caution due to the intrinsic limitation of the study design.

Coronary artery disease (CAD) is a life-threatening medical emergency which needs urgent medical attention. Percutaneous coronary intervention (PCI) is common and necessary for patients with CAD. The effect of hypercholesterolemia and diabetes on long-term outcomes in patients with stable CAD receiving PCI is unclear. In this study, patients with stable CAD who underwent PCI were prospectively divided into 4 groups according to the presence or absence of diabetes or hypercholesterolemia. Clinical characteristics, risk factors, medications, angiographic findings, and outcome predictors were analyzed and long-term outcomes compared between groups. Of the 1676 patients studied, those with hypercholesterolemia and diabetes had the highest all-cause mortality rate after PCI (P

Supplemental Digital Content is available in the text, Background: Cases of multiple tumors are rarely reported in China. In our study, a 57-year-old female patient had concurrent squamous cell carcinoma, mucoepidermoid carcinoma, brain cancer, bone cancer, and thyroid cancer, which has rarely been reported to date. Methods: To determine the relationship among these multiple cancers, available DNA samples from the thyroid, lung, and skin tumors and from normal thyroid tissue were sequenced using whole exome sequencing. Results: The notable discrepancies of somatic mutations among the 3 tumor tissues indicated that they arose independently, rather than metastasizing from 1 tumor. A novel deleterious germline mutation (chr22:29091846, G->A, p.H371Y) was identified in CHEK2, a Li–Fraumeni syndrome causal gene. Examining the status of this novel mutation in the patient's healthy siblings revealed its de novo origin. Conclusion: Our study reports the first case of Li–Fraumeni syndrome-like in Chinese patients and demonstrates the important contribution of de novo mutations in this type of rare disease.

Rationale:Clostridium difficile infections (CDIs) have been reported in China, but detailed clinical symptoms of coinfection by 2 C difficile ribotypes have not been documented.Patients concerns:An 83-year-old male with a 10-day history of diarrhea and urinary tract infection was admitted to

The global epidemiological landscape of childhood acute gastroenteritis (AGE) is changing after the introduction of 2 effective rotavirus vaccines in 2006. A comprehensive evaluation for viral etiology of childhood AGE in Taiwan, where rotavirus vaccination was provided by the private sector since 2006, is lacking. From 2009 to 2011, children younger than 5 years of age with AGE who were hospitalized at 3 sentinel hospitals were enrolled in this surveillance study. Stool specimens were tested for rotavirus, norovirus, enteric adenovirus, and astrovirus. The epidemiologic and clinical information was collected by questionnaire-based interviews and chart reviews. Viral agents were detected in 1055 (37.5%) of 2810 subjects, with rotavirus (21.2%) being the leading cause of disease, followed by norovirus (14.9%), enteric adenovirus (3.74%), astrovirus (2.10%), and a mixture of at least 2 of 4 above-mentioned viruses (4.06%). The majority (56%) of the viral AGE occurred in children 10 were independent factors respectively associated with an increased risk of norovirus (adjusted odds ratio [aOR] 9.034, P = 0.0003) and rotavirus (aOR, 3.284, P

Background Lymphangioleiomyomatosis (LAM) is a rare disease affecting young women caused by abnormal proliferation of smooth muscle-like cells (LAM cells) in the lungs and extrapulmonary sites (extrapulmonary LAM). The objective of this case series is to demonstrate marked regression in 2 cases of retroperitoneal LAM after treatment with everolimus, an mTOR inhibitor. Methods We enrolled 2 cases with large volume, extrapulmonary pelvic LAM, and evaluated them with contrast-enhanced abdominal computed tomographic (CT) scans at presentation and serially during treatment with everolimus. Results were objectively quantified using the Response Evaluation Criteria in Solid Tumors, RECIST, Version 1.1. Results After 12 to 18 months of treatment with everolimus, both patients showed substantial reduction in the volume of their tumors. The first had about 50% regression of the pelvic LAM and renal angiomyolipoma (AML). The second patient had extensive abdomino-pelvic LAM which after treatment showed complete remission. Both patients have not demonstrated disease progression after nearly 4 and 2 years of follow-up, respectively. Conclusions This case series demonstrates the enormous value of mTOR inhibitors (specifically everolimus) in the management of extrapulmonary pelvic LAM, of which there is no effective treatment currently available.

Kawasaki disease (KD) is a systemic vasculitis of unknown etiology. IFNG gene encoding interferon (IFN)-γ, produced by natural killer cells and T cells, has been suggested to play an important role in the immunopathogenesis of Kawasaki disease. The aim of this study was to examin the correlation of gene polymorphisms of the IFNG gene and plasma levels of IFN-γ in KD patients and their outcomes. A total of 950 subjects (381 KD and 569 controls) were recruited. Three tagging single-nucleotide polymorphisms (rs2069718, rs1861493, rs2069705) were selected for TaqMan allelic discrimination assay. Clinical phenotypes, coronary artery lesions (CAL), coronary artery aneurysms (CAA) and intravenous immunoglobulin (IVIG) treatment outcomes were collected for analysis. Plasma IFN-γ levels were also measured with an enzyme-linked immunosorbent assay. Polymorphisms of the IFNG gene were significantly different between the normal controls and KD patients. The G allele of rs1861493 conferred a better response to IVIG treatment in KD patients. AA allele frequencies of rs1861493 were also associated with a significantly higher risk of CAA in KD patients. Furthermore, the plasma IFN-γ level was lower in the AA allele than in the GG allele of rs1861493 both before and after IVIG treatment in KD patients. This study provides the first evidence supporting an association between IFNG gene polymorphisms, susceptibility of KD, IVIG responsiveness, and plasma IFN-γ levels in KD patients.

Several authors have described anatomic variations of the aortic arch in 13% to 20% of the patients who do not have aortic disease. However, few studies have evaluated these patterns in the thoracic aortic dissection (TAD). In the authors’ knowledge, this is the first survey that specifically investigates the frequency of these variations in a broad, nonselected group of Chinese patients with aortic dissection. Furthermore, it compares this group with a group of patients without aortic disease. The objective of this study was to define the variation frequency of the aortic arch branches pattern using the tomographic studies of 525 Chinese patients with a diagnosis of TAD. The Stanford classification was used to set the site of the initial tear of the dissection. In addition, we performed an epidemiological analysis of the aortic arch anatomic variations in TAD, and its possible implications for surgical or endovascular treatment. The general hypothesis proposal asserted that Chinese patients with dissection of the aorta have a similar incidence of variations of the aortic arch to the patients without aortic disease. A retrospective study of cases and controls was carried out using the tomographic studies (CT) of all patients admitted to the First Affiliated Hospital of Zhengzhou University, located at Henan-China, with a confirmed diagnosis of aortic dissection from January 2012 until December 2014. The group of cases consisted of 525 patients: 374 men and 151 women, with a mean age of 52.27 years (range, 20–89). The average age of the patients with Stanford A and B aortic dissection was 49.46 and 53.67, respectively. The control group consisted of 525 unselected patients without TAD who underwent a CT scan of the chest due to other indications. This group consisted of 286 men and 239 women, with a mean age of 53.60 years (range, 18–89). All the patients with aneurysm or dissection were excluded from the control group. We performed a statistical analysis of demographic data. The study found 7 different patterns of the aortic arch on both groups of cases and controls. Within the 525 patients with TAD were observed 85 (16.19%) anatomical variations, while the control group showed 112 variations (21.33%); P = 0.033. The most common anatomical variant was the bovine arch, found in 62 (11.80%) cases of TAD compared with 77 (14.66%) in the control group; P = 0.172. Anatomical variations were observed in 14.32% of the patients with Stanford A dissection and 17.09% of the patients with Stanford B dissection; P = 0.425. Patients with Stanford A dissection showed the pattern of bovine arch in 23 (13.21%) of 174 cases. In contrast, the patients with Stanford B dissection showed it in 39 (11.11%) of 351 cases; P = 0.481. The anatomical variant defined as vertebral artery of direct origin of the aortic arch was more frequent in the patients with Stanford B dissection (5.12%). The patients with Stanford A dissection presented this pattern in 1.14% of the cases; P = 0.025. This study observed an increased frequency of aortic dissection in the subgroup from 41 to 60 years old. In the subgroup from 41 to 60 years old without TAD, a greater frequency of anatomical variations were found than in the patients with TAD (20.81% vs 14.23%; P = 0.050). The same fashion was seen in patients older than 80 years (27.27% vs 0%; P = 0.030). The anatomical variations of the aortic arch with TAD occurred in 14.97% of the male patients and 19.20% of the female patients compared to 21.67% to 20.92% in the control group; P = 0.026 and P = 0.681, respectively. The aortic arch variations were found less frequently in the TAD group than in the control group in the present Chinese series. The bovine arch was considered the variant pattern of the major frequency in the patients with TAD and the control group. The anatomical variant of 4 branches, defined as vertebral artery of direct origin of the aortic arch, was more frequent in patients with Stanford B aortic dissection than in the patients with Stanford A. This finding might show an association between the geometry of the aortic arch and the site of onset of first intimal tear of dissection.