Sequential multimodal treatments with chemotherapy and surgery for advanced soft tissue sarcoma may be associated with better survival than chemotherapy.

BACKGROUND: In patients with advanced soft tissue sarcoma (STS), surgery had been reported to be associated with superior overall survival (OS). Chemotherapy details for such patients were less reported, and whether multimodal treatment with surgery and chemotherapy provides extra survival benefit remains unclear. METHODS: We retrospectively reviewed patients with newly diagnosed advanced STS treated at National Taiwan University Hospital from January 1, 2011, to December 31, 2017. OS was calculated from the day of diagnosis of advanced STS to the day of death or last follow-up. Baseline patient characteristics and details regarding surgery and chemotherapy were recorded. RESULTS: A total of 545 patients were diagnosed with STS from 2011 to 2017, of which 226 patients had advanced STS. The median age was 54.7 years, and 54% of patients were women. Approximately 38% of patients with advanced STS underwent surgery and exhibited a trend of longer OS compared with who did not (median = 18.6 vs. 11.9 months, p = 0.083). In the chemotherapy subgroup, the benefit of surgery was more prominent (median = 21.9 vs. 16.5 months, p = 0.037). Patients who received chemotherapy prior to surgery exhibited numerically longer OS than those who underwent surgery first (median = 33.9 vs. 18.3 months, p = 0.155). After adjusting other clinical factors, chemotherapy remained an independent factor associated with favourable OS. CONCLUSION: Surgery may be more beneficial for the patients who receive chemotherapy. Our results support evaluation of sequential multimodal treatments strategy including surgery and chemotherapy in patients with advanced STS.

Scutellaria baicalensis Induces Cell Apoptosis and Elicits Mesenchymal-Epithelial Transition to Alleviate Metastatic Hepatocellular Carcinoma via Modulating HSP90ß.

Hepatocellular carcinoma is one of the most common malignant tumors in the world and shows strong metastatic potential. Current medicine for hepatocellular carcinoma therapy is invalid, while Scutellaria baicalensis Georgi exhibits the pharmaceutical potential to treat liver diseases and liver cancer. Herein, we verified the inhibitory properties and the pivotal molecules regimented by Scutellaria baicalensis on advanced hepatocellular carcinoma. At first, the viability of SK-Hep-1 cells was significantly reduced under treatment of Scutellaria baicalensis extract in a dose-dependent manner without affecting the growth of normal hepatocyte. Scutellaria baicalensis extract application could remarkably cause apoptosis of SK-Hep-1 cells through p53/cytochrome C/poly-ADP ribose polymerase cascades and arrest the cell cycle at the G1/S phase by downregulating cyclin-dependent kinases. Meanwhile, administration of Scutellaria baicalensis extract remarkably attenuated the migration capability as well as suppressed matrix metalloproteinase activity of advanced hepatocellular carcinoma cells. The proteome profiles and network analysis particularly implied that exposure to Scutellaria baicalensis extract downregulated the expression of HSP90ß, and the clinical stage of hepatocellular carcinoma is also positively correlated with the HSP90ß level. Combined treatment of Scutellaria baicalensis extract and HSP90ß siRNAs could markedly enhance the ubiquitination activity and the degradation of vimentin to subsequently inhibit the metastatic property of SK-Hep-1 cells. Moreover, application of Scutellaria baicalensis extract and HSP90ß siRNAs depleted phosphorylation of AKT, which stimulated the expression of p53 and consecutively triggered cell apoptosis. These findings suggest that HSP90ß may be a prospective target for the effective therapy of advanced hepatocellular carcinoma via accelerating apoptosis of hepatocellular carcinoma cells and eliciting mesenchymal-epithelial transition with the administration of Scutellaria baicalensis extract.

From Helices to Crystals: Multiscale Representation of Chirality in Double-Helix Structures.

Single crystals with chiral shapes aroused the interest of chemists due to their fascinating polarization rotation properties. Although the formation of large-scale spiral structures is considered to be a potential factor in chiral crystals, the precise mechanism behind their formation remains elusive. Herein, we present a rare phenomenon involving the multitransfer and expression of chirality at micro-, meso-, and macroscopic levels, starting from chiral carbon atoms and extending to the double-helical secondary structure, ultimately resulting in the chiral geometry of crystals. The assembly of the chiral double helices is facilitated by the dual characteristics of amide groups derived from amino acids, which serve as both hydrogen bond donors and receptors, similar to the assembly pattern observed in DNA. Crystal face analysis and theoretical morphology reveal two critical factors for the mechanism of the chiral crystal: inherent intrinsically symmetrical distribution of crystal faces and their acquired growth. Importantly, the magnetic circular dichroism (MCD) study reveals the strong magneto-optical response of the hypersensitive f-f transition in the UV-vis-NIR region, which is much stronger than previously observed signals. Remarkably, an external magnetic field can reverse the CD signal. This research highlights the potential of lanthanide-based chiral helical structures as promising magneto-optical materials.

Inhibition of CDK9 exhibits anticancer activity in hepatocellular carcinoma cells via targeting ribonucleotide reductase.

Cyclin-dependent kinase 9 (CDK9) inhibitors are a novel category of anticancer treatment for cancers. However, their effects on hepatocellular carcinoma (HCC) are rarely investigated. Human ribonucleotide reductase (RR, which consists of RRM1 and RRM2 subunits) catalyzes the conversion of ribonucleoside diphosphate into 2'-deoxyribonucleoside diphosphate to maintain the homeostasis of nucleotide pools, which play essential roles in DNA synthesis and DNA repair. In this study, we identified that CDK9 protein expression in adjacent non-tumor tissues predicted HCC patients' overall and progression-free survivals. The anticancer activity of a CDK9-selective inhibitor, LDC000067, on HCC cells was positively associated with its ability to inhibit the expression of RRM1 and RRM2. LDC000067 downregulated RRM1 and RRM2 expression through post-transcriptional pathway. Specifically, LDC000067 triggered RRM2 protein degradation via multiple pathways, including proteasome-, lysosome-, and calcium-dependent pathways. Furthermore, CDK9 positively correlates with RRM1 or RRM2 expression in HCC patients, and the expressions of these three genes were associated with the higher infiltration of immune cells in HCC. Taken together, this study identified the prognostic relevance of CDK9 in HCC and the molecular mechanism for the anticancer effect of CDK9 inhibitors on HCC.

Anterior gradient 2 induces resistance to sorafenib via endoplasmic reticulum stress regulation in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) accounts for almost 80% of all liver cancer cases and is the sixth most common cancer and the second most common cause of cancer-related death worldwide. The survival rate of sorafenib-treated advanced HCC patients is still unsatisfactory. Unfortunately, no useful biomarkers have been verified to predict sorafenib efficacy in HCC. RESULTS: We assessed a sorafenib resistance-related microarray dataset and found that anterior gradient 2 (AGR2) is highly associated with overall and recurrence-free survival and with several clinical parameters in HCC. However, the mechanisms underlying the role of AGR2 in sorafenib resistance and HCC progression remain unknown. We found that sorafenib induces AGR2 secretion via posttranslational modification and that AGR2 plays a critical role in sorafenib-regulated cell viability and endoplasmic reticulum (ER) stress and induces apoptosis in sorafenib-sensitive cells. In sorafenib-sensitive cells, sorafenib downregulates intracellular AGR2 and conversely induces AGR2 secretion, which suppresses its regulation of ER stress and cell survival. In contrast, AGR2 is highly intracellularly expressed in sorafenib-resistant cells, which supports ER homeostasis and cell survival. We suggest that AGR2 regulates ER stress to influence HCC progression and sorafenib resistance. CONCLUSIONS: This is the first study to report that AGR2 can modulate ER homeostasis via the IRE1α-XBP1 cascade to regulate HCC progression and sorafenib resistance. Elucidation of the predictive value of AGR2 and its molecular and cellular mechanisms in sorafenib resistance could provide additional options for HCC treatment.

Use of rocuronium and sugammadex for video-assisted thoracoscopic surgery is associated with reduced duration of chest tube drainage: a propensity score-matched analysis.

BACKGROUND: We investigated the influence of different neuromuscular blocking agents and reversal agents during anaesthesia on early removal of chest tube drainage after video-assisted thoracoscopic surgery (VATS). METHODS: This retrospective single-centre study included patients who underwent VATS after tracheal intubation under general anaesthesia. Patients received either cisatracurium and neostigmine (n=547) or rocuronium and sugammadex (n=151). Quantitative neuromuscular monitoring was used and one chest tube (size 24 Fr) was inserted. To reduce potential bias, 140 patients from each group were matched by propensity score for sex, age, body mass index and indication for VATS. Primary outcome was duration of chest tube drainage after surgery. RESULTS: Use of rocuronium and sugammadex was associated with a shorter duration of chest tube drainage (2 [1-2] vs 2 [1-3] days; P=0.049) and a 63% reduction in delayed chest tube removal (odds ratio 0.37; 95% confidence interval [CI]: 0.20-0.67; P=0.005). This group also had a lower incidence of postoperative atelectasis (P=0.047) and consolidation (P=0.008). Each 1 h increase in the duration of anaesthesia was associated with a 1.57-fold increase in the delayed removal of the chest tube (95% CI: 1.25-1.96; P=0.005). CONCLUSIONS: During general anaesthesia for VATS, compared with cisatracurium and neostigmine, use of rocuronium and sugammadex was associated with a significant decrease in the incidence of postoperative delayed removal of the chest tube, atelectasis, and pulmonary consolidation.

In-center Automated Peritoneal Dialysis: Clinical Features, Practice Patterns, and Patient Survival From a 6-year Cohort Study in China.

INTRODUCTION: In-center automated peritoneal dialysis (APD) has been more frequently adopted in clinical practice for maintenance PD patients in China. For a better understanding of its clinical uptake, this retrospective study reviewed incident PD patients for a period of 6 years, investigating the practice pattern of in-center APD, factors associated with the use of in-center APD, and report on the patient survival compared to the non-users of APD among hospitalised PD patients. METHODS: This was a cohort study of all incident PD patients who met the inclusion criteria from 2013/01/01 to 2018/09/30, and were followed until death, cessation of PD, loss to follow-up, or 2018/12/31. Clinical characteristics, patient outcomes, and detailed data on APD sessions were recorded. We used time-dependent Cox model to estimate the variables associated with the initiation of in-center APD, and marginal structural model through inverse probability weighting to adjust for time-varying APD use on the causal pathway to all-cause mortality. RESULTS: A total of 651 subjects over 17501 patient-months were enrolled. Of these, 633 (97.2%) PD patients were hospitalised at least once during follow-up, and 369 (56.7%) received in-center APD at a certain point, and the timing of APD use during the first 3 months, first year and first 2 years since PD inception were 14.8%, 45.4% and 74.8%, respectively. A total of 12553 in-center APD sessions were recorded, where 85.9% used 4 bags of 5L-exchanges per prescription. Time-dependent Cox model showed that diabetes (hazard ratio [HR], 1.39, 95% confidence interval [CI], 1.09-1.76), urine output (HR 0.80, 95% CI 0.70-0.92), serum albumin (HR 0.84, 95%CI 0.72-0.99), hemoglobin (HR 0.88, 95%CI 0.77-0.99), and Ca×P (HR 1.19, 95%CI 1.06-1.35) were significantly associated with in-center APD use. Among all hospitalised PD patients, the estimated hazard ratio corresponding to the marginal causal effect of in-center APD use on all-cause mortality is 0.13 (95% CI 0.05-0.31, P<0.001). Significant survival benefit (adjusted-HR 0.56, 95%CI 0.33-0.95) associated with starting APD after the first PD year was observed among in-center APD users. CONCLUSIONS: In-center APD is used intensively during the first 2 years of PD and is associated with certain clinical features. Over all a significant survival benefit of in-center APD use was observed.

The essential anti-angiogenic strategies in cartilage engineering and osteoarthritic cartilage repair.

In the cartilage matrix, complex interactions occur between angiogenic and anti-angiogenic components, growth factors, and environmental stressors to maintain a proper cartilage phenotype that allows for effective load bearing and force distribution. However, as seen in both degenerative disease and tissue engineering, cartilage can lose its vascular resistance. This vascularization then leads to matrix breakdown, chondrocyte apoptosis, and ossification. Research has shown that articular cartilage inflammation leads to compromised joint function and decreased clinical potential for regeneration. Unfortunately, few articles comprehensively summarize what we have learned from previous investigations. In this review, we summarize our current understanding of the factors that stabilize chondrocytes to prevent terminal differentiation and applications of these factors to rescue the cartilage phenotype during cartilage engineering and osteoarthritis treatment. Inhibiting vascularization will allow for enhanced phenotypic stability so that we are able to develop more stable implants for cartilage repair and regeneration.

Simulated microgravity altered the proliferation, apoptosis, and extracellular matrix formation of L929 fibroblasts and the transforming growth factor-ß1/Smad3 signaling pathway.

Exposure to microgravity can adversely affect the fitness of astronauts. The integrity of the skin plays a crucial role in protecting against mechanical forces and infections, fluid imbalance, and thermal dysregulation. In brief, the skin wound may cause unknown challenges to the implementation of space missions. Wound healing is a physiological process that relies on the synergistic action of inflammatory cells, extracellular matrix (ECM), and various growth factors to maintain the integrity of skin after trauma. Fibroblasts are present almost throughout the entire process of wound repair, especially in the scar formation at the endpoint of wound healing. However, there is limited knowledge about the extent to which fibroblasts are affected by the lack of gravity during wound healing. In this study, we utilized the rotary cell culture system, a ground-based facility that mimics the weightless condition, to study the alterations of L929 fibroblast cells under simulated microgravity (SMG). Our results demonstrated that the SM condition exerted negative influences on the proliferation and ECM formation of the L929 fibroblast. Whereas, the apoptosis of fibroblast was significantly upregulated upon exposure to SMG conditions. Moreover, the transforming growth factor-ß1/Smad3 (TGF-ß1/smad3) signaling pathway of L929 fibroblast related to wound repair was also altered significantly under a weightless environment. Overall, our study provided evidence that fibroblasts are strongly sensitive to SMG and elucidated the potential value of the TGF-ß1/Smad3 signaling pathway modulating wound healing in the future practice of space medicine.

Stripping Massage and Literature Review in Post-Thoracoscopic Chest Pain Management.

The aim of this randomized study was to investigate whether stripping massage (SM) of myofascial trigger points in the lower rhomboid muscle could alleviate chest pain in patients following thoracoscopic surgery. In addition, a literature review was conducted to assess the effectiveness of various pain management techniques. Sixty adult patients who reported a visual analog scale (VAS) score of 4 or higher were randomly assigned to receive conventional analgesics alone (conventional group) or combined with SM twice daily for 2 weeks (SM group). VAS scores and the use of additional analgesics were evaluated on postoperative days 1, 3, 7, 14, and 30. Using the PubMed and Cochrane Library databases, a review of current pain management techniques was carried out up to January 31, 2022. A subgroup analysis was also performed to examine the treatment effect during different surgical periods and techniques. Results showed that the SM group had significantly lower VAS scores on postoperative days 3, 7, 14, and 30 (p < 0.001), as well as a shorter hospitalization duration and reduced need for additional analgesics (p < 0.001). The literature review included a total of 20 studies (2,342 cases of chest pain relief after thoracoscopic surgery), which indicated that serratus anterior plane (SAP) blocks were commonly used as a perioperative approach to reduce pain and opioid consumption. SM and SAP can both serve as adjuvant treatments for chest pain in patients following thoracoscopic surgery, with SM being a safe and noninvasive pain control option after hospital discharge.

Sesamin suppresses angiotensin-II-enhanced oxidative stress and hypertrophic markers in H9c2 cells.

Myocardial hypertrophy plays a crucial role in cardiovascular disease (CVD) development. Myocardial hypertrophy is an adaptive response by myocardial cells to stress after cardiac injury to maintain cardiac output and function. Angiotensin II (Ang-II) regulates CVD through the renin-angiotensin-aldosterone system, and its signaling in cardiac myocytes leads to excessive reactive oxygen species (ROS) production, oxidative stress, and inflammation. Sesamin (SA), a natural compound in sesame seeds, has anti-inflammatory and anti-apoptotic effects. This study investigated whether SA could attenuate hypertrophic damage and oxidative injuries in H9c2 cells under Ang-II stimulation. We found that SA decreased the cell surface area. Furthermore, Ang-II treatment reduced Ang-II-increased ANP, BNP, and ß-MHC expression. Ang-II enhanced NADPH oxidase activity, ROS formation, and decreased Superoxide Dismutase (SOD) activity. SA treatment reduces Ang-II-caused oxidative injuries. We also found that SA mitigates Ang-II-induced apoptosis and pro-inflammatory responses. In conclusion, SA could attenuate Ang-II-induced cardiac hypertrophic injuries by inhibiting oxidative stress, apoptosis, and inflammation in H9c2 cells. Therefore, SA might be a potential supplement for CVD management.

Guest-Driven Self-Assembly and Chiral Induction of Photofunctional Lanthanide Tetrahedral Cages.

Chiral luminescent lanthanide-organic cages have many potential applications in enantioselective recognition, sensing, and asymmetric catalysis. However, due to the paucity of structures and their limited cavities, host-guest chemistry with lanthanide-organic cages has remained elusive so far. Herein, we report a guest-driven self-assembly and chiral induction approach for the construction of otherwise inaccessible Ln4L4-type (Ln = lanthanide ions, i.e., EuIII, TbIII; L = ligand) tetrahedral hosts. Single crystal analyses on a series of host-guest complexes reveal remarkable guest-adaptive cavity breathing on the tetrahedral cages, reflecting the advantage of the variation tolerance on coordination geometry of the f-elements. Meanwhile, noncovalent confinement of pyrene within the lanthanide cage not only leads to diminishment of its excimer emission but also facilitates guest to host energy transfer, opening up a new sensitization window for the lanthanide luminescence on the cage. Moreover, stereoselective self-assembly of either Λ4- or Δ4- type Eu4L4 cages has been realized via chiral induction with R/S-BINOL or R/S-SPOL templates, as confirmed by NMR, circular dichroism (CD), and circularly polarized luminescence (CPL) with high dissymmetry factors (glum) up to ±0.125.

A metabolic biomarker panel of restless legs syndrome in peritoneal dialysis patients.

BACKGROUND: Restless legs syndrome (RLS) is a neuromotor disorder, and dialysis patients are more likely to develop RLS. RLS often causes sleep disorders, anxiety and depression in patients. It will increase the risk of death and severely affect the life of patients. At present, RLS has not received enough recognition and attention, and the misdiagnosis rate can reach more than 10%. METHODS: The discovery set selected 30 peritoneal dialysis (PD) patients and 27 peritoneal dialysis patients with RLS (PD-RLS). A metabolomics method based on ultra performance liquid chromatography tandem quadrupole time-of-flight mass spectrometric method (UPLC-Q-TOF/MS) was used to analyze the differential metabolites of the two groups. 51 PD patients and 51 PD-RLS patients were included in the validation set. The receiver operating characteristic (ROC) analysis was used to evaluate the early diagnostic biomarkers, and the correlation between the differential metabolites and laboratory test indexes was analyzed to explore the biological function of the differential metabolites. RESULTS: Through the integrated analysis, four metabolites can be used as markers for the diagnosis of PD-RLS, including Hippuric acid, Phenylacetylglutamine, N,N,N-Trimethyl-L-alanyl-L-proline betaine and Threonic acid. Through ROC analysis, it is found that they can be used as a metabolic biomarker panel, and the area under the curve of this combination is more than 0.9, indicating that the panel has good diagnostic and predictive ability. CONCLUSION: Metabolomics based on UPLC-Q-TOF/MS technology can effectively identify the potential biomarkers, and provide a theoretical basis for the early diagnosis, prevention and treatment on PD-RLS.

Repurposing of ingenol mebutate for treating human colorectal cancer by targeting S100 calcium-binding protein A4 (S100A4).

Colorectal cancer (CRC) is the world's second most common cause of cancer-related death. Novel treatments are still urgently needed. S100 calcium-binding protein A4 (S100A4) was demonstrated to be an anticancer therapeutic target. Herein, we found that higher S100A4 expression was associated with a poorer prognosis in publicly available cohorts and a Taiwanese CRC patient cohort. To identify repurposed S100A4 inhibitors, we mined the Connectivity Map (CMap) database for clinical drugs mimicking the S100A4-knockdown gene signature. Ingenol mebutate, derived from the sap of the plant Euphorbia peplus, is approved as a topical treatment for actinic keratosis. The CMap analysis predicted ingenol mebutate as a potent S100A4 inhibitor. Indeed, both messenger RNA and protein levels of S100A4 were attenuated by ingenol mebutate in human CRC cells. In addition, CRC cells with higher S100A4 expressions and/or the wild-type p53 gene were more sensitive to ingenol mebutate, and their migration and invasion were inhibited by ingenol mebutate. Therefore, our results suggest the repurposing of ingenol mebutate for treating CRC by targeting S100A4.

A chemical probe inhibitor targeting STAT1 restricts cancer stem cell traits and angiogenesis in colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is a worldwide cancer with rising annual incidence. New medications for patients with CRC are still needed. Recently, fluorescent chemical probes have been developed for cancer imaging and therapy. Signal transducer and activator of transcription 1 (STAT1) has complex functions in tumorigenesis and its role in CRC still needs further investigation. METHODS: RNA sequencing datasets in the NCBI GEO repository were analyzed to investigate the expression of STAT1 in patients with CRC. Xenograft mouse models, tail vein injection mouse models, and azoxymethane/dextran sodium sulfate (AOM/DSS) mouse models were generated to study the roles of STAT1 in CRC. A ligand-based high-throughput virtual screening approach combined with SWEETLEAD chemical database analysis was used to discover new STAT1 inhibitors. A newly designed and synthesized fluorescently labeled 4',5,7-trihydroxyisoflavone (THIF) probe (BODIPY-THIF) elucidated the mechanistic actions of STAT1 and THIF in vitro and in vivo. Colonosphere formation assay and chick chorioallantoic membrane assay were used to evaluate stemness and angiogenesis, respectively. RESULTS: Upregulation of STAT1 was observed in patients with CRC and in mouse models of AOM/DSS-induced CRC and metastatic CRC. Knockout of STAT1 in CRC cells reduced tumor growth in vivo. We then combined a high-throughput virtual screening approach and analysis of the SWEETLEAD chemical database and found that THIF, a flavonoid abundant in soybeans, was a novel STAT1 inhibitor. THIF inhibited STAT1 phosphorylation and might bind to the STAT1 SH2 domain, leading to blockade of STAT1-STAT1 dimerization. The results of in vitro and in vivo binding studies of THIF and STAT1 were validated. The pharmacological treatment with BODIPY-THIF or ablation of STAT1 via a CRISPR/Cas9-based strategy abolished stemness and angiogenesis in CRC. Oral administration of BODIPY-THIF attenuated colitis symptoms and tumor growth in the mouse model of AOM/DSS-induced CRC. CONCLUSIONS: This study demonstrates that STAT1 plays an oncogenic role in CRC. BODIPY-THIF is a new chemical probe inhibitor of STAT1 that reduces stemness and angiogenesis in CRC. BODIPY-THIF can be a potential tool for CRC therapy as well as cancer cell imaging.

Differential effect of herbal tea extracts on free fatty acids-, ethanol- and acetaminophen-induced hepatotoxicity in FL83B hepatocytes.

In recent years, herbal tea consumption becomes popular because of the potential health benefits and attractive flavors. However, there is also a growing concern that herbal supplements contribute to the drug-drug/drug-herb interactions and hepatotoxicity. In this study, FL83B mouse hepatocytes were used as an in vitro mode of hepatotoxicity induced by free fatty acids, including palmitic acid (PA) and oleic acid (OA), ethanol, and acetaminophen. Herbal tea extracts were obtained from eight common herbal plants, including Verbena officinalis L., Hyssopus officinalis L., Salvia officinalis L., Urtica dioica L., Hemerocallis fulva (L.) L., Citrus maxima (Burm.) Merr., Citrus limon (L.) Osbeck, and Ficus formosana Maxim. MTT assay was used to evaluate the impact of these herbal tea extracts on hepatoxocitity. We found that these herbal tea extracts per se did not exhibit hepatotoxicity, and had no effect on OA-induced hepatotoxicity. However, extracts from Verbena officinalis L., Hyssopus officinalis L., Salvia officinalis L., and Hemerocallis fulva (L.) L. exhibited protective effect against PA-induced hepatotoxicity. In addition, herbal tea extracts from Verbena officinalis L., Hyssopus officinalis L., Salvia officinalis L., Urtica dioica L., Hemerocallis fulva (L.) L., and Ficus formosana Maxim. exhibited protective effect against acetaminophen-induced hepatotoxicity. Interestingly, all these herbal tea extracts enhanced ethanol-induced hepatotoxicity. Our results suggest that herbal tea extracts have differential effects on different modes of hepatotoxicity.

The management of postoperative upper alimentary tract fistulas: A single-center experience of endoscopic tissue glue repair and recommendations of a systematic review.

BACKGROUND/PURPOSE: The appropriate management of postoperative upper alimentary tract fistula (UATF) remains uncertain. The efficacy of esophagogastroduodenoscopy (EGD) tissue glue repair in the treatment of patients with postoperative UATF was explored. We also conducted a systematic review of the literature regarding the inpatient management of UATF. METHODS: Totally 24 patients received EGD tissue glue repair for postoperative UATF at our institute from April 2014 to April 2020. Independent characteristics of size of fistula, location of the UATF, complications, and recurrences were analyzed. PubMed and Cochrane Library databases were reviewed. A pooled analysis was performed, and subgroup analysis was conducted separately for different anatomic locations and techniques. RESULTS: With a mean follow-up of 40 months, the fistula failed to close with EGD tissue glue repair in 2 of 24 patients (8.3%). Eight patients required repeated EGD tissue glue repair, which was more frequent in oral or thoracic UATF (p = 0.053), but all achieved a successful seal in the EGD tissue after glue repair alone (n = 22). The fistula size was correlated with the demand for repeated EGD tissue glue repair (p = 0.017). Besides, a total of 30 studies regarding 2356 cases of postoperative UATF between 2010 and 2021 were retrieved and analyzed. Several non-operative methods were generally accepted as the initial approach, with a non-inferior success rate compared to operative techniques. CONCLUSION: The results suggest that no single approach toward UATF is superior in terms of success rate and healing time. The potential advantages of EGD tissue glue repair after drainage were more suitable for patients with postoperative UATF and multiple comorbidities.

Comparison of perioperative outcomes between intubated and nonintubated thoracoscopic surgery in children.

BACKGROUND/PURPOSE: This study aimed to compare our experiences of nonintubated video-assisted thoracoscopic surgery (VATS) for pneumothorax and lung tumor resections with that of intubated VATS in pediatric patients. METHODS: In total, 17 nonintubated and 64 intubated pediatric VATS were performed between January 2012 and December 2018. Patient characteristics, operation period, comorbidities, precedent lung surgery, diagnosis, type of anesthesia, side and type of procedure, and perioperative outcomes were collected from medical records. Perioperative outcome data included induction time, operation time, postoperative chest tube drainage duration, and length of stay. Simple linear regression and multiple linear regression analyses were used to determine the influence of selected variables on perioperative outcomes. RESULTS: The mean age was 16.2 years in the intubated group and 15.2 years in the nonintubated group. Comorbidities including malignancy and asthma were noted in 9 intubated patients and 6 nonintubated patients. Nonintubated VATS was performed in 9 pneumothorax surgeries and 8 lung tumor resections. Five patients breathed oxygen through a face mask, 3 patients through a high-flow nasal cannula, and 9 patients through a laryngeal mask airway. No patient required tracheal intubation or thoracotomy. No major operative complications were noted in either group. After adjustments for statistically relevant confounders, the multiple regression analysis showed that the nonintubated technique influenced the length of stay, leading to a reduction of 0.75 days. CONCLUSION: Nonintubated VATS is feasible and safe in selected children undergoing bullectomy or wedge resections for lung tumors. The nonintubated approach might enhance postoperative recovery.

Magnolol inhibits cancer stemness and IL-6/Stat3 signaling in oral carcinomas.

BACKGROUND/PURPOSE: Cancer stem cells (CSCs) have been known to be implicated in tumorigenesis, metastasis, and drug resistance in oral squamous cell carcinomas (OSCC). In this study, we aimed to investigate whether magnolol, a polyphenolic component derived from Magnolia officinalis, exhibited the anti-CSCs properties. METHODS: The cytotoxicity of magnolol was tested using normal gingival epithelioid SG cells and sphere-forming OSCC-CSCs isolated from SAS, OECM1, and GNM cells. Secondary sphere-forming ability, the proportion of ALDH1 positive cells, Transwell migration, and invasion capacities were examined as well. The chemosensitive effects of magnolol were investigated using MTT, secondary sphere-forming, and invasion assays. RESULTS: Magnolol exerted a higher cytotoxicity of OSCC-CSCs and cancer stemness features, including self-renewal ability, the expression CSC marker, migration, and invasion capacities were all downregulated in magnolol-treated OSCC-CSCs. Moreover, administration of magnolol potentiated the effect of cisplatin, including a decrease in cell viability, self-renewal, and invasion activities. In addition, we observed that the secretion of IL-6 and phosphorylation of Stat3 were decreased in OSCC-CSCs treated with magnolol. CONCLUSION: Our data suggest that magnolol is able to target CSCs and suppress the cancer stemness properties, at least in part, via IL-6/Stat3 signaling. Besides, a dietary supplement of magnolol may function as an adjunct to cisplatin treatment.

Long Non-Coding RNA MIR31HG Promotes the Transforming Growth Factor ß-Induced Epithelial-Mesenchymal Transition in Pancreatic Ductal Adenocarcinoma Cells.

The epithelial-to-mesenchymal transition (EMT) describes a biological process in which polarized epithelial cells are converted into highly motile mesenchymal cells. It promotes cancer cell dissemination, allowing them to form distal metastases, and also involves drug resistance in metastatic cancers. Transforming growth factor ß (TGFß) is a multifunctional cytokine that plays essential roles in development and carcinogenesis. It is a major inducer of the EMT. The MIR31 host gene (MIR31HG) is a newly identified long non-coding (lnc)RNA that exhibits ambiguous roles in cancer. In this study, a cancer genomics analysis predicted that MIR31HG overexpression was positively correlated with poorer disease-free survival of pancreatic ductal adenocarcinoma (PDAC) patients, which was associated with upregulation of genes related to TGFß signaling and the EMT. In vitro evidence demonstrated that TGFß induced MIR31HG expression in PDAC cells, and knockdown of MIR31HG expression reversed TGFß-induced EMT phenotypes and cancer cell migration. Therefore, MIR31HG has an oncogenic role in PDAC by promoting the EMT.