Curcumin Inhibits TORC1 and Prolongs the Lifespan of Cells with Mitochondrial Dysfunction.

Aging is an inevitable biological process that contributes to the onset of age-related diseases, often as a result of mitochondrial dysfunction. Understanding the mechanisms behind aging is crucial for developing therapeutic interventions. This study investigates the effects of curcumin on postmitotic cellular lifespan (PoMiCL) during chronological aging in yeast, a widely used model for human postmitotic cellular aging. Our findings reveal that curcumin significantly prolongs the PoMiCL of wildtype yeast cells, with the most pronounced effects observed at lower concentrations, indicating a hormetic response. Importantly, curcumin also extends the lifespan of postmitotic cells with mitochondrial deficiencies, although the hormetic effect is absent in these defective cells. Mechanistically, curcumin inhibits TORC1 activity, enhances ATP levels, and induces oxidative stress. These results suggest that curcumin has the potential to modulate aging and offer therapeutic insights into age-related diseases, highlighting the importance of context in its effects.

Single-Incision Laparoscopic Totally Extraperitoneal Sublay Repair of Lumbar Hernia: A Novel Technique.

Background: Lumbar hernia is a rare disease with low incidence, and no golden standard surgical procedure has been established for lumbar hernias. The single-incision laparoscopic totally extraperitoneal sublay (SIL-TES) technique became a novel surgical technique for lumbar hernias. Methods: This retrospective study included 20 patients who underwent SIL-TES repair for lumbar hernia between April 2020 and March 2024. The baseline patient characteristics, intraoperative data, postoperative data, satisfaction score, and Carolina Comfort Scale scores were collected. Results: The results revealed that the SIL-TES technique for lumbar hernia repair is associated with a low complication rate, nonrecurrence, high satisfaction score, and high quality of life after surgery. Conclusions: The SIL-TES technique could be a feasible and effective surgical technique for lumbar hernias. A controlled study is needed for further confirmation.

Predicting the potential deterioration of Barrett's esophagus based on gut microbiota: a Mendelian randomization analysis.

Esophageal adenocarcinoma (EAC) is one of the most malignant tumors in the digestive system. To make thing worse, the scarcity of treatment options is disheartening. However, if detected early, there is a possibility of reversing the condition. Unfortunately, there is still a lack of relevant early screening methods. Considering that Barrett's esophagus (BE), a precursor lesion of EAC, has been confirmed as the only known precursor of EAC. Analyzing which BE cases will progress to EAC and understanding the processes and mechanisms involved is of great significance for early screening of such patients. Considering the significant alterations in the gut microbiota of patients with BE and its potential role in the progression to EAC, this study aims to analyze the relationship between BE, EAC, and GM to identify potential diagnostic biomarkers and therapeutic targets. This study utilized comprehensive statistical data on gut microbiota from a large-scale genome-wide association meta-analysis conducted by the MiBioGen consortium (n = 18,340). Subsequently, we selected a set of single nucleotide polymorphisms (SNPs) that fell below the genome-wide significance threshold (1 × 10-5) as instrumental variables. To investigate the causal relationship between gut microbiota and BE and EAC, we employed various MR analysis methods, including Inverse Variance Weighting (IVW), MR-Egger regression, weighted median (WM), and weighted mean. Additionally, we assessed the level of pleiotropy, heterogeneity, and stability of genetic variations through MR-Egger intercept test, MR-PRESSO, Cochran's Q test, and "leave-one-out" sensitivity analysis. Furthermore, we conducted reverse MR analysis to identify the causal relationships between gut microbiota and BE and EAC. The results from the Inverse Variance-Weighted (IVW) analysis indicate that Alistipes (P = 4.86 × 10-2), Lactobacillus (P = 2.11 × 10-2), Prevotella 7 (P = 4.28 × 10-2), and RuminococcaceaeUCG004 (P = 4.34 × 10-2) are risk factors for Barrett's esophagus (BE), while Flavonifractor (P = 8.81 × 10-3) and RuminococcaceaeUCG004 (P = 4.99 × 10-2) are risk factors for esophageal adenocarcinoma (EAC). On the other hand, certain gut microbiota genera appear to have a protective effect against both BE and EAC. These include Eubacterium (nodatum group) (P = 4.51 × 10-2), Holdemania (P = 1.22 × 10-2), and Lactococcus (P = 3.39 × 10-2) in the BE cohort, as well as Eubacterium (hallii group) (P = 4.07 × 10-2) and Actinomyces (P = 3.62 × 10-3) in the EAC cohort. According to the results of reverse MR analysis, no significant causal effects of BE and EAC on gut microbiota were observed. Furthermore, no significant heterogeneity or pleiotropy was detected in the instrumental variables. We have established a causal relationship between the gut microbiota and BE and EAC. This study holds profound significance for screening BE patients who may be at risk of deterioration, as it can provide them with timely medical interventions to reverse the condition.

Experimental investigation and simulation analysis of cast-steel joints under vertical pressure.

The joint made of cast steel is frequently utilized within a treelike column structure to ensure a smooth transition. It is of great significance in ensuring the overall structural safety, but currently, the mechanical property and bearing capacity of this type of joint cannot be fully understood. This study investigates the load characteristics of three-forked cast steel joints through concrete experiments, finite element analysis, and regression method formula derivation, filling the gap in mechanical properties and calculation formulas of forked cast steel joints. Initially, a comprehensive model of the cast-steel joint, sourced from a practical engineering, underwent vertical load testing. Detailed scrutiny of stress distribution and vertical displacement of the tested joint was conducted based on the experimental outcomes. Subsequently, a finite element model of the tested joint was constructed using SolidWorks and subjected to analysis via ANSYS. The numerical findings were juxtaposed with experimental data and extrapolated to encompass other parametric scenarios. Ultimately, a regression analysis method was employed to derive a calculation formula for the load-carrying capacity of branch-bearing cast-steel joints. The regression analysis method can accurately obtain the load-bearing capacity calculation formula for tree-shaped joint models and can be extended to determine corresponding branch and main pipe dimensions, as well as the deviation angle between branches and the main pipe, under known load conditions. This improves design efficiency and accuracy. Comparative analysis reveals a substantial concurrence among experimental, finite element analysis, and formula-based predictive outcomes. The maximum error between experimental results and those obtained from finite element analysis is 9.02%. The maximum error between the results calculated using the load-bearing capacity formula derived from regression methods and those from finite element analysis is only 1.9%.

Tanshinone IIA induces ER stress and JNK activation to inhibit tumor growth and enhance anti-PD-1 immunotherapy in non-small cell lung cancer.

BACKGROUND: Non-small cell lung cancer (NSCLC) remains at the forefront of new cancer cases, and there is an urgent need to find new treatments or improve the efficacy of existing therapies. In addition to the application in the field of cerebrovascular diseases, recent studies have revealed that tanshinone IIA (Tan IIA) has anticancer activity in a variety of cancers. PURPOSE: To investigate the potential anticancer mechanism of Tan IIA and its impact on immunotherapy in NSCLC. METHODS: Cytotoxicity and colony formation assays were used to detect the Tan IIA inhibitory effect on NSCLC cells. This research clarified the mechanisms of Tan IIA in anti-tumor and programmed death-ligand 1 (PD-L1) regulation by using flow cytometry, transient transfection, western blotting and immunohistochemistry (IHC) methods. Besides, IHC was also used to analyze the nuclear factor of activated T cells 1 (NFAT2) expression in NSCLC clinical samples. Two animal models including xenograft mouse model and Lewis lung cancer model were used for evaluating tumor suppressive efficacy of Tan IIA. We also tested the efficacy of Tan IIA combined with programmed cell death protein 1 (PD-1) inhibitors in Lewis lung cancer model. RESULTS: Tan IIA exhibited good NSCLC inhibitory effect which was accompanied by endoplasmic reticulum (ER) stress response and increasing Ca2+ levels. Moreover, Tan IIA could suppress the NFAT2/ Myc proto oncogene protein (c-Myc) signaling, and it also was able to control the Jun Proto-Oncogene(c-Jun)/PD-L1 axis in NSCLC cells through the c-Jun N-terminal kinase (JNK) pathway. High NFAT2 levels were potential factors for poor prognosis in NSCLC patients. Finally, animal experiments data showed a stronger immune activation phenotype, when we performed treatment of Tan IIA combined with PD-1 monoclonal antibody. CONCLUSION: The findings of our research suggested a novel mechanism for Tan IIA to inhibit NSCLC, which could exert anti-cancer effects through the JNK/NFAT2/c-Myc pathway. Furthermore, Tan IIA could regulate tumor PD-L1 levels and has the potential to improve the efficacy of PD-1 inhibitors.

Clinical Evaluation of the Effect of Encorafenib on Bupropion, Rosuvastatin, and Coproporphyrin I and Considerations for Statin Coadministration.

BACKGROUND AND OBJECTIVES: Encorafenib is a kinase inhibitor indicated for the treatment of patients with unresectable or metastatic melanoma or metastatic colorectal cancer, respectively, with selected BRAF V600 mutations. A clinical drug-drug interaction (DDI) study was designed to evaluate the effect of encorafenib on rosuvastatin, a sensitive substrate of OATP1B1/3 and breast cancer resistance protein (BCRP), and bupropion, a sensitive CYP2B6 substrate. Coproporphyrin I (CP-I), an endogenous substrate for OATP1B1, was measured in a separate study to deconvolute the mechanism of transporter DDI. METHODS: DDI study participants received a single oral dose of rosuvastatin (10 mg) and bupropion (75 mg) on days - 7, 1, and 14 and continuous doses of encorafenib (450 mg QD) and binimetinib (45 mg BID) starting on day 1. The CP-I data were collected from participants in a phase 3 study who received encorafenib (300 mg QD) and cetuximab (400 mg/m2 initial dose, then 250 mg/m2 QW). Pharmacokinetic and pharmacodynamic analysis was performed using noncompartmental and compartmental methods. RESULTS: Bupropion exposure was not increased, whereas rosuvastatin Cmax and area under the receiver operating characteristic curve (AUC) increased approximately 2.7 and 1.6-fold, respectively, following repeated doses of encorafenib and binimetinib. Increase in CP-I was minimal, suggesting that the primary effect of encorafenib on rosuvastatin is through BCRP. Categorization of statins on the basis of their metabolic and transporter profile suggests pravastatin would have the least potential for interaction when coadministered with encorafenib. CONCLUSION: The results from these clinical studies suggest that encorafenib does not cause clinically relevant CYP2B6 induction or inhibition but is an inhibitor of BCRP and may also inhibit OATP1B1/3 to a lesser extent. Based on these results, it may be necessary to consider switching statins or reducing statin dosage accordingly for coadministration with encorafenib. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT03864042, registered 6 March 2019.

Microbes mediated immunogenic cell death in cancer immunotherapy.

Immunogenic cell death (ICD) is one of the 12 distinct cell death forms, which can trigger immune system to fight against cancer cells. During ICD, a number of cellular changes occur that can stimulate an immune response, including the release of molecules called damage-associated molecular patterns (DAMPs), signaling to immune cells to recognize and attack cancer cells. By virtue of their pivotal role in immune surveillance, ICD-based drug development has been a new approach to explore novel therapeutic combinations and personalized strategies in cancer therapy. Several small molecules and microbes can induce ICD-relevant signals and cause cancer cell death. In this review, we highlighted the role of microbe-mediate ICD in cancer immunotherapy and described the mechanisms through which microbes might serve as ICD inducers in cancer treatment. We also discussed current attempts to combine microbes with chemotherapy regimens or immune checkpoint inhibitors (ICIs) in the treatment of cancer patients. We surmise that manipulation of microbes may guide personalized therapeutic interventions to facilitate anticancer immune response.

Magnetic activated carbon from spent coffee grounds: iron-catalyzed CO2 activation mechanism and adsorption of antibiotic lomefloxacin from aqueous medium.

The facile fabrication of low-cost adsorbents possessing high removal efficiency and convenient separation property is an urgent need for water treatment. Herein, magnetic activated carbon was synthesized from spent coffee grounds (SCG) by Fe-catalyzed CO2 activation at 800 °C for 90 min, and magnetization and pore formation were simultaneously achieved during heat treatment. The sample was characterized by N2 adsorption-desorption, XRD, VSM, SEM, and FTIR. Batch adsorption experiments were conducted using lomefloxacin (LMO) as the probing pollutant. Preparation mechanism was revealed by TG-FTIR and XRD. Experimental results showed that Fe3O4 derived from Fe species can be reduced to Fe by carbon at high temperatures, followed by subsequent reoxidation to Fe3O4 by CO2, and the redox cycle between Fe and Fe3O4 favored the formation of pores. The promotion effects of Fe species on CO2 activation can be quantitatively reflected by the yield of CO as the signature gaseous product, and the suitable activation temperate range was determined to be 675 to 985 °C. The BET surface area, total pore volume, and saturated magnetization value of the product were 586 m2 g-1, 0.327 cm3 g-1, and 11.59 emu g-1, respectively. The Langmuir model was applicable for the adsorption isotherm data for LMO with the maximum adsorption capacity of 95 mg g-1, and thermodynamic analysis revealed that the adsorption process was endothermic and spontaneous. This study demonstrated that Fe-catalyzed CO2 activation was an effective method of converting SCG into magnetic separable adsorbent for LMO removal from aqueous medium.

Lateral single incision laparoscopic totally extraperitoneal hernioplasty (L-SILTEP) after laparoscopic radical prostatectomy: A rare case report with literature review.

INTRODUCTION: Single-incision laparoscopic totally extraperitoneal hernioplasty is a commonly used surgical procedure for the treatment of inguinal hernia. However, it is difficult to use traditional single incision laparoscopic totally extraperitoneal hernioplasty to treat inguinal hernia after laparoscopic radical prostatectomy. We successfully and smoothly cured a patient with left inguinal hernia after laparoscopic radical prostatectomy using lateral single incision laparoscopic totally extraperitoneal hernioplasty. CASE PRESENTATION: We report the case of a 70-year-old man who underwent laparoscopic radical prostatectomy 2 years earlier and had an evanescent mass in the left inguinal region for 1 month. DIAGNOSIS: On the basis of preoperative abdominal computed tomography and intraoperative findings, the patient was diagnosed with a left indirect inguinal hernia, and post-laparoscopic radical prostatectomy. INTERVENTIONS: The patient underwent lateral single incision laparoscopic totally extraperitoneal hernioplasty. OUTCOMES: The patient recovered well after the operation, and there were no postoperative complications or recurrence of inguinal hernia 3 months after the operation. CONCLUSION: For patients who have undergone laparoscopic radical prostatectomy, lateral single-incision laparoscopic totally extraperitoneal hernioplastycan be performed.

ß-Elemene enhances erlotinib sensitivity through induction of ferroptosis by upregulating lncRNA H19 in EGFR-mutant non-small cell lung cancer.

Nearly half of all Asian non-small cell lung cancer (NSCLC) patients harbour epidermal growth factor receptor (EGFR) mutations, and first-generation EGFR tyrosine kinase inhibitors (TKIs) are one of the first-line treatments that have improved the outcomes of these patients. Unfortunately, 20% of these patients can not benefit from the treatment. The basis of this primary resistance is poorly understood. Therefore, overcoming EGFR-TKI primary resistance and maintaining the efficacy of TKIs has become a key issue. ß-Elemene, a sesquiterpene compound extracted from Curcuma aromatica Salisb. (wenyujing), has shown potent antitumor effects. In this research, we found that ß-elemene combined with erlotinib enhanced the cytotoxicity of erlotinib to primary EGFR-TKI-resistant NSCLC cells with EGFR mutations and that ferroptosis was involved in the antitumor effect of the combination treatment. We found that lncRNA H19 was significantly downregulated in primary EGFR-TKI-resistant NSCLC cell lines and was upregulated by the combination treatment. Overexpression or knockdown of H19 conferred sensitivity or resistance to erlotinib, respectively, in both in vitro and in vivo studies. The high level of H19 enhanced the cytotoxicity of erlotinib by inducing ferroptosis. In conclusion, our data showed that ß-elemene combined with erlotinib could enhance sensitivity to EGFR-TKIs through induction of ferroptosis via H19 in primary EGFR-TKI-resistant lung cancer, providing a promising strategy to overcome EGFR-TKI resistance in NSCLC patients.

Modified Flowing Material Balance Equation for Shale Gas Reservoirs.

To determine original gas-in-place, this study establishes a flowing material balance equation based on the improved material balance equation for shale gas reservoirs. The method considers the free gas in the matrix and fracture, the dissolved gas in kerogen, and the pore volume occupied by adsorbed phase simultaneously, overcoming the problem of incomplete consideration in the earlier models. It also integrates the material balance method with the flowing material balance method to obtain the average formation pressure, eliminating the problem with the previous method where shutting down of wells was needed to monitor the formation pressure. The volume of the adsorbed gas on the ground is converted into volume of the adsorbed phase in the formation using the volume conservation method to characterize the pore volume occupied by the adsorbed phase, which solves the problem of the previous model that the adsorbed phase was neglected in the pore volume. The model proposed in this study is applied to the Fuling Shale Gas Field in southwest China and compared with other flowing material balance equations, and the results show that the single-well control area calculated by the model proposed in this study is closer to the real value, indicating that the calculations in this study are more accurate. Furthermore, the calculations show that the dissolved gas takes up a large fraction of the total reserves and cannot be ignored. The sensitivity analyses of critical parameters demonstrate that (a) the greater the porosity of the fracture, the greater the free gas storage; (b) the values of Langmuir volume and TOC can significantly affect the results of the reservoir calculation; and (c) the adsorbed phase occupies a smaller pore volume when the Langmuir volume is smaller, the Langmuir pressure is higher, or the adsorbed phase density is higher. The findings of this study can provide better understanding of the necessity to take into account the dissolved gas in the kerogen, the pore volume occupied by the adsorbed phase, and the fracture porosity when evaluating reserves. The method could be applied to the calculation of pressure, recovery of free gas phase and adsorbed phase, original gas-in-place, and production predictions, which could help for better guidance of reserve potential estimations and development strategies of shale gas reservoirs.

Andrographolide suppresses non-small-cell lung cancer progression through induction of autophagy and antitumor immune response.

Despite recent advances in diagnosis and therapeutic strategies, treatment of non-small-cell lung cancer (NSCLC) remains unsatisfactory in terms of prognosis. Andrographolide (AD), a principal active component of Andrographis paniculata (Burm.f.) Nees, exerts anti-cancer therapeutic properties. AD has been used for centuries in China for clinical treatment of viral infections. However, the pharmacological biology of AD in NSCLC remains unknown. In this study, AD regulated autophagy and PD-L1 expression in NSCLC. Molecular dynamics simulations indicated that AD bound directly to signal transducer and activator of transcription-3 (STAT3) with high affinity. Proteomics analysis indicated that AD reduced the expression of tumour PD-L1 in NSCLC by suppressing JAK2/STAT3 signalling. AD modulated the P62-dependent selective autophagic degradation of PD-L1 by inhibiting STAT3 phosphorylation. In vivo study revealed that AD suppressed tumour growth in H1975 xenograft mice and Lewis lung carcinoma cell models, and better efficacy was obtained at higher concentrations. AD prolonged the survival time of the mice and enhanced the treatment efficacy of anti-PD-1 mAb immunotherapy by stimulating CD8+ T cell infiltration and function. This work elucidated the specific mechanism by which AD inhibited NSCLC. Treatment with the combination of AD and anti-PD-1 mAb immunotherapy could be a potential strategy for patients with NSCLC.

Comparative review of outcomes: single-incision laparoscopic total extra-peritoneal sub-lay (SIL-TES) mesh repair versus laparoscopic intraperitoneal onlay mesh (IPOM) repair for ventral hernia.

To compare outcomes between single-incision laparoscopic totally extra-peritoneal sub-lay (SIL-TES) mesh repair and laparoscopic intraperitoneal onlay mesh (IPOM) repair of ventral hernia (VH). A retrospective selection of 104 patients who underwent VH repair (50 and 54 in the SIL-TES and IPOM groups, respectively) was made. Patient data were collected, and quality of life was evaluated using Carolinas Comfort Scale (CCS) 1 month and 3 months after surgery. There were no significant differences in sex, American Society of Anesthesiologists class, defect size, mesh area, estimated blood loss, and complication rate between the groups. Age was lower, body mass index was higher, prevalence of primary VH was significantly higher (p < 0.0001), and pain was less at 24 and 48 h post procedure (p < 0.0001) in the SIL-TES group. Drainage placement was more (p < 0.0001), operation time was shorter (p = 0.012), and hospitalization duration and total hospitalization cost were greater in the IPOM group than that in SIL-TES group (8.3 ± 0.3 vs 4.3 ± 0.4 days, p < 0.0001; $7126.9 ± 141.4 vs $2937.3 ± 58.3, p < 0.0001, respectively). Pain and movement limitation scores evaluated by CCS were significantly worse at 1 month (4.93 ± 0.28 vs 1.75 ± 0.28: p < 0.0001; 2.52 ± 0.24 vs 1.15 ± 0.18: p < 0.0001, respectively) and 3 months (4.32 ± 0.37 vs 0.9 ± 0.29: p < 0.0001; 2.06 ± 0.25 vs 0.69 ± 0.11: p < 0.0001, respectively) in IPOM group, compared with the according scores in SIL-TES group. There was no readmission within 30 days and no hernia recurrence at mean follow-up of 12 months. SIL-TES mesh repair is safe and effective and is superior to IPOM repair.

Ginseng polysaccharides alter the gut microbiota and kynurenine/tryptophan ratio, potentiating the antitumour effect of antiprogrammed cell death 1/programmed cell death ligand 1 (anti-PD-1/PD-L1) immunotherapy.

OBJECTIVE: Programmed death 1 and its ligand 1 (PD-1/PD-L1) immunotherapy is promising for late-stage lung cancer treatment, however, the response rate needs to be improved. Gut microbiota plays a crucial role in immunotherapy sensitisation and Panax ginseng has been shown to possess immunomodulatory potential. In this study, we aimed to investigate whether the combination treatment of ginseng polysaccharides (GPs) and αPD-1 monoclonal antibody (mAb) could sensitise the response by modulating gut microbiota. DESIGN: Syngeneic mouse models were administered GPs and αPD-1 mAb, the sensitising antitumour effects of the combination therapy on gut microbiota were assessed by faecal microbiota transplantation (FMT) and 16S PacBio single-molecule real-time (SMRT) sequencing. To assess the immune-related metabolites, metabolomics analysis of the plasma samples was performed. RESULTS: We found GPs increased the antitumour response to αPD-1 mAb by increasing the microbial metabolites valeric acid and decreasing L-kynurenine, as well as the ratio of Kyn/Trp, which contributed to the suppression of regulatory T cells and induction of Teff cells after combination treatment. Besides, the microbial analysis indicated that the abundance of Parabacteroides distasonis and Bacteroides vulgatus was higher in responders to anti-PD-1 blockade than non-responders in the clinic. Furthermore, the combination therapy sensitised the response to PD-1 inhibitor in the mice receiving microbes by FMT from six non-responders by reshaping the gut microbiota from non-responders towards that of responders. CONCLUSION: Our results demonstrate that GPs combined with αPD-1 mAb may be a new strategy to sensitise non-small cell lung cancer patients to anti-PD-1 immunotherapy. The gut microbiota can be used as a novel biomarker to predict the response to anti-PD-1 immunotherapy.

The effect of health education on the quality of life of postoperative patients with gastric cancer: a systematic review and meta-analysis.

BACKGROUND: Gastric cancer is one of the most common malignant tumors of the digestive tract worldwide. This study aims to evaluate the effect of health education on gastric cancer patients' quality of life after surgery. METHODS: China National Knowledge Infrastructure (CNKI) and Wanfang Data (WFD) were searched to obtain relevant studies. Key words: postoperative gastric cancer/health education/quality of life. A total of 88 subject-related literatures were retrieved, and 7 literatures that met the requirements were screened out and included in the meta-analysis research. Cochrane software Revman 5.0 was used to perform heterogeneity test, sensitivity analysis and pool analysis of the included literature. RESULTS: A total of 7 relevant studies meeting the requirements were included, involving 772 postoperative gastric cancer patients. According to the heterogeneity test results, the fixed effects model and the random effects model were adopted in this study. The results showed that the quality of life score of the health education group was higher than that of the control group (P<0.001), with an OR (95% CI) value of 9.78 (8.59-10.99). The scores of physical function, role function, emotional function, cognitive function, and social function in the experimental group were higher than those in the control group (P<0.001), with OR (95% CI) values of 8.13 (6.65-9.60), 8.99 (7.84-10.14), 9.84 (8.64-11.50), 6.55 (5.59-7.71), and 9.79 (8.59-10.99), respectively. DISCUSSION: Health education can improve the overall health score of patients with gastric cancer after surgery. It can also improve the scores of physical function, role function, emotional function, cognitive function, and social function, and can significantly improve patients' quality of life.

Metabolomics and integrated network pharmacology analysis reveal Tricin as the active anti-cancer component of Weijing decoction by suppression of PRKCA and sphingolipid signaling.

Currently, conventional methods of treating non-small cell lung cancer (NSCLC) have many disadvantages. An alternative effective therapy with minimal adverse reactions is urgently needed. Weijing decoction (WJD), which is a classic ancient Chinese herbal prescription, has been used successfully to treat pulmonary system diseases containing lung cancer in the clinic. However, the key active component and target of Weijing decoction are still unexplored. Therefore, for the first time, our study aims to investigate the pharmacological treatment mechanism of Weijing decoction in treating NSCLC via an integrated model of network pharmacology, metabolomics and biological methods. Network pharmacology results conjectured that Tricin is a main bioactive component in this formula which targets PRKCA to suppress cancer cell growth. Metabolomics analysis demonstrated that sphingosine-1-phosphate, which is regulated by sphingosine kinase 1 and sphingosine kinase 2, is a differential metabolite in plasma between the WJD-treated group and the control group, participating in the sphingolipid signaling. In vitro experiments demonstrated that Tricin had vital effects on the proliferation, pro-apoptosis, migration and colony formation of Lewis lung carcinoma cells. Through a series of validation assays, Tricin inhibited the tumor growth mainly by suppressing PRKCA/SPHK/S1P signaling and antiapoptotic signaling. On the other hand, Weijing formula could inhibit the tumor growth and prolong the survival time. A high dosage of Tricin was much more potent in animal experiments. In conclusion, we confirmed that Weijing formula and its primary active compound Tricin are promising alternative treatments for NSCLC patients.

Employing a Xiphoid-umbilicus Approach in an Endoscopic Totally Extraperitoneal Procedure for the Preperitoneal Repair of Midline Ventral Hernias.

OBJECTIVES: Endoscopic totally extraperitoneal sublay (TES) repair seems to be a promising procedure for treating ventral hernias because repairing at the preperitoneal layer reduces damage to the natural musculoaponeurotic structures of the abdominal wall. This article reports the preliminary surgical results after such a procedure with a xiphoid-umbilicus approach for a midline ventral hernia of the middle-upper abdomen. MATERIALS AND METHODS: Fifteen cases with a small midline ventral hernia scheduled for preperitoneal repair with a TES procedure with a xiphoid-umbilicus approach were included. Patient demographics, hernia characteristics, operative variables, and surgical results were recorded and analyzed. RESULTS: The patients' average age was 55.80±15.33 years, body mass index was 26.49±2.98, defect size was 4.59±2.28 cm2, and the most frequent region was M3. Five of 15 procedures were conducted in a bottom-up direction, and 10 of 15 with single-port surgery. Only 1 repair failed due to severe peritoneal damage. The operation duration was 120.4±47.7 minutes. All patients recovered quickly and uneventfully, and no case needed readmission. No severe intraoperative and postoperative complications occurred. Only 1 case developed seroma, and there was no surgical site infection, pain, trocar site hernia, and recurrence observed during short-term follow-up (3 to 12 mo). CONCLUSIONS: Endoscopic preperitoneal repair helps reduce damage to the abdominal wall during a TES procedure. Compared with a suprapubic approach, employing a xiphoid-umbilicus approach facilitates preperitoneal repair for small ventral hernias of the middle-upper abdomen. This will be a future option for minimally invasive surgical repair of such ventral hernias (Supplemental Digital Content 1, Video, http://links.lww.com/SLE/A287).

Plumbagin suppresses non-small cell lung cancer progression through downregulating ARF1 and by elevating CD8+ T cells.

Non-small cell lung cancer (NSCLC) is one of the most frequently diagnosed cancers and the leading causes of cancer death worldwide. Therefore, new therapeutic agents are urgently needed to improve patient outcomes. Plumbagin (PLB), a natural sesquiterpene present in many Chinese herbal medicines, has been reported for its anti-cancer activity in various cancer cells. In this study, the effects and underlying mechanisms of PLB on the tumorigenesis of NSCLC were investigated. PLB dose-dependently inhibited the growth of NSCLC cell lines. PLB promoted ROS production, activated the endoplasmic reticulum (ER) stress pathway, and induced cell apoptosis, accompanied by the decreased expression level of ADP-ribosylation factor 1 (ARF1) in NSCLC cancer cells, and those effects of PLB could be reversed by the pretreatment with N-acetyl-L-cysteine (NAC). More importantly, the calcium chelator (BM) significantly reversed PLB-induced cell apoptosis. Furthermore, PLB significantly inhibited the growth of both H1975 xenograft and LLC1 tumors and exhibited antitumor activity by enhancing the number and the effector function of CD8+ T cells in KRASLA2 mice model and the LLC1 xenograft. Our findings suggest that PLB exerts potent antitumor activity against NSCLC in vitro and in vivo through ARF1 downregulation and induction of antitumor immune response, indicating that PLB is a new novel therapeutic candidate for the treatment of patients with NSCLC.