Novel Anti-Viral Properties of the Herbal Extract of Davallia mariesii against Influenza A Virus.

Gu-Sui-Bu, the dried rhizome of Davallia mariesii, is a traditional Chinese herbal remedy with a significant history of treating osteoporosis and inflammatory conditions. However, its potential as an anti-influenza agent and its underlying mechanisms of action remain unexplored. To obtain a more potent extract from D. mariesii and gain insights into its mechanism of action against influenza A virus (IAV), we utilized a partitioning process involving organic solvents and water, resulting in the isolation of butanolic subfractions of the D. mariesii extract (DMBE). DMBE exhibited a broad anti-viral spectrum, effectively inhibiting IAV, with an EC50 of 24.32 ± 6.19 µg/mL and a selectivity index of 6.05. We subsequently conducted a series of in vitro assays to evaluate the antiviral effects of DMBE and to uncover its mechanisms of action. DMBE was found to inhibit IAV during the early stages of infection by hindering the attachment of the virus onto and its penetration into host cells. Importantly, DMBE was observed to hinder IAV-mediated cell-cell fusion. It also inhibited neuraminidase activity, plaque size, and the expression levels of phospho-AKT. In summary, this study provides evidence for the effectiveness of D. mariesii as a complementary and alternative herbal remedy against IAV. Specifically, our data highlight DMBE's capabilities in inhibiting viral entry and the release of virions.

Outcomes after fertility-sparing surgery of early-stage ovarian cancer: A nationwide population-based study.

BACKGROUND: Fertility-sparing surgery (FSS) is an alternative choice of young patients who have not completed their family planning and still have fertility needs. The aims of this study were to compare the outcomes of early-stage epithelial ovarian cancer (EOC) patients undergoing FSS and radical comprehensive staging surgery (RCS), and the suitability of FSS. METHODS: A total of 1297 patients aged between 20 and 44 years with newly diagnosed early-stage EOC were recruited from the Taiwan Cancer Registry database between 2009 and 2017. Site-specific surgery codes were used to distinguish patients in FSS group or RCS group. Cancer-specific survival (CSS) was evaluated using Kaplan-Meier method with log-rank test and Cox regression model. RESULTS: There were 401 and 896 patients in FSS and RCS group. Patients in FSS group were with younger age and mostly had Stage I disease. In contrast, patients in RCS group were older. There were more Stage II, high-grade (Grade 3) disease, and adjuvant chemotherapy in RCS group. Stage and tumor grade were two independent factors correlating with CSS and the type of surgery showed no effect on CSS (HR: 1.09, 95% CI: 0.66-1.77, p = 0.73) in multivariable analysis. In multivariable analysis, the clear cell carcinoma group who underwent FSS demonstrated better CSS compared to those in the RCS group (HR: 0.28, 95% CI: 0.06-0.82, p = 0.04). A total of 17 women who underwent FSS developed second malignancies of the uterine corpus or contralateral ovary. CONCLUSION: FSS can be a safe alternative procedure in selected young patients of Stage I EOC who have fertility desire. Endometrial biopsy before or during FSS and regular surveillance to detect recurrence are mandatory for ovarian cancer patients undergoing FSS.

Ribociclib leverages phosphodiesterase 4 inhibition in the treatment of neutrophilic inflammation and acute respiratory distress syndrome.

INTRODUCTION: Overwhelming neutrophil activation and oxidative stress significantly contribute to acute respiratory distress syndrome (ARDS) pathogenesis. However, the potential of repurposing ribociclib, a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor used clinically in cancer treatment, for treating neutrophilic ARDS remains uncertain. This study illustrated the ability and underlying mechanism of ribociclib for treating ARDS and neutrophilic inflammation. METHODS: Primary human neutrophils were used to determine the therapeutic effects of ribociclib on respiratory bursts, chemotactic responses, and inflammatory signaling. In vitro and silico analyses were performed to determine the underlying molecular mechanisms. The potential of ribociclib repurposing was evaluated using an in vivo ARDS model in lipopolysaccharide (LPS)-primed mice. RESULTS: We found that treatment using ribociclib markedly limited overabundant oxidative stress (reactive oxygen species [ROS]) production and chemotactic responses (integrin levels and adhesion) in activated human neutrophils. Ribociclib was also shown to act as a selective inhibitor of phosphodiesterase 4 (PDE4), thereby promoting the cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) pathway, leading to the inhibition of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) phosphorylation, and calcium influx. Notably, prophylactic administration and post-treatment with ribociclib ameliorated neutrophil infiltration, lung inflammation, accumulation of oxidative stress, pulmonary destruction, and mortality in mice with LPS-induced ARDS. CONCLUSION: We demonstrated for the first time that ribociclib serves as a novel PDE4 inhibitor for treating neutrophilic inflammation and ARDS. The repurposing ribociclib and targeting neutrophilic PDE4 offer a potential off-label alternative for treating lung lesions and other inflammatory conditions.

BPR3P0128, a non-nucleoside RNA-dependent RNA polymerase inhibitor, inhibits SARS-CoV-2 variants of concern and exerts synergistic antiviral activity in combination with remdesivir.

Viral RNA-dependent RNA polymerase (RdRp), a highly conserved molecule in RNA viruses, has recently emerged as a promising drug target for broad-acting inhibitors. Through a Vero E6-based anti-cytopathic effect assay, we found that BPR3P0128, which incorporates a quinoline core similar to hydroxychloroquine, outperformed the adenosine analog remdesivir in inhibiting RdRp activity (EC50 = 0.66 µM and 3 µM, respectively). BPR3P0128 demonstrated broad-spectrum activity against various severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern. When introduced after viral adsorption, BPR3P0128 significantly decreased SARS-CoV-2 replication; however, it did not affect the early entry stage, as evidenced by a time-of-drug-addition assay. This suggests that BPR3P0128's primary action takes place during viral replication. We also found that BPR3P0128 effectively reduced the expression of proinflammatory cytokines in human lung epithelial Calu-3 cells infected with SARS-CoV-2. Molecular docking analysis showed that BPR3P0128 targets the RdRp channel, inhibiting substrate entry, which implies it operates differently-but complementary-with remdesivir. Utilizing an optimized cell-based minigenome RdRp reporter assay, we confirmed that BPR3P0128 exhibited potent inhibitory activity. However, an enzyme-based RdRp assay employing purified recombinant nsp12/nsp7/nsp8 failed to corroborate this inhibitory activity. This suggests that BPR3P0128 may inhibit activity by targeting host-related RdRp-associated factors. Moreover, we discovered that a combination of BPR3P0128 and remdesivir had a synergistic effect-a result likely due to both drugs interacting with separate domains of the RdRp. This novel synergy between the two drugs reinforces the potential clinical value of the BPR3P0128-remdesivir combination in combating various SARS-CoV-2 variants of concern.

Does the diagnostic timing of cancer-associated thromboembolism influence the survival outcome in ovarian cancer patients?

BACKGROUND/PURPOSE: Efforts were made to explore the influence of diagnostic timing for cancer-associated thromboembolic events on survival of ovarian cancer patients. METHODS: We reviewed the medical records of 75 ovarian cancer patients with thromboembolism and evaluated the prognostic factors affecting disease-free survival and overall survival. RESULTS: These 75 patients were classified into two categories by the diagnostic timing of the thromboembolism, during (33 cases) and after (42 cases) initial diagnosis of ovarian cancer groups. The diagnostic timing of thromboembolism was not related to disease-free survival or overall survival of the studied population. Advanced disease stage, clear cell histology, interval debulking surgery, no recurrence/persistence of ovarian cancer, and patients treated with anticoagulant(s) treatment >3 months were associated with the disease-free survival. Advanced disease stage, clear cell histology, body mass index (BMI) ≥24 kg/m2 at the diagnosis of ovarian cancer, and no recurrence/persistence of ovarian cancer influenced the overall survival. In the subgroup analysis, compared to the after initial ovarian cancer diagnosis group, patients with stage I/II disease, BMI <24 kg/m2 at the diagnosis of ovarian cancer, or primary debulking surgery in the during cancer diagnosis group had longer disease-free survival, and overall survival benefit was observed in cases with stage I/II disease, or primary debulking surgery. CONCLUSION: The diagnostic timing of thromboembolism was not related to disease-free or overall survival of ovarian cancer patients, but associated with that of specific patient subgroups.

Impact of adjuvant treatment on survival in patients with 2023 FIGO stage IIC endometrial cancer: a retrospective analysis from two tertiary centers in Korea and Taiwan.

OBJECTIVE: In early-stage endometrial cancer, aggressive histologic types (grade 3 endometrioid, serous, clear cell, carcinosarcomas, undifferentiated, mixed, and other unusual types) are associated with an increased risk of distant metastases and worse survival. However, the optimal adjuvant treatment for these patients remains controversial. The present study investigated the outcomes of different adjuvant treatments in patients with 2023 FIGO stage IIC endometrial cancer. METHODS: We retrospectively identified patients with 2023 FIGO stage IIC endometrial cancer who underwent surgery followed by either adjuvant treatment or observation from 2000 to 2020 at two tertiary centers in Korea and Taiwan. Recurrence-free survival (RFS) and overall survival (OS) were evaluated using Kaplan-Meier estimates and Cox proportional-hazards models. We also analyzed recurrence patterns after different adjuvant treatments. RESULTS: A total of 272 patients were identified; 204 received adjuvant treatment postoperatively, whereas 68 only underwent observation. Adjuvant treatment was not associated with improved RFS or OS. Non-endometrioid histologic types (p=0.003) and presence of lymphovascular space invasion (LVSI, p=0.002) were associated with worse RFS, whereas only non-endometrioid histologic types impacted OS (p=0.004). In subgroup analyses, adjuvant treatment improved OS in patients with LVSI (p=0.020) and in patients with both LVSI and grade 3 endometrioid histologic type (p=0.007). We found no difference in locoregional and distant recurrence between patients undergoing adjuvant treatment or observation. CONCLUSION: In this study, the addition of adjuvant treatment was associated with an OS benefit for patients with LVSI, especially those with grade 3 endometrioid tumors.

Eucalyptus-derived essential oils alleviate microbes and modulate inflammation by suppressing superoxide and elastase release.

The Eucalyptus tree, belonging to the myrtle family, grows all over the world for its pharmaceutical and industrial benefits. In this article, we present a comparative analysis of the chemical composition of the hydrodistilled oils obtained from three different Eucalyptus species growing in Egypt viz. E. citriodora, E. camaldulensis, and E. ficifolia. Gas Chromatography-Mass Spectrometric guided analysis resulted in the identification of a total of 20 metabolites in E. citriodora oil with citronellal (54.9%) and citronellol (25.4%) being the most dominant components. ß-cymene (12.7%) and 1,8-cineole (11.7%) were the major volatile constituents identified in E. camaldulensis oil, while trans-ß-ocimene (22.4%), 1,8-cineole (13.5%), and L-trans-pinocarveol (12.5%) were the dominating components in the oil of E. ficifolia. The essential oils of the studied species were evaluated for their in vitro anti-inflammatory, antiviral including anti-SARS-CoV-2 (severe acute respiratory syndrome corona virus 2), antibacterial, and antifungal activities. E. citriodora oil displayed the highest inhibitory activity on the release of the superoxide radical (32%) and elastase enzyme (31%) in human neutrophils, while E. ficifolia oil had enhancing effects on elastase. The latter showed significant antiviral effects against hepatitis A, herpes simplex, and coxsackie viruses with IC50 values at 2.1, 2.5, and 5.6 µg/mL, respectively. Moderate antibacterial and antifungal activities were observed for Eucalyptus oils with Staphylococcus aureus being the most susceptible bacterial strain. E. ficifolia oil, similarly, displayed the best antibacterial activity with minimum inhibitory concentration (MIC) value at ca. 25 µg/mL (for S. aureus). On the contrary, E. camaldulensis oil was the most active against Candida albicans with an MIC value at 45 µg/mL. In silico studies were performed with a number of macromolecular drug targets for confirming the biological activities of the identified compounds and for interpreting their ADME (absorption-distribution-metabolism-elimination) parameters.

An activity-based functional test for identifying homologous recombination deficiencies across cancer types in real time.

Homologous recombination (HR)-mediated DNA repair is a prerequisite for maintaining genome stability. Cancer cells displaying HR deficiency (HRD) are selectively eliminated by poly(ADP-ribose) polymerase inhibitors (PARPis). To date, sequencing of HR-associated genes and analyzing genome instability have been used as clinical predictions for PARPi therapy. However, these genetic tests cannot reflect dynamic changes in the HR status. Here, we have developed a virus- and activity-based functional assay to quantify real-time HR activity directly. Instead of focusing on a few HR-associated genes, our functional assay detects endpoint HR activity and establishes an activity threshold for identifying HRD across cancer types, validated by PARPi sensitivity and BRCA status. Notably, this fluorescence-based assay can be applied to primary ovarian cancer cells from patients to reflect their level of HRD, which is associated with survival benefits. Thus, our work provides a functional test to predict the response of primary cancer cells to PARPis.

Design and evaluation of oral formulation for apixaban.

Non-valvular atrial fibrillation (NVAF) is a common form of cardiac arrhythmia that affects 1-1.5% of adults and roughly 10% of elderly adults with dysphagia. Apixaban is an anticoagulant referred to as a factor Xa inhibitor, which has been shown to reduce the risk of stroke and systemic embolism in cases of NVAF. Our objective in the current study was to formulate an orally disintegrating film to facilitate the administration of apixaban to elderly patients who have difficulty swallowing. Researchers have used a wide variety of cellulose-based or non-cellulose-based polymers in a variety of combinations to achieve specific characteristics related to film formation, disintegration performance, drug content, in vitro drug release, and stability. One of the two formulations in this study was specify that bioequivalence criteria met with respect to Cmax of the reference drug (ELIQUIS®) in terms of pharmacokinetic profile. Further research will be required to assess the applicability of orodispersible films created using colloidal polymers of high and low molecular weights to other drugs with poor solubility in water.

Factors Predicting the Health Status of Women with Ovarian Cancer During Five Treatment Phases.

OBJECTIVE: The combined impact of disease status and treatment phase on the quality of life (QoL) of women with ovarian cancer has not been fully considered. Therefore, this clinical, epidemiologic study compared the QoL of patients with ovarian cancer between five different treatment phases and identified the factors predicting their QoL through multivariate modeling. DATA SOURCES: This study had a cross-sectional survey design. The participants total of 183 were recruited from the inpatient and outpatient departments of the medical center in northern Taiwan. QoL was measured using the Quality of Life Scales QLQ-C30 and QLQ-OV28 and the Pittsburgh Sleep Quality Index. The patient's clinical characteristics data were obtained from the databank of the Taiwan Gynecologic Cancer Network, a registry of active patients being treated with gynecologic cancer. CONCLUSION: Chemotherapeutic agents were the major predictors of poor global health status in patients with ovarian cancer. However, good sleep was beneficial to patients' QoL. The study results can be used as a reference to adjust oncological treatment regimens for more effective symptom management and to promote patient education to improve patients' QoL. IMPLICATIONS FOR NURSING PRACTICE: The predicting factors can be considered by physicians and nurses to adjust treatment regimens and enhance patient education.

Dual inhibition of BTLA and PD-1 can enhance therapeutic efficacy of paclitaxel on intraperitoneally disseminated tumors.

BACKGROUND: Expression of immune checkpoints in the tumor microenvironment is one mechanism underlying paclitaxel (PTX) chemoresistance. This study aimed to investigate whether the addition of checkpoint blockade to PTX can improve the therapeutic efficacy against apparently disseminated intraperitoneal tumors. METHODS: We analyzed the in vivo expression of various immune checkpoints in CD3+CD8+ cytotoxic T cells from tumor-bearing mice treated with or without PTX and validated the tumor-killing activities of selected checkpoint-expressing T-cell subpopulations ex vivo. The regulation of selected checkpoints was investigated in vitro. The therapeutic effects of inhibition of a targeted checkpoint pathway with antibodies added to PTX therapy were examined. RESULTS: CD3+CD8+ T cells expressed with herpes virus entry mediator (HVEM), programmed cell death 1 (PD-1), and T-cell immunoglobulin domain and mucin domain 3 (TIM-3) in tumor-bearing hosts treated with PTX had effective tumoricidal activities. In addition to PTX and cytokines, B and T lymphocyte attenuator (BTLA) or homologous to lymphotoxin, exhibits inducible expression and competes with herpes simplex virus (HSV) glycoprotein D for binding to HVEM, a receptor expressed on T lymphocytes (LIGHT) interacting with HVEM can regulate the expression of PD-1 on CD3+CD8+ T cells. Interleukin (IL)-15 increased the percentage of HVEMhighgranzyme B (GZMB)+ cells among CD3+CD8+ T cells, which was suppressed by the BTLA/HVEM signal. LIGHT induced the percentage of HVEM+GZMB+ cells but not HVEMhighGZMB+ cells among CD3+CD8+ T cells. Expression of IL-15, BTLA, or LIGHT was detected in CD19+ B cells and regulated by damage-associated molecular patterns/Toll-like receptor interactions. In the tumor-bearing hosts treated with PTX, certain proportions of BTLA+ B or PD-1+ T lymphocytes were still noted. When dual inhibition of BTLA and PD-1 was added to PTX, the antitumor effects on intraperitoneally disseminated tumors can be significantly improved. CONCLUSIONS: Dual blockade of BTLA on B cells and PD-1 on cytotoxic T cells may have clinical potential for enhancing the efficacy of PTX in the treatment of tumors with intraperitoneal spread, including epithelial ovarian carcinomas.

Comparison of Minimally Invasive and Open Surgery for the Treatment of Endometrial Cancer with a High Risk of Recurrence: A Propensity Score Matching Study in Korea and Taiwan.

BACKGROUND: This study compared oncologic outcomes between minimally invasive surgery (MIS) and open surgery for the treatment of endometrial cancer with a high risk of recurrence. METHODS: This study included patients with endometrial cancer who underwent primary surgery at two tertiary centers in Korea and Taiwan. Low-grade advanced-stage endometrial cancer (endometrioid grade 1 or 2) or endometrial cancer with aggressive histology (endometrioid grade 3 or non-endometrioid) at any stage was considered to have a high risk of recurrence. We conducted 1:1 propensity score matching between the MIS and open surgery groups to adjust for the baseline characteristics. RESULTS: Of the total of 582 patients, 284 patients were included in analysis after matching. Compared with open surgery, MIS did not show a difference in disease-free survival [hazard ratio (HR) 1.09; 95% confidence interval (CI) 0.67-1.77, P = 0.717] or overall survival (HR 0.67; 95% CI 0.36-1.24, P = 0.198). In the multivariate analysis, non-endometrioid histology, tumor size, tumor cytology, depth of invasion, and lymphovascular space invasion were risk factors for recurrence. There was no association between the surgical approach and either recurrence or mortality in the subgroup analysis according to stage and histology. CONCLUSIONS: MIS did not compromise survival outcomes for patients with endometrial cancer with a high risk of recurrence when compared with open surgery.

Recurrent pineal parenchymal tumor of intermediate differentiation with intratumoral hemorrhage: A case report and review of the literature.

Pineal apoplexy is a rare clinical condition. Its common symptoms include headaches, nausea, vomiting, ataxia, and gaze paralysis. These symptoms are mainly caused by obstructive hydrocephalus or direct compression of the cerebellum or midbrain. There have been no previous reports on the development of a recurrent pineal parenchymal tumor of intermediate differentiation (PPTID) with intratumoral hemorrhage. We report a case of PPTID with intratumoral hemorrhage. A 44-year-old woman developed recurrent PPTID following tumor removal and ventriculoperitoneal shunting in 2010. She visited the emergency department in April 2021 for sudden-onset dizziness and generalized weakness. Blurring of vision occurred and progressed over the previous month. Neurological examination revealed upward conjugate gaze paralysis. Brain computed tomography revealed a hyperdense lesion in the pineal region, and a recurrent tumor with hemorrhage was suspected. Magnetic resonance imaging of the brain confirmed a pineal tumor with intratumoral hemorrhage. The pineal tumor and hematoma were surgically removed via the suboccipital transtentorial approach. The patient was discharged from the hospital 2 weeks after the surgery. The pathological findings were consistent with the diagnosis of recurrent PPTID. PPTID is a rare tumor, accounting for less than 0.1% of primary central nervous system tumors. Pineal apoplexy is rare, and its incidence and clinical significance remain unclear. There have only been nine reported cases of pineal apoplexy, associated with pineal parenchymal tumors. The recurrence of PPTID with apoplectic hemorrhage after 10 years has not been reported. Despite its rarity, PPTID with apoplexy should be considered in patients with PPTID who develop sudden-onset neurological symptoms.

Anti-inflammatory and antiviral activities of flavone C-glycosides of Lophatherum gracile for COVID-19.

Lophatherum gracile (L. gracile) has long been used as a functional food and herbal medicine. Previous studies have demonstrated that extracts of L. gracile attenuate inflammatory response and inhibit SARS-CoV-2 replication; however, the underlying active constituents have yet to be identified. This study investigated the bioactive components of L. gracile. Flavone C-glycosides of L. gracile were found to dominate both anti-inflammatory and antiviral effects. A simple chromatography-based method was developed to obtain flavone C-glycoside-enriched extract (FlavoLG) from L. gracile. FlavoLG and its major flavone C-glycoside isoorientin were shown to restrict respiratory bursts and the formation of neutrophil extracellular traps in activated human neutrophils. FlavoLG and isoorientin were also shown to inhibit SARS-CoV-2 pseudovirus infection by interfering with the binding of the SARS-CoV-2 spike on ACE2. These results provide scientific evidence indicating the efficacy of L. gracile as a potential supplement for treating neutrophil-associated COVID-19.

Outcome and prognostic factors of unexpected ovarian carcinomas.

BACKGROUND: We investigated risk factors influencing the outcome of unexpected ovarian carcinomas. METHODS: We reviewed the ovarian carcinoma patients treated at atertiary medical institution between 2000 and 2017 and analyze the clinico-pathological characteristics, treatment strategies, recurrence status, and outcome. RESULTS: A total of 112 women (65 primary laparoscopic surgery [LSC] and 47 laparotomic surgery [LAPA]) were included in the analysis. The LSC group had smaller ovarian tumors (10.5 ± 7.3 cm vs. 16.6 ± 8.7 cm, p = 0.031) and higher incidence of subsequent staging surgery (56.9% vs. 25.5%, p = 0.0001) compared to the LAPA group. There were 98/112 (86.6%) of early stages (I/II) diseases. The difference between the recurrent rate (27.7% vs. 31.9%), disease-free survival (DFS), and overall survival (OS) were not significant among surgical groups. In the multivariate analysis, FIGO stage (stage II hazard ratio [HR] 6.61, p = 0.007; stage III HR 8.40, p = 0.002) was the only prognostic factor for DFS. FIGO stage (stage II HR 20.78, p = 0.0001; stage III HR 7.99, p = 0.017), histological type (mucinous HR 12.49, p = 0.036), and tumor grade (grade 3 HR 35.01, p = 0.003) were independent prognostic factors for OS, while women with latency >28 days from primary to staging surgery had significantly poorer OS (p = 0.008). Women with latency >28 days between primary surgery and adjuvant chemotherapy had similar DFS (p = 0.31) and a trend of poorer OS (p = 0.064). CONCLUSIONS: The prognosis of unexpected ovarian cancer is independent from the primary surgical procedure and comprehensive staging surgery should be performed at close proximity after the diagnosis of unexpected ovarian malignancy.

A retrospective comparative study between robotic thyroidectomy through transoral vestibular approach and bilateral breast-axillary approach / 中华外科杂志

Objective: To compare the surgical outcome of robotic thyroidectomy through transoral approach and the bilateral breast-axillary approach. Methods: Retrospective analysis was made on the clinical data of patients who performed transoral robotic thyroidectomy (TORT group) or bilateral breast-axillary approach (BABA group) in the Department of Thyroid and Breast Surgery, the 960th Hospital of People's Liberation Army from July 2020 to May 2022. Both groups received lobectomy with lymph node dissection of the central region. A total of 100 cases were included in the study, including 48 cases in the TORT group and 52 cases in the BABA group. The propensity score matching method was used for 1∶1 matching of patients between the 2 groups, with a match tolerance of 0.03. There were 31 patients in each group successfully matched. In the TORT group, there were 5 males and 26 females, aged (33.2±7.9) years (range: 21 to 53 years). While there were 4 males and 27 females in the BABA group, aged (34.6±9.2) years (range: 19 to 58 years). The t test, Mann-Whitney U test, χ2 test or Fisher exact test were used to compare the clinical efficacy between the two groups. Results: All the patients successfully completed robotic thyroid surgery without conversion to open surgery. Compared with BABA group, the TORT group had longer operation time ((211.3±57.2) minutes vs. (126.2±37.8) minutes, t=6.915, P<0.01), shorter drainage tube retention time ((5.4±1.0) days vs. (6.4±1.2) days, t=-3.544, P=0.001), shorter total hospital stay ((6.6±1.2) days vs. (7.4±1.3) days, t=-2.353, P=0.022), and higher cosmetic score (9.46±0.25 vs. 9.27±0.26, t=2.925, P=0.005). There was no significant difference between the two groups in the number of lymph nodes dissection, metastasis in the central compartment, and the incidence of postoperative complications (all P>0.05). Conclusions: Compared with the bilateral breast-axillary approach, the transoral vestibular approach of robotic thyroidectomy is also safe and effective. It shows similar surgical results to the bilateral breast-axillary approach in strictly selected patients, but the postoperative recovery speed is much faster, and the hospital stay is shorter. Transoral robotic thyroidectomy is a more recommended surgical method for patients with high aesthetic demand.

Lonicerae Japonicae Flos Attenuates Neutrophilic Inflammation by Inhibiting Oxidative Stress.

Lonicerae japonicae flos (LJ) is an Asian traditional herb that is used as a dietary supplement, tea, and beverage to clear heat and quench thirst. However, no studies investigated its effect on activated human neutrophils, which played a crucial role in the bad prognosis of coronavirus disease of 2019 (COVID-19) patients by aggravating lung inflammation and respiratory failure. Herein, we evaluated the anti-inflammatory effect of LJ ethanol extract (LJEE) on human neutrophils activated by N-formyl-methionyl-leucyl-phenylalanine (fMLF). Our experimental results indicated that LJEE suppressed fMLF-activated superoxide anion (O2•-) generation, the expression of CD11b, and cell adhesion and migration, as well as the formation of neutrophil extracellular traps in human neutrophils. Further in-depth mechanical investigation revealed that pretreatment with LJEE accelerated the Ca2+ clearance, but did not affect the phosphorylation of mitogen-activated protein kinases (MAPKs) and protein kinase B (Akt) in activated human neutrophils. In addition, LJEE displayed a dose-dependent reactive oxygen species (ROS) scavenger activity, which assisted its anti-inflammatory activity. From the bioassay-coupled chromatographic profile, chlorogenic acids were found to dominate the anti-inflammatory effects of LJEE. Moreover, LJ water extract (LJWE) demonstrated an interrupting effect on the severe acute respiratory syndrome coronavirus-2 spike protein (SARS-CoV-2-Spike)/angiotensin-converting enzyme 2 (ACE2) binding. In conclusion, the obtained results not only supported the traditional use of LJ for heat-clearance, but also suggested its potential application in daily health care during the COVID-19 pandemic.

Does para-aortic lymphadenectomy improve survival in pathologically diagnosed early-stage grade 3 endometrioid and non-endometrioid endometrial cancers? A retrospective cohort study in Korea and Taiwan.

PURPOSE: The therapeutic effect of para-aortic lymphadenectomy in early-stage high-grade endometrial cancer remains controversial. In this study, we investigated whether combined pelvic and para-aortic lymphadenectomy has a survival benefit compared to pelvic lymphadenectomy alone in patients with pathologically diagnosed FIGO stage I-II grade 3 endometrioid and non-endometrioid endometrial cancers. METHODS: We retrospectively reviewed the medical records of 281 patients with histologically confirmed FIGO stage I-II grade 3 endometrioid and non-endometrioid endometrial cancers who underwent pelvic lymphadenectomy alone or combined pelvic and para-aortic lymphadenectomy in staging surgery at two tertiary centers in Korea and Taiwan. Prognostic factors to predict outcomes in these cases were also analyzed. RESULTS: Among 281 patients, 144 underwent pelvic lymphadenectomy alone and 137 underwent combined pelvic and para-aortic lymphadenectomy. Within a median follow-up of 45 months, there was no significant difference in recurrence-free survival (RFS) and overall survival (OS) between the two groups. In multivariable analysis, age at diagnosis ≥60 years (HR = 2.20, 95% CI 1.25-3.87, p = 0.006) and positive lymph-vascular space invasion (LVSI) (HR = 2.79, 95% CI 1.60-4.85, p < 0.001) were associated with worse RFS, and only non-endometrioid histology was associated with worse OS (HR = 3.18, 95% CI 1.42-7.12, p = 0.005). In further subgroup analysis, beneficial effects of combined pelvic and para-aortic lymphadenectomy on RFS and OS were not observed. CONCLUSIONS: In this study, combined pelvic and para-aortic lymphadenectomy could not improve survival compared to pelvic lymphadenectomy alone in patients with FIGO stage I-II grade 3 endometrioid and non-endometrioid endometrial cancers. Therefore, para-aortic lymphadenectomy may be omitted for these cases.