Improved positional accuracy of dental implant placement using a haptic and machine-vision-controlled collaborative surgery robot: A pilot randomized controlled trial.

AIM: To compare the implant accuracy, safety and morbidity between robot-assisted and freehand dental implant placement. MATERIALS AND METHODS: Subjects requiring single-site dental implant placement were recruited. Patients were randomly allocated to freehand implant placement and robot-assisted implant placement. Differences in positional accuracy of the implant, surgical morbidity and complications were assessed. The significance of intergroup differences was tested with an intention-to-treat analysis and a per-protocol (PP) analysis (excluding one patient due to calibration error). RESULTS: Twenty patients (with a median age of 37, 13 female) were included. One subject assigned to the robotic arm was excluded from the PP analysis because of a large calibration error due to the dislodgement of the index. For robot-assisted and freehand implant placement, with the PP analysis, the median (25th-75th percentile) platform global deviation, apex global deviation and angular deviation were 1.23 (0.9-1.4) mm/1.9 (1.2-2.3) mm (p = .03, the Mann-Whitney U-test), 1.40 (1.1-1.6) mm/2.1 (1.7-3.9) mm (p < .01) and 3.0 (0.9-6.0)°/6.7 (2.2-13.9)° (p = .08), respectively. Both methods showed limited damage to the alveolar ridge and had similar peri- and post-operative morbidity and safety. CONCLUSIONS: Robot-assisted implant placement enabled greater positional accuracy of the implant compared to freehand placement in this pilot trial. The robotic system should be further developed to simplify surgical procedures and improve accuracy and be validated in properly sized trials assessing the full spectrum of relevant outcomes.

A crossover study to evaluate the pharmacokinetics and bioequivalence of hydroxychloroquine tablets in healthy Chinese subjects.

AIMS: Hydroxychloroquine (HCQ) has a high variability and a long half-life in the human body. The purpose of this study was to evaluate the bioequivalence of a generic HCQ tablet (test preparation) versus a brand HCQ tablet (reference preparation) under fasting and fed conditions in a crossover design. MATERIALS AND METHODS: This was an open-label, two-period randomized, single-dose, crossover study in 47 healthy Chinese subjects who were sequentially and randomly allocated either to the fed group (high-fat meal; n = 23) or the fasting group (n = 24). Participants in each group were randomized to the two arms to receive either a single 200-mg dose of the test preparation or a 200-mg dose of the reference preparation. The application of the two preparations in each patient was separated by a 28-day washout period, regarded as sufficiently long to avoid significant interference from residual drug in the body. Whole blood samples were collected over 72 hours after drug administration. RESULTS: A total of 23 subjects completed both the fed and the fasting parts of the trial. There were no significant differences in Cmax, AUC0-72h, and T1/2 between the test and reference preparation (p < 0.05). Food had no significant effect on Cmax and T1/2 (p < 0.05), but AUC0-72h values were significantly reduced under fed condition compared to fasting condition (p < 0.05). The 90% confidence intervals (CIs) for the geometric mean ratios (GMRs) of Cmax and AUC0-72h were 0.84 - 1.05 and 0.89 - 0.98 in the fed study, and 0.97 - 1.07 and 0.97 - 1.05 in the fasting study, respectively. The carryover effect due to non-zero blood concentrations resulted in higher AUC0-72h values in the second period for both test and reference formulations and had no effect on the statistical results. No serious adverse events were reported. CONCLUSION: The investigation demonstrated that the test and reference preparations are bioequivalent and well tolerated under both fasting and fed conditions in healthy Chinese subjects.

Accuracy of traditional open-tray impression, stereophotogrammetry, and intraoral scanning with prefabricated aids for implant-supported complete arch prostheses with different implant distributions: An in vitro study.

STATEMENT OF PROBLEM: Conventional impression techniques for complete arch implant-supported fixed dental prostheses (CIFDPs) are technique sensitive. Stereophotogrammetry (SPG) and intraoral scanning (IOS) may offer alternatives to conventional impression making. PURPOSE: The purpose of this in vitro study was to assess the accuracy and passive fit of IOS with prefabricated aids, SPG, and open tray impression (OI) for CIFDPs with different implant distributions. MATERIAL AND METHODS: Three definitive casts with 4 parallel implants (4-PARA), 4 inclined implants (4-INCL), and 6 parallel implants (6-PARA) were fabricated. Three recording techniques were tested: IOS with prefabricated aids, SPG, and OI. The best and the worst scans were selected to fabricate 18 milled aluminum alloy frameworks. The trueness and precision of distance deviation (∆td and ∆pd), angular deviation (∆tθand ∆pθ), root mean square errors (∆tRMS for ∆pRMS), and passive fit score of frameworks were recorded. Two-way ANOVA was applied. RESULTS: SPG showed the best trueness and precision (95%CI of ∆td/∆tθ/∆tRMS, 31 to 39 µm, 0.22 to 0.28 degrees, 20 to 23 µm; 95%CI of ∆pd/∆pθ/∆pRMS, 9 to 11 µm, 0.06 to 0.08 degrees, 8 to 10 µm), followed by OI (61 to 83 µm, 0.33 to 0.48 degrees, 28 to 48 µm; 66 to 81 µm, 0.29 to 0.38 degrees, 32 to 41 µm) and IOS (143 to 193 µm, 0.37 to 0.50 degrees, 81 to 96 µm; 89 to 111 µm, 0.27 to 0.31 degrees, 51 to 62 µm). Tilted implants were associated with increased distance deviation. Increased implant number was associated with improved recording precision. The passive fit of frameworks was negatively correlated with the RMS error, and the correlation coefficient was -0.65 (P=.003). CONCLUSIONS: SPG had the best accuracy. Implant distributions affected implant precision. The RMS error can be used to evaluate the passive fit of frameworks.

Repurposing of the FGFR inhibitor AZD4547 as a potent inhibitor of necroptosis by selectively targeting RIPK1.

Necroptosis is a form of regulated necrosis involved in various pathological diseases. The process of necroptosis is controlled by receptor-interacting kinase 1 (RIPK1), RIPK3, and pseudokinase mixed lineage kinase domain-like protein (MLKL), and pharmacological inhibition of these kinases has been shown to have therapeutic potentials in a variety of diseases. In this study, using drug repurposing strategy combined with high-throughput screening (HTS), we discovered that AZD4547, a previously reported FGFR inhibitor, is able to interfere with necroptosis through direct targeting of RIPK1 kinase. In both human and mouse cell models, AZD4547 blocked RIPK1-dependent necroptosis. In addition, AZD4547 rescued animals from TNF-induced lethal shock and inflammatory responses. Together, our study demonstrates that AZD4547 is a potent and selective inhibitor of RIPK1 with therapeutic potential for the treatment of inflammatory disorders that involve necroptosis.

Comparative study of first-principles approaches for effective Coulomb interaction strength Ueff between localized f-electrons: Lanthanide metals as an example.

As correlation strength has a key influence on the simulation of strongly correlated materials, many approaches have been proposed to obtain the parameter using first-principles calculations. However, a comparison of the different Coulomb strengths obtained using these approaches and an investigation of the mechanisms behind them are still needed. Taking lanthanide metals as an example, we research the factors that affect the effective Coulomb interaction strength, Ueff, by local screened Coulomb correction (LSCC), linear response (LR), and constrained random-phase approximation (cRPA) in the Vienna Ab initio Simulation Package. The Ueff LSCC value increases from 4.75 to 7.78 eV, Ueff LR is almost stable at about 6.0 eV (except for Eu, Er, and Yb), and Ueff cRPA shows a two-stage decreasing trend in both light and heavy lanthanides. To investigate these differences, we establish a scheme to analyze the coexistence and competition between the orbital localization and the screening effect. We find that LSCC and cRPA are dominated by the orbital localization and the screening effect, respectively, whereas LR shows the balance of the competition between the two factors. Additionally, the performance of these approaches is influenced by different starting points from the Perdew-Burke-Ernzerhof (PBE) and PBE + U, especially for cRPA. Our results provide useful knowledge for understanding the Ueff of lanthanide materials, and similar analyses can also be used in the research of other correlation strength simulation approaches.

Accuracy of intraoral scan with prefabricated aids and stereophotogrammetry compared with open tray impressions for complete-arch implant-supported prosthesis: A clinical study.

OBJECTIVES: The aim of this clinical study was to compare the accuracy of intraoral scan system (IOS) with prefabricated aids and stereophotogrammetry (SPG) compared with open tray implant impression (OI) for complete-arch implant-supported fixed dental prostheses (CIFDP). MATERIALS AND METHODS: Patients needing CIFDP were enrolled in this study. OI, reference standard, IOS with prefabricated aids, and SPG were performed for each patient. Distance and angle deviations between all pairs of abutment analogs, root mean square (RMS) errors between the aligned test and reference model, and chairside time were measured. The effect of inter-abutment distance, jaw (maxilla or mandible), number of implants, and arch length on deviations was analyzed. The mixed effect model was applied to analyze deviations and RMS errors. RESULTS: Fifteen consecutive individuals (6 females and 9 males, 47-77 years old) with 22 arches (9 upper and 13 lower jaws) and 115 implants were included. There was no significant difference in distance deviation comparing SPG and IOS with OI (p > .05). IOS showed a significantly greater angle deviation and RMS errors than SPG (median 0.40° vs. 0.31°, 69 µm vs. 45 µm, p < .01). The inter-abutment distance was negatively correlated with the accuracy of SPG and IOS (p < .05). The chairside time for IOS, SPG, and OI was 10.49 ± 3.50, 14.71 ± 2.86, and 20.20 ± 3.01 min, respectively (p < .01). CONCLUSIONS: The accuracy of SPG and IOS with prefabricated aids was comparable. IOS was the most efficient workflow.

Family function, self-efficacy, care hours per day, closeness and benefit finding among stroke caregivers in China: A moderated mediation model.

AIMS AND OBJECTIVES: The aim of this study was to explore the moderated mediation mechanism of the relationships among family function, self-efficacy, care hours per day, closeness and benefit finding in family caregivers of patients with stroke in China. BACKGROUND: Benefit finding can provide a new means of resolving depression among family members caring for an ill loved one. However, current research has paid little attention to the benefit finding of family caregivers of stroke patients in China. DESIGN: A cross-sectional study. METHODS: Three hundred fifty family caregivers of patients with stroke were recruited from community service centres and hospitals in Zhengzhou, China. The participants completed the family APGAR index, caregiver benefit finding scale and Chinese general self-efficacy scale during a study conducted in 2017. Descriptive analyses and a moderated mediation model were computed. Reporting adhered to the STROBE checklist. RESULTS: A total of 311 family caregivers completed this study. Closeness between family caregivers and patients with stroke moderated the relationship between family function and caregiver benefit finding. Self-efficacy partially mediated the relationship between family function and caregiver benefit finding; moreover, care hours per day moderated the mediation. CONCLUSION: This study shows important factors associated with benefit finding in family caregivers of patients with stroke. This indicates elements that could help improve benefit finding intervention programmes for family caregivers of patients with stroke. RELEVANCE TO CLINICAL PRACTICE: The findings in our study provide valuable information on benefit finding and indicate some interventions to improve the mental health of family caregivers of stroke patients.

Targeting cancer-associated fibroblast-secreted WNT2 restores dendritic cell-mediated antitumour immunity.

OBJECTIVE: Solid tumours respond poorly to immune checkpoint inhibitor (ICI) therapies. One major therapeutic obstacle is the immunosuppressive tumour microenvironment (TME). Cancer-associated fibroblasts (CAFs) are a key component of the TME and negatively regulate antitumour T-cell response. Here, we aimed to uncover the mechanism underlying CAFs-mediated tumour immune evasion and to develop novel therapeutic strategies targeting CAFs for enhancing ICI efficacy in oesophageal squamous cell carcinoma (OSCC) and colorectal cancer (CRC). DESIGN: Anti-WNT2 monoclonal antibody (mAb) was used to treat immunocompetent C57BL/6 mice bearing subcutaneously grafted mEC25 or CMT93 alone or combined with anti-programmed cell death protein 1 (PD-1), and the antitumour efficiency and immune response were assessed. CAFs-induced suppression of dendritic cell (DC)-differentiation and DC-mediated antitumour immunity were analysed by interfering with CAFs-derived WNT2, either by anti-WNT2 mAb or with short hairpin RNA-mediated knockdown. The molecular mechanism underlying CAFs-induced DC suppression was further explored by RNA-sequencing and western blot analyses. RESULTS: A negative correlation between WNT2+ CAFs and active CD8+ T cells was detected in primary OSCC tumours. Anti-WNT2 mAb significantly restored antitumour T-cell responses within tumours and enhanced the efficacy of anti-PD-1 by increasing active DC in both mouse OSCC and CRC syngeneic tumour models. Directly interfering with CAFs-derived WNT2 restored DC differentiation and DC-mediated antitumour T-cell responses. Mechanistic analyses further demonstrated that CAFs-secreted WNT2 suppresses the DC-mediated antitumour T-cell response via the SOCS3/p-JAK2/p-STAT3 signalling cascades. CONCLUSIONS: CAFs could suppress antitumour immunity through WNT2 secretion. Targeting WNT2 might enhance the ICI efficacy and represent a new anticancer immunotherapy.

Immunogenicity correlation in cynomolgus monkeys between Luminex-based total IgG immunoassay and pseudovirion-based neutralization assay for a 14-valent recombinant human papillomavirus vaccine.

A new virus-like particle based vaccine covering 14 types of high-risk and disease-inducing human papillomavirus (HPV) can offer better coverage against HPV-induced diseases, particularly cervical cancers. However, the assessment of immunogenicity of the vaccine is an important task, representing not only its significant clinical characteristics, but also a major challenge, in terms of both the suitability of methods and the clinical sample testing throughput supporting clinical development. This work covers the development and evaluation of a method based on Luminex technology (a coded-bead and flow-cytometric approach) to assess the HPV-type specific total immunoglobulin G (IgG). This method can evaluate the antibodies in sera post immunization against multiple types of HPV simultaneously (i.e., with multiplexing capability), save time and cost, and improve test throughput with higher sensitivity and precision than the classical, plate-based enzyme-linked immunoassay and competitive Luminex-based immunoassays. Using cynomolgus monkeys as model, we demonstrated the good correlation between the results from the pseudovirion-based neutralization assay (PBNA), and the Luminex-based total IgG assay, supporting that the latter method can be considered as a viable, dependable replacement method for the PBNA supporting immunogenicity evaluation of HPV vaccine in preclinical development and clinical investigation.

A prospective epidemiological analysis of controlling nutritional status score with the poor functional outcomes in Chinese patients with haemorrhagic stroke.

Nutritional Risk Screening index is a standard tool to assess nutritional risk, but epidemiological data are scarce on controlling nutritional status (CONUT) as a prognostic marker in acute haemorrhagic stroke (AHS). We aimed to explore whether the CONUT may predict a 3-month functional outcome in AHS. In total, 349 Chinese patients with incident AHS were consecutively recruited, and their malnutrition risks were determined using a high CONUT score of ≥ 2. The cohort patients were divided into high-CONUT (≥ 2) and low-CONUT (< 2) groups, and primary outcomes were a poor functional prognosis defined as the modified Rankin Scale (mRS) score of ≥ 3 at post-discharge for 3 months. Odds ratios (OR) with 95 % confidence intervals (CI) for the poor functional prognosis at post-discharge were estimated by using a logistic analysis with additional adjustments for unbalanced variables between the high-CONUT and low-CONUT groups. A total of 328 patients (60·38 ± 12·83 years; 66·77 % male) completed the mRS assessment at post-discharge for 3 months, with 172 patients at malnutrition risk at admission and 104 patients with a poor prognosis. The levels of total cholesterol and total lymphocyte counts were significantly lower in high-CONUT patients than low-CONUT patients (P = 0·012 and < 0·001, respectively). At 3-month post discharge, there was a greater risk for the poor outcome in the high-CONUT compared with the low-CONUT patients at admission (OR: 2·32, 95 % CI: 1·28, 4·17). High-CONUT scores independently predict a 3-month poor prognosis in AHS, which helps to identify those who need additional nutritional managements.

Activation of the endocannabinoid system mediates cardiac hypertrophy induced by rosiglitazone.

Rosiglitazone (RSG) is a synthetic agonist of peroxisome proliferator-activated receptor-γ (PPARγ), which plays a central role in the regulation of metabolism. Meta-analyses have suggested that RSG is associated with increased cardiovascular risk. However, the mechanisms underlying such adverse cardiac effects are still poorly understood. Here, we found that activation of PPARγ by RSG stimulated the endocannabinoid system (ECS), a membrane lipid signaling system, which induced cardiac hypertrophy. In neonatal rat cardiomyocytes, RSG increased the level of anandamide (AEA); upregulated the expression of N-acyl phosphatidylethanolamine phospholipase D (NapePLD), a key enzyme for AEA synthesis; and downregulated the expression of fatty acid amide hydrolase (FAAH), the enzyme responsible for the degradation of AEA. Importantly, PPARγ activation increased the expression of cannabinoid receptor type 1 (CB1) through an identified binding site for PPARγ in the CB1 promoter region. Moreover, both the in vitro and in vivo results showed that inhibition of the ECS by rimonabant, an antagonist of CB1, attenuated RSG-induced cardiac hypertrophy, as indicated by decreased expression of cardiac hypertrophy markers (ANP and BNP), deactivation of the mTOR pathway, and decreased cardiomyocyte size. Thus, these results demonstrated that the ECS functions as a novel target of PPARγ and that the AEA/CB1/mTOR axis mediates RSG-induced cardiac remodeling.

CHMFL-26 is a highly potent irreversible HER2 inhibitor for use in the treatment of HER2-positive and HER2-mutant cancers.

Oncogene HER2 is amplified in 20%-25% of human breast cancers and 6.1%-23.0% of gastric cancers, and HER2-directed therapy significantly improves the outcome for patients with HER2-positive cancers. However, drug resistance is still a clinical challenge due to primary or acquired mutations and drug-induced negative regulatory feedback. In this study, we discovered a potent irreversible HER2 kinase inhibitor, CHMFL-26, which covalently targeted cysteine 805 of HER2 and effectively overcame the drug resistance caused by HER2 V777L, HER2 L755S, HER2 exon 20 insertions, and p95-HER2 truncation mutations. CHMFL-26 displayed potent antiproliferation efficacy against HER2-amplified and mutant cells through constant HER2-mediated signaling pathway inhibition and apoptosis induction. In addition, CHMFL-26 suppressed tumor growth in a dose-dependent manner in xenograft mouse models. Together, these results suggest that CHMFL-26 may be a potential novel anti-HER2 agent for overcoming drug resistance in HER2-positive cancer therapy.

Clinical evaluation of narrow-diameter implants versus standard-diameter implants with lateral bone augmentation in posterior jaws: Three-year results of a randomized controlled trial.

BACKGROUND: The aim of this study was to compare the 3-year clinical outcomes of narrow-diameter implants (NDI) with standard-diameter implants (SDI) in conjunction with lateral bone augmentation in atrophic posterior jaws. MATERIALS AND METHODS: Fifty patients were included and randomly assigned into two groups: Patients in Group 1 received NDI (Ø3.5 mm); patients in Group 2 received SDI (Ø4.3 mm) with simultaneous lateral bone augmentation. Implant survival rates, complications, crestal bone loss, peri-implant conditions, treatment cost, and patient satisfaction were compared. RESULTS: Three patients dropped out the follow-up. No implant loss was observed. The difference in technical complication rates between the two groups was 3.8% (95% CI: -13.7% to 21.3%). No significant differences in crestal bone loss were found between two groups at 3-year follow-up (0.55 ± 0.76 vs 0.41 ± 0.41 mm, p = .429). A total of 20.8% (5/24) of NDI were diagnosed with mucositis and 8.3% (2/24) with peri-implantitis. A total of 17.4% (4/23) of SDI showed mucositis and (1/23) 4.3% showed peri-implantitis. The total cumulative cost of treatment per patient in Group 1 (2849.6 USD, 95% CI: 2726.8-2972.4) was significantly lower than that in Group 2 (3581.4 USD, 95% CI, 3460.9-3701.9) over the 3-year follow-up (p < .01). The patient satisfaction rating of operation was significantly higher in Group 1 (85.42 ± 7.41 vs 80.48 ± 7.95, p = .033). DISCUSSION: NDI yielded favorable implant survival, acceptable technical and biological complications, and high patient satisfaction supporting single crowns in the atrophic posterior region after 3-year follow-up. NDI might be a reasonable alternative in horizontally deficient posterior jaws. TRIAL REGISTRATION: Clinicaltrials.gov identifier: ChiCTR1800020426.

Fasting blood glucose-to-glycated hemoglobin ratio and all-cause mortality among Chinese in-hospital patients with acute stroke: a 12-month follow-up study.

BACKGROUND: Stroke is a leading cause of death and functional impairment in older people. To assess the prospective association between fasting blood glucose-to-glycated hemoglobin ratio and all-cause mortality and poor prognosis in stroke patients. METHODS: A total of 971 Chinese inpatients with acute stroke (mean age of 65.7) were consecutively enrolled in the prospective clinical study and followed up for 12 months after discharge. Stress hyperglycemia was measured using the ratio of fasting blood glucose (FBG, mmol/L)/glycated hemoglobin (HbA1c, %). The primary outcome was all-cause mortality, and secondary outcomes were poor prognosis defined as infectious complications, a National Institutes of Health Stroke Scale (NIHSS) score ≥ 6, a Barthel Index score ≤ 60, or a modified Rankin Scale (mRS) score of 3-6, presented as multivariate-adjusted odds ratios (ORs) with 95% confidence intervals (CIs) across the quartiles of the FBG/HbA1c ratio. RESULTS: There were 35 (4.1%) all-cause deaths at 3 months and 85 (11.4%) at 12 months. The inpatients with the highest quartile of the FBG/HbA1c ratio had a higher risk of all-cause death at 3 months (adjusted OR: 5.16, 95% CI: 1.03-25.74) and at 12 months (adjusted OR: 2.59, 95% CI: 1.14-5.89)) and a higher risk of infectious complications (adjusted OR 2.37, 95% CI 1.27-4.43) and dysfunction (adjusted OR 1.79, 95% CI 1.06-3.01) during hospitalization than inpatients with the lowest quartile. CONCLUSIONS: Stress hyperglycemia, measured by the FBG/HbA1c ratio, was associated with an increased risk of adverse outcomes, including all-cause death, infectious complications, and dysfunction after stroke.

Intermediate risk pulmonary embolism concomitant with or without lung cancer: a wide spectrum of features.

OBJECTIVES: We aimed to investigate the differences in clinical features between pulmonary embolism (PE) patients concomitant with lung cancer and without lung cancer (LC) and gain further understanding of the impact of lung cancer on pulmonary embolism. METHODS: This retrospective study sampled 114 patients diagnosed with pulmonary embolism from January 2017 to April 2021 in the First Affiliated Hospital of Soochow University. The patients were categorized into the LC group (n = 22) or non-LC group (n = 92). Myocardial injury, coagulation and blood cell parameters, along with imaging findings, were analyzed for the two groups. The primary outcome measure was the 90-day mortality. RESULTS: Of the 114 patients with pulmonary embolism in the present study, the 90 intermediate-risk patients were enrolled for further investigations. Compared to the non-LC group, patients in the LC group had milder myocardial injury, more severe coagulation function disorder, a higher incidence of central PE and a smaller change in diameter of the main pulmonary artery. We found that the occurrence of pericardial effusion created the risk of lung cancer in patients with pulmonary embolism, but there was no increase in the 90-day mortality for non-LC group versus LC group. CONCLUSION: Intermediate risk PE patients concomitant with lung cancer seem to be more likely to present specific clinical features, accordingly, clinicians must pay great attention to PE patients concomitant with lung cancer and implement effective treatments to simultaneously manage the two conditions.

[In vitro "benefit-risk" evaluation and network regulation mechanism of Colquhounia Root Tablets and its key material basis].

Colquhounia Root Tablets, prepared from Tripterygium, is effective for rheumatoid arthritis, diabetic nephropathy, and membranous nephropathy. However, the adverse reactions, such as liver injury, nausea, and vomiting, limit its application. This study aims to evaluate the advantages and risk of Colquhounia Root Tablets and its key active components in the treatment of rheumatoid arthritis, diabetic nephropathy, and membranous nephropathy and explore the potential mechanism in treating different diseases based on in vitro efficacy and toxicity assessment and biomolecular network analysis. First, the components of Colquhounia Root Tablets absorbed in blood were detected via ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry, and the influence of Colquhounia Root Tablets and its key components triptolide and celastrol on viability of human hepatocyte L02, human rheumatoid fibroblast-like synovial cell MH7 A, human renal tubular epithelial cell HK-2, and mouse podocyte MPC-5 was detected by cell counting kit 8(CCK8) assay. Then the expression of inflammatory cytokines of MH7 A and HK-2 cells was detected by enzyme-linked immunosorbent assay(ELISA). Moreover, the expression of nephrin and podocin in MPC-5 cells was measured by Western blot, and the expression of cytoskeletal protein by immunofluorence assay. Candidate targets of components from Colquhounia Root Tablets absorbed in blood were retrieved from TCMIP v2.0, and targets of the three diseases from GEO. The "disease-related genes-drug targets" network was constructed based on STRING, followed by pathway enrichment. Finally, molecular docking was performed by AutoDock Vina to explore the binding affinity of triptolide and celastrol with putative targets in the key signaling pathway. RESULTS:: showed that Colquhounia Root Tablets, triptolide, and celastrol can obviously reduce the levels of inflammatory cytokines in supernatant of MH7 A and HK-2 cells and enhance the expression of nephrin and podocin in MPC-5 cells. In addition, triptolide had the strongest toxicity to L02 cells, while Huobahuagen Tablets had the least toxicity to hepatocytes. Network analysis revealed that Colquhounia Root Tablets may intervene the three diseases through PI3 K/HIF1α/NOS signaling pathway. Both triptolide and celastrol had high binding affinities to corresponding targets in this signaling pathway. In conclusion, Colquhounia Root Tablets exerts similar effects on rheumatoid arthritis, diabetic nephropathy, and membranous nephropathy to triptolide and celastrol, but the toxicity was lower. PI3 K/HIF1α/NOS signaling pathway may be the common pathway of Colquhounia Root Tablets in the treatment of the three diseases.

Differential and paradoxical roles of new-generation antidepressants in primary astrocytic inflammation.

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) are commonly used new-generation drugs for depression. Depressive symptoms are thought to be closely related to neuroinflammation. In this study, we used up-to-date protocols of culture and stimulation and aimed to understand how astrocytes respond to the antidepressants. METHODS: Primary astrocytes were isolated and cultured using neurobasal-based serum-free medium. The cells were treated with a cytokine mixture comprising complement component 1q, tumor necrosis factor α, and interleukin 1α with or without pretreatments of antidepressants. Cell viability, phenotypes, inflammatory responses, and the underlying mechanisms were analyzed. RESULTS: All the SSRIs, including paroxetine, fluoxetine, sertraline, citalopram, and fluvoxamine, show a visible cytotoxicity within the range of applied doses, and a paradoxical effect on astrocytic inflammatory responses as manifested by the promotion of inducible nitric oxide synthase (iNOS) and/or nitric oxide (NO) and the inhibition of interleukin 6 (IL-6) and/or interleukin 1ß (IL-1ß). The SNRI venlafaxine was the least toxic to astrocytes and inhibited the production of IL-6 and IL-1ß but with no impact on iNOS and NO. All the drugs had no regulation on the polarization of astrocytic A1 and A2 types. Mechanisms associated with the antidepressants in astrocytic inflammation route via inhibition of JNK1 activation and STAT3 basal activity. CONCLUSIONS: The study demonstrated that the antidepressants possess differential cytotoxicity to astrocytes and function differently, also paradoxically for the SSRIs, to astrocytic inflammation. Our results provide novel pieces into understanding the differential efficacy and tolerability of the antidepressants in treating patients in the context of astrocytes.

Validity and reliability of the Chinese version of the partners at care transitions measure.

BACKGROUND: The Partners at Care Transitions Measure (PACT-M) is a measure that assesses the quality and safety of care during the transition from hospital to home from the patient's perspective. The aim of this study was to examine the psychometric properties of the Chinese version of the PACT-M in Mainland China. METHODS: This was a cross-sectional study. A convenience sample of patients was recruited from three tertiary hospitals affiliated with Zhengzhou University, China. A total of 402 participants were interviewed before discharge, and 306 participants were interviewed one month after discharge from hospital to home using the Chinese version of the PACT-M. The statistical methods used in this study include the critical ratio value, item total correlation, test-retest, Cronbach's alpha, confirmatory factor analysis and exploratory factor analysis. RESULTS: The Chinese version of the PACT-M consists of PACT-M1 and PACT-M2, both of which have two dimensions, the number of items in both parts are consistent with the original English language version. The Cronbach's alpha values of the PACT-M1 and PACT-M2 were 0.802 and 0.741, and the test-retest reliability values were 0.885 and 0.837. The item content validity index and scale content validity index values of the PACT-M1 and PACT-M2 were all 1.0. CONCLUSION: The Chinese version of the PACT-M shows acceptable validity and reliability and can be used to assess the quality and safety of transitional care from hospital to home from the patient's perspective in mainland China.

RNA editing of SLC22A3 drives early tumor invasion and metastasis in familial esophageal cancer.

Like many complex human diseases, esophageal squamous cell carcinoma (ESCC) is known to cluster in families. Familial ESCC cases often show early onset and worse prognosis than the sporadic cases. However, the molecular genetic basis underlying the development of familial ESCC is mostly unknown. We reported that SLC22A3 is significantly down-regulated in nontumor esophageal tissues from patients with familial ESCC compared with tissues from patients with sporadic ESCCs. A-to-I RNA editing of the SLC22A3 gene results in its reduced expression in the nontumor esophageal tissues of familial ESCCs and is significantly correlated with lymph node metastasis. The RNA-editing enzyme ADAR2, a familial ESCC susceptibility gene identified by our post hoc genome-wide association study, is positively correlated with the editing level of SLC22A3 Moreover, functional studies showed that SLC22A3 is a metastasis suppressor in ESCC, and deregulation of SLC22A3 facilitates cell invasion and filopodia formation by reducing its direct association with α-actinin-4 (ACTN4), leading to the increased actin-binding activity of ACTN4 in normal esophageal cells. Collectively, we now show that A-to-I RNA editing of SLC22A3 contributes to the early development and progression of familial esophageal cancer in high-risk individuals.

Lewis Acidic PSbP Pincer Ligand in Pt-Catalyzed 1,6-Enyne Cycloisomerization: A Theoretical Study.

The progressively improved heterobimetallic antimony transition metal complex PSbP-Pt (I1) provides superior activity in catalyzed 1,6-enyne cycloisomerization. Our DFT calculations demonstrate that the noninnocent character of the antimony ligand enhances the self-activation of the catalyst precursor through a substrate-aided intramolecular chloride migration, which triggers subsequent reaction. Designed alternative redox noninnocent active species with strong electron-withdrawing groups also show promising catalytic ability due to an electron-deficient antimony ligand, which lowers the typical reaction barrier for the cycloisomerization of 1,6-enyne.