[Observation of the consistency between intellectualized and manual-based cognitive assessment tools in the outpatient clinic].

Objective: The intellectualized versions of the Montreal Cognitive Assessment Scale (MoCA) and the Mini-mental State Examination (MMSE) (i-MoCA/i-MMSE) were developed. The validity of this system was evaluated in a clinical sample through comparing with the manual-based assessments. Methods: A total of 88 patients [aged (66.82±11.37) years, 30 males and 58 females] were enrolled in the outpatient clinic of Xuanwu Hospital of Capital Medical University with complaints of cognitive decline, from February to October 2023. All participants completed manual-based and intellectualized assessments in a randomized order, with an interval of 2 weeks to control for the practice effect. The reliability of the intellectualized version of assessments was evaluated based on the manual-based version using the Concordance correlation coefficient (CCC). The difference between the intellectualized and the manual-based assessments was tested by the Repeated ANCOVA with demographic information controlled. The accuracy of evaluation of the i-MoCA and i-MMSE was analyzed by the Receiver Operating Characteristic (ROC) analysis. Results: High concordance was observed between the intellectualized version and the manual-based assessments (CCCMoCA=0.87, CCCMMSE=0.83). Controlling for basic demographic information, there was no significant difference in the scores of the intellectualized version and the manual-based assessments (all P>0.05). The accuracy of i-MoCA in screening patients with cognitive impairment was 94.3% (sensitivity=94.6%, specificity=78.1%), while the accuracy of i-MMSE in screening patients with cognitive impairment was 94.9% (sensitivity=94.9%, specificity=77.6%). In addition, the majority of subdomains measured by the cognitive assessments exhibited high consistency across the intellectualized the manual-based versions (CCCMoCA=0.32-0.78; CCCMMSE=0.54-0.79). Conclusion: Both the i-MoCA and i-MMSE showed high consistency and diagnostic accuracy with the manual-based versions in terms of overall cognitive function and subdomains.

Roxadustat protects rat renal tubular epithelial cells from hypoxia-induced injury through the TGF-ß1/Smad3 signaling pathway.

OBJECTIVE: Roxadustat is used to treat renal anemia. The renoprotective effect of roxadustat needs to be further confirmed, and the mechanism of action is unknown. This study aims to evaluate the effect and mechanism of roxadustat in hypoxia-related nephropathy with the renal tubular epithelial cell line NRK-52E. MATERIALS AND METHODS: The cell Counting Kit-8 (CCK-8) assay was employed to assess cellular proliferation in the current investigation. Flow cytometry was used to conduct cell apoptosis analysis. The utilization of electron microscopy facilitated the identification of changes in cellular ultrastructure. Immunofluorescence was used to detect the expression trend of hypoxia-inducible factor-1α (HIF-1α). The connective tissue growth factor (CTGF), transforming growth factor-ß1 (TGF-ß1), Smad family member 3 (Smad3), p-Smad3, α-smooth muscle actin (α-SMA), collagen I, and HIF-1α were assessed by western blotting. Real-time fluorescent quantitative PCR (RT-qPCR) was used to measure TGF-ß1 and Smad3 mRNA. RESULTS: Significant growth inhibition and increased apoptosis were observed in NRK-52E cells cultured under hypoxic conditions (1% and 5% O2), which can be rescued by roxadustat. From a morphological perspective, it has been observed that roxadustat can counteract cellular damage features produced by hypoxia. These features include the contraction of the nuclear envelope and an increase in the formation of apoptotic bodies. Roxadustat increases HIF-1α expression acutely at 24 h, followed by a gradual reduction of HIF-1α expression to levels significantly below that of the hypoxia group by 72 h. Roxadustat can also inhibit hypoxia-induced increased expression of CTGF, TGF-ß1, p-Smad3, α-SMA, collagen I, and HIF-1α. Combined treatment with roxadustat and siRNA against TGF-ß1 synergistically reduced the expression of CTGF and HIF-1α, while the effect on TGF-ß1 and p-Smad3 were comparable to that of the individual treatment alone. Comparably, the combined administration of roxadustat and siRNA targeting Smad3 had a synergistic impact on diminishing the expression of CTGF. CONCLUSIONS: These findings indicate that roxadustat attenuates experimental renal fibrosis likely by inhibiting the TGF-ß1/Smad3 pathways, while its effect on CTGF and HIF-1α may involve other signaling pathways.

[A single-center study on the distribution and antibiotic resistance of pathogens causing bloodstream infection in patients with hematological malignancies].

Objective: To study the incidence of bloodstream infections, pathogen distribution, and antibiotic resistance profile in patients with hematological malignancies. Methods: From January 2018 to December 2021, we retrospectively analyzed the clinical characteristics, pathogen distribution, and antibiotic resistance profiles of patients with malignant hematological diseases and bloodstream infections in the Department of Hematology, Nanfang Hospital, Southern Medical University. Results: A total of 582 incidences of bloodstream infections occurred in 22,717 inpatients. From 2018 to 2021, the incidence rates of bloodstream infections were 2.79%, 2.99%, 2.79%, and 2.02%, respectively. Five hundred ninety-nine types of bacteria were recovered from blood cultures, with 487 (81.3%) gram-negative bacteria, such as Klebsiella pneumonia, Escherichia coli, and Pseudomonas aeruginosa. Eighty-one (13.5%) were gram-positive bacteria, primarily Staphylococcus aureus, Staphylococcus epidermidis, and Enterococcus faecium, whereas the remaining 31 (5.2%) were fungi. Enterobacteriaceae resistance to carbapenems, piperacillin/tazobactam, cefoperazone sodium/sulbactam, and tigecycline were 11.0%, 15.3%, 15.4%, and 3.3%, with a descending trend year on year. Non-fermenters tolerated piperacillin/tazobactam, cefoperazone sodium/sulbactam, and quinolones at 29.6%, 13.3%, and 21.7%, respectively. However, only two gram-positive bacteria isolates were shown to be resistant to glycopeptide antibiotics. Conclusions: Bloodstream pathogens in hematological malignancies were broadly dispersed, most of which were gram-negative bacteria. Antibiotic resistance rates vary greatly between species. Our research serves as a valuable resource for the selection of empirical antibiotics.

[Transoral robotic surgery for treatment of lingual thyroglossal duct cyst].

Objective: To investigate the feasibility, safety and efficacy of transoral robotic surgery (TORS) in the treatment of lingual thyroglossal duct cyst (LTGDC). Methods: The clinical data of 10 patients with LTGDC treated with TORS in Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology from May 2017 to November 2020 were analyzed retrospectively,including 6 males and 4 females, aged 5-44 years. The cysts were fully exposed, and resection usually started from the cephalic side of lesions. The range of resection was 3 to 5 mm away from the lesions, and partial hyoid bone was removed if necessary. Intra-operative robotic set-up time,operation time and estimated blood loss,and post-operative local bleeding, dyspnea and recovery time for oral intake were analyzed. SPSS 12.0 software was used for statistical analysis. Results: The cysts in all 10 patients were successfully resected by TORS with da Vinci Si surgical system. The mean robotic set-up and exposure time, operation time, estimated intraoperative blood loss and recovery time for oral intake were (15.5±7.1) min, (17.6±7.4) min, (8.9±6.4)ml and (2.3±2.2)days, respectively. No patient required tracheostomy intra-or post-operatively, and no symptoms of airway obstruction, postoperative bleeding, pharyngeal fistula, hoarseness and neurological impairment occurred after operation. The patients were followed up for 5 to 47 months, with median follow-up time of 17 months, and no recurrence was observed. Conclusion: TORS is safe and feasible for resection of LTGDC, with rapid recovery and low recurrence rate.

[Analysis of the effect of microwave ablation in the treatment of small liver cancer].

Objective: To explore the clinical effect of microwave ablation in the treatment of early small liver cancer (≤3 cm). Methods: 103 cases with small liver cancer (tumor number < 3 and maximum tumor diameter < 3 cm) who underwent microwave ablation from November 2016 to November 2018 were retrospectively collected. The rate of residual lesions, recurrence rate one-year after the operation, and surgical complications were observed and grouped according to tumor size (< 2 cm and≥2 cm group) and tumor numbers (solitary and 2 ~ 3 lesion groups). The therapeutic effects of each group were compared and analyzed. Results: The tumor residual rate and one-year recurrence rate of small liver cancer after microwave ablation were 11.7% and 35.0%, respectively. The post-ablation syndrome incidence rate was 52.4%, with no serious adverse events. Compared with tumors < 2 cm, patients with≥2 cm had a higher postoperative residual rate (χ(2) = 7.651, P = 0.006), and the one-year recurrence rate of more solitary nodular tumors was lower (χ(2) = 10.125, P = 0.001). Conclusion: Microwave ablation is a safe and effective treatment for early small liver cancer, and it is more effective for small solitary nodules (< 2 cm).

Paeonol inhibits proliferation and induces cell apoptosis of human T24 and 5637 bladder cancer cells in vitro and in vivo

Purpose Paeonol is a natural chemical medicine derived from the bark of peony root, which has been found to inhibit tumor activity in various tumor cell lines, and can play a synergistic anti-tumor effect with chemotherapy or radiotherapy. Methods We used paeonol to act on human bladder cancer T24 and 5637 cells, and established xenograft tumor in nude mice by subcutaneous injection of T24 cells. Results CCK-8 assay and plate cloning experiments showed that paeonol could inhibit the proliferation of T24 and 5637 cells in vitro. The results of flow cytometry and the detection of BAX, Bcl-2 and Caspase-3 proteins suggested that paeonol can induce apoptosis of T24 and 5637 cells in vitro. Tumor formation, TUNEL detection and immunohistochemical results of Ki67, BAX, Bcl-2 and Caspase-3 in nude mice showed that paeonol could inhibit T24 cell proliferation and induce apoptosis in vivo, thus inhibiting tumor growth. Further research revealed that paeonol could reduce phosphorylation expression of PI3K and AKT in T24 and 5637 cells. Conclusion We confirmed that paeonol could inhibit proliferation and induce apoptosis of human bladder cancer T24 and 5637 cells in vitro and in vivo, inhibit the growth of T24 tumor-forming nude mice, and possibly play a role by inhibiting the PI3K/AKT signaling pathway, so as to provide a potential therapeutic drug for bladder cancer (AU)

Paeonol inhibits proliferation and induces cell apoptosis of human T24 and 5637 bladder cancer cells in vitro and in vivo.

PURPOSE: Paeonol is a natural chemical medicine derived from the bark of peony root, which has been found to inhibit tumor activity in various tumor cell lines, and can play a synergistic anti-tumor effect with chemotherapy or radiotherapy. METHODS: We used paeonol to act on human bladder cancer T24 and 5637 cells, and established xenograft tumor in nude mice by subcutaneous injection of T24 cells. RESULTS: CCK-8 assay and plate cloning experiments showed that paeonol could inhibit the proliferation of T24 and 5637 cells in vitro. The results of flow cytometry and the detection of BAX, Bcl-2 and Caspase-3 proteins suggested that paeonol can induce apoptosis of T24 and 5637 cells in vitro. Tumor formation, TUNEL detection and immunohistochemical results of Ki67, BAX, Bcl-2 and Caspase-3 in nude mice showed that paeonol could inhibit T24 cell proliferation and induce apoptosis in vivo, thus inhibiting tumor growth. Further research revealed that paeonol could reduce phosphorylation expression of PI3K and AKT in T24 and 5637 cells. CONCLUSION: We confirmed that paeonol could inhibit proliferation and induce apoptosis of human bladder cancer T24 and 5637 cells in vitro and in vivo, inhibit the growth of T24 tumor-forming nude mice, and possibly play a role by inhibiting the PI3K/AKT signaling pathway, so as to provide a potential therapeutic drug for bladder cancer.

Clinical characteristics of very late-onset neuromyelitis optica spectrum disorder.

BACKGROUND: The typical age at onset of neuromyelitis optica spectrum disorder (NMOSD) is between 30 and 40 years. A growing awareness about the disease and advances in diagnostic techniques have led to an increase in the number of patients being diagnosed with very late-onset (VLO) NMOSD. This study compared the clinical characteristics, treatments, and prognoses between patients with VLO-NMOSD or late-onset (LO) NMOSD. METHODS: Patients in our study were assigned to two groups based on age at onset of the disease: LO-NMOSD (50-70 years old at onset) and VLO-NMOSD (> 70 years old at onset). We compared clinical characteristics, magnetic resonance imaging of lesions, prognosis, and treatments between the two groups. RESULTS: We collected data from 12 VLO-NMOSD patients with a median age at onset of 74.0 years (interquartile range, 72.6-75.9 years) and 104 LO-NMOSD patients with a median age at onset of 56.0 years (55.8-57.9 years). There were a high proportion of female patients in both the VLO-NMOSD group (9, 75.0%) and the LO-NMOSD group (91, 87.5%). Our study indicated that VLO-NMOSD patients had significantly higher expanded disability status scale (EDSS) scores (8.5 vs 4.0, p = 0.01), higher motor disability rates (41.7% vs 9.6%, p = 0.002), and higher mortality rates (25.0 vs 4.8%, p = 0.044) at last follow-up. However, patients with VLO-NMOSD had lower rates of immunosuppressant usage (50.0% vs 76.9%, p = 0.044). Age at onset was positively correlated with EDSS score at remission (r = 0.49, p < 0.001). CONCLUSION: VLO-NMOSD was associated with higher EDSS score at remission, higher rates of mortality and motor disability, but lower rates of immunosuppressive treatment usage than LO-NMOSD. Future studies are needed to understand the effects of NMOSD on older patients, and to seek suitable treatment to improve their prognosis.

Effects of sDR5-Fc fusion protein on infant mice with ulcerative colitis via the TRAIL-DR5 pathway.

To explore effects of the sDR5-Fc fusion protein on ulcerative colitis of infant mice via the TRAIL-DR5 pathway, 50 female mice were randomly divided into 5 groups, i.e., control group (group A), dextran sulfate sodium group (group B), hIgG group (group C), 10 mg/kg sDR5-Fc group (group D), and 20 mg/ kg sDR5-Fc group (group E). The acute ulcerative colitis models were established. The weights and disease activity index (DAI) of each group were monitored daily. In addition, the pathological changes of colon tissues were observed by Hematoxylin-Eosin staining. The number of macrophages in colon tissues was detected by immunohistochemistry assay. Changes in the expression of inflammatory factors in colon tissues were detected by quantitative real-time polymerase chain reaction (PCR). Lipopolysaccharide (LPS) of different concentrations was utilized alone or in combination with TRAIL to stimulate the NCM460 cells. The activation of NLRP3 inflammasomes was detected by Western blot. The apoptosis of NCM460 cells was detected by flow cytometry. The results showed that in groups B and C, the body weights decreased, the DAI increased, the colon epithelial cells were injured, the inflammatory cells were infiltrated, and the macrophages in colon tissues increased significantly. In groups D and E, the body weights increased, the DAI decreased, the inflammation was significantly improved, the macrophages decreased significantly, and the gene expression levels of NLRP3, Caspase-1, and IL-1ß decreased significantly. Thus, sDR5-Fc could inhibit the activation of NLRP3 inflammasomes induced by TRAIL, thereby decreasing the apoptosis of NCM460 cells. In conclusion, the sDR5-Fc fusion protein could block the TRAIL-DR5 pathway to reduce the expression of NLRP3 inflammasomes, thereby improving ulcerative colitis.

[Safety and effectiveness of transoral robotic surgery for oropharyngeal cancer: a pilot study].

Objective: To evaluate the indication, safety and effectiveness of transoral robotic surgery (TORS) for oropharyngeal cancer based on our preliminary experience. Methods: Twelve patients, including six with tonsil cancer, five with tongue base cancer and one with posterior pharyngeal wall cancer, who underwent TORS with Da Vinci Si surgical system from March 2017 to October 2018 at Tongji Hospital of Huazhong University of Science Technology were respectively analyzed. And the surgical time, intraoperative blood loss, postoperative local bleeding, dyspnea, nerve function injury, oral intake time, whether or not to receive chemoradiotherapy were analyzed. Results: All tumors in the 12 patients were en bloc removed by TORS. Surgical time ranged from 25 to 80 min with an average of 34.2 min. The blood loss ranged from 10 ml to 50 ml with an average of 20.8 ml. The recovery time for oral intake ranged from 1 day to 30 days with an average of 8.4 days. No patient underwent tracheostomy after TORS. Also, no patient manifested with airway obstruction, bleeding or nerve injury symptoms after operation. All 12 patients reached pathologically negative surgical margins. The patients were followed up for 4 to 22 months, with a median of 12 months. All patients who combined with more advanced than T3 stage, or more advanced than N2 stage were recommended to oncologist, then, followed with radiotherapy or chemoradiotherapy if no relevant contradictions occurred. No local recurrence or distant metastasis case was found. Conclusion: With proper indications, the application of TORS in oropharyngeal cancer is a relatively safe, effective and minimal invasive therapy, which merits more clinical applications.

Accumulation of High Levels of Monocytic Myeloid-Derived Suppressor Cells Enhances Graft Survival in Almost-Tolerant Kidney Transplant Recipients.

BACKGROUND: Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature cells that suppress immune responses during organ transplantation and participate in mediating long-term graft survival and immune tolerance in animal transplant models. However, their role in regulating transplant tolerance in human subjects is not well understood. In the present study, we investigated the role of MDSCs in mediating long-term graft survival in almost-tolerant kidney transplant recipients (ATKTRs) and the mechanism(s) responsible for increasing MDSC numbers in these recipients. METHODS: Peripheral blood mononuclear cells (PBMCs) from whole blood samples were collected from 30 ATKTRs (graft survival, > 10 years after kidney transplant [KTx]) treated with low doses of immunosuppressive drugs and with stable kidney function, 10 short-term graft survival kidney transplant recipients (STKTRs; graft survival, ∼1-3 years post-KTx) with stable kidney function, and 10 healthy donors (HDs). MDSC and regulatory T cell (Tregs) levels were analyzed using multicolor flow cytometry in PBMCs. RESULTS: ATKTRs had significantly higher levels of monocytic MDSCs (P < .001) and CD4+CD25+FoxP3+ Tregs than STKTRs and HDs. Furthermore, the M-MDSC levels correlated positively with the survival rates, estimated glomerular filtration rates (eGFRs) of grafts, and the levels of CD4+CD25+FoxP3+ Tregs in ATKTRs. CONCLUSIONS: Accumulation of high levels of MDSCs was observed in ATKTRs. Changes in MDSC levels may play important roles in mediating transplant tolerance and regulating Tregs. Therefore, we propose that MDSCs may be potentially used for recognizing tolerant transplant recipients and guiding dosage reduction for immunosuppressive drugs for KTx.

The effects of food on the pharmacokinetics of mitiglinide tablets in healthy volunteers and a novel mass-spectrometric (UPLC-MS/MS) method for such studies.

WHAT IS KNOWN AND OBJECTIVE: Mitiglinide (MGN) is a new insulinotropic agent of the glinide class with rapid onset. The effects of food intake on the pharmacokinetic (PK) profile of mitiglinide tablets after single oral administration have not yet been reported in healthy adults. We aimed to assess the effects of food intake on the PK properties of mitiglinide (MGN) tablets, using a novel analytical method, after single escalating oral doses in healthy Chinese volunteers. METHODS: In this open-label, randomized, single-dose (three distinct doses), two-way crossover PK study, three doses of MGN 5, 10 or 20 mg were administered to healthy adult volunteers after an overnight fast (fasted condition) or low-fat breakfast (fed condition) (period 1). After 7 days, the participants received the same dose under the opposite fed/fasted condition (period 2). Serial blood samples were obtained before and through 8 h after study drug administration. Concentrations of MGN in plasma were determined using UPLC-MS/MS. Adverse events (AEs) were monitored and recorded on each in-clinic day. RESULTS AND DISCUSSION: Twenty-four Chinese volunteers (eight [four men, four women] volunteers per group) were enrolled in the study. The extent of absorption of MGN was similar in both fed and fasted conditions at single doses in the range 5-20 mg. Food intake was associated with decreases in C(max) by 60·4% to 65·2% in the three dose groups and greatly delayed T(max) [0·36(Standard deviation 0·16) vs. 1·75(0·92) hours with 5 mg, 0·29(0·19) vs. 1·97(0·81) hours with 10 mg and 0·30(0·10) vs. 1·18(0·68) hours with 20 mg; all, P < 0·05]. t(1/2) , CL/F and V/F (P > 0·05) were unaffected. MRT(0-8) at the 5 and 10-mg doses, but not at the 20-mg dose, were markedly lower in fasted volunteers than fed volunteers (P < 0·05). WHAT IS NEW AND CONCLUSIONS: Using a novel UPLC-MS/MS method, we showed that food intake affected the rate but not the extent of absorption of MGN within the 5- to 20-mg dose range. Gender did not appear to affect the PK properties of MGN in either fasted or fed states. MGN should be preferably taken before food.