Identification of candidate genes for Fusarium head blight resistance from QTLs using RIL population in wheat.

Fusarium head blight (FHB) stands out as one of the most devastating wheat diseases and leads to significantly grain yield losses and quality reductions in epidemic years. Exploring quantitative trait loci (QTL) for FHB resistance is a critical step for developing new FHB-resistant varieties. We previously constructed a genetic map of unigenes (UG-Map) according to the physical positions using a set of recombinant-inbred lines (RILs) derived from the cross of 'TN18 × LM6' (TL-RILs). Here, the number of diseased spikelets (NDS) and relative disease index (RDI) for FHB resistance were investigated under four environments using TL-RILs, which were distributed across 13 chromosomes. A number of 36 candidate genes for NDS and RDI from of 19 stable QTLs were identified. The average number of candidate genes per QTL was 1.89, with 14 (73.7%), two (10.5%), and three (15.8%) QTLs including one, two, and 3-10 candidate genes, respectively. Among the 24 candidate genes annotated in the reference genome RefSeq v1.1, the homologous genes of seven candidate genes, including TraesCS4B02G227300 for QNds/Rdi-4BL-4553, TraesCS5B02G303200, TraesCS5B02G303300, TraesCS5B02G303700, TraesCS5B02G303800 and TraesCS5B02G304000 for QNds/Rdi-5BL-9509, and TraesCS7A02G568400 for QNds/Rdi-7AL-14499, were previously reported to be related to FHB resistance in wheat, barely or Brachypodium distachyon. These genes should be closely associated with FHB resistance in wheat. In addition, the homologous genes of five genes, including TraesCS1A02G037600LC for QNds-1AS-2225, TraesCS1D02G017800 and TraesCS1D02G017900 for QNds-1DS-527, TraesCS1D02G018000 for QRdi-1DS-575, and TraesCS4B02G227400 for QNds/Rdi-4BL-4553, were involved in plant defense responses against pathogens. These genes should be likely associated with FHB resistance in wheat.

A small molecule compound targeting hemagglutinin inhibits influenza A virus and exhibits broad-spectrum antiviral activity.

Influenza A virus (IAV) is a widespread pathogen that poses a significant threat to human health, causing pandemics with high mortality and pathogenicity. Given the emergence of increasingly drug-resistant strains of IAV, currently available antiviral drugs have been reported to be inadequate to meet clinical demands. Therefore, continuous exploration of safe, effective and broad-spectrum antiviral medications is urgently required. Here, we found that the small molecule compound J1 exhibited low toxicity both in vitro and in vivo. Moreover, J1 exhibits broad-spectrum antiviral activity against enveloped viruses, including IAV, respiratory syncytial virus (RSV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), human coronavirus OC43 (HCoV-OC43), herpes simplex virus type 1 (HSV-1) and HSV-2. In this study, we explored the inhibitory effects and mechanism of action of J1 on IAV in vivo and in vitro. The results showed that J1 inhibited infection by IAV strains, including H1N1, H7N9, H5N1 and H3N2, as well as by oseltamivir-resistant strains. Mechanistic studies have shown that J1 blocks IAV infection mainly through specific interactions with the influenza virus hemagglutinin HA2 subunit, thereby blocking membrane fusion. BALB/c mice were used to establish a model of acute lung injury (ALI) induced by IAV. Treatment with J1 increased survival rates and reduced viral titers, lung index and lung inflammatory damage in virus-infected mice. In conclusion, J1 possesses significant anti-IAV effects in vitro and in vivo, providing insights into the development of broad-spectrum antivirals against future pandemics.

Gefitinib, an effective treatment option for patients with pulmonary enteric adenocarcinoma harboring compound EGFR L858R and A871G mutation.

Pulmonary enteric adenocarcinoma (PEAC) is a rare lung adenocarcinoma with morphological and immunohistochemical similarities to colorectal adenocarcinoma and intestinal differentiation. PEAC belongs to the group of non-small-cell lung carcinoma (NSCLC) and is defined as having a more than 50% intestinal differentiation component. We report a postoperative (T4N2M0 stage IIIb) PEAC patient with EGFR L858R + A871G combined mutation. Following surgery, the patient underwent treatment with the first-generation EGFR-TKI, gefitinib, and achieved an impressive 5-year progression-free survival (PFS). This suggests that gefitinib may serve as an effective treatment option for PEAC patients with EGFR L858R + A871G compound mutations.

Treatment of inferior pole fracture of the patella with tension-free external immobilization.

BACKGROUND: Inferior pole fracture of the patella (IPFP) has small and comminuted fracture blocks that are hard to immobilize, and early mobilization may lead to loss of fracture reduction and immobilization failure. Therefore, a difficulty of treatment is to achieve rigid immobilization with early functional exercise. Here, a new treatment method of tension-free external immobilization is put forward. METHODS: The clinical data of 11 IPFP patients treated with tension-free external immobilization from May 2016 to June 2019 were retrospectively analyzed. There were six males and five females aged 39.0 ± 12.8 years (range 18-53 years). IPFP was caused by traffic accidents in five cases and falls in six cases. All cases had unilateral closed injuries, including four in the left knee and seven in the right knee. The preoperative range of motion of the knee was 22.0 ± 7.5° (10-30°). The time from injury to operation was 4.5 ± 1.3 d (3-7 d). The operation-related indices were recorded, and the function of the affected knee was assessed by the Böstman score. RESULTS: All operations were successful. The operation time was 56.4 ± 8.4 mi (45-70 min), the intraoperative blood loss was 54.1 ± 14.6 mL (40-80 mL), and the length of hospital stay was 7.5 ± 1.9 d (5-11 d). The mean follow-up time was 20.4 ± 7.6 months (12-36 months), the duration of fracture healing was 8.9 ± 1.5 weeks (7-12 weeks), and the removal time of the external immobilization device was 10.4 ± 0.9 weeks (9-12 weeks). At the last follow-up, the range of motion had no significant difference between the affected knee (129.7 ± 3.3°, range 125-135°) and the unaffected knee (130.8 ± 3.8°, range 126-137°) (t = 0.718, p < 0.05). The Böstman score of the knee was 29.2 ± 1.0 points (27-30 points), including 10 excellent cases (90.9%) and one good case (9.1%). CONCLUSION: Tension-free external immobilization is a feasible treatment for IPFP. It can help with early functional exercise and achieve a satisfactory clinical effect.

Double-trajectory lumbar screw placement guided by a set of 3D-printed surgical guide templates: a cadaver study.

BACKGROUND: To improve the strength of posterior spine fixation in patients with osteoporosis, some scholars have proposed a method of simultaneously inserting traditional pedicle screws and cortical bone trajectory screws into the pedicle. However, due to the difficulty of the operation and few clinical applications, the safety and accuracy of this method are still unclear. The purpose of this study was to investigate the safety and accuracy of double-trajectory lumbar screw placement guided by surgical guide templates. METHODS: Six wet lumbar specimens were selected for computed tomography (CT) scanning, a three-dimensional (3D) model of the lumbar spine was established using computer software, and surgical guide templates for double-trajectory [traditional pedicle trajectory (TPT) and cortical bone trajectory (CBT)] lumbar screw placement at various segments of the lumbar spine were designed and printed using a 3D printer. Screw placement was guided only by the surgical guide template, with no fluoroscopy. Postoperative CT examination was performed to determine whether the screw penetrated the screw path and the location and depth of penetration of the cortex. The preoperative and postoperative sagittal and axial angles of CBT screws or TPT screws were also measured and compared. RESULTS: Four screws were placed in each vertebral body of six lumbar specimens for a total of 120 screws. Screw grades: 99 screws as grade 0, 15 as grade 1, six as grade 2, and zero as grade 3. Thus, grade 0 accounted for 82.5% of the screws. No significant differences in the preoperative and postoperative angles of the screws were found (P > 0.05). CONCLUSIONS: 3D-printed surgical guide templates for double-trajectory screw placement can reduce the difficulty of surgery and the use of intraoperative fluoroscopy. Using such templates is a safe, feasible, and accurate screw placement method.

Design of custom-made navigational template of femoral head and pilot research in total hip resurfacing arthroplasty.

BACKGROUND: To develop a novel custom-made navigational template for accurate prosthesis implantation in total hip resurfacing arthroplasty (THRA) by computer-aided technology. METHODS: The template was produced based on data preoperatively acquired from computed tomography (CT) scan. The position of the drill guide was obtained according to the anatomical axis of the femoral neck which was defined by the point of the femoral head center and another point of the femoral neck center. The final direction of the drill guide was confirmed by a valgus angle. The surface of the template was constructed based on the inverse of the femoral neck surface. Then the template was made of acrylate resin by using rapid prototyping (RP) technique. Finally, all the templates were verified in 17 cadavers arranged for THRA and postoperative medical images were employed to evaluate the accuracy and validity of the template. RESULTS: The templates had achieved a high fitting with the femoral neck surface, and there were no guide failures. Postoperative evaluation revealed that the Kirschner-wires pass through the center of the femoral head and femoral neck, presenting a relative expected and acceptable valgus angle to the central axis of the femoral neck. The lateral offset showed the relative valgus angle achieved as expected, the horizontal offset showed that no obvious antero-posterior deviation occured. The comparison between the preoperative Neck-shaft angle (NSA) and the postoperative Stem-shaft angle (SSA) showed there is no significant difference(P > 0.05). CONCLUSION: The novel custom-made navigational template of femoral head can effectively assist surgeons for accurately implanting the femoral head components to the desired position in THRA.

Comparison of the 3D-printed operation guide template technique and the free-hand technique for S2-alar-iliac screw placement.

BACKGROUND: To compare the safety and accuracy of the 3D-printed operation guide template technique and the free-hand technique in the placement of the S2-alar-iliac (S2AI) screw. METHODS: We conducted a retrospective analysis of 47 patients undergoing S2AI screw placement in our hospital, divided into the 3D-printed operation guide template group and the free-hand screw placement group. The duration of single S2AI screw placement was documented in all patients. A postoperative CT scan was performed to assess screw placement effectiveness according to the distance from the screw tip to the breach of the cortical bone wall. RESULTS: In total, 42 screws were placed in the guide template group, with an average screw placement duration of 151.6 ± 44.8 s. Screw placement grading was as follows: 40 screws in grade 0, two in grade 1, and none in grades 2 and 3. This grading resulted in excellent and good rates of 95.2% and 100%, respectively. In total, 52 screws were placed in the free-hand group, with an average screw placement duration of 138.3 ± 45.9 s. Screw placement grading was as follows: 42 screws in grade 0, seven in grade 1, three in grade 2, and none in grade 3. This grading resulted in excellent, good and acceptable rates 80.8%, 94.2% and 100%, respectively. Screw placement duration did not significantly differ between the groups (p > 0.05). The excellent rate of screw placement was greater in the guide template group than in the free-hand group (p < 0.05), but the good and acceptable rates did not significantly differ between the two groups (p > 0.05). CONCLUSION: Both techniques can be applied to S2AI screw placement. The 3D-printed guide technique is superior to the free-hand technique in terms of safety and accuracy.

Value of whole exome sequencing for syndromic retinal dystrophy diagnosis in young patients.

BACKGROUND: Several retinal dystrophies are associated with syndromic features including such conditions as Bardet-Biedl and Joubert syndromes. Cohen syndrome is an autosomal recessive disorder associated with multiple clinical manifestations including developmental delay, acquired microcephaly, myopia, pigmentary retinopathy, joint hypermobility, truncal obesity, friendly disposition and intermittent neutropenia. In young patients, diagnosis is difficult, because several of the characteristic features may not be present until school age or later years and the intermittent neutropenia is not always detectable. DESIGN: This was a prospective study using whole exome sequencing in syndromic retinal dystrophy. It was undertaken in a hospital and research institute setting. PARTICIPANTS: Participants in this study were members of a consanguineous Australian family of Lebanese ethnicity with two siblings with retinal dystrophy, microcephaly and developmental delay. METHODS: Detailed clinical evaluation was undertaken. Whole exome capture and sequencing of patient genomic DNA samples was followed by sequence alignment, variant detection, comparison and prioritization. MAIN OUTCOME MEASURES: Pathogenic variant identification in the disease-causing gene in affected individuals. RESULTS: We identified a novel homozygous deletion leading to a frameshift mutation in VPS13B, c.11327del, p.(Asn3776Thrfs*102), the disease gene associated with Cohen syndrome. CONCLUSIONS: This report emphasizes the value of a broad-based whole exome sequencing approach in disease gene identification in the syndromic retinal dystrophies, where all disease characteristics may not be present in young patients to allow a clinical diagnosis. This facilitates improved prognostic and genetic information for patients and families.

MMP13 mutations are the cause of recessive metaphyseal dysplasia, Spahr type.

Metaphyseal dysplasia, Spahr type (MDST; OMIM 250400) was described in 1961 based on the observation of four children in one family who had rickets-like metaphyseal changes but normal blood chemistry and moderate short stature. Its molecular basis and nosologic status remained unknown. We followed up on those individuals and diagnosed the disorder in an additional member of the family. We used exome sequencing to ascertain the underlying mutation and explored its consequences on three-dimensional models of the affected protein. The MDST phenotype is associated with moderate short stature and knee pain in adults, while extra-skeletal complications are not observed. The sequencing showed that MDST segregated with a c.619T>G single nucleotide transversion in MMP13. The predicted non-conservative amino acid substitution, p.Trp207Gly, disrupts a crucial hydrogen bond in the calcium-binding region of the catalytic domain of the matrix metalloproteinase, MMP13. The MDST phenotype is associated with recessive MMP13 mutations, confirming the importance of this metalloproteinase in the metaphyseal growth plate. Dominant MMP13 mutations have been associated with metaphyseal anadysplasia (OMIM 602111), while a single child homozygous for a MMP13 mutation had been previously diagnosed as "recessive metaphyseal anadysplasia," that we conclude is the same nosologic entity as MDST. Molecular confirmation of MDST allows distinction of it from dominant conditions (e.g., metaphyseal dysplasia, Schmid type; OMIM # 156500) and from more severe multi-system conditions (such as cartilage-hair hypoplasia; OMIM # 250250) and to give precise recurrence risks and prognosis.

Heterochronous multiple primary prostate cancer and lymphoma: A case report.

BACKGROUND: Multiple primary malignant tumors (MPMTs) are rare type of cancer, especially when solid tumors are the first and lymphoma is the second primary malignancy. We report a patient with heterochronous MPMTs consisting of prostate cancer and rectal diffuse large B-cell lymphoma (DLBCL). CASE SUMMARY: We report a 77-year-old male patient diagnosed with prostate cancer who was treated with radiation therapy and one year of endocrine therapy with bicalutamide (50 mg per day) and an extended-release implant of goserelin (1/28 d). Seven years later, rectal DLBCL with lung metastases was found. CONCLUSION: Although rare, the possibility of prostate cancer combined with a double primary cancer of DLBCL can provide a deeper understanding.

Synchronous Double Primary Tumors of Liver (Small Cell Neuroendocrine Carcinoma and Hepatocellular carcinoma): A Case Report.

This study presents a case of dual primary liver cancer involving small cell neuroendocrine carcinoma and hepatocellular carcinoma. The 58-year-old Chinese male patient, who has a medical history of viral hepatitis B, presented with right upper abdominal pain persisting for one month. Imaging studies indicated the presence of multiple liver masses in segments V and VII-VIII, as well as a mass in the left lung. Subsequent hepatic biopsy performed on both segments confirmed the presence of hepatocellular carcinoma in segment V and small cell neuroendocrine carcinoma in segment VII-VIII. After undergoing one cycle of chemotherapy, the lung mass exhibited a reduction in size, while the liver masses showed an inadequate response. Subsequently, the patient underwent Transcatheter Arterial Chemoembolization (TACE) and Hepatic Artery Infusion Chemotherapy (HIAC), resulting in partial remission (PR). However, the patient was diagnosed with brain metastasis and subsequently treated with Sorafenib and Tirelizumab, a Programmed Death 1 (PD-1) immune checkpoint inhibitor. The efficacy evaluation indicated stability, and no severe adverse effects were observed at the time of writing. The patient's survival time was 16 months.

Development and biomechanical analysis of an axially controlled compression spinal rod for lumbar spondylolysis.

BACKGROUND: To elucidate the differences in mechanical performance between a novel axially controlled compression spinal rod (ACCSR) for lumbar spondylolysis (LS) and the common spinal rod (CSR). METHODS: A total of 36 ACCSRs and 36 CSRs from the same batch were used in this study, each with a diameter of 6.0 mm. Biomechanical tests were carried out on spinal rods for the ACCSR group and on pedicle screw-rod internal fixation systems for the CSR group. The spinal rod tests were conducted following the guidelines outlined in the American Society for Testing and Materials (ASTM) F 2193, while the pedicle screw-rod internal fixation system tests adhered to ASTM F 1798-97 standards. RESULTS: The stiffness of ACCSR and CSR was 1559.15 ±â€…50.15 and 3788.86 ±â€…156.45 N/mm (P < .001). ACCSR's yield load was 1345.73 (1297.90-1359.97) N, whereas CSR's was 4046.83 (3805.8-4072.53) N (P = .002). ACCSR's load in the 2.5 millionth cycle of the fatigue four-point bending test was 320 N. The axial gripping capacity of ACCSR and CSR was 1632.53 ±â€…165.64 and 1273.62 ±â€…205.63 N (P = .004). ACCSR's torsional gripping capacity was 3.45 (3.23-3.47) Nm, while CSR's was 3.27 (3.07-3.59) Nm (P = .654). The stiffness of the pedicle screws of the ACCSR and CSR group was 783.83 (775.67-798.94) and 773.14 (758.70-783.62) N/mm (P = .085). The yield loads on the pedicle screws of the ACCSR and CSR group was 1345.73 (1297.90-1359.97) and 4046.83 (3805.8-4072.53) N (P = .099). CONCLUSION: Although ACCSR exhibited lower yield load, stiffness, and fatigue resistance compared to CSR, it demonstrated significantly higher axial gripping capacity and met the stress requirement of the human isthmus. Consequently, ACCSR presents a promising alternative to CSR for LS remediation.

Potential Role of Superoxide Dismutase 3 (SOD3) in Resistance to Influenza A Virus Infection.

Influenza A virus infection induces the production of excessive reactive oxygen species (ROS). Overproduction of ROS can overwhelm the antioxidant defense system, leading to increasing intensive oxidative stress. However, antioxidant defense against oxidative damage induced by influenza A virus infection, and in particular the significance of the SOD3 response in the pathogenesis of influenza virus infection, has not been well characterized. Here, we investigated the potential role of SOD3 in resistance to influenza A virus infection. In this study, SOD3, as an important antioxidant enzyme, was shown to be highly elevated in A549 cells following influenza A virus infection. Furthermore, inhibition of SOD3 impacted viral replication and virulence. We found that SOD3 disrupts IAV replication by impairing the synthesis of vRNA, whereas it did not affect viral ribonucleoprotein nuclear export. In addition, overexpression of SOD3 greatly reduced the levels of ROS caused by influenza A virus infection, regulated the inflammatory response to virus infection by inhibiting the phosphorylation of p65 of the NF-κB signaling pathway, and inhibited virus-induced apoptosis to a certain extent. Taken together, these findings indicate that SOD3 is actively involved in influenza A virus replication. Pharmacological modulation or targeting of SOD3 may pave the way for a novel therapeutic approach to combating influenza A virus infection.

Development and validation of prognostic nomogram for patients with metastatic gastric adenocarcinoma based on the SEER database.

The aim of this study was to investigate the prognostic factors affecting overall survival in patients with metastatic gastric adenocarcinoma and to establish a nomogram prediction model for comprehensive clinical application. Data from 2370 patients with metastatic gastric adenocarcinoma between 2010 and 2017 were retrieved from the surveillance, epidemiology, and end results database. They were randomly divided into a training set (70%) and a validation set (30%), univariate and multivariate Cox proportional hazards regressions were used to screen important variables that may affect overall survival and to establish the nomogram. The nomogram model was evaluated using a receiver operating characteristic curve, calibration plot, and decision curve analysis. Internal validation was performed to test the accuracy and validity of the nomogram. Univariate and multivariate Cox regression analyses revealed that, age, primary site, grade, and American joint committee on cancer. T, bone metastasis, liver metastasis, lung metastasis, tumor Size, and chemotherapy were identified as independent prognostic factors for overall survival and were included in the prognostic model to construct a nomogram. The prognostic nomogram showed good overall survival risk stratification ability for the area under the curve, calibration plots, and decision curve analysis in both the training and validation sets. Kaplan-Meier curves further showed that patients in the low-risk group had better overall survival. This study synthesizes the clinical, pathological, therapeutic characteristics of patients with metastatic gastric adenocarcinoma, establishes a clinically effective prognostic model, and that can help clinicians to better evaluate the patient's condition and provide accurate treatment.

Top 100 cited articles in the thromboangiitis obliterans: a bibliometric analysis and visualized study.

OBJECTIVE: Thromboangiitis obliterans (TAO) is one of the most common types of peripheral arterial disease (PAD). This study aimed to explore the characteristics of the top 100 most cited articles in the TAO. METHODS: A bibliometric analysis based on the Web of Science (WOS) database was performed. Literature was retrieved and ranked by the citations. Listed below are the top 100 citations, including original articles, reviews, full-length proceeding papers, and case reports that were included for analysis. The type of literature, research areas, and languages were recorded. The trends of citations including the total citations, an analysis of publication and citation numbers were conducted each year. We analyzed citations from highly cited countries, authors, institutions, and journals. Research hotspots were gathered by a visualized analysis of author keywords. RESULTS: Most of the highly cited literature was original articles. A rising trend was observed in the number of citations per year. The peaks in the number of highly cited articles appeared in the year 1998 and 2006. The majority of the articles focused on the cardiovascular system and surgery. Journal of Vascular Surgery published most of the highly cited articles. The USA and Japan contributed nearly half the number of highly cited articles. Mayo Clinic and Nagoya University were highly cited institutions. Shionoya S and Olin JW were both the author with the largest number of citations and the most highly cited author in the reference. Articles that were highly cited most often addressed the following topics: "vasculitis", "autoimmune disease", and "critical limb ischemia". Keywords that were mostly used in recent years were "stem cell therapy", "progenitor therapy", and "immunoadsorption". The detection of bursts of author keywords showed the following: "permeability", "differentiation", and "critical limb ischemia" are recent keywords that have burst. CONCLUSIONS: In this study, the highly cited contributors in the field of TAO research were identified. Most cited articles in the top 100 focused on the cardiovascular system and surgery. Treatment and pathophysiology including stem cell therapy, progenitor therapy, genetics, autoimmunity, and inflammation are the hotspots of TAO.

Incidence of lumbar spondylolysis in athletes with low back pain: A systematic evaluation and single-arm meta-analysis.

BACKGROUND: Low back pain (LBP) is a common chief complaint from athletes. Lumbar spondylolysis (LS) is a common sport injury. Severe LS is likely to cause spinal instability, resulting in lumbar spondylolisthesis or lumbar disc herniation, and even damage to the spinal nerve roots. The incidence of LS is approximately 5% in the adult population, and nearly half of young athletes with LBP are diagnosed with LS. This meta-analysis analyzed the incidence of LS in athletes with LBP. METHODS: PubMed, Embase, Cochrane (Cochrane Central Register of Controlled Trials), and Web of Science databases were systematically searched for published case report and retrospective analyses related to the topic from the date of database creation to January 1,2023. Relevant literature was screened and information extracted, and risk of bias was assessed for included studies using the methodological index for non-randomized-studies scale. Single-arm Meta-analysis was performed using R4.04 software. Heterogeneity was quantified by Cochran Q test and Higgins I2. Funnel plots were used to visualize publication bias, and Egger test and Begg test were used to statistical tests. RESULTS: A total of 9 studies (835 patients) were included in this study. Meta-analysis revealed that the prevalence of LS in athletes with LBP was estimated at 41.7%, [95% CI = (0.28-0.55)], but this prevalence varied considerably with the gender and age of the athletes. CONCLUSION: The estimated prevalence of LS in athletes with LBP is 41.7%, and future correlations between the prevalence of LS in adolescent athletes worldwide need to be assessed from different perspectives, including biomechanical, hormonal, anatomical, behavioral, and gender differences.

Association of TAP1 and TAP2 polymorphisms with the outcome of persistent HBV infection in a northeast Han Chinese population.

OBJECTIVE: Transporter associated with antigen processing (TAP) plays a central role in a cellular immune response against HBV. Polymorphisms exist at the coding region of TAP and alter its structure and function. The aim of this study was to evaluate the potential relationship between polymorphisms of TAP and different outcomes of persistent HBV infection in a Han population in northeastern China. MATERIAL AND METHODS: 189 HBV spontaneously recovered (SR) subjects, 571 HBV-infected patients including 180 chronic hepatitis B (CHB), 196 liver cirrhosis (LC) and 195 hepatocellular carcinoma (HCC) individuals were included in this study. TAP1-333 Ile/Val and -637 Asp/Gly, TAP2-651 Arg/Cys and -687 Stop/Gln were genotyped in all the samples by using a PCR-RFLP method. RESULTS: The frequency of TAP1-637-Gly (allele G) was significantly higher in persistently HBV-infected individuals (CHB and LC) than that of SR subjects (OR = 1.58, 95% CI 1.12-2.45, p = 0.024; OR = 1.78, 95% CI 1.27-2.68, p = 0.002) by a logistic regression analysis. In addition, the statistically significant difference in the distribution of TAP2-651-Cys (allele T) was observed between HCC cases and SR controls (OR = 2.30, 95% CI 1.51-3.72, p < 0.001), and TAP2-687-Gln (allele C) in CHB patients was more common than that in SR subjects (OR = 1.41, 95% CI 1.13-1.97, p = 0.021). The data also revealed that haplotype 687 Gln-651 Cys-637 Gly-333 Ile was strongly associated with persistent HBV infection (CHB, LC and HCC) (p < 0.001, < 0.05 and < 0.001, respectively). CONCLUSION: These results suggested that TAP variants were likely to play a substantial role in different outcomes of persistent HBV infection in the studied population.

The Landscape of Early Growth Response Family Members 1-4 in Hepatocellular Carcinoma: Their Biological Roles and Diagnostic Utility.

The incidence of hepatocellular carcinoma (HCC), which is one of the most frequent types of cancer seen all over the world, is steadily growing from year to year. EGR genes are members of the early growth response (EGR) gene family. It has been shown that EGR genes play an increasingly essential role in the development of tumors and the progression of numerous malignancies. However, the possible diagnostic and prognostic roles of EGR genes in HCC have only been examined in a limited number of studies. Expression and methylation data on EGR family members were obtained from TCGA datasets. The prognostic values of EGR members were studied. Additionally, the correlations of EGR members with immune cells were assessed through the single-sample gene set enrichment analysis (ssGSEA). In this study, we found that the expression of EGR1, EGR2, EGR3, and EGR4 was distinctly decreased in HCC specimens compared with nontumor specimens. ROC assays confirmed that they have a strong ability in screening HCC specimens from nontumor specimens. According to the findings of Pearson's correlation, EGR1, EGR2, EGR3, and EGR4 were found to have a negative association with the methylation level. Survival study revealed that EGR1, EGR2, and EGR3 were associated with the clinical outcome of HCC patients. Immune cell enrichment analysis demonstrated that the expressions of all EGR members were positively related to the levels of most types of immune cells, such as macrophages, NK cells, B cells, T cells, eosinophils, and CD8 T cells. Overall, the current work demonstrated the expression mode and prognostic value of EGR members in HCC in a comprehensive manner, offering insights for further research of the EGR family as possible clinical biomarkers in HCC.

Nisoldipine Inhibits Influenza A Virus Infection by Interfering with Virus Internalization Process.

Influenza virus infections and the continuing spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are global public health concerns. As there are limited therapeutic options available in clinical practice, the rapid development of safe, effective and globally available antiviral drugs is crucial. Drug repurposing is a therapeutic strategy used in treatments for newly emerging and re-emerging infectious diseases. It has recently been shown that the voltage-dependent Ca2+ channel Cav1.2 is critical for influenza A virus entry, providing a potential target for antiviral strategies. Nisoldipine, a selective Ca2+ channel inhibitor, is commonly used in the treatment of hypertension. Here, we assessed the antiviral potential of nisoldipine against the influenza A virus and explored the mechanism of action of this compound. We found that nisoldipine treatment could potently inhibit infection with multiple influenza A virus strains. Mechanistic studies further revealed that nisoldipine impaired the internalization of the influenza virus into host cells. Overall, our findings demonstrate that nisoldipine exerts antiviral effects against influenza A virus infection and could serve as a lead compound in the design and development of new antivirals.

Accuracy of S2 Alar-Iliac Screw Placement Under the Guidance of a 3D-Printed Surgical Guide Template.

OBJECTIVE: To evaluate the safety and accuracy of S2 alar-iliac (S2AI) screw placement guided by a 3-dimensional (3D)-printed surgical guide template. METHODS: The data of 27 patients treated with S2AI screws were analyzed. S2AI surgical guide templates were designed and printed, and S2AI screw placement was completed intraoperatively with the guide templates. Postoperative computed tomography was performed to measure screw path parameters, namely the sagittal angle (SA), the transverse angle (TA), the horizontal distance (HD) between the entry point of the screw and the median sacral crest, and the vertical distance (VD) between the entry point of the screw and the lower edge of the first posterior sacral foramen. Screw placement was graded according to the Oh grading criteria. RESULTS: A total of 54 S2AI screws were placed. The screw grades were as follows: 52 screws were considered grade 0, 2 were grade 1, none were grade 2, and none were grade 3. Thus grade 0 accounted for 96.3% of the screws. When the preoperatively planned SA (32.3° ± 2.0°), TA (42.1° ± 3.9°), HD (5.1 ± 1.1) mm, and VD (19.0 ± 2.4) mm were compared with the corresponding postoperative SA (31.9° ± 3.8°), TA (42.5° ± 4.0°), HD (4.9 ± 1.1) mm, and VD (19.1 ± 2.3) mm, no significant differences were identified (P > 0.05). CONCLUSIONS: S2AI screw placement assisted by a 3D-printed surgical guide is safe and accurate.