Background: The effects of perioperative ketamine and esketamine on postoperative nausea and vomiting (PONV) remain unclear. This study aimed to clarify their impact on PONV and related adverse events. Methods: We performed a meta-analysis of randomized controlled trials and observational studies comparing ketamine or esketamine with control agents. The primary outcome was a pooled analysis of PONV and nausea-only data. PONV, postoperative nausea (PON), and postoperative vomiting (POV) were also analyzed separately. Subgroup analyses were conducted by comparator type (placebo, opioid, or non-opioid) and dose categories. Meta-regression was used to assess dose-response relationships. Results: Fifty-five studies (n = 6676) were included. Ketamine and esketamine did not significantly reduce the incidence of pooled PONV risk (risk ratio [RR]: 0.95, 95% CI [0.87–1.04], P = 0.274). No benefit was found versus placebo. Compared with opioids, PONV was reduced (RR = 0.50, 95% CI [0.32–0.77], P = 0.002), but not in the pooled analysis (RR = 0.69, 95% CI [0.43–1.08], P = 0.107). Conversely, compared with non-opioid controls, ketamine/esketamine increased the pooled PONV risk (RR = 1.46, 95% CI [1.03–2.05], P = 0.032). No significant dose-response relationship was found. Both agents increased hallucinations (RR = 1.73, 95% CI [1.35–2.20], P = 0.0002) and drowsiness (RR = 2.18, 95% CI [1.13–4.21], P = 0.024). Conclusions Ketamine and esketamine did not significantly reduce PONV overall. While they showed benefits compared with opioid-based regimens, they may be less effective than non-opioid adjuvants. However, their neuropsychiatric and sedative risks warrant cautious use.

Gastric cancer with peritoneal metastasis (GCPM) is a common and lethal manifestation of advanced gastric cancer, with a median survival of only 5-11 months. This consensus was developed by 30 experts from Asia (China, Japan, Korea, and Singapore) using the Delphi method and the GRADE evidence grading system. A total of 29 statements were formulated, covering the diagnosis and assessment of GCPM, indications for laparoscopic exploration and NIPS (normothermic intraperitoneal and systemic treatment), treatment regimens, prevention and management of complications, criteria for conversion surgery, and postoperative intraperitoneal therapy. The consensus aims to standardize clinical practice and improve the prognosis of patients with GCPM.

Purpose: Adjuvant chemotherapy (AC) is recommended for muscle-invasive or lymph node-positive upper urinary tract urothelial carcinoma (UTUC) after radical nephroureterectomy (RNU). However, disease recurrences are frequently observed in pT1 disease, and AC may increase the risk of overtreatment in pT2 UTUC patients. This study aimed to validate a risk-adapted scoring model for selecting UTUC patients with ≤pT2 disease who would benefit from AC. Materials and Methods: We retrospectively analyzed 443 ≤pT2 UTUC patients who underwent RNU. A risk-adapted scoring model was applied, categorizing patients into low- or high-risk groups. Recurrence-free survival (RFS) and cancer-specific survival (CSS) were analyzed according to risk group. Results: Overall, 355 patients (80.1%) and 88 patients (19.9%) were categorized into the low- and high-risk groups, respectively, with the latter having higher pathological stages, concurrent carcinoma in situ, and synchronous bladder tumors. Disease recurrence occurred in 45 patients (10.2%), among whom 19 (5.4%) and 26 (29.5%) belonged to the low- and high-risk groups, respectively (p<0.001). High-risk patients had significantly shorter RFS (64.3% vs. 93.6% at 60 months; hazard ratio [HR] 13.66; p<0.001) and worse CSS (80.7% vs. 91.5% at 60 months; HR 4.25; p=0.002). Multivariate analysis confirmed that pT2 stage and the high-risk group were independent predictors of recurrence and cancer-specific death (p<0.001). Decision curve analysis for RFS showed larger net benefits with our model than with the T stage model. Conclusions The risk-adapted scoring model effectively predicts recurrence and identifies optimal candidates for AC post RNU in non-metastatic UTUC.

Viral load and the duration of viral shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are important determinants of the transmission of coronavirus disease 2019.In this study, we examined the effects of viral doses on the lung and spleen of K18-hACE2 transgenic mice by temporal histological and transcriptional analyses. Approximately, 1×105 plaque-forming units (PFU) of SARS-CoV-2 induced strong host responses in the lungs from 2 days post inoculation (dpi) which did not recover until the mice died, whereas responses to the virus were obvious at 5 days, recovering to the basal state by 14 dpi at 1×102 PFU. Further, flow cytometry showed that number of CD8+ T cells continuously increased in 1×102 PFU-virusinfected lungs from 2 dpi, but not in 1×105 PFU-virus-infected lungs. In spleens, responses to the virus were prominent from 2 dpi, and number of B cells was significantly decreased at 1×105PFU; however, 1×102 PFU of virus induced very weak responses from 2 dpi which recovered by 10 dpi. Although the defense responses returned to normal and the mice survived, lung histology showed evidence of fibrosis, suggesting sequelae of SARS-CoV-2 infection. Our findings indicate that specific effectors of the immune response in the lung and spleen were either increased or depleted in response to doses of SARS-CoV-2. This study demonstrated that the response of local and systemic immune effectors to a viral infection varies with viral dose, which either exacerbates the severity of the infection or accelerates its elimination.

Objective: This study aimed to evaluate the potential of PDRN and explore its combined effect with adipose tissue-derived MSCs (AdMSCs) in treating canine OA. Methods: To study the impact of PDRN, canine chondrocytes, synoviocytes, and AdMSCs were exposed to various PDRN concentrations, and viability was assessed using cell counting kit-8. The OA model was created by treating chondrocytes and synoviocytes with lipopolysaccharide, followed by treatment under three different conditions: PDRN alone, AdMSCs alone, and a combination of PDRN and AdMSCs. Using real-time quantitative polymerase chain reaction, the anti-inflammatory effects and mechanisms were investigated by quantitatively assessing pro-inflammatory cytokines, collagen degradation markers, adenosine A2a receptor (ADORA2A), and nuclear factor-kappa B. Results: PDRN alone and combined with AdMSCs significantly reduced the expression of pro-inflammatory cytokines and collagen degradation markers in an OA model. PDRN promoted AdMSC proliferation and upregulated ADORA2A expression. AdMSCs exhibited comprehensive anti-inflammatory effects through paracrine effects, and both substances reduced inflammatory gene expression through different mechanisms, potentially enhancing therapeutic effects. Conclusions and Relevance: The results indicate that PDRN is a safe and effective antiinflammatory material that can be used independently or as an adjuvant for AdMSCs.Although additional research is necessary, this study is significant because it provides a foundation for future research at the cellular level.

Polychlorinated biphenyls (PCBs) were once used throughout various industries; however, because of their persistence in the environment, exposure remains a global threat to the environment and human health. The Kv1.3 and Kv1.5 channels have been implicated in the immunotoxicity and cardiotoxicity of PCBs, respectively. We determined whether 3,3′,4,4′-tetrachlorobiphenyl (PCB77), a dioxin-like PCB, alters human Kv1.3 and Kv1.5 currents using the Xenopus oocyte expression system. Exposure to 10 nM PCB77 for 15 min enhanced the Kv1.3 current by approximately 30.6%, whereas PCB77 did not affect the Kv1.5 current at concentrations up to 10 nM. This increase in the Kv1.3 current was associated with slower activation and inactivation kinetics as well as right-shifting of the steady-state activation curve. Pretreatment with PCB77 significantly suppressed tumor necrosis factor-α and interleukin-10 production in lipopolysaccharide-stimulated Raw264.7 macrophages. Overall, these data suggest that acute exposure to trace concentrations of PCB77 impairs immune function, possibly by enhancing Kv1.3 currents.

Background: Propofol-based total intravenous anesthesia (TIVA) improves long-term outcomes after cancer surgery compared with inhalation anesthesia. However, its effect on patients undergoing non-small cell lung cancer (NSCLC) surgery remains unclear. We aimed to compare the oncological outcomes of TIVA and inhalation anesthesia after curative resection of early-stage NSCLC. Methods: We analyzed the medical records of patients diagnosed with stage I or II NSCLC who underwent curative resection at a tertiary university hospital between January 2010 and December 2017. The primary outcomes were recurrence-free survival (RFS) and overall survival (OS) according to anesthesia type. Results: We included 1,508 patients with stage I/II NSCLC. The patients were divided into the TIVA (n = 980) and Inhalation (n = 528) groups. The two groups were well-balanced in terms of baseline clinical characteristics. The TIVA group demonstrated significantly improved RFS (7.7 years, 95% CI [7.37, 8.02]) compared with the Inhalation group (6.8 years, 95% CI [6.30, 7.22], P = 0.003). Similarly, TIVA was superior to inhalation agents with respect to OS (median OS; 8.4 years, 95% CI [8.08, 8.69] vs. 7.3 years, 95% CI [6.81, 7.71]; P < 0.001). Multivariable Cox regression analysis revealed that TIVA was an independent prognostic factor related to recurrence (hazard ratio [HR]: 1.24, 95% CI [1.04, 1.47], P = 0.014) and OS (HR: 1.39, 95% CI [1.12, 1.72], P = 0.002). Conclusions Propofol-based TIVA was associated with better RFS and OS than inhalation anesthesia in patients with stage I/II NSCLC who underwent curative resection.

Purpose: We compared the surgical outcomes and complications of conventional, sutured scleral fixation and flanged intrascleral intraocular lens (IOL) fixation. Methods: We retrospectively analyzed the medical records of patients who underwent conventional, sutured scleral fixation or flanged intrascleral IOL fixation and who were then observed for more than 6 months. The best-corrected visual acuity (BCVA), operation time, spherical equivalent (SEQ), astigmatism, and postoperative complications were recorded up to 6 months after surgery. Results: Of sixty-nine enrolled eyes, 39 underwent conventional, sutured scleral fixation (“sutured” group) and 30 flanged intrascleral IOL fixation (“sutureless” group). The operation time was significantly shorter in the sutureless group than in the sutured group (56.3 ± 11.8 vs. 77.7 ± 17.9 minutes, p < 0.001). In both groups, the BCVA and SEQ improved significantly at all visits after surgery compared to the baseline values p < 0.05). There was no between-group difference in BCVA, SEQ, astigmatism, or complications. Conclusions Compared to conventional, sutured scleral fixation, flanged intrascleral IOL fixation afforded equivalent improvements in visual acuity but with a shorter surgical duration. Therefore, flanged intrascleral IOL fixation is a useful alternative to conventional, sutured scleral fixation.

Background: Cytoplasmic polyadenylation element binding (CPEB) proteins are sequencespecific RNA-binding proteins that control translation via cytoplasmic polyadenylation. We previously reported that CPEB1 or CPEB4 knockdown suppresses TAK1 and SMAD signaling in an in vitro study. Objective: This study aimed to investigate whether suppression of CPEB1 or CPEB4 expression inhibits scar formation in a mice model of acute dermal wound healing. Methods: CPEB1 and CPEB4 expression levels were suppressed by siRNA treatment. Skin wounds were created by pressure-induced ulcers in mice. Images of the wound healing were obtained using a digital camera and contraction was measured by ImageJ. mRNA and protein expression was analyzed using quantitative real time polymerase chain reaction and western blotting, respectively. Results: Wound contraction was significantly decreased by pre-treatment with CPEB1 or CPEB4 siRNA compared to the control. Suppression of CPEB1 or CPEB4 expression decreased TAK1 signaling by reducing the levels of TLR4 and TNF-α, phosphorylated TAK1, p38, ERK, JNK, and NF-κB-p65. Decreased levels of phosphorylated SMAD2 and SMAD3 indicated a reduction in SMAD signaling as well. Consequently, the expression of α-SMA, fibronectin, and type I collagen decreased. Conclusion CPEB1 siRNA or CPEB4 siRNA inhibit scar formation by modulating the TAK1 and SMAD signaling pathways. Our study highlights CPEB1 and CPEB4 as potential therapeutic targets for the treatment of scar formation.

Purpose: The purpose of this study was to investigate the effectiveness of the elastic compression stockings and Kinesio taping on muscle activity and mechanical properties in healthy women during the heel raise exercise that causes muscle fatigue. Methods: Participants were divided into the elastic compression stockings group (ESG, n= 8), Kinesio taping group (KTG, n= 8), and control group (CG, n= 8). All participants performed the heel raise exercise to cause muscle fatigue. Muscle activity, stiffness, and the muscle tone of the gastrocnemius and tibialis anterior were measured before and after the heel raise exercise. Results: In the gastrocnemius, muscle activity was significantly increased after the heel raise exercise in both the ESG and KTG (p< 0.05).There was a significant difference in the change in the gastrocnemius muscle activity between the groups (p< 0.05). Post hoc analysis showed that the ESG exhibited a significantly greater change in gastrocnemius muscle activity than the CG (p< 0.05). The muscle stiffness of the gastrocnemius was significantly decreased after the heel raise exercise in the ESG (p< 0.05). The muscle tone of the gastrocnemius was significantly increased after the heel raise exercise in the control group (p< 0.05). There were no significant differences in the change in the gastrocnemius stiffness and muscle tone between the groups (p> 0.05). In the tibialis anterior, there were no significant differences in muscle activity, stiffness, and muscle tone between and within the groups (p> 0.05). Conclusion Our findings suggest that the use of elastic compression stockings and Kinesio taping during the heel raise exercise are beneficial and delay muscle fatigue in the gastrocnemius.