Expression level and clinical significance of NBAT-1 in human cancers: a systematic review and meta-analysis.

PURPOSE: There is an aberrant expression of NBAT-1 in various human cancers, which was proven to limit the proliferation, invasion, and metastasis of tumour cells via multiple approaches. Most existing research focuses on sample size and discrete outcomes. Thus, a quantitative meta-analysis was performed to elucidate the prognostic value of lncRNA NBAT-1 expression in cancer patients. MATERIALS AND METHODS: Using Web of Science and PubMed, two researchers independently identified relevant studies to explore the association between the pathological features of human cancers and NBAT-1 expression levels. Then two scholars conducted literature screening according to exclusion criteria and admission criteria, and finally conducted statistical analysis through data extraction with StataSE 12.0. RESULTS: A total of 12 eligible studies with 1600 patients were included in the meta-analysis eventually. It is indicated that the low expression level of lncRNA NBAT-1 was closely related to distant metastasis [RR = 0.50, 95% CI (0.33, 0.76), and P = 0.00], deep tumour invasion [RR = 0.62, 95% CI (0.49,0.80), and P = 0.00], poor histological grade [RR = 0.68, 95% CI (0.57, 0.81), and P = 0.00], advanced TNM stage [RR = 0.66, 95% CI (0.55, 0.79), and P = 0.00], large tumour volume[RR = 0.72, 95% CI (0.55, 0.93), and P = 0.01], and lymph node metastasis [RR = 0.62, 95% CI (0.46, 0.84), and P = 0.00], suggesting that it may serve as biomarkers for patients with poor prognosis. CONCLUSION: Reduced expression of NBAT-1 can predict poor prognosis in several cancers, as found in the meta-analysis, demonstrating that NBAT-1 can serve as a promising prognostic factor of human cancers.

An immune-related lncRNA pairs signature to identify the prognosis and predict the immune landscape of laryngeal squamous cell carcinoma.

BACKGROUND: Laryngeal squamous cell carcinoma (LSCC) is the most common squamous cell carcinoma. Though significant effort has been focused on molecular pathogenesis, development, and recurrence of LSCC, little is known about its relationship with the immune-related long non-coding RNA (lncRNA) pairs. METHODS: After obtaining the transcriptome profiling data sets and the corresponding clinical characteristics of LSCC patients and normal samples from The Cancer Genome Atlas (TCGA) database, a series of bioinformatic analysis was conducted to select the differently expressed immune-related lncRNAs and build a signature of immune-related lncRNA pairs. Then, the effectiveness of the signature was validated. RESULTS: A total of 111 LSCC patients and 12 normal samples' transcriptome profiling data sets were retrieved from TCGA. 301 differently expressed immune-related lncRNAs were identified and 35,225 lncRNA pairs were established. After univariate Cox analysis, LASSO regression and multivariate Cox analysis, 7 lncRNA pairs were eventually selected to construct a signature. The riskscore was computed using the following formula: Riskscore = 0.95 × (AL133330.1|AC132872.3) + (-1.23) × (LINC01094|LINC02154) + 0.65 × (LINC02575|AC122685.1) + (-1.15) × (MIR9-3HG|LINC01748) + 1.45 × (AC092687.3|SNHG12) + (-0.87) × (AC090204.1|AL158166.1) + 0.64 × (LINC01063|Z82243.1). Patients were classified into the high-risk group (> 1.366) and the low-risk group (< 1.366) according to the cutoff value (1.366), which is based on the 5-year riskscore ROC curve. The survival analysis showed that the low-risk group had a better prognosis (P < 0.001). The riskscore was better than other clinical characteristics in prognostic prediction and the area under the curves (AUCs) for the 1-, 3-, and 5-year survivals were 0.796, 0.946, and 0.895, respectively. Combining age, gender, grade, stage, and riskscore, a nomograph was developed to predict survival probability in LSCC patients. Then, the riskscore was confirmed to be related with the content of tumor-infiltration immune cells and the model could serve as a potential predictor for chemosensitivity. CONCLUSION: We successfully established a more stable signature of 7 immune-related lncRNA pairs, which has demonstrated a better prognostic ability for LSCC patients and may assist clinicians to precisely prescribe chemo drugs.

Median nerve block increases the success rate of radial artery cannulation in women with gestational hypertension undergoing cesarean section.

BACKGROUND: The radial artery cannulation helps to maintain the stability of maternal hemodynamics and reduce complications, however, it is difficult for women with gestational hypertension. Ultrasound-guided median nerve block can cause arterial vasodilation, which may improve the success rate of radial artery cannulation. METHODS: Ninety-two women with gestational hypertension and risks of intra-operative bleeding undergoing cesarean section following failed ultrasound-guided cannulation were identified and randomized into the median nerve block group and control group. Median nerve block was performed under the guidance of ultrasound in the middle forearm and 5 ml of 0.5% lidocaine was injected. Subcutaneous local block was administered in the control group. The ultrasound-guided radial artery cannulation was performed ten minutes after blocking. Baseline measurements (T1) were performed after 10 minutes of rest. All variables were measured again at 10 (T2) and 30 (T3) minutes after median nerve block or local block. The primary outcome was the success rate of radial artery cannulation within 10 minutes after blocking. The puncture time, number of attempts, the overall complications, and ultrasonographic measurements including radial artery diameter and cross-sectional area were recorded before (T1), 10 minutes (T2) after, and 30 minutes (T3) after block. RESULTS: A total of 92 pregnant women were identified and completed the follow-up. As compared to control group, the first-attempt success rate of radial artery cannulation was significantly higher (95.7% vs78.3%, p = 0.027) and procedure time to success was significantly shorter (118 ± 19 s vs 172 ± 66 s, p < 0.001) in median nerve group. Median nerve group also had a significantly less overall number of attempts (p = 0.024). Compared with control group, the diameter and cross-sectional area of radial artery increased significantly at the T2 and T3 points in median nerve group (p < 0.001), as well as percentage change of radial artery diameter and CSA. No difference was observed in the overall complication at chosen radial artery, which including vasospasm (21.7% vs 28.3%; p = 0.470) and hematoma (4.3% vs 8.7%; p = 0.677). CONCLUSIONS: Ultrasound-guided median nerve block can increase the first-attempt success rate of chosen radial artery cannulation in women with gestational hypertension and risks of intra-operative bleeding undergoing cesarean section following failed radial artery cannulation, and especially for those anesthesiologists with less experienced in radial artery cannulation. TRIAL REGISTRATION: ChiCTR2100052862; http://www.chictr.org.cn , Principal investigator: MEN, Date of registration: 06/11/2021.

Density Functional Method Study on the Cooperativity of Intermolecular H-bonding and π-π+ Stacking Interactions in Thymine-[Cnmim]Br (n = 2, 4, 6, 8, 10) Microhydrates.

The exploration of the ionic liquids' mechanism of action on nucleobase's structure and properties is still limited. In this work, the binding model of the 1-alkyl-3-methylimidazolium bromide ([Cnmim]Br, n = 2, 4, 6, 8, 10) ionic liquids to the thymine (T) was studied in a water environment (PCM) and a microhydrated surroundings (PCM + wH2O). Geometries of the mono-, di-, tri-, and tetra-ionic thymine (T-wH2O-y[Cnmim]+-xBr−, w = 5~1 and x + y = 0~4) complexes were optimized at the M06-2X/6-311++G(2d, p) level. The IR and UV-Vis spectra, QTAIM, and NBO analysis for the most stable T-4H2O-Br−-1, T-3H2O-[Cnmim]+-Br−-1, T-2H2O-[Cnmim]+-2Br−-1, and T-1H2O-2[Cnmim]+-2Br−-1 hydrates were presented in great detail. The results show that the order of the arrangement stability of thymine with the cations (T-[Cnmim]+) by PCM is stacking > perpendicular > coplanar, and with the anion (T-Br−) is front > top. The stability order for the different microhydrates is following T-5H2O-1 < T-4H2O-Br−-1 < T-3H2O-[Cnmim]+-Br−-1 < T-2H2O-[Cnmim]+-2Br−-1 < T-1H2O-2[Cnmim]+-2Br−-1. A good linear relationship between binding EB values and the increasing number (x + y) of ions has been found, which indicates that the cooperativity of interactions for the H-bonding and π-π+ stacking is varying incrementally in the growing ionic clusters. The stacking model between thymine and [Cnmim]+ cations is accompanied by weaker hydrogen bonds which are always much less favorable than those in T-xBr− complexes; the same trend holds when the clusters in size grow and the length of alkyl chains in the imidazolium cations increase. QTAIM and NBO analytical methods support the existence of mutually reinforcing hydrogen bonds and π-π cooperativity in the systems.

Effects of combined warmed preoperative forced-air and warmed perioperative intravenous fluids on maternal temperature during cesarean section: a prospective, randomized, controlled clinical trial.

BACKGROUND: Preventing the frequent perioperative hypothermia incidents that occur during elective caesarean deliveries would be beneficial. This trial aimed at evaluating the effect of preoperative forced-air warming alongside perioperative intravenous fluid warming in women undergoing cesarean sections under spinal anesthesia. METHODS: We randomly allocated 135 women undergoing elective cesarean deliveries to either the intervention group (preoperative forced-air and intravenous fluid warming, n = 69) or the control group (no active warming, n = 66). The primary outcome measure was the core temperature change between groups from baseline to the end of the surgical procedure. Secondary outcomes included thermal comfort scores, the incidences of shivering and hypothermia (< 36 °C), the core temperature on arrival at the post-anesthesia care unit, neonatal axillary temperature at birth, and Apgar scores. RESULTS: Two-way repeated measures ANOVA revealed significantly different core temperature changes (from the pre-spinal temperature to that at the end of the procedure) between groups (F = 13.022, P < 0.001). The thermal comfort scores were also higher in the intervention group than in the control group (F = 9.847, P = 0.002). The overall incidence of perioperative hypothermia was significantly lower in the intervention group than in the control group (20.6% vs. 51.6%, P < 0.0001). CONCLUSIONS: Warming preoperative forced-air and perioperative intravenous fluids may prevent maternal hypothermia, reduce maternal shivering, and improve maternal thermal comfort for patients undergoing cesarean sections under spinal anesthesia. TRIAL REGISTRATION: The study was registered with the Chinese Clinical Trial Registry (registration number: ChiCTR1800019117) on October26, 2018.

TAB3 overexpression promotes cell proliferation in non-small cell lung cancer and mediates chemoresistance to CDDP in A549 cells via the NF-κB pathway.

Transforming growth factor-activated kinase 1 (TAK1)-binding protein 3 (TAB3) is essential for the activation of the nuclear factor kappa B (NF-κB) pathway and has important roles in cell survival. However, the contribution of TAB3 to non-small cell lung cancer (NSCLC) remains elusive. In the present study, Western blotting and immunohistochemistry assays demonstrated that TAB3 expression was frequently increased in NSCLC tissues and cells. In addition, chi-square test and Kaplan-Meier analysis revealed that upregulation of TAB3 expression correlated with a more invasive tumor phenotype and poor prognosis. In addition, a series of experiments, including serum starvation-refeeding experiment and TAB3-siRNA transfection assay, showed that TAB3 expression promoted NSCLC cell proliferation. Furthermore, the effect of TAB3 expression on the sensitivity to cis-diamminedichloroplatinum (CDDP) and possible signaling transduction pathways was investigated. When the expression of TAB3 was inhibited by siRNA transfection, the sensitivity to CDDP was enhanced. Moreover, it showed that downregulation of TAB3 enhanced CDDP-induced A549 cell apoptosis through the inhibition of the NF-κB pathway. These results suggest that TAB3 plays a critical role in NSCLC progression and chemoresistance and that TAB3 depletion may be a promising approach to lung cancer therapy.

Nemo-like kinase (NLK) inhibits the progression of NSCLC via negatively modulating WNT signaling pathway.

Nemo-like kinase (NLK), an evolutionarily conserved serine/threonine kinase, is a critical regulator of various cancers. NLK expression was evaluated by Western blot in 8 paired fresh non-small-cell lung cancer (NSCLC) tissues and immunohistochemistry (IHC) on 83 paraffin-embedded slices. NLK was lowly expressed in NSCLC and significantly associated with NSCLC histological differentiation, clinical stage, lymph node status, and Ki-67. Multivariate analysis indicated that low NLK expression was an independent prognostic factor for NSCLC patients' low survival rate. In vitro, after the release of NSCLC cell line A549 from serum starvation, the expression of NLK was downregulated, whereas the cell-cycle-related proteins were upregulated. In addition, we used RNA interference to knock down NLK expression, then observed its effects on NSCLC's growth in vitro. Western blot analyses indicated that deletion of NLK was positively correlated with cell-cycle-related proteins. The present investigation demonstrated that suppression of NLK expression resulted in significant promotion of proliferation in NSCLC cells. And flow cytometry further indicated that loss of NLK promoted cell proliferation by facilitating S-phase and mitotic entry. Besides, the transcription activity of ß-catenin/TCF in A549 cells was remarkably enhanced when NLK was knocked down, which suggested that NLK participated in NSCLC cell proliferation via medulating Wnt signaling pathway. Based on these findings, we can provide a potential strategy for NSCLC therapy.

Two-dimensional ß-MnOOH nanosheets with high oxidase-mimetic activity for smartphone-based colorimetric sensing.

Manganese (Mn) is a versatile transition element with diverse oxidation states and significant biological importance. Mn-based nanozymes have emerged as promising catalysts in various applications. However, the direct use of manganese oxides as oxidase mimics remains limited and requires further improvement. In this study, we focus on hydroxylated manganese (MnOOH), specifically the layered form ß-MnOOH which exhibits unique electronic and structural characteristics. The two-dimensional ß-MnOOH nanosheets were synthesized through a hydrothermal approach and showed remarkable oxidase-like activity. These nanosheets effectively converted the oxidase substrate, 3,3',5,5'-tetramethylbenzidine (TMB), into its oxidized form by initiating the conversion of dissolved oxygen into ·O2-, 1O2 and ·OH. However, in the presence of L-cysteine (L-Cys), the catalytic activity of ß-MnOOH was significantly inhibited, enabling highly sensitive detection of L-Cys. This sensing strategy was successfully applied for smartphone-based L-Cys assay, offering potential utility in the diagnosis of Cys-related diseases. The exploration of layered ß-MnOOH nanosheets as highly active oxidase mimics opens up new possibilities for catalytic and biomedical applications.

Ligustilide enhances pregnancy outcomes via improvement of endometrial receptivity and promotion of endometrial angiogenesis in rats.

Ligustilide (LIG) is the main active ingredient of Angelica sinensis (Oliv.) Diels, which could promote focal angiogenesis to exert neuroprotection. However, there was no report that verified the exact effects of LIG on endometrial angiogenesis and the pregnancy outcomes. To explore the effects of LIG on low endometrial receptivity (LER) and angiogenesis, pregnancy rats were assigned into Control (saline treatment), LER (hydroxyurea-adrenaline treatment), LIG 20 mg/kg and LIG 40 mg/kg groups. Hematoxylin and eosin (H&E) staining was performed to evaluate endometrial morphology. Quantitative real-time PCR, immunofluorescence staining, western blot and immunohistochemistry staining were employed to assess the expression of endometrial receptivity factors and angiogenesis-related gene/protein, respectively. RNA sequencing was used to analyze the effects of LIG on LER caused by Kidney deficiency and blood stasis. We found that endometrial thickness and the implanted embryo number were substantially reduced in the hydroxyurea-adrenaline-treated pregnancy rats. At the same time, the gene and protein expressions of ERα, LIF, VEGFA and CD31 in the endometrium were markedly reduced, while the expressions of MUC1, E-cadherin were increased in the LER group. Administration of LIG raised the endometrial thickness and implanted embryos, as well as reversed the expressions of these factors. Collectively, our findings revealed that LIG could facilitate embryo implantation via recovery of the endometrium receptivity and promotion of endometrial angiogenesis.

Predictive modeling for identifying infection risk following spinal surgery: Optimizing patient management.

Infection is known to occur in a substantial proportion of patients following spinal surgery and predictive modeling may provide a useful means for identifying those at higher risk of complications and poor prognosis, which could help optimize pre- and postoperative management strategies. The outcome measure of the present study was to investigate the occurrence of all-cause infection during hospitalization following scoliosis surgery. To meet this aim, the present study retrospectively analyzed 370 patients who underwent surgery at the Second Affiliated Hospital, Zhejiang University School of Medicine (Hangzhou, China) between January 2016 and October 2022, and patients who either experienced or did not experience all-cause infection while in hospital were compared in terms of their clinicodemographic characteristics, surgical variables and laboratory test results. Logistic regression was subsequently applied to data from a subset of patients in order to build a model to predict infection, which was validated using another subset of patients. All-cause, in-hospital postoperative infections were found to have occurred in 66/370 patients (17.8%). The following variables were included in a predictive model: Sex, American Society of Anesthesiologists (ASA) classification, body mass index (BMI), diabetes mellitus, hypertension, preoperative levels of white blood cells and preoperative C-reactive protein (CRP) and duration of surgery. The model exhibited an area under the curve of 0.776 against the internal validation set. In conclusion, dynamic nomograms based on sex, ASA classification, BMI, diabetes mellitus, hypertension, preoperative levels of white blood cells and CRP and duration of surgery may have the potential to be a clinically useful predictor of all-cause infection following scoliosis. The predictive model constructed in the present study may potentially facilitate the real-time visualization of risk factors associated with all-cause infection following surgical procedures.

Vacuolar protein sorting 4B, an ATPase protein positively regulates the progression of NSCLC via promoting cell division.

Vacuolar protein sorting 4B (VPS4B), a member of ATPase family proteins, plays a crucial role in lysosome-dependent degradation. Recently, it was found that VPS4B could negatively regulate breast cancer progression through promoting lysosomal-dependent degradation for EGFR. Nevertheless, other studies found that VPS4B was also essential for cell division and mitosis through insuring the maintenance of centrosome and spindle assembly. Thus, the role of VPS4B in cancer biology remains under debate. In this study, we analyzed the clinical significance of VPS4B in NSCLC. The expression of VPS4B was evaluated by Western blot in 8 paired fresh NSCLC tissues and immunohistochemistry on 105 paraffin-embedded slices. VPS4B was highly expressed in NSCLC and significantly associated with NSCLCs tumor size, histological differentiation, clinical stage and Ki-67. Besides, high VPS4B expression was an independent prognostic factor for NSCLC patients' poor survival. To determine whether VPS4B could regulate the proliferation of NSCLC cells, we knocked down the expression of VPS4B and analyzed the proliferation of A549 NSCLC cells using Western blot, CCK8 and flow cytometry assays, which together indicated that loss of VPS4B could inhibit cell cycle progress. These data suggest that VPS4B may promote the progression of NSCLC and be a biotarget for NSCLCs therapy.

Molecular typing and prognostic risk models for ovarian cancer: a study based on cell differentiation trajectory.

Ovarian cancer is a heterogeneous disease with different molecular phenotypes. We performed molecular typing of ovarian cancer using cell differentiation trajectory analysis and proposed a prognostic risk scoring model. Using the copy number variation provided by inferCNV, we identified malignant tumor cells. Then, ovarian cancer samples were divided into four subtypes based on differentiation-related genes (DRGs). There were significant differences in survival rates, clinical features, tumor microenvironment scores, and the expression levels of ICGs among the subtypes. Based on nine DRGs, a prognostic risk score model was generated (AUC at 1 year: 0.749; 3 years: 0.651). Then we obtained a nomogram of the prognostic variable combination, including risk scores and clinicopathological characteristics, and predicted the 1-, 3- and 5-year overall survival. Finally, we explored some issues of immune escape using the established risk model. Our study demonstrates the significant influence of cell differentiation on predicting prognosis in OV patients and provides new insights for OV treatment and potential immunotherapeutic strategies.

Safety and efficacy of radiotherapy/chemoradiotherapy combined with immune checkpoint inhibitors for non-small cell lung cancer: A systematic review and meta-analysis.

Background: It is now widely accepted that radiotherapy (RT) can provoke a systemic immune response, which gives a strong rationale for the combination of RT and immune checkpoint inhibitors (ICIs). However, RT is a double-edged sword that not only enhances systemic antitumor immune response, but also promotes immunosuppression to some extent. Nevertheless, many aspects regarding the efficacy and safety of this combination therapy remain unknown. Therefore, a systematic review and meta-analysis was performed in order to assess the safety and efficacy of RT/chemoradiotherapy (CRT) and ICI combination therapy for non-small cell lung cancer (NSCLC) patients. Methods: PubMed and several other databases were searched (according to specific criteria) to find relevant studies published prior to the 28th of February 2022. Results: 3,652 articles were identified for screening and 25 trials containing 1,645 NSCLC patients were identified. For stage II-III NSCLC, the one- and two-year overall survival (OS) was 83.25% (95% confidence interval (CI): 79.42%-86.75%) and 66.16% (95% CI: 62.3%-69.92%), respectively. For stage IV NSCLC, the one- and two-year OS was 50% and 25%. In our study, the pooled rate of grade 3-5 adverse events (AEs) and grade 5 AEs was 30.18% (95% CI: 10.04%-50.33%, I2: 96.7%) and 2.03% (95% CI: 0.03%-4.04%, I2: 36.8%), respectively. Fatigue (50.97%), dyspnea (46.06%), dysphagia (10%-82.5%), leucopenia (47.6%), anaemia (5%-47.6%), cough (40.09%), esophagitis (38.51%), fever (32.5%-38.1%), neutropenia (12.5%-38.1%), alopecia (35%), nausea (30.51%) and pneumonitis (28.53%) were the most common adverse events for the combined treatment. The incidence of cardiotoxicity (0%-5.00%) was low, but it was associated with a high mortality rate (0%-2.56%). Furthermore, the incidence of pneumonitis was 28.53% (95% CI: 19.22%-38.88%, I2: 92.00%), grade ≥ 3 pneumonitis was 5.82% (95% CI: 3.75%-8.32%, I2: 57.90%) and grade 5 was 0%-4.76%. Conclusion: This study suggests that the addition of ICIs to RT/CRT for NSCLC patients may be both safe and feasible. We also summarize details of different RT combinations with ICIs to treat NSCLC. These findings may help guide the design of future trials, the testing of concurrent or sequential combinations for ICIs and RT/CRT could be particularly useful to guide the treatment of NSCLC patients.

Hyperoside exerts protective effects against anticardiolipin antibody-induced recurrent pregnancy loss in vivo and in vitro.

BACKGROUND: Women with antiphospholipid syndrome (APS) or antiphospholipid antibodies (aPLs) are at high risk for obstetric complications, including recurrent pregnancy loss (RPL). However, effective treatments for RPL are lacking. OBJECTIVE: This study aimed to reveal the function and underlying mechanism of hyperoside (Hyp) in RPL associated with antiphospholipid antibodies (aCLs). METHODS: The pregnant rats (N = 24) were divided randomly into four groups: normal human-IgG (NH-IgG); aCL-pregnancy loss (aCL-PL); aCL-PL + Hyp (40 mg/kg/day); aCL-PL + low molecular weight heparin (LMWH, 525 µg/kg/day). HTR-8 cells were treated with 80 µg/mL aCL to establish the cell models of miscarriage. RESULTS: In pregnant rats, aCL-IgG injection raised the abortion rate of embryos, while Hyp treatment inhibited the effects. Additionally, Hyp inhibited the platelet activation and uteroplacental insufficiency caused by aCL. In vivo and in vitro experiments further suggested that Hyp suppressed aCL-induced inflammation and apoptosis by downregulating NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome-related factors and decreasing apoptotic rates. After aCL administration, Hyp therapy downregulated the expression of purinergic ligand-gated ion channel 7 (P2X7), which is reported to induce cytokine release and apoptosis. Furthermore, we found that the treatment of 3'-O-(4-Benzoyl) benzoyl-ATP (BzATP, an agonist of the P2X7 receptor) reversed the inhibitory effects of Hyp on cell function. CONCLUSIONS: Hyp exerts protective effects on aCL-induced pregnancy loss by preventing platelet activation-mediated P2X7/NLRP3 pathway. Therefore, Hyp may provide a feasible pharmaceutical strategy for the treatment of RPL.

High-intensity focused ultrasound ablation combined with systemic therapy for unresectable colorectal cancer liver metastasis: A propensity score-matched analysis.

OBJECTIVE: Unresectable colorectal cancer liver metastasis (CRLM) remains a challenging obstacle that often prevents curative treatment. In this study, we retrospectively analyzed the efficacy and safety of high-intensity focused ultrasound (HIFU) as a local adjuvant therapy for systemic chemotherapy for patients with unresectable CRLM. HIFU is a noninvasive method previously demonstrated as efficacious for various solid malignancies. METHODS: Propensity score matching was used for the combination therapy group (HIFU group, n = 59) and the observation group receiving systemic therapy only (No-HIFU group, n = 59). In addition, the survival benefit, adverse effects, and factors affecting prognosis following HIFU were evaluated. RESULTS: The disease control rate was 77.9% and 62.7%, and the objective remission rate was 18.9% and 6.8% in the HIFU and non-HIFU groups, respectively. The survival analysis showed that median progression-free survival (mPFS) was 12.0 months and 11.0 months for the HIFU and non-HIFU groups, respectively (p = 0.002). The univariate and multivariate analysis showed that pre-treatment colorectal cancer liver metastasis lesion size was significantly associated with mPFS. In addition, patients that received a combination treatment for CRLM lesions <5.0 cm had a longer mPFS when compared to those receiving systemic therapy alone (13.0 months vs. 11.0 months, p = 0.001). In the HIFU group, patients with lesions <5.0 cm had a longer mPFS than patients with lesions ≥5.0 cm (13.0 months vs. 10.0 months, p = 0.04) (Figure 3B,C). Most treatment-related adverse events observed in both groups were grade 1-2. Only four cases (6.8%) of grade 1-2 skin burns were observed in patients in the HIFU group; no other statistically significant adverse events were observed. CONCLUSIONS: Our study showed that HIFU ablation targeting unresectable CRLM alongside systemic therapy safely and significantly improved local control rates and prolonged mPFS, especially for lesions smaller than 5.0 cm.

New prognostic system specific for epidermal growth factor receptor-mutated lung cancer brain metastasis.

Introduction: Brain metastases (BM) from lung cancer are heterogeneous, and accurate prognosis is required for effective treatment strategies. This study aimed to identify prognostic factors and develop a prognostic system exclusively for epidermal growth factor receptor (EGFR)-mutated lung cancer BM. Methods: In total, 173 patients with EGFR-mutated lung cancer from two hospitals who developed BM and received tyrosine kinase inhibitor (TKI) and brain radiation therapy (RT) were included. Univariate and multivariate analyses were performed to identify significant EGFR-mutated BM prognostic factors to construct a new EGFR recursive partitioning analysis (RPA) prognostic index. The predictive discrimination of five prognostic scoring systems including RPA, diagnosis-specific prognostic factors indexes (DS-GPA), basic score for brain metastases (BS-BM), lung cancer using molecular markers (lung-mol GPA) and EGFR-RPA were analyzed using log-rank test, concordance index (C-index), and receiver operating characteristic curve (ROC). The potential predictive factors in the multivariable analysis to construct a prognostic index included Karnofsky performance status, BM at initial lung cancer diagnosis, BM progression after TKI, EGFR mutation type, uncontrolled primary tumors, and number of BM. Results and discussion: In the log-rank test, indices of RPA, DS-GPA, lung-mol GPA, BS-BM, and EGFR-RPA were all significant predictors of overall survival (OS) (p ≤ 0.05). The C-indices of each prognostic score were 0.603, 0.569, 0.613, 0.595, and 0.671, respectively; The area under the curve (AUC) values predicting 1-year OS were 0.565 (p=0.215), 0.572 (p=0.174), 0.641 (p=0.007), 0.585 (p=0.106), and 0.781 (p=0.000), respectively. Furthermore, EGFR-RPA performed better in terms of calibration than other prognostic indices.BM progression after TKI and EGFR mutation type were specific prognostic factors for EGFR-mutated lung cancer BM. EGFR-RPA was more precise than other models, and useful for personal treatment.

Inferior Vena Cava Collapsibility Index Can Predict Hypotension and Guide Fluid Management After Spinal Anesthesia.

PURPOSE: We hypothesized that inferior vena cava collapsibility index (IVCCI)-guided fluid management would reduce the incidence of postspinal anesthesia hypotension in patients undergoing non-cardiovascular, non-obstetric surgery. METHODS: A receiver operating characteristic (ROC) curve was used to determine the diagnostic value of IVCCI for predicting hypotension after induction of spinal anesthesia and calculate the cut-off value. Based on the cut-off variation value, the following prospective randomized controlled trial aimed to compare the incidence of postspinal anesthesia hypotension between the IVCCI-guided fluid administration group and the standard fluid administration group. Secondary outcomes included the rate of vasoactive drug administration, the amount of fluid administered, and the incidence of nausea and vomiting. RESULTS: ROC curve analysis revealed that IVCCI had a sensitivity of 83.9%, a specificity of 76.3%, and a positive predictive value of 84% for predicting postspinal anesthesia hypotension at a cut-off point of >42%. The area under the curve (AUC) was 0.834 (95% confidence interval: 0.740-0.904). According to the cut-off variation value of 42%, the IVCCI-guided group exhibited a lower incidence of hypotension than the standard group [9 (15.3%) vs. 20 (31.7%), P = 0.032]. Total fluid administered was lower in the IVCCI-guided group than in the standard group [330 (0-560) mL vs. 345 (285-670) mL, P = 0.030]. CONCLUSIONS: Prespinal ultrasound scanning of the IVCCI provides a reliable predictor of hypotension following spinal anesthesia at a cut-off point of >42%. IVCCI-guided fluid management before spinal anesthesia can reduce the incidence of hypotension following spinal anesthesia.

Efficacy and safety of radiotherapy/chemoradiotherapy combined with immune checkpoint inhibitors for locally advanced stages of esophageal cancer: A systematic review and meta-analysis.

Background: Radiotherapy (RT)/Chemoradiotherapy (CRT) are important treatments for all stages of esophageal cancer (EC). The combination of immune checkpoint inhibitors (ICIs) with RT/CRT seems to be promising avenue for the treatment of EC. Therefore, a systematic review and meta-analysis was performed in order to assess the safety and efficacy of RT/CRT and ICI combination therapy for EC patients. Methods: PubMed and several other databases were searched (according to specific criteria) to find relevant studies published prior to the 31st of December 2021. Results: 1962 articles were identified for screening, and six trials containing 668 patients were identified and pooled to determine the one- and two-year overall survival (OS), which were 84.5% (95% confidence interval (CI): 69.9%-100%) and 68.3% (95% CI: 49.0%-95.1%), respectively. Additionally, the rate of pooled grade 3-5 adverse reactions was 41.0% (95% CI: 31.2%-51.2%). The rate of specific grade 3-5 adverse reactions are as follows: lymphopenia (36.8%-60%), esophagitis (20%), anastomotic leakage (18%), esophageal fistula (10%), pain (10%), leukopenia (5.3%-10%), esophageal hemorrhage (2.5%-5%), chyle leakage (3%), fatigue (5%), cough (2.7%-5%), diarrhea (2.7%), pulmonary embolism (2.5%) and allergic reaction (2.5%). The pooled rate of pneumonitis of grade 3-5 and grade 1-5 was 0.8% (95% CI: 0.1%-0.16%, I2: 0%) and 5.4% (95% CI: 2.0%-14.2%, I2: 82%). For thoracic complication, esophagitis was 63.6% (95% CI: 42.4%-80.6%), which appeared to be more frequent with the combination of ICIs to RT/CRT (12%-37.7%). Other thoracic complications include esophageal hemorrhage (2.5%-10%), esophageal fistula (6%-10%) and anastomotic leakage (6%-21%). Additionally, some of the trials did not report cardiac related adverse reactions. The subgroup analyses also revealed that the pooled rate patients with grade 3-5 pneumonitis was higher for CRT/RT with concurrent and sequential ICI treatment (1.9%) than other groups (0.8%). Conclusion: This study suggests that the addition of ICIs to RT/CRT for EC patients may be both safe and feasible. However, larger randomized studies are needed to confirm these results.

Salvage high intensity focused ultrasound for residual or recurrent cervical cancer after definitive chemoradiotherapy.

Objective: The treatment of residual/recurrent cervical cancer within a previously irradiated area is challenging and generally associated with a poor outcome. Local treatments such as salvage surgery and re-irradiation are usually traumatic and have limited efficacy. High intensity focused ultrasound (HIFU) treatment can directly ablate solid tumors without damaging neighboring healthy tissue. However, the HIFU studies for these patients are limited. Experience gained over the course of 10 years with the use of HIFU for the management of residual/recurrent cervical cancer after chemoradiotherapy is reported herein. Methods: 153 patients with residual/recurrent cervical cancer in a previously irradiated field who received HIFU treatment between 2010 and 2021 were retrospectively analyzed. Adverse effects, survival benefit and factors affecting prognosis were given particular attention. Results: A total of 36 patients (23.5%) achieved a partial response following HIFU treatment and 107 patients (69.9%) had stable disease. The objective response and disease control rates were 23.5% and 93.5%, respectively. The median progression-free survival (mPFS) and median overall survival (mOS) were 17.0 months and 24.5 months, respectively. Moreover, patients with lesions ≥1.40 cm before HIFU treatment and a shrinkage rate ≥ 30% after treatment had a higher mPFS and mOS, and patients with lesions ≤1.00 cm after HIFU treatment had a higher mPFS (P=<0.05). All the treatment-related adverse events were limited to minor complications, which included skin burns, abdominal pain and vaginal discharge. Conclusions: HIFU treatment is likely a preferred option for cervical cancer patients with residual disease or recurrence following CRT that can safely improve the local control rate and extend survival.