The Effect of Dexmedetomidine as a Local Anesthetic Adjuvant for Iliac Fascia Compartment Block on Postoperative Delirium in Elderly Patients Undergoing Elective Hip Surgery.

INTRODUCTION: We analyzed the effect of dexmedetomidine (DEX) as a local anesthetic adjuvant on postoperative delirium (POD) in elderly patients undergoing elective hip surgery. METHODS: In this study, 120 patients undergoing hip surgery were enrolled and randomly assigned to two groups: fascia iliaca compartment block with DEX + ropivacaine (the Y group, n = 60) and fascia iliaca compartment block with ropivacaine (the R group, n = 60). The primary outcomes: presence of delirium during the postanesthesia care unit (PACU) period and on the first day (D1), the second day (D2), and the third day (D3) after surgery. The secondary outcomes: preoperative and postoperative C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), occurrence of insomnia on the preoperative day, day of operation, D1 and D2; HR values of patients in both groups before iliac fascia block (T1), 30 min after iliac fascia block (T2), at surgical incision (T3), 20 min after incision (T4), when they were transferred out of the operating room (T5) and after leaving the recovery room (T6) at each time point; VAS for T1, PACU, D1, D2; the number of patients requiring remedial analgesics within 24 h after blockade and related complications between the two groups. RESULTS: A total of 97 patients were included in the final analysis, with 11 and 12 patients withdrawing from the R and Y groups, respectively. The overall incidence of POD and its incidence in the PACU and ward were all lesser in the Y group than in the R group (p < 0.05). Additionally, fewer cases required remedial analgesia during the PACU period, and more vasoactive drugs were used for maintaining circulatory system stability in the Y group as compared to the R group (p < 0.05). At the same time, the incidence of intraoperative and postoperative bradycardia in the Y group was higher than that in the R group, accompanied by lower postoperative CRP and ESR (all p < 0.05). CONCLUSION: Ultrasound-guided high fascia iliaca compartment block with a combination of ropivacaine and DEX can reduce the incidence of POD, the use of intraoperative opioids and postoperative remedial analgesics, and postoperative inflammation in elderly patients who have undergone hip surgery, indicating that this method could be beneficial in the prevention and treatment of POD.

Risk factors associated with postoperative delirium in elderly patients undergoing hip surgery.

Objective: We retrospectively analyzed the occurrence of postoperative delirium following hip surgery and the associated risk factors. The aim was to establish a clinical foundation for preventing postoperative delirium after hip surgery. Methods: We retrospectively selected elderly patients who had hip surgery at our hospital between January 2022 and August 2022. We included patients who experienced delirium in the observation group and those who did not encounter delirium in the control group. We then proceeded to compare various indicators among these two groups of patients. Results: We analyzed a total of 97 cases of hip surgery, and among them, 32 cases experienced postoperative delirium, resulting in an incidence rate of 32.9%. Various factors were found to be linked to the development of postoperative delirium, including age, height, gender (male), preoperative erythrocyte sedimentation rate (ESR), postoperative ESR, preoperative lactate levels, pain scores on the first day after surgery, type of surgical procedure, and the occurrence of delirium in the post-anesthesia care unit (PACU delirium). Additionally, it was observed that 75% of patients who had PACU delirium also experienced postoperative delirium. Conclusion: Postoperative delirium in patients who have hip surgery had an incidence rate of 32.9%. This phenomenon is linked to various factors that pose a risk, such as the patient age, height, gender, preoperative ESR levels, postoperative ESR levels, preoperative lactate levels, pain scores on the day following surgery, and the specific surgical procedure performed. The likelihood of experiencing delirium increases by 12% for every additional 10 years in patient age. Additionally, the occurrence of delirium in the PACU is a strong indicator of the likelihood of experiencing postoperative delirium.

Nephroprotective Effects of Cardamonin on Renal Ischemia Reperfusion Injury/UUO-Induced Renal Fibrosis.

Acute kidney injury and chronic renal fibrosis are intractable pathological processes to resolve, yet limited strategies are able to effectively address them. Cardamonin (CAD) is a flavonoid with talented antioxidant, anti-inflammatory capacity, and satisfactory biosafety. In our study, animal and cellular models of renal ischemia/reperfusion (I/R) and unilateral ureteral obstruction (UUO) were successfully constructed to confirm whether CAD confers protective effects and underlying mechanisms. Animal experiments demonstrated that CAD application (100 mg/kg) distinctly ameliorated tissue damage and improved renal function. Meanwhile, the continuous oral administration of CAD after UUO surgery efficiently inhibited renal fibrosis as confirmed by hematoxylin-eosin (H&E), Sirius red, and Masson staining as well as the downregulated mRNA and protein expression of collagen I, α-smooth muscle actin (α-SMA), collagen III, and fibronectin. Interestingly, in transforming growth factor ß1 (TGF-ß1)-stimulated and hypoxia/reoxygenation (H/R)-exposed human kidney-2 (HK-2) cells, protective effects of CAD were again authenticated. Meanwhile, we performed bioinformatics analysis and constructed the "ingredient-target-pathway-disease" network to conclude that the potential mechanisms of CAD protection may be through the regulation of oxidative stress, inflammation, apoptosis, and mitogen-activated protein kinase (MAPK) pathway. Furthermore, experimental data validated that CAD evidently decreased the reactive oxygen species (ROS) production and malondialdehyde (MDA) content while depressing the mRNA and protein expression of inflammatory markers (tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and Il-1ß) and inhibiting apoptosis as evidenced by decreased levels of P53, BAX, cleaved caspase-3, and apoptotic rate in renal I/R and UUO models. In addition, the impact of CAD on restraining oxidative stress and inflammation was attributed to its ability to elevate antioxidant enzyme activities including catalase, superoxide dismutase 1 (SOD1), and superoxide dismutase 2 (SOD2) and to inhibit the inflammation-associated MARK/nuclear factor-κB (MAPK/NF-κB) signaling pathway. In conclusion, cardamonin restored the antioxidative capacity to block oxidative stress and suppressed the MAPK/NF-κB signaling pathway to alleviate inflammatory response, thus mitigating I/R-generated acute kidney injury/UUO-induced renal fibrosis in vivo and in vitro, which indicated the potential therapeutic advantage of cardamonin in attenuating acute and chronic kidney injuries.

Does the periportal end of a double-lumen endobronchial tube need to be fixed to prevent dislocation of the cuffed end caused by a change in position? A randomized controlled trial.

OBJECTIVE: This study aimed to evaluate the effects on the dislocation and misalignment of the cuffed end of a double-lumen endobronchial tube (DLT) when a patient moves from a horizontal to a lateral position without fixation. METHODS: A total of 148 patients who had undergone video-assisted thoracoscope surgery were enrolled and randomly divided into two groups: a group in which the periportal end of the DLT was fixed with tape (group I; n = 74) and a group in which the periportal end of the DLT remained unfixed (group II; n = 74). Both groups were given an intravenous induction for double-lumen endobronchial intubation and then moved from a horizontal position to a lateral position, after which the alignment of the bronchial cuffed end of the DLT was assessed using a fiberoptic bronchoscope. RESULTS: After lateral position, the dislocation rate of group I and group II was 44.6% and 20.2%, and the misalignment rate was 27.0% and 8.1%, respectively, the incidence of dislocation and misalignment was significantly lower in group II than in group I after the change to a lateral position (p < 0.05). After lateral position, the total rate of airway injury was 25.7% in group I and 5.4% in group II, the incidence of airway injury was significantly lower in group II than in group I (p < 0.05), as was the incidence of sore throat, hoarseness, and cough on postoperative day 1 (p < 0.05). The average outward dislocation of the periportal end of the DLT in group II was 1.5 cm. CONCLUSION: A DLT without periportal fixation is less likely to be displaced and poorly aligned when the patient moves from a horizontal to a lateral position, which could facilitate intra-operative management and reduce the incidence of postoperative complications.

Through a randomized controlled trial, this study innovatively found that no double-lumen endobronchial tube (DLT) peripheral tape binding can prevent the dislocation and misalignment of the DLT bronchial cuffed end in patients undergoing thoracic surgery from horizontal to lateral position.

Effect of individualized PEEP titration by ultrasonography on perioperative pulmonary protection and postoperative cognitive function in patients with chronic obstructive pulmonary disease.

OBJECTIVE: To evaluate the effect of the individualized positive end-expiratory pressure (PEEP) lung protection ventilation strategy by combining driving pressure (ΔP) and pulmonary ultrasound (LUS)-based titration on lung function and postoperative cognitive function in patients with chronic obstructive pulmonary disease (COPD) during laparoscopic surgery. METHODS: A total of 108 patients with COPD undergoing laparoscopic gastrointestinal surgery under general anesthesia were included in this study. They were randomly divided into three groups (n = 36): traditional volume ventilation group (Group C), fixed PEEP 5 cmH2O group (Group P), and ΔP combined with LUS-based PEEP titration in the resuscitation room group (Group T). All three groups were given volume ventilation mode, I:E = 1:2; In group C, VT was 10 mL/kg and PEEP was 0 cmH2O; In groups P and T, VT was 6 mL/kg and PEEP was 5 cmH2O; After mechanical ventilation for 15 min in Group T, ΔP in combination with LUS was used to titrate PEEP. The oxygenation index (PaO2/FiO2), airway platform pressure (Pplat), dynamic lung compliance (Cdyn), Montreal Cognitive Assessment (MoCA), and venous interleukin-6(IL-6) were recorded at the corresponding time points, and the final PEEP value in Group T was recorded. RESULTS: The final PEEP value of Group T was (6.4 ± 1.2) cmH2O; Compared with groups C and P: PaO2/FiO2 and Cdyn in Group T were significantly increased (P < 0.05) and value of IL-6 was significantly decreased (P < 0.05) at the corresponding time points. Compared with group C, the MoCA score on day 7 after surgery in Group T was significantly higher (P < 0.05). CONCLUSION: Compared with the traditional ventilation strategy, the individualized ΔP combined with LUS-based PEEP titration in patients with COPD during the perioperative period of laparoscopic surgery can play a better role in lung protection and can improve postoperative cognitive function.

[Retracted] Effects of cisplatin on the LSD1-mediated invasion and metastasis of prostate cancer cells.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that the cell invasion assay data shown for the 'LSD1siRNA+DDP' experiment in Fig. 3A on p. 2515 were strikingly similar to data appearing in different form in Fig. 3 in another article written by different authors at different research institutes [Liu Y, Li M, Zhang G and Pang Z: MicroRNA-10b overexpression promotes non-small cell lung cancer cell proliferation and invasion. Eur J Med Res 18: 41, 2013]. Owing to the fact that the contentious data in the above article had already been published prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they accepted the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 14: 2511-2517, 2016; DOI: 10.3892/mmr.2016.5571].

Taselisib moderates neuropathic pain through PI3K/AKT signaling pathway in a rat model of chronic constriction injury.

BACKGROUND: Neuropathic pain is a chronic condition commonly caused by inflammation-induced disturbances or lesions of somatosensory functions in the nervous system. The aim of this study was to investigate the effects and mechanisms of Taselisib on chronic constriction injury (CCI)-induced neuropathic pain in rats. METHODS: The rats were divided into four groups: sham group, sham + Taselisib (10 mg/kg orally once a day) group, CCI group, and CCI + Taselisib (10 mg/kg orally once a day) group. Pain behavioral tests, recorded by measuring paw withdrawal threshold (PWT) and thermal withdrawal latency (TWL), were conducted on days 0, 3, 7, 14, and 21 after surgery. After testing, the animals were euthanized and spinal dorsal horns were collected. Pro-inflammatory cytokines were quantified using ELISA and qRT-PCR. PI3K/pAKT signaling was assessed using Western blot and immunofluorescence. RESULTS: PWT and TWL were significantly reduced after CCI surgery, but were successfully increased by Taselisib treatment. Taselisib treatment notably suppressed the upregulation of pro-inflammatory cytokines, including IL-6, IL-1ß, and TNF-⍺. Taselisib treatment significantly reduced the elevated phosphorylation of AKT and PI3K induced by CCI. CONCLUSION: Taselisib can alleviate neuropathic pain by inhibiting the pro-inflammatory response, potentially through the PI3K/AKT signaling pathway.

miR-3682-3p Activated by c-Myc Aggravates the Migration and Stemness in Hepatocellular Carcinoma Cells by Regulating PTEN/PI3K/AKT/ß-Catenin Signaling.

BACKGROUND: Hepatocellular carcinoma (HCC) is a leading cancer worldwide. miRNA has been linked to cancer processes. We want to figure out what the underlying mechanism and functions of miR-3682-3p are in HCC. METHODS: Thirty pairs of tumor tissues and adjacent tissues were obtained from HCC patients. mRNA and protein expressions were detected by quantitative real-time PCR and Western blot, respectively. The migration and invasion were measured using transwell or wound-healing assays. Dual luciferase and ChIP assays were utilized to detect gene interactions. RESULTS: miR-3682-3p was highly expressed in HCC tissues and cell lines. Silencing of miR-3682-3p inhibited cell migration and invasion, increased E-cadherin expression, and decreased N-cadherin, vimentin, and snail expressions, as well as the SOX2, OCT4, and Bmi1 expression, thereby restraining EMT and stemness of HCC in vitro. miR-3682-3p was positively activated by c-Myc and could directly target PTEN to activate PI3K/AKT/ß-catenin pathway. In addition, inhibition of PTEN weakened the anti-migration and anti-stemness effects of miR-3682-3p downregulation in HCC cells. CONCLUSION: miR-3682-3p promoted HCC migration and stemness through PTEN/PI3K/AKT/ß-catenin signaling, implying that miR-3682-3p might be a promising target for HCC clinical treatment.

STEAP3 Affects Ferroptosis and Progression of Renal Cell Carcinoma Through the p53/xCT Pathway.

Renal cell carcinoma is particularly sensitive to ferroptosis, an iron-dependent non-apoptotic form of cell death. This mechanism does not require activation of caspase or the participation of other apoptotic effector molecules (such as BAX or BAK), nor is it accompanied by the morphological characteristics or biochemical processes of apoptosis. The STEAP3 gene was found because it promotes tumor apoptosis in prostate cancer, but its role in renal cell carcinoma has not been studied in depth. Through real-time quantitative polymerase chain reaction, we found that the expression of the STEAP3 gene was upregulated in renal cell carcinoma tissue samples and cell lines, and it was found to be highly expressed in renal cell carcinoma tissue through immunohistochemistry. This upregulation is related to poor survival and prognosis of patients. We used erastin, a ferroptosis inducer, found that renal cell carcinoma became more susceptible to ferroptosis after knocking down STEAP3. The results indicate that renal cell carcinoma cell lines with knocked down STEAP3 expression are more sensitive to ferroptosis, and this effect occurs through the p53/xCT pathway. In summary, our research helps to identify new biomarkers and provides new targets for the treatment of renal cell carcinoma.

Effect of doxofylline on pulmonary inflammatory response and oxidative stress during mechanical ventilation in rats with COPD.

OBJECTIVE: To evaluate the effects of doxofylline on inflammatory responses and oxidative stress during mechanical ventilation in rats with chronic obstructive pulmonary disease (COPD). METHODS: Eight-week-old male Sprague Dawley rats were selected, and the COPD rat model was constructed. The rats were randomly divided into a model group (group M), a model + normal saline group (group N), a doxofylline group (group D), and a control group fed with conventional chow and given normal oxygen supply (group C) (n = 12 in each group). Tracheal intubation and mechanical ventilation were conducted in the rats in each group after anesthesia. A real-time intravenous infusion with 50 mg/kg of doxofylline was conducted in group D, and there was no drug intervention in groups C, N and M. Pathological manifestations of the pulmonary tissues were observed and compared among the groups. And some indicators were evaluated. RESULTS: (1) The pulmonary tissues of the rats in groups M, N, and D exhibited typical pathological histological changes of COPD. (2) Groups M, N, and D showed increased Ppeak, PaCO2, total white blood cell count in BALF, and IL-8, TNF-α, and MDA levels in the pulmonary tissue and BALF, and decreased PaO2 and IL-10 and SOD levels, compared with group C. (3). Group D showed decreased Ppeak, PaCO2, total white blood cell count in BALF, and IL-8, TNF-α, and MDA levels in the pulmonary tissue, and increased PaO2 and IL-10 and SOD levels, compared with group N or M. CONCLUSION: Doxofylline was shown to improve ventilation and air exchange during mechanical ventilation in rats with COPD, reduce the inflammatory response and oxidative stress, and mitigate the degree of pulmonary tissue injury.

LncRNA SNHG16 promotes colorectal cancer cell proliferation, migration, and epithelial-mesenchymal transition through miR-124-3p/MCP-1.

Colorectal cancer (CRC) has been the third leading cause of cancer-associated deaths. LncRNA SNHG16 is reported to be involved in metastasis of CRC cells. However, the mechanism by which SNHG16 regulates CRC progression is poorly understood. The proliferation of CRC cells was examined by MTT. Wound healing and transwell assay were used to measure migration and invasion ability. RT-qPCR and western blot were used to examine gene expression. Immunofluorescence was conducted to evaluate the EMT of CRC cells. Luciferase reporter assay were used to confirm direct interaction between miR-124-3p and SNHG16 or MCP-1. The interaction between miR-124-3p and SNHG16 was detected by RIP and RNA pull down assay. H&E staining was used to test the histomorphological changes of hepatic metastatic nodules. Finally, xenograft tumor experiment was utilized to determine tumor growth in vivo. SNHG16 and miR-124-3p were dysregulated in human colorectal tumors or cells. Knockdown of SNHG16 led to attenuate cell proliferation, migration, invasion, and EMT of CRC cells. And xenograft tumor experiment showed that SNHG16 might influence tumor growth. In contrast, miR-124-3p exerted the antitumor effects. Knockdown of miR-124-3p can reverse the effect of sh-SNHG16 on CRC cells. miR-124-3p could directly bind to SNHG16 or MCP-1. More importantly, MCP-1 acts as a critical effector mediating the role of SNHG16/ miR-124-3p in CRC cells. In summary, our data suggest that SNHG16 plays a contributory role in proliferation, migration, and EMT of CRC cells via miR-124-3p/MCP-1 axis, which offers a rationale for targeting SNHG16 and developing therapeutic drugs to treat CRC.

Knockdown of TRIM8 Protects HK-2 Cells Against Hypoxia/Reoxygenation-Induced Injury by Inhibiting Oxidative Stress-Mediated Apoptosis and Pyroptosis via PI3K/Akt Signal Pathway.

BACKGROUND: Acute kidney injury (AKI) emerges as an acute and critical disease. Tripartite motif 8 (TRIM8), one number of the TRIM protein family, is proved to participate in ischemia/reperfusion (I/R) injury. However, whether TRIM8 is involved in renal I/R injury and the associated mechanisms are currently unclear. PURPOSE: This study aimed to investigate the precise role of TRIM8 and relevant mechanisms in renal I/R injury. MATERIALS AND METHODS: In this study, human renal proximal tubular epithelial cells (HK-2 cells) underwent 12 hours of hypoxia and 2 h, 3 h or 4 h of reoxygenation to establish an in vitro hypoxia/reoxygenation (H/R) model. The siRNAs specific to TRIM8 (si-TRIM8) were transfected into HK-2 cells to knockdown TRIM8. The cell H/R model included various groups including Control, H/R, H/R+DMSO, H/R+NAC, si-NC+H/R, si-TRIM8+H/R and si-TRIM8+LY294002+H/R. The cell viability and levels of reactive oxygen species (ROS), hydrogen peroxide (H2O2), mRNA, apoptotic proteins, pyroptosis-related proteins and PI3K/AKT pathway-associated proteins were assessed. RESULTS: In vitro, realtime-quantitative PCR and western-blot analysis showed that the mRNA and protein expression of TRIM8 were obviously upregulated after H/R treatment in HK-2 cells. Compared with the H/R model group, knockdown of TRIM8 significantly increased cell viability and reduced the levels of ROS, H2O2, apoptotic proteins (Cleaved caspasebase-3 and BAX) and pyroptosis-related proteins (NLRP3, ASC, Caspase-1, Caspase-11, IL-1ß and GSDMD-N). Western-blot analysis also authenticated that PI3K/AKT pathway was activated after TRIM8 inhibition. The application of 5 mM N-acetyl-cysteine, one highly efficient ROS inhibitor, significantly suppressed the expression of apoptotic proteins and pyroptosis-related proteins. Moreover, the combined treatment of TRIM8 knockdown and LY294002 reversed the effects of inhibiting oxidative stress. CONCLUSION: Knockdown of TRIM8 can alleviate H/R-induced oxidative stress by triggering the PI3K/AKT pathway, thus attenuating pyropyosis and apoptosis in vitro.

Low-Intensity Exercise Modulates Gut Microbiota to Fight Against Radiation-Induced Gut Toxicity in Mouse Models.

Radiation-induced gastrointestinal (GI) tract toxicity halts radiotherapy and degrades the prognosis of cancer patients. Physical activity defined as "any bodily movement produced by skeletal muscle that requires energy expenditure" is a beneficial lifestyle modification for health. Here, we investigate whether walking, a low-intensity form of exercise, could alleviate intestinal radiation injury. Short-term (15 days) walking protected against radiation-induced GI tract toxicity in both male and female mice, as judged by longer colons, denser intestinal villi, more goblet cells, and lower expression of inflammation-related genes in the small intestines. High-throughput sequencing and untargeted metabolomics analysis showed that walking restructured the gut microbiota configuration, such as elevated Akkermansia muciniphila, and reprogramed the gut metabolome of irradiated mice. Deletion of gut flora erased the radioprotection of walking, and the abdomen local irradiated recipients who received fecal microbiome from donors with walking treatment exhibited milder intestinal toxicity. Oral gavage of A. muciniphila mitigated the radiation-induced GI tract injury. Importantly, walking did not change the tumor growth after radiotherapy. Together, our findings provide novel insights into walking and underpin that walking is a safe and effective form to protect against GI syndrome of patients with radiotherapy without financial burden in a preclinical setting.

Development and Validation of a Model Including Distinct Vascular Patterns to Estimate Survival in Hepatocellular Carcinoma.

Importance: Because of tumor heterogeneity, traditional clinical variables remain insufficient to predict recurrence, which impairs long-term survival among patients undergoing radical hepatectomy for hepatocellular carcinoma (HCC). Vessels encapsulating tumor clusters (VETC) constitute a novel vascular pattern distinct from microvascular invasion (MVI), representing biological aggressiveness of HCC. Objective: To establish a model to estimate individualized recurrence-free survival (RFS) in HCC by integrating VETC and MVI. Design, Setting, and Participants: This prognostic study included 498 patients undergoing radical hepatectomy for HCC from 5 academic centers in China from January 1, 2013, to December 31, 2016, and consisted of 3 cohorts: training (243 [48.8%]), internal validation (122 [24.5%]), and external validation (133 [26.7%]). Follow-up was completed on March 30, 2020, and the data were analyzed from December 1 to 31, 2020. Exposures: VETC, MVI, tumor number, and maximum tumor size. Main Outcomes and Measures: The primary end point was RFS. The risk score for relative recurrence and nomogram for absolute RFS probability were derived from the final model, which contained variables recommended by multivariate least absolute shrinkage and selection operator Cox proportional hazards regression analysis. Their performance was quantified using the Harrell concordance index (C index), the time-dependent area under the receiver operating characteristic curve, and calibration curves and was compared with 6 prognostic systems. Recurrence-free survival was estimated by the Kaplan-Meier method, and RFS curves were compared using a log-rank test. Results: Among the 498 patients, 432 (86.7%) were men; the mean (SD) age at diagnosis was 51.4 (11.3) years. Independent predictors for RFS identified included VETC, MVI, tumor number, and maximum tumor size, which were incorporated into the multivariate model (VMNS model). The C index (0.702; 95% CI, 0.653-0.752) for the VMNS score of the training cohort was significantly higher than those of 6 conventional systems (0.587 [95% CI, 0.535-0.638] to 0.657 [95% CI, 0.606-0.708]). Different recurrence risk groups defined by the VMNS score showed significantly different 2-year RFS (low-risk group, 81.4% [SE, 0.036]; medium-risk group, 62.1% [SE, 0.054]; high-risk group, 30.1% [SE, 0.079]; P < .001). Calibration curves of the VMNS nomogram showed good agreement between the nomogram-predicted RFS probability and actual RFS proportion. The internal and external validation cohorts confirmed the results. Conclusions and Relevance: The VMNS model enabled individualized prognostication of RFS in patients with HCC undergoing curative resection.

Histone Methyltransferase G9a Promotes the Development of Renal Cancer through Epigenetic Silencing of Tumor Suppressor Gene SPINK5.

BACKGROUND: Renal cell carcinoma (RCC) accounts for approximately 2-3% of malignant tumors in adults, while clear cell renal cell carcinoma accounts for 70-85% of kidney cancer cases, with an increasing incidence worldwide. G9a is the second histone methyltransferase found in mammals, catalyzing lysine and histone methylation. It regulates gene transcription by catalyzing histone methylation and interacting with transcription factors to alter the tightness of histone-DNA binding. The main purpose of this study is to explore the role and mechanism of G9a in renal cell carcinoma. METHODS: Firstly, we investigated the expression of G9a in 80 clinical tissues and four cell lines. Then, we explored the effect of G9a-specific inhibitor UNC0638 on proliferation, apoptosis, migration, and invasion of two renal cancer cell lines (786-O, SN12C). In order to study the specific mechanism, G9a knocking down renal cancer cell line was constructed by lentivirus. Finally, we identified the downstream target genes of G9a using ChIP experiments and rescue experiments. RESULTS: The results showed that the specific G9a inhibitor UNC0638 significantly inhibited the proliferation, migration, and invasion of kidney cancer in vivo and in vitro; similar results were obtained after knocking down G9a. Meanwhile, we demonstrated that SPINK5 was one of the downstream target genes of G9a through ChIP assay and proved that G9a downregulate the expression of SPINK5 by methylation of H3K9me2. Therefore, targeting G9a might be a new approach to the treatment of kidney cancer. CONCLUSION: G9a was upregulated in renal cancer and could promote the development of renal cancer in vitro and in vivo. Furthermore, we identified SPINK5 as one of the downstream target genes of G9a. Therefore, targeting G9a might be a new treatment for kidney cancer.

Effect of Doxofylline on Reducing the Inflammatory Response in Mechanically Ventilated Rats with Chronic Obstructive Pulmonary Disease.

Objective: To evaluate the effect of doxofylline on reducing the inflammatory response in mechanically ventilated rats with chronic obstructive pulmonary disease (COPD). Methods: A total of 40 eight-week-old male Sprague Dawley rats were randomly divided into four groups of 10 rats each: a control group (group C), a model group (group M), a model + natural saline group (group N), and a doxofylline group (group D). Then mechanical ventilation, drug intervention, and the extraction of the experimental material were performed in each group. Pulmonary tissue samples were taken after 120 minutes of mechanical ventilation and the pulmonary histopathological changes and the wet/dry (W/D) weight ratio of the pulmonary tissue were identified. The levels of tumor necrosis factor α (TNF-α) and interleukin 10 (IL-10) were detected using an enzyme-linked immunosorbent assay, and the expression levels of c-Jun-N-terminal kinase (JNK) and phosphorylated c-Jun N-terminal kinase (p-JNK) were detected using immunohistochemistry. Results: Compared with group C, the pulmonary histopathology in groups M, N, and D showed typical changes associated with COPD. Furthermore, the W/D weight ratio and levels of TNF-α, JNK, and p-JNK in the pulmonary tissue increased in groups M, N, and D (P < 0.05), while the levels of IL-10 decreased (P < 0.05). Compared with group M, no statistically significant changes in the above indicators were detected in the pulmonary tissue of group N (P > 0.05). Compared with group N, the W/D weight ratio and levels of TNF-α, JNK, and p-JNK in the pulmonary tissue decreased in group D (P < 0.05), while the levels of IL-10 increased (P < 0.05). Conclusion: Doxofylline might attenuate pulmonary inflammatory responses in mechanically ventilated rats with COPD, and the JNK/stress-activated protein kinase signaling pathway is involved in doxofylline's inhibition of inflammatory responses in the pulmonary tissue of rats with COPD.

The predictive value of vessels encapsulating tumor clusters in treatment optimization for recurrent early-stage hepatocellular carcinoma.

BACKGROUND: The predictive value of vessels encapsulating tumor clusters (VETC) in recurrent early-stage hepatocellular carcinoma (HCC) remains unclear. Therefore, the aim of the present study was to investigate the prognostic significance of VETC in patients with recurrent early-stage HCC after repeat hepatic resection (RHR) or radiofrequency ablation (RFA). METHODS: From December 2005 to December 2016, 138 patients receiving RHR and 188 patients receiving RFA were recruited. VETC was evaluated by immunohistochemical staining for CD34. The survival outcomes of patients with VETC pattern or not were investigated. RESULTS: There was no significant difference between the RHR and RFA groups in disease-free survival (DFS) or overall survival (OS) as determined by the univariate analysis of the whole cohort. In the subgroup analysis of the VETC-positive cohort, the patients in the RHR group showed a longer median DFS time in contrast to those in the RFA group (15.0 vs. 5.0 months, p = 0.001). Similarly, the patients in the RHR group showed a longer median OS time in contrast to those in the RFA group (39.5 vs. 19 months, p = 0.001). In the VETC-negative cohort, no significant differences in DFS and OS rates between the RHR and RFA groups were observed (p > 0.05). CONCLUSIONS: The results of our study suggested that RHR was relatively safe and superior to RFA in improving survival outcomes for recurrent early-stage HCC after initial hepatectomy. Furthermore, the VETC pattern may represent a reliable marker for selecting HCC patients who may benefit from RHR.

The Mechanism of Penehyclidine Hydrochloride and Its Effect on the Inflammatory Response of Lung Tissue in Rats with Chronic Obstructive Pulmonary Disease During Mechanical Ventilation.

BACKGROUND: Penehyclidine hydrochloride is a selective antagonist of M1 and M3 receptors. Clinical studies suggest that it is a potential drug for the treatment of chronic obstructive pulmonary disease (COPD). The purpose of this study was to evaluate the effect of penehyclidine hydrochloride on the inflammatory response of lung tissue during mechanical ventilation in rats with COPD and explore the role of the c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) signaling pathway. METHODS: Eight-week-old male Sprague Dawley rats were exposed to cigarette smoke for 30 minutes every day for two months, and on the first and thirtieth days, 200 ug of lipopolysaccharide was injected into the trachea. Two months later, the rats were randomly divided into the control group (C), model group (M), model + normal saline group (N), and penehyclidine hydrochloride group (H) to undergo anesthesia and mechanical ventilation. In group H, 1 mg/kg of penehyclidine hydrochloride was injected intravenously. RESULTS: The results showed that: ① Compared with group C, the other groups all showed typical chronic obstructive pathological changes in the lung tissue; their wet/dry weight ratio (W/D), TNF-α, JNK, and p-JNK levels increased (P < 0.05), and their interleukin (IL)-10 levels decreased (P < 0.05). ② Compared with group M, there was no significant change in the lung tissue indexes in group N (P > 0.05). ③ Compared with group N, the W/D, TNF-α, JNK, and p-JNK levels in group H decreased (P < 0.05), while the levels of IL-10 increased (P < 0.05). CONCLUSION: Penehyclidine hydrochloride can alleviate the pulmonary inflammatory response in rats with COPD undergoing mechanical ventilation. The JNK/SAPK signaling pathway may be involved in this process.

Risk factors analysis of COVID-19 patients with ARDS and prediction based on machine learning.

COVID-19 is a newly emerging infectious disease, which is generally susceptible to human beings and has caused huge losses to people's health. Acute respiratory distress syndrome (ARDS) is one of the common clinical manifestations of severe COVID-19 and it is also responsible for the current shortage of ventilators worldwide. This study aims to analyze the clinical characteristics of COVID-19 ARDS patients and establish a diagnostic system based on artificial intelligence (AI) method to predict the probability of ARDS in COVID-19 patients. We collected clinical data of 659 COVID-19 patients from 11 regions in China. The clinical characteristics of the ARDS group and no-ARDS group of COVID-19 patients were elaborately compared and both traditional machine learning algorithms and deep learning-based method were used to build the prediction models. Results indicated that the median age of ARDS patients was 56.5 years old, which was significantly older than those with non-ARDS by 7.5 years. Male and patients with BMI > 25 were more likely to develop ARDS. The clinical features of ARDS patients included cough (80.3%), polypnea (59.2%), lung consolidation (53.9%), secondary bacterial infection (30.3%), and comorbidities such as hypertension (48.7%). Abnormal biochemical indicators such as lymphocyte count, CK, NLR, AST, LDH, and CRP were all strongly related to the aggravation of ARDS. Furthermore, through various AI methods for modeling and prediction effect evaluation based on the above risk factors, decision tree achieved the best AUC, accuracy, sensitivity and specificity in identifying the mild patients who were easy to develop ARDS, which undoubtedly helped to deliver proper care and optimize use of limited resources.