Efficacy and safety of levosimendan in patients with sepsis: a systematic review and network meta-analysis.

Objective: We conducted a systematic review to assess the advantages and disadvantages of levosimendan in patients with sepsis compared with placebo, milrinone, and dobutamine and to explore the clinical efficacy of different concentrations of levosimendan. Methods: PubMed, Web of Science, Cochrane Library, Embase, CNKI, Wanfang data, VIP, and CBM databases were searched using such keywords as simendan, levosimendan, and sepsis. The search time was from the establishment of the database to July 2023. Two researchers were responsible for literature screening and data collection respectively. After the risk of bias in the included studies was evaluated, network meta-analysis was performed using R software gemtc and rjags package. Results: Thirty-two randomized controlled trials (RCTs) were included in the network meta-analysis. Meta-analysis results showed that while levosimendan significantly improved CI levels at either 0.1 µg/kg/min (mean difference [MD] [95%CrI] = 0.41 [-0.43, 1.4]) or 0.2 µg/kg/min (MD [95%CrI] =0.54 [0.12, 0.99]). Levosimendan, at either 0.075 µg/kg/min (MD [95% CrI] =0.033 [-0.75, 0.82]) or 0.2 µg/kg/min (MD [95% CrI] = -0.014 [-0.26, 0.23]), had no significant advantage in improving Lac levels. Levosimendan, at either 0.1 µg/kg/min (RR [95% CrI] = 0.99 [0.73, 1.3]) or 0.2 µg/kg/min (RR [95% CrI] = 1.0 [0.88, 1.2]), did not have a significant advantage in reducing mortality. Conclusion: The existing evidence suggests that levosimendan can significantly improve CI and lactate levels in patients with sepsis, and levosimendan at 0.1 µg/kg/min might be the optimal dose. Unfortunately, all interventions in this study failed to reduce the 28-day mortality. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023441220.

Treatment of Sinus Graft Infection After Sinus Floor Elevation: A Series of Four Case Reports.

This report of cases aims to share our treatment experiences in 4 sinus graft infection cases after sinus floor elevation and simultaneous implant placement. The preoperative and postoperative intraoral and radiographic photographs were collected and used to assess the treatment outcomes. The sinus cavity status, bone augmentation results, and implant stability were used as measurements to determine the treatment effectiveness. Four patients received partial graft removal as their surgical treatment for sinus graft infection combined with antibiotic therapy, with or without immediate secondary grafting. After early intervention, antibiotic therapy, and partial debridement of the infected sinus grafts, radiographic and clinical outcomes indicate successful resolution of the graft infection and stable bone graft levels around the implants. The keys to the successful management of the sinus graft infection were: early detection of the infection; early intervention, including partial debridement of the infected graft particles; and antibiotic therapy.

Molecular mechanism of ensitrelvir inhibiting SARS-CoV-2 main protease and its variants.

SARS-CoV-2 poses an unprecedented threat to the world as the causative agent of the COVID-19 pandemic. Among a handful of therapeutics developed for the prevention and treatment of SARS-CoV-2 infection, ensitrelvir is the first noncovalent and nonpeptide oral inhibitor targeting the main protease (Mpro) of SARS-CoV-2, which recently received emergency regulatory approval in Japan. Here we determined a 1.8-Å structure of Mpro in complex with ensitrelvir, which revealed that ensitrelvir targets the substrate-binding pocket of Mpro, specifically recognizing its S1, S2, and S1' subsites. Further, our comprehensive biochemical and structural data have demonstrated that even though ensitrelvir and nirmatrelvir (an FDA-approved drug) belong to different types of Mpro inhibitors, both of them remain to be effective against Mpros from all five SARS-CoV-2 variants of concern, suggesting Mpro is a bona fide broad-spectrum target. The molecular mechanisms uncovered in this study provide basis for future inhibitor design.

Clinical Outcomes of Alveolar Ridge Augmentation with In Situ Autogenous Block Bone: A Retrospective Review.

PURPOSE: To present clinical outcomes of alveolar ridge augmentation using in situ autogenous block bone and to compare the outcomes with previous studies. MATERIALS AND METHODS: The medical records of patients with a severe horizontal bone defect in a partially edentulous alveolar ridge (width < 3.5 mm), who received bone augmentation using in situ autogenous block bone, were retrospectively reviewed. After a 6-month or longer healing period, the augmentation effect was examined before implant placement. Cone beam computed tomography (CBCT) was performed before and after surgeries. The alveolar width of the bone grafts was measured on the CBCT images. RESULTS: A total of 16 patients (22 grafts) were included. Graft exposure was seen in three grafts, which were classified as failed cases. The augmentation volume at implant placement in the failed cases was significantly lower than that of the successful cases. There were no significant differences in augmentation between anterior maxillary and mandibular implant sites. CONCLUSION: Autogenous bone grafting using in situ block bone is an effective and reliable approach for horizontal bone augmentation in the mandible and anterior maxilla that eliminates second donor site morbidity. Complete release of the buccal flap and tension-free suture is the key to avoiding wound dehiscence and ensuring the effectiveness of bone augmentation.

A zinc/PyBisulidine catalyzed asymmetric Mannich reaction of N-tosyl imines with 3-acyloxy-2-oxindoles.

A Zn-PyBisulidine catalyzed asymmetric Mannich reaction of 3-acyloxy-2-oxindoles has been developed. Various quaternary substituted 3-acyloxy-2-oxindoles bearing vicinal amino alcohol motifs were obtained in good to excellent yields with moderate to excellent dr and excellent enantioselectivities. The utility of this reaction was demonstrated by the easy removal of the acyl group to give C3-hydroxy derivatives and their application as a key skeleton of the ligand for the Ni-catalyzed enantioselective Henry reaction.

Reversal of Enantioselectivity in the Copper-Aminophenol Sulfonamide Catalyzed Alkynylation of Isatins by Slightly Tuning the Ligand Structure and Basic Additives.

A series of new chiral aminophenol sulfonamide ligands with a monochiral arm has been developed for the first Cu(I) catalyzed enantiodivergent alkynylation of isatins. Dramatic reversal of enantioselectivity was accomplished by slightly tuning the substituted benzenesulfonamide and achiral basic additives. A wide range of both terminal alkynes and isatins are tolerated by this new catalyst system with up to 99% yield and 97% ee.

Cooperative Heterobimetallic Zinc/Alkaline Earth Metal Catalysis: A Zn/Sr Aminophenol Sulfonamide Complex for Catalytic Asymmetric Michael Addition of 3-Acetoxy-2-oxindoles to ß-Ester Enones.

A heterobimetallic zinc/strontium catalyst has been developed for the asymmetric Michael addition of 3-acetoxy-2-oxindoles to ß-ester enones in high yields with excellent enantioselectivities and high diastereoselectivities. This process represents that 3-acetoxy-2-oxindoles can be used as a stable air- and base-tolerant precursor for chiral 3-substituted 3-hydroxy-2-oxindoles.

LncRNA ELF3-AS1 is involved in the regulation of oral squamous cell carcinoma cell proliferation by reprogramming glucose metabolism.

PURPOSE: The present study aims to investigate the role of ELF3-AS1 in oral squamous cell carcinoma (OSCC). PATIENTS AND METHODS: A total of 112 patients with OSCC were admitted in Guangdong Provincial Stomatological Hospital from March 2016 to March 2019. RT-qPCR, cells and transient transfections, cell proliferation rate measurements and Western blots were carried out to analyze the samples. RESULTS: In the present study, we showed that ELF3-AS1 and glucose transporter 1 (GLUT1) were both upregulated in OSCC tissues, and those two factors were positively correlated. In OSCC cells, ELF3-AS1 overexpression resulted in upregulation, while ELF3-AS1 siRNA silencing caused downregulated expression of GLUT1 and glucose uptake. ELF3-AS1 and GLUT1 overexpression resulted in increased rate of OSCC cells, while ELF3-AS1 and GLUT1 siRNA silencing resulted in decreased proliferation rate of OSCC cells. In addition, GLUT1 siRNA silencing attenuated the effects of ELF3-AS1 overexpression. CONCLUSION: Therefore, ELF3-AS1 promotes the proliferation of OSCC cells by reprogramming glucose metabolism.

Elevated hydrostatic pressure promotes ameloblastoma cell invasion through upregulation of MMP-2 and MMP-9 expression via Wnt/ß-catenin signalling.

BACKGROUND: The process of marsupialization involves the release of intracystic pressure and the fluid contained within. Marsupialization of cystic ameloblastoma is controversial; therefore, we investigated how hydrostatic pressure influences biological behaviours of ameloblastoma cells and its underlying mechanisms. MATERIALS AND METHODS: An ameloblastoma epithelial cell line, hTERT+ -AM, was exposed to different hydrostatic pressures with or without Dickkopf-related protein 1 (also known as DKK), a canonical Wnt signalling pathway inhibitor. A CCK-8 assay, a monolayer wound assay, and a Transwell assay were used to determine cell proliferation, migration and invasion, respectively. qRT-PCR and Western blot were used to detect expression of MMP-2, MMP-9, RANKL and other downstream targets of Wnt signalling. RESULTS: Elevated hydrostatic pressure promoted migration and invasion of ameloblastoma cells, but inhibited proliferation. Expression of MMP-2, MMP-9, LEF-1, cyclin D1, c-Jun and c-Myc was significantly upregulated under elevated hydrostatic pressure, and these effects could be abolished by DKK1. Expression of RANKL, which is thought to be a downstream target of Wnt signalling, did not significantly change under elevated hydrostatic pressure. CONCLUSIONS: This study indicates that elevated hydrostatic pressure promotes the migration and invasion of ameloblastoma cells by activating the Wnt/ß-catenin pathway, thereby increasing expression of MMP-2, MMP-9 and other Wnt signalling downstream targets. This suggests that marsupialization may reduce invasiveness and reverse the bone resorption process by lowering intracystic hydrostatic pressure in cystic ameloblastoma.

Marsupialization of mandibular cystic ameloblastoma: Retrospective study of 7 years.

BACKGROUND: This retrospective study investigated the reduction rate and speed of shrinkage after marsupialization in mandibular cystic ameloblastoma and clarified whether marsupialization is appropriate for unicystic ameloblastoma and multicystic ameloblastoma. METHODS: Sixty-three patients with mandibular cystic ameloblastoma were initially treated with marsupialization. Premarsupialization and postmarsupialization panoramic radiographs were reviewed for reduction rate and speed of shrinkage, and then were evaluated with age, sex, tumor location, and tumor type. RESULTS: The overall recurrence rate was 4.5% (2/44). The average reduction rate after marsupialization was 65.6%. No significant difference was found between unicystic ameloblastoma and multicystic ameloblastoma in reduction rate. The speed of shrinkage of unicystic ameloblastoma was significantly faster than that of multicystic ameloblastoma (P < .05). Similarly, patients with multicystic ameloblastoma had longer marsupialization periods than those with unicystic ameloblastoma (P < .05). CONCLUSION: Marsupialization is effective in reducing tumor size for both unicystic ameloblastoma and multicystic ameloblastoma. Marsupialization plus second-stage curettage is recommended as the primary treatment for mandibular cystic ameloblastoma.

[Comparison of two different flap designs in removal of impacted wisdom tooth].

PURPOSE: The purpose of this study was to compare the effect of two different flap designs on surgical removal of impacted mandibular third molars. METHODS: Four hundred patients who required removal of impacted mandibular third molars were included in the study. They were divided into group A and group B randomly. Patients in group A received distal incision flap and group B underwent angular incision flap. The effect of flap design on surgical time, incidence of dry socket, pain, swelling and trismus was evaluated postoperatively. Data analysis was carried out with SPSS 13.0 software package. RESULTS: The surgical time was longer in group A than in group B 3 days postoperatively. Facial swelling and trismus were less in group A than in group B 3 days postoperatively. There was no significant difference in two groups 7 days postoperatively. CONCLUSIONS: The distal incision flap design can release facial swelling and trismus in surgical removal of impacted mandibular third molars.

A study on the inhibition of VEGF expression in salivary gland adenoid cystic carcinoma cells via iNOS gene RNAi in vitro.

In this study, we aimed to explore the effect of inducible nitric oxide synthase (iNOS) on vascular endothelial growth factor (VEGF) expression in salivary gland adenoid cystic carcinoma (SACC). Using RNAi, we transfected chemically synthesised iNOS siRNA into ACC-M cells (a highly metastatic adenoid cystic carcinoma cell line) and detected the change in the gene and protein expression levels of iNOS and VEGF by qRT-PCR and Western blotting. A transwell invasiveness assay was used to examine the changes in invasive ability of ACC-M cells. Cell growth was determined using a CCK-8 assay. Apoptosis and cell-cycle phases were detected by flow cytometry. We found that silencing iNOS down-regulated the expression of VEGF and then inhibited cell growth and invasiveness of SACC cells, while it increased apoptosis. Therefore, we concluded that iNOS can regulate VEGF expression and iNOS may be a therapeutic target.

Cervical metastases from squamous cell carcinoma of hard palate and maxillary alveolus: a retrospective study of 10 years.

BACKGROUND: The purpose of this study was to investigate the incidence of cervical metastasis in squamous cell carcinoma (SCC) of hard palate and maxillary alveolus and to define its impact factors. METHODS: We conducted a retrospective study of patients surgically treated for SCC of hard palate and maxillary alveolus from 2002 to 2011. In situ hybridization was performed to detect high-risk human papillomavirus (HPV) infection. RESULTS: The incidences of cervical metastasis and occult metastasis were 17.2% (11/64) and 9.8% (5/51), respectively. The pT classification and vascular invasion were correlated with cervical metastasis. Occult metastatic risk was significantly higher among patients with pT4. Presence of positive nodes impaired prognosis significantly. CONCLUSION: SCC of hard palate and maxillary alveolus has nonnegligible incidences of both overall and occult metastasis, which were highly associated with pT classification. We recommend routine, synchronous elective neck dissection for T4 lesions, whereas observation is an alternative for T1 to T3 lesions.