The potential mechanism of Bupleurum against anxiety was predicted by network pharmacology study and molecular docking

Metabolic Brain Disease - Bupleurum chinense DC. (Chaihu) is a traditional Chinese medicine (TCM) used in the treatment of anxiety. But the anxiolytic mechanisms of bupleurum are still unclear....     

Association of PD-L1 gene rs4143815 C>G polymorphism and human cancer susceptibility: A systematic review and meta-analysis

Programmed death ligand 1(PD-L1) mediated immune escape play important roles in the development of cancer. The gene polymorphism of PD-L1, in particular rs4143815 C?>?G, has been associated with the cancer risks, but with conflicting results. Therefore, this meta-analysis was aimed to assess the association between rs4143815 C?>?G and cancer susceptibility. A systematic literature search was performed to select the studies and the pooled odds ratio (OR) with 95% confidence interval (CI) was used to evaluate the strength of association. Eleven eligible studies containing 3711 cases and 3704 controls were enrolled in the meta-analysis. The results suggested that there is a strong association between rs4143815 C?>?G and the cancer risks (G vs. C: OR?=?1.386, 95% CI: 1.132–1.696, p?=?0.002; GG vs. CG?+?CC: OR?=?1.843 95% CI: 1.300–2.613, p?=?0.002; GG?+?CG vs. CC: OR?=?1.280, 95% CI: 1.040–1.576, p?=?0.020). Subgroup analysis based on cancer type suggested that PD-L1 rs4143815 C?>?G might increase the susceptibility to gastric cancer (G vs. C: OR?=?1.842, 95% CI: 1.403–2.418, p?<?0.001) and bladder cancer (G vs. C: OR?=?2.015, 95% CI: 1.556–2.608, p?<?0.001), and genotype GG carriers of PD-L1 rs4143815 C?>?G might have higher risks of HCC (GG vs. CG?+?CC: OR?=?2.226 95% CI: 1.562–3.172, p?<?0.001). PD-L1 rs4143815 C?>?G might confer an increased cancer risk, indicating this SNP may contribute to the pathogenesis of cancer and might be used as a potential biomarker to predict the susceptibility to cancer.     

Successful Treatment for BK Virus Nephropathy by Leflunomide in a Kidney Transplant Patient: A Case Report

IntroductionThe immunosuppressant agents in kidney transplantation (KT) may lead to various complications such as opportunistic infections and malignancies. BK virus associated nephropathy is a significant complication following KT, and it can result in graft failure. BK virus causes tubulointerstitial nephritis, ureter stenosis, and even graft failure in KT recipients with impaired immune system. We described a 63-year-old woman, who was a hepatitis C carrier and on dialysis for 22 years before KT, who received cadaveric-donor KT 2 years previously. She reported decreasing urine output and general weakness. The serum creatinine level was slightly increased from 2.94 to 4.38 mg/dL.MethodsImmunosuppressant medications including prednisolone, everolimus, cyclosporin, and mycophenolate sodium were continued as maintenance therapy post KT. Kidney biopsy was performed due to deterioration of graft function.ResultsThe kidney biopsy showed consistent results with early-stage polyomavirus nephropathy, characterized by focal viral cytopathic changes with positive immunohistochemical signals and mesangial proliferative glomerulonephritis, immune-complex-mediated (Fig 1 and Fig 2). Negative C4d staining at peritubular capillary was reported. The dosage of mycophenolate sodium was tapered from 720 to 360 mg daily and that of everolimus increased from 0.5 to 1.0 mg daily due to BK viral infection with BK nephropathy. The serum creatinine level was 2.75 mg/dL after treatment.ConclusionEarly detection of BK nephropathy and decreasing immunosuppressant agents are the mainstay of treatment. Substituting leflunomide for mycophenolate sodium and increasing dosage of everolimus has been proposed to solve BK nephropathy. We presented that the use of leflunomide in such situation is in a timely manner.     

Three-dimensional measurement of radiographic bone–implant contact lengths of zygomatic implants in zygomatic bone: a retrospective study of 66 implants in 28 patients

Zygomatic implant treatment is widely applied for severe maxillary atrophy to help rehabilitate the maxillary dentition. This retrospective study was performed to evaluate the actual radiographic bone–implant contact (rBIC) lengths of zygomatic implants. The records of 28 patients who underwent zygomatic implant surgery and subsequent follow-up examinations between August 2013 and September 2018 in the Department of Oral and Maxillofacial Surgery, Taipei Tzu Chi Hospital were reviewed. The surgeries were performed by a single surgeon using the same treatment protocol. All patients had a computed tomography scan at 1 year after the surgery. Using three-dimensional imaging software, an investigator measured the rBIC lengths of 66 implants and documented their clinical status. The implant survival rate was 100%. The mean rBIC length was significantly longer in male patients than in female patients (20.80 ± 5.88 mm versus 17.79 ± 6.34 mm; P = 0.028). The mean rBIC length of double zygomatic implants was significantly longer when compared to that of single implants (21.11 ± 6.23 mm versus 17.75 ± 5.85 mm; P = 0.027). This article is novel in reporting the exact rBIC lengths of zygomatic implants in a clinical setting. The results showed that zygomatic implants are a viable treatment modality for full-mouth rehabilitation.     

Real-World Palbociclib Use in HR+/HER2− Advanced Breast Cancer in Canada: The IRIS Study

Background: Palbociclib is a selective cyclin-dependent kinase (CDK) 4/6 inhibitor used in combination with aromatase inhibitors or fulvestrant for patients with hormone receptor-positive (HR+) human epidermal growth factor receptor 2 (HER2)-negative advanced/metastatic breast cancer (ABC/MBC). Palbociclib was the first CDK 4/6 inhibitor approved for HR+/HER2− ABC/MBC treatment in Canada in combination with letrozole (P+L) as an initial endocrine-based therapy (approved March 2016), or with fulvestrant (P+F) following disease progression after prior endocrine therapy (approved May 2017). The Ibrance Real World Insights (IRIS) study ({"type":"clinical-trial","attrs":{"text":"NCT03159195","term_id":"NCT03159195"}}NCT03159195) collected real-world outcomes data for palbociclib-treated patients in several countries, including Canada. Methods: This retrospective chart review included women with HR+/HER2− ABC/MBC receiving P+L or P+F in Canada. Physicians reviewed medical records for up to 14 patients, abstracting demographic and clinical characteristics, treatment patterns, and clinical outcomes. Progression-free rates (PFRs) and survival rates (SRs) at 6, 12, 18, and 24 months were estimated via Kaplan–Meier analysis. Results: Thirty-three physicians examined medical records for 247 patients (P+L, n = 214; P+F, n = 33). Median follow-up was 8.8 months for P+L and 7.0 months for P+F. Most patients were initiated on palbociclib 125 mg/d (P+L, 90.2%; P+F, 84.8%). Doses were reduced in 16.6% of P+L and 14.3% of P+F patients initiating palbociclib at 125 mg/d. The PFR for P+L was 90.3% at 12 months and 78.2% at 18 months; corresponding SRs were 95.6% and 93.0%. For P+F, 6-month PFR was 91.0%; 12-month SR was 100.0%. Conclusions: Dose reduction rates were low and PFR and SR were high in this Canadian real-world assessment of P+L and P+F treatments, suggesting that palbociclib combinations are well tolerated and effective.     

RNA sequencing screening of differentially expressed genes after spinal cord injury

In the search for a therapeutic schedule for spinal cord injury, it is necessary to understand key genes and their corresponding regulatory networks involved in the spinal cord injury process. However, ad hoc selection and analysis of one or two genes cannot fully reveal the complex molecular biological mechanisms of spinal cord injury. The emergence of second-generation sequencing technology(RNA sequencing) has provided a better method. In this study, RNA sequencing technology was used to analyze differentially expressed genes at different time points after spinal cord injury in rat models established by contusion of the eighth thoracic segment. The numbers of genes that changed significantly were 944, 1362 and 1421 at 1, 4 and 7 days after spinal cord injury respectively. After gene ontology analysis and temporal expression analysis of the differentially expressed genes, C5ar1, Socs3 and CCL6 genes were then selected and identified by real-time polymerase chain reaction and western blot assay. The mRNA expression trends of C5ar1, Socs3 and CCL6 genes were consistent with the RNA sequencing results. Further verification and analysis of C5ar1 indicate that the level of protein expression of C5ar1 was consistent with its nucleic acid level after spinal cord injury. C5ar1 was mainly expressed in neurons and astrocytes. Finally, the gene Itgb2,which may be related to C5ar1, was found by Chilibot database and literature search. Immunofluorescence histochemical results showed that the expression of Itgb2 was highly consistent with that of C5ar1. Itgb2 was expressed in astrocytes. RNA sequencing technology can screen differentially expressed genes at different time points after spinal cord injury. Through analysis and verification, genes strongly associated with spinal cord injury can be screened. This can provide experimental data for further determining the molecular mechanism of spinal cord injury, and also provide possible targets for the treatment of spinal cord injury. This study was approved ethically by the Laboratory Animal Ethics Committee of Jiangsu Province, China(approval No. 2018-0306-001) on March 6, 2018.