Ascending colon cancer metastasized to the right testicle: a case report.

BACKGROUND: Testicular metastasis from malignant solid tumors is extremely rare. It is usually found by chance during autopsy or pathological examination of testicular specimens. Therefore, we consider it necessary to report our patient's case of testicular metastasis from colon cancer. CASE PRESENTATION: We report a 61-year-old Han Chinese male patient who presented to our clinic with progressive painless swelling of the right testicle for 2 years. Positron emission tomography-computed tomography scans showed increased 18F-fluorodeoxyglucose metabolism in the right testicle, possibly owing to distant metastasis. His previous medical history suggested that he had undergone laparoscopic-assisted right hemicolectomy for ascending colon cancer 4 years ago. Considering the ascending colon cancer metastasis to the right testicle, we performed a right radical testicular resection through an inguinal approach. Postoperative histological examination showed intestinal metastatic adenocarcinoma. CONCLUSION: Colon cancer metastasis to the testes is uncommon. The clinical and imaging manifestations of this tumor are nonspecific, so the diagnosis relies on postoperative pathology. If testicular metastasis is found, treatment principles for advanced colon cancer should be followed.

Identifying risk factors for hypoxemia during emergence from anesthesia in patients undergoing robot-assisted laparoscopic radical prostatectomy.

Robot-assisted laparoscopic radical prostatectomy (RALP) has emerged as an effective treatment for prostate cancer with obvious advantages. This study aims to identify risk factors related to hypoxemia during the emergence from anesthesia in patients undergoing RALP. A cohort of 316 patients undergoing RALP was divided into two groups: the hypoxemia group (N = 134) and the non-hypoxemia group (N = 182), based on their postoperative oxygen fraction. Comprehensive data were collected from the hospital information system, including preoperative baseline parameters, intraoperative data, and postoperative recovery profiles. Risk factors were examined using multiple logistic regression analysis. The study showed that 38.9% of patients had low preoperative partial pressure of oxygen (PaO2) levels. Several clinical parameters showed significant differences between the hypoxemia group and the non-hypoxemia group, including weight (P < 0.0001), BMI (P < 0.0001), diabetes mellitus (P = 0.044), history of emphysema and pulmonary alveoli (P < 0.0001), low preoperative PaO2 (P < 0.0001), preoperative white blood cell count (P = 0.012), preoperative albumin (P = 0.048), intraoperative bleeding (P = 0.043), intraoperative CO2 accumulation (P = 0.001), duration of surgery (P = 0.046), postoperative hemoglobin level (P = 0.002), postoperative hypoxemia (P = 0.002), and early postoperative fever (P = 0.006). Multiple logistic regression analysis revealed BMI (adjusted odds ratio = 0.696, 95% confidence interval 0.612-0.719), low preoperative PaO2 (adjusted odds ratio = 9.119, 95% confidence interval 4.834-17.203), and history of emphysema and pulmonary alveoli (adjusted odds ratio = 2.804, 95% confidence interval 1.432-5.491) as independent factors significantly associated with hypoxemia on emergence from anesthesia in patients undergoing RALP. Our results demonstrate that BMI, lower preoperative PaO2, and a history of emphysema and pulmonary alveolar disease are independent risk factors associated with hypoxemia on emergence from anesthesia in patients undergoing RALP. These findings provide a theoretical framework for surgeons and anesthesiologists to facilitate strategies to mitigate postoperative hypoxemia in this unique patient population.

circPVT1 Inhibits the Proliferation and Aids in Prediction of the Prognosis of Bladder Cancer.

Background: Circular RNA PVT1 (circPVT1) is aberrantly expressed in several cancers, but its functional role and clinical relevance in bladder urothelial carcinoma (BLCA) remain unknown. This study aimed to identify the expression level of circPVT1 in BLCA and investigated its functional relevance with BLCA progression both in vitro and in vivo. Methods: GEPIA, UALCAN, and OncoLnc were referred to presented data. Quantitative real-time PCR (qPCR) was used for the measurement of transnational expression of genes in BLCA specimens and cell lines. Immunohistochemistry (IHC) and fluorescence in situ hybridization analysis (FISH) assays were performed to detect HER2 amplification, Pearson's correlation analysis to analyze the correlation between circPVT1 expression and clinical characteristics, Cox regression and K-M survival analyses to analyze prognostic factors. A nomogram was constructed for predicting prognosis. The proliferation of cells was measured by CCK-8 and colony formation assay, and the proliferation in vivo was evaluated using nude mouse models. qPCR was used to detect the expression of proliferation-related genes. Results: circPVT1 was but mRNA PVT1 was not significantly overexpressed in BLCA. A high circPVT1 expression was associated with a better survival and negative HER2, but not with age, gender, and T stage. circPVT1 was an independent prognostic factor for the overall survival of BLCA patients. Knocking down circPVT1 promoted BLCA proliferation in vitro and in vivo. Knocking down circPVT1 upregulated ERBB2, MKI67, and PCNA expression and downregulated TP53 expression, but exerted no influence on CCND1 and CCNB1 expression. Conclusion: circPVT1 is a tumor suppressor and novel prognostic biomarker for BLCA.

ADSCs labeled with SPIONs tracked in corpus cavernosum of rat and miniature pig by MR imaging and histological examination.

Adipose tissue-derived stem cells (ADSCs) have been shown to improve erectile function in animal models of erectile dysfunction. However, few studies have been carried out using a reliable in vivo imaging method to trace transplanted cells in real time, which is necessary for systematic investigation of cell therapy. The study aims to explore the feasibility of non-invasively monitoring intracavernous injection of ADSCs in rat and miniature pig corpus cavernosum using in vivo magnetic resonance (MR) imaging. Thirty-six male Sprague Dawley rats (10 weeks old) and six healthy, sexually mature male miniature pigs (20 kg weight) were obtained. ADSCs were isolated from paratesticular fat of donor rats and cultured. Then ADSCs were labeled with superparamagnetic iron oxide nanoparticles (SPIONs), a type of MR imaging contrast agent, before transplantation into rats and pigs. After intracavernous injection, all rats and pigs underwent and were analyzed by MR imaging at the day of ADSC transplantation and follow-up at 1, 2 and 4 weeks after transplantation. In addition, penile histological examination was performed on all rats and pigs before (n = 6) and at 1 day (n = 6), 1 week (n = 6), 2 weeks (n = 6) or 4 weeks (n = 12) after ADSC transplantation. SPION-labeled ADSCs demonstrated a strong decreased signal intensity compared with distilled water, unlabeled ADSCs or agarose gel. SPION-labeled ADSCs showed a hypointense signal at all concentrations, and the greatest hypointense signal was observed at the concentration of 1 × 106. MR images of the corpus cavernosum showed a hypointense signal located at the injection site. T2*-weighted signal intensity increased over the course of 1 week after ADSCs transplantation, and demonstrated a similar MR signal with that before ADSCs transplantation. After SPION-labeled ADSC injection, T2*-weighted MR imaging clearly demonstrated a marked hypointense signal in pig corpus cavernosum. The T2*-weighted signal faded over time, similar to the MR imaging results in rats. Obvious acute inflammatory exudation was induced by intracavernous injection, and the T2*-weighted signal intensity of these exudation was higher than that of the injection site. The presence of iron was detected by Prussian blue staining, which demonstrated ADSC retention in rat corpus cavernosum. Lack of cellular infiltrations were demonstrated by H&E staining before and 4 weeks after transplantation, which indicated no negative immune response by rats. Prussian blue staining was positive for iron oxide nanoparticles at 2 weeks after transplantation. SPION-labeled ADSCs showed a clear hypointense signal on T2-weight MRI in vitro and in vivo. The MR signal intensity in the corpus cavernosum of the rats and miniature pigs faded and disappeared over time after ADSC transplantation. These findings suggested that MR imaging could trace transplanted ADSCs in the short term in the corpus cavernosum of animals.

Identification of biomarkers, pathways, and therapeutic targets for EGFR-TKI resistance in NSCLC.

This study aimed to map the hub genes and potential pathways that might be involved in the molecular pathogenesis of EGFR-TKI resistance in NSCLC. We performed bioinformatics analysis to identify differentially expressed genes, their function, gene interactions, and pathway analysis between EGFR-TKI-sensitive and EGFR-TKI-resistant patient-derived xenotransplantation samples based on Gene Expression Omnibus database. Survival analysis was performed via the GEPIA database (GEO). The relationship between the key gene ITGAM and the therapeutic candidates was retrieved from DGIdb. A total of 1,302 differentially expressed genes were identified based on GEO. The PPI network highlighted 10 potential hub genes. Only ITGAM was linked to poor DSF in NSCLC patients. A total of 10 drugs were predicted to be potential therapeutics for NSCLC with EGFR-TKI resistance. This study indicates the hub genes related to EGFR-TKI resistance in NSCLC through bioinformatics technologies which can improve the understanding of the mechanisms of EGFR-TKI resistance and provide novel insights into therapeutics.

Inhibition of the MLCK/MLC2 pathway protects against intestinal heat stroke-induced injury in rats.

Intestinal barrier dysfunction often exists in the heat stroke (HS) pathological process, which increases intestinal permeability and induces endotoxemia. The upregulation of MLCK is a crucial player affecting intestinal permeability. This study aimed to explore whether inhibiting myosin light chain kinase (MLCK) can improve HS-induced intestinal injury in rats. Twelve-week-old Wistar male rats were divided into three groups: the control group, the HS model group, and the treatment group [HS model + ML-7 (MLCK inhibitor)]. HS impaired the tight junctions in the rat gut and increased permeability. Additionally, increased inflammatory factors in serum, activation of apoptosis, and downregulation of tight junction proteins were observed in intestinal cells. ML-7 significantly inhibited the MLCK/p-MLC2 signaling pathway, increased the expression of tight junction proteins, reduced intestinal permeability, reduced apoptosis and alleviated the intestinal damage caused by HS. ML-7 inhibited HS-induced apoptosis of intestinal epithelial cells by regulating the ERK/p38/HSP70 axis. Furthermore, inhibition of MLCK upregulated HSP70 expression through activation of the ERK pathway and inhibited cell apoptosis by abolishing the p38 MAPK pathway. In conclusion, inhibiting the MLCK/p-MLC2 signaling pathway reduces HS-induced intestinal permeability and protects the intestinal mucosal barrier.

Variability of radiotherapy volume delineation: PSMA PET/MRI and MRI based clinical target volume and lymph node target volume for high-risk prostate cancer.

PURPOSE: A comparative retrospective study to assess the impact of PSMA Ligand PET/MRI ([68 Ga]-Ga-PSMA-11 and [18F]-F-PSMA-1007 PET/MRI) as a new method of target delineation compared to conventional imaging on whole-pelvis radiotherapy for high-risk prostate cancer (PCa). PATIENTS AND METHODS: Forty-nine patients with primary high-risk PCa completed the whole-pelvis radiotherapy plan based on PSMA PET/MRI and MRI. The primary endpoint compared the size and overlap of clinical target volume (CTV) and nodal gross tumour volume (GTVn) based on PSMA PET/MRI and MRI. The diagnostic performance of two methods for pelvic lymph node metastasis (PLNM) was evaluated. RESULTS: In the radiotherapy planning for high-risk PCa patients, there was a significant correlation between MRI-CTV and PET/MRI-CTV (P = 0.005), as well as between MRI-GTVn and PET/MRI-GTVn (P < 0.001). There are non-significant differences in the CTV and GTVn based on MRI and PET/MRI images (P = 0.660, P = 0.650, respectively). The conformity index (CI), lesion coverage factor (LCF) and Dice similarity coefficient (DSC) of CTVs were 0.999, 0.953 and 0.954. The CI, LCF and DSC of GTVns were 0.927, 0.284, and 0.32. Based on pathological lymph node analysis of 463 lymph nodes from 37 patients, the sensitivity, specificity of PET/MRI in the diagnosis of PLNM were 77.78% and 99.76%, respectively, which were higher than those of MRI (P = 0.011). Eight high-risk PCa patients who finished PSMA PET/MRI changed their N or M stage. CONCLUSION: The CTV delineated based on PET/MRI and MRI differ little. The GTVn delineated based on PET/MRI encompasses metastatic pelvic lymph nodes more accurately than MRI and avoids covering pelvic lymph nodes without metastasis. We emphasize the utility of PET/MRI fusion images in GTVn delineation in whole pelvic radiotherapy for PCa. The use of PSMA PET/MRI aids in the realization of more individual and precise radiotherapy for PCa.

Tumor-penetrating nanoplatform with ultrasound "unlocking" for cascade synergistic therapy and visual feedback under hypoxia.

BACKGROUND: Combined therapy based on the effects of cascade reactions of nanoplatforms to combat specific solid tumor microenvironments is considered a cancer treatment strategy with transformative clinical value. Unfortunately, an insufficient O2 supply and the lack of a visual indication hinder further applications of most nanoplatforms for solid tumor therapy. RESULTS: A visualizable nanoplatform of liposome nanoparticles loaded with GOD, H(Gd), and PFP and grafted with the peptide tLyP-1, named tLyP-1H(Gd)-GOD@PFP, was constructed. The double-domain peptide tLyP-1 was used to specifically target and penetrate the tumor cells; then, US imaging, starvation therapy and sonodynamic therapy (SDT) were then achieved by the ultrasound (US)-activated cavitation effect under the guidance of MR/PA imaging. GOD not only deprived the glucose for starvation therapy but also produced H2O2, which in coordination with 1O2 produced by H(Gd), enable the effects of SDT to achieve a synergistic therapeutic effect. Moreover, the synergistic therapy was enhanced by O2 from PFP and low-intensity focused ultrasound (LIFU)-accelerated redox effects of the GOD. The present study demonstrated that the nanoplatform could generate a 3.3-fold increase in ROS, produce a 1.5-fold increase in the maximum rate of redox reactions and a 2.3-fold increase in the O2 supply in vitro, and achieve significant tumor inhibition in vivo. CONCLUSION: We present a visualizable nanoplatform with tumor-penetrating ability that can be unlocked by US to overcome the current treatment problems by improving the controllability of the O2 supply, which ultimately synergistically enhanced cascade therapy.

Nanoenabled Tumor Energy Metabolism Disorder via Sonodynamic Therapy for Multidrug Resistance Reversal and Metastasis Inhibition.

Cancer multidrug resistance (MDR) is an important reason that results in chemotherapy failure. As a main mechanism of MDR, overexpressed P-glycoprotein (P-gp) utilizes adenosine triphosphate (ATP) to actively pump chemotherapy drugs out of cells. In addition, metabolic reprogramming of drug-resistant tumor cells (DRTCs) exacerbates the specific hypoxic microenvironment and promotes tumor metastasis and recurrence. Therefore, we propose a novel sonodynamic therapy (SDT) paradigm to induce energy metabolism disorder and drug resistance change of DRTCs. A US-controlled "Nanoenabled Energy Metabolism Jammer" (TL@HPN) is designed using perfluoropentane (PFP) adsorbing oxygen in the core, and a targeting peptide (CGNKRTR) is attached to the liposome as the delivery carrier shell to incorporate hematoporphyrin monomethyl ether (HMME) and paclitaxel (PTX). The TL@HPN with ultrasonic/photoacoustic imaging (PAI/USI) precisely controlled the release of drugs and oxygen after being triggered by ultrasound (US), which attenuated the hypoxic microenvironment. SDT boosted the reactive oxygen species (ROS) content in tumor tissues, preferentially inducing mitochondrial apoptosis and maximizing immunogenic cell death (ICD). Persistently elevated oxidative stress levels inhibited ATP production and downregulated P-gp expression by disrupting the redox balance and electron transfer of the respiratory chain. We varied the effect of TL@HPN combined with PD-1/PD-L1 to activate autoimmunity and inhibit tumor metastasis, providing a practical strategy for expanding the use of SDT-mediated tumor energy metabolism.

Baicalin improves the energy levels in the prefrontal cortex of mice exposed to chronic unpredictable mild stress.

Depression is gradually becoming a primary mental disease threatening human health. Therefore, there is an urgent need to clarify the pathogenesis of depression and identify new effective natural antidepressants. This study aimed to investigate the antidepressant effects of baicalin and explore its potential mechanism in a mouse model of depression induced by chronic unpredictable mild stress (CUMS). Following a 6-week exposure to CUMS, mice were treated with baicalin (10 mg/kg) or fluoxetine (10 mg/kg) for 4 weeks by oral gavage. A sucrose preference test and a forced swimming test were performed to evaluate depression-like behaviors, and the levels of adenosine triphosphate (ATP) in the prefrontal cortex were measured. Moreover, gene expression and enzyme activities related to ATP production, and mitochondrial function, were monitored. The results indicated that baicalin and fluoxetine could alleviate CUMS-induced depression-like behaviors of mice. In addition, baicalin significantly elevated the ATP content and the expression of genes hexokinase 1 (Hk1), pyruvate dehydrogenase E1 alpha 1 (Pdha-1), isocitrate dehydrogenase (Idh), peroxisome proliferator-activated receptor, gamma, coactivator 1 alpha (Pgc-1α), and sirtuin-1 (Sirt1) in the prefrontal cortex. Furthermore, baicalin increased the activity of the respiratory chain complexes I and V as well as the mitochondrial membrane potential. In conclusion, baicalin may exert its antidepressant effect partly by upregulating the expression of some genes coding for enzymes involved in the glycolysis and the tricarboxylic acid cycle, and improving the mitochondrial function to enhance the ATP level in the brain.

Femoral artery variation was found during V-A ECMO catheterization.

BACKGROUND: High bifurcation of the deep femoral artery (DFA) is rare in clinical practice, and patients with this variation are less likely to receive venoarterial extracorporeal membrane oxygenation (V-A ECMO) treatment. Therefore, the method by which V-A ECMO is introduced in patients with vascular variation is very important. CASE PRESENTATION: A 52-year-old male patient had ST elevation myocardial infarction due to coronary heart disease. Angiography showed tripartite coronary artery lesions, and coronary artery stenting supported by V-A ECMO was needed. Vascular evaluation before ECMO catheterization revealed high bifurcation of the bilateral DFA located at the inguinal ligament. After discussion, the perfusion cannula was placed in the left superficial femoral artery (SFA) towards the heart, and the distal perfusion catheter (DPC) was placed in the left SFA towards the distal end. Nevertheless, after the patient's heart recovered, necrosis of the toe of the left lower limb still occurred. CONCLUSION: Common femoral artery assessment must be performed before V-A ECMO for patients with high bifurcation of the DFA. Incision catheterization and DPC placement are recommended. After decannulation, arterial repair under direct visualisation is recommended, and rigorous distal vascular assessment and management are needed.

Pre-Procedural Anxiety and Associated Factors Among Women Seeking for Cervical Cancer Screening Services in Shenzhen, China: Does Past Screening Experience Matter?

Background: Research gaps exist in addressing the psychological harm related to the cervical cancer screening. Anxiety is the most common distress driven by the screening procedures, which may be affected by past screening experience (PSE) but with uncertainty. This study aimed to evaluate the pre-procedural anxiety in cervical cancer screening and to identify the influence attributed to PSE. Methods: A cross-sectional survey targeted women seeking for cervical cancer screening services was conducted from June 5th to December 31st, 2020 in Shenzhen. The 20-item state anxiety scale of the State-Trait Anxiety Inventory (STAI-S) was applied to measure pre-procedural anxiety, in which a score of 40 or higher was regarded with anxiety symptom. Logistic regression models were established to explore potential associated factors of pre-procedural anxiety both for women with and without PSE. Results: Overall, 3,651 women were enrolled, in which 36.1% had never been screened and the remaining 63.9% had been screened at least once before. Women without PSE demonstrated more prevalent pre-procedural anxiety (74.5% vs. 67.8%, P <0.001) than their experienced counterparts. Among women without PSE, having heard of cervical cancer screening was associated with a lower likelihood of pre-procedural anxiety (OR: 0.37, 95%CI: 0.25~0.56). Among experienced women, participating three or more times screening was negatively associated with anxiety symptom (OR: 0.67, 95%CI: 0.53~0.84), however, both receiving screening within three years (OR: 1.58, 95%CI: 1.27~1.97) and unknowing previous screening results (OR: 1.42, 95%CI: 1.11~1.82) increased the susceptibility of pre-procedural anxiety. Conclusions: Women participating in cervical cancer screening commonly present pre-procedural anxiety. The association between PSE and pre-procedural anxiety may be influenced by past screening times, interval, and results. Psychological counseling according to women's PSE before cervical cancer screening is warranted of necessity.

Gross tumor volume delineation in primary prostate cancer on 18F-PSMA-1007 PET/MRI and 68Ga-PSMA-11 PET/MRI.

BACKGROUND: We aimed to assess the clinical value of 18F-PSMA-1007 and 68Ga-PSMA-11 PET/MRI in the gross tumor volume (GTV) delineation of radiotherapy for prostate cancer (PCa). METHODS: Sixty-nine patients were retrospectively enrolled (57 in the 18F subgroup and 12 in the 68Ga subgroup). Three physicians delineated the GTV and tumor length by the visual method and threshold method with thresholds of 30%, 40%, 50%, and 60% SUVmax. The volume correlation and differences in GTVs were assessed. The dice similarity coefficient (DSC) was applied to estimate the spatial overlap between GTVs. For 51 patients undergoing radical prostatectomy, the tumor length (Lpath) of the maximum area was measured, and compared with the longest tumor length obtained based on the images (LMRI, LPET/MRI, LPET, LPET30%, LPET40%, LPET50%, LPET60%) to determine the best delineation method. RESULTS: In the 18F subgroup, (1) GTV-PET/MRI (p < 0.001) was significantly different from the reference GTV-MRI. DSC between them was > 0.7. (2) GTV-MRI (R2 = 0.462, p < 0.05) was the influencing factor of DSC. In the 68Ga subgroup, (1) GTV-PET/MRI (p < 0.05) was significantly different from the reference GTV-MRI. DSC between them was > 0.7. (2) There was a significant correlation between GTV-MRI (r = 0.580, p < 0.05) and DSC. The longest tumor length measured by PET/MRI was in good agreement with that measured by histopathological analysis in both subgroups. CONCLUSION: It is feasible to visually delineate GTV on PSMA PET/MRI in PCa radiotherapy, and we emphasize the utility of PET/MRI fusion images in GTV delineation. In addition, the overlap degree was the highest between GTV-MRI and GTV-PET/MRI, and it increased with increasing volume.

Comparison of postoperative cough-related quality of life and recovery between sublobectomy and lobectomy for early-stage non-small cell lung cancer patients: a longitudinal study.

BACKGROUND: Cough is a common complication after pulmonary surgery. Previous studies lacked a standard measure to assess postoperative cough-related quality of life and recovery. The purpose of this study is to compare postoperative cough regarding changes in health-related quality of life (HRQOL) and recovery trajectory between video-assisted thoracic surgery (VATS) lobectomy and sublobectomy (segmentectomy or wedge resection) for early-stage non-small cell lung cancer (NSCLC) patients via the Leicester Cough Questionnaire in Mandarin Chinese (LCQ-MC). METHODS: Overall, 156 patients with NSCLC underwent either VATS lobectomy or VATS sublobectomy; LCQ-MC was used to report the impact of postoperative cough on HRQOL for 6 months after surgery. The total scores of LCQ-MC range from 3 to 21, with a higher score indicating better health. Recovery from postoperative cough was defined as LCQ-MC scores returning to preoperative levels. The sensitivity of LCQ-MC to changes in postoperative cough recovery over time was evaluated via its ability to distinguish between surgery types. RESULTS: The VATS sublobectomy group reported significantly higher mean LCQ-MC scores at 1 month after surgery, but no significant difference postoperatively at 3 and 6 months after surgery, and returned to preoperative physical (69 vs. 99 days), psychological (67 vs. 99 days), social (50 vs. 98 days) and total (69 vs. 99 days) scores faster than the VATS lobectomy group (all p < 0.05). CONCLUSION: VATS sublobectomy had generally better HRQOL and faster recovery of postoperative cough than VATS lobectomy. In addition, the LCQ-MC performed satisfactorily in describing the longitudinal changes in postoperative cough.

Validation of the simplified cough symptom score in non-small cell lung cancer patients after surgery.

BACKGROUND: The simplified Cough Symptom Score (sCSS) is a practical and simple tool for measuring cough severity. However, the sCSS is a consensus of experts, and has not been strictly validated among the non-small cell lung cancer (NSCLC) patients. We used the sCSS and investigated the validity, reliability, and repeatability of this instrument. METHODS: A total of 219 NSCLC patients completed the sCSS, Leicester Cough Questionnaire in Mandarin-Chinese (LCQ-MC) and cough Visual Analog Scale (VAS). 60 patients completed the LCQ and Global Rating of Change (GRC) at follow-up visits after 2-4 weeks. Concurrent validity, internal consistency, and repeatability were assessed. RESULTS: Analyses of concurrent validity showed significant correlations between the sCSS and the LCQ-MC (r = - 0.356 to - 0.580) and cough VAS (r = 0.555). The correlation of the nighttime score with the LCQ-MC and cough VAS was more closely than that of the daytime score (r = - 0.364 to - 0.545 and r = 0.502 vs. r = - 0.233 to - 0.449 and r = 0.450). Internal consistency was acceptable (Cronbach's α of 0.74-0.90). The internal consistency of the sCSS between the nighttime and daytime scores was 0.428. The repeatability was high (intraclass correlation coefficients of 0.760). CONCLUSION: The sCSS is a reliable, valid instrument for assessing postoperative cough in NSCLC patients.

Early versus Delayed Minimally Invasive Intervention for Acute Necrotizing Pancreatitis: An Updated Systematic Review and Meta-Analysis.

BACKGROUND: Nowadays, minimally invasive intervention (MII) has largely replaced delayed open surgery in acute necrotizing pancreatitis (ANP). However, the timing of MII remains unclear. The present study investigated the effect of early versus delayed MII on complications in ANP. METHODS: Studies evaluating the impact of the timing of MII on complications in ANP patients were thoroughly searched on PubMed, Embase, Cochrane Library, and Web of Science from inception to June 2022. The primary outcome of interest was mortality. Secondary outcomes were the incidence of complications. RESULTS: Nine studies reporting 870 patients undergoing MII for ANP were included. No significant difference was found in mortality between the early and delayed intervention groups. In addition, the timing of MII was not associated with the incidence of new-onset respiratory failure, new-onset cardiovascular failure, new-onset renal failure, new-onset multiple organ failure, gastrointestinal fistula or perforation, pancreatic fistula, stent migration, bleeding, venous thrombosis, and new-onset pancreatic endocrine insufficiency. Notably, in the subgroup analysis of biliary and Asian ANP patients, early intervention was associated with a significantly higher risk of new-onset renal failure than delayed intervention. CONCLUSIONS: Early intervention is safe and recommended only for patients with indications for intervention, such as infection.

Dexmedetomidine alleviates hepatic ischaemia-reperfusion injury via the PI3K/AKT/Nrf2-NLRP3 pathway.

Hepatic ischaemia-reperfusion (I/R) injury constitutes a tough difficulty in liver surgery. Dexmedetomidine (Dex) plays a protective role in I/R injury. This study investigated protective mechanism of Dex in hepatic I/R injury. The human hepatocyte line L02 received hypoxia/reoxygenation (H/R) treatment to stimulate cell model of hepatic I/R. The levels of pyroptosis proteins and inflammatory factors were detected. Functional rescue experiments were performed to confirm the effects of miR-494 and JUND on hepatic I/R injury. The levels of JUND, PI3K/p-PI3K, AKT/p-AKT, Nrf2, and NLRP3 activation were detected. The rat model of hepatic I/R injury was established to confirm the effect of Dex in vivo. Dex reduced pyroptosis and inflammation in H/R cells. Dex increased miR-494 expression, and miR-494 targeted JUND. miR-494 inhibition or JUND upregulation reversed the protective effect of Dex. Dex repressed NLRP3 inflammasome by activating the PI3K/AKT/Nrf2 pathway. In vivo experiments confirmed the protective effect of Dex on hepatic I/R injury. Overall, Dex repressed NLRP3 inflammasome and alleviated hepatic I/R injury via the miR-494/JUND/PI3K/AKT/Nrf2 axis.

Tandem mass tag-based quantitative proteomic analysis of the liver reveals potential protein targets of Xiaochaihutang in CUMS model of depression.

Depression is a global mental disorder disease and greatly threatened human health. Xiaochaihutang (XCHT) has been used successfully in treatment of depression for many years in China, but the mechanism is unclear. Using the chronic unpredictable mild stress (CUMS) mice model of depression, the present study aimed to reveal possible antidepressant mechanisms of XCHT from the perspective of liver by analyzing hepatic proteomics in mice. Bioinformatics analysis identified 31 differentially expressed proteins (DEPs), including 5 upregulated and 26 downregulated proteins, between the CUMS model and XCHT groups. The bile secretion pathway was found by KEGG pathway analysis of these DEPs. Four of the 31 differentially expressed proteins, including 2 active proteins involved in bile secretion, carbonic anhydrase 2 (CA2) and cystic fibrosis transmembrane conductance regulator (CFTR), were selected to verify their genes. Four genes (Cyp7a1, Fxr, Shp and Ntcp) related to bile acid synthesis and transport were further investigated by quantitative real-time polymerase chain reaction (qRT-PCR). Both biochemical tests and gene studies demonstrated that CUMS affected bile acid synthesis and transport, while XCHT regulated this pathway. The results indicated that there may be a potential relationship between CUMS induced depression and hepatic injury caused by increased bile acid, and also provide a novel insight to understand the underlying anti-depression mechanisms of XCHT.

Effects of resveratrol on the levels of ATP, 5-HT and GAP-43 in the hippocampus of mice exposed to chronic unpredictable mild stress.

Growing evidence suggested that energy deficiency might be involved in the pathophysiological mechanism of depression. Energy deficiency, mainly results from mitochondrial damage, can lead to the dysfunction of synaptic neurotransmission, and further cause depressive-like behavior. The antidepressant effect of resveratrol had been widely demonstrated in previous studies; however, the underlying mechanism remains poorly understood. The present study aimed to investigate whether the antidepressant effects of resveratrol involved in the energy levels and neurotransmission in the hippocampus. We found that resveratrol and fluoxetine significantly attenuated depressive-like behaviors induced by chronic unpredictable mild stress (CUMS), which evidenced by the increased sucrose preference and the reduced immobility time in a forced swimming test. In addition, resveratrol increased hippocampal ATP levels, decreased Na+-K+-ATPase and pyruvate levels, and upregulated the levels of mitochondrial DNA (mtDNA), mRNA expression of sirtuin (SIRT)1 and peroxisome proliferator-activated receptor γ coactivator (PGC)1α. Furthermore, resveratrol and fluoxetine increased serotonin (5-HT) levels and downregulated the mRNA expression of 5-HT transporter (SERT) in the hippocampus. The decreased protein expression of growth-associated protein (GAP)-43 induced by CUMS was also ameliorated by resveratrol and fluoxetine. These findings demonstrated the antidepressant effects of resveratrol and suggested that resveratrol was able to promote mitochondrial biogenesis, enhance ATP and 5-HT levels, as well as upregulate GAP-43 expression in the hippocampus.

Transcriptomic analysis reveals the mechanism of sulfasalazine-induced liver injury in mice.

Liver injury is one of the main toxic effect of sulfasalazine (SASP). However, the toxicological mechanism of SASP-induced liver injury remains unclear. In the present study, the liver injury was induced by orally treatment with SASP for 4 weeks in mice. The hepatic mRNA profiles were detected by RNA sequencing and the differentially expressed genes (DEGs) were analyzed by bioinformatics methods. The elevated serum levels of alanine aminotransferase (ALT), alkaline phosphatase (ALP) and total bilirubin (TBIL), combined with the hepatic histopathological features verified that liver injury was successfully caused by SASP. Transcriptomic results showed that 187 genes (fold change > 1.5 and P < 0.05) were differentially expressed, of which 106 genes were up-regulated and 81 genes were down-regulated in SASP-treated group. Moreover, the further analysis showed that these 187 differentially expressed genes (DEGs) were enriched in 123 GO terms, which mainly including oxidation-reduction process, oxidoreductase activity and epoxygenase P450 pathway. KEGG pathway analysis showed 30 pathways including chemical carcinogenesis, retinol metabolism, arachidonic acid metabolism, linoleic acid metabolism and glutathione metabolism. Among these 187 DEGs, the top 22 hub genes were screened from network of protein-protein interaction (PPI) and verified by qRT-PCR. The results showed that the mRNA levels of hepatic drug-metabolizing enzymes, including cyp2b50, cyp2c50, cyp2c39, cyp2c38, cyp2c29, cyp2c54, cyp2c55, cyp2a5, gsta1, gsta2, gstt2, gstm2 and ephx1, were significantly up-regulated, while egfr and egr1 were down-regulated in SASP-treated group. Moreover, the mRNA levels of egfr and cyp2c55 exhibited a dose-dependent changes in SASP groups. Western blotting verified that the changes of protein levels of EGFR and CYP2C55 were consistent with mRNA levels. Considering that egfr has the highest score in PPI degree and cyp2c55 has the largest fold change in qPCR analysis, our present results suggested that the toxicological mechanisms of SASP-induced liver injury might be related to multi-biological processes and pathways, and egfr and cyp2c55 may play important roles in SASP-induced liver injury. The present study would be helpful for better understanding the hepatotoxic mechanism of SASP. However, the precise mechanism still needs further research.