Plin4 exacerbates cadmium-decreased testosterone level via inducing ferroptosis in testicular Leydig cells.

Strong evidence indicates that environmental stressors are the risk factors for male testosterone deficiency (TD). However, the mechanisms of environmental stress-induced TD remain unclear. Based on our all-cause male reproductive cohort, we found that serum ferrous iron (Fe2⁺) levels were elevated in TD donors. Then, we explored the role and mechanism of ferroptosis in environmental stress-reduced testosterone levels through in vivo and in vitro models. Data demonstrated that ferroptosis and lipid droplet deposition were observed in environmental stress-exposed testicular Leydig cells. Pretreatment with ferrostatin-1 (Fer-1), a specific ferroptosis inhibitor, markedly mitigated environmental stress-reduced testosterone levels. Through screening of core genes involved in lipid droplets formation, it was found that environmental stress significantly increased the levels of perilipins 4 (PLIN4) protein and mRNA in testicular Leydig cells. Further experiments showed that Plin4 siRNA reversed environmental stress-induced lipid droplet deposition and ferroptosis in Leydig cells. Additionally, environmental stress increased the levels of METTL3, METTL14, and total RNA m6A in testicular Leydig cells. Mechanistically, S-adenosylhomocysteine, an inhibitor of METTL3 and METTL14 heterodimer activity, restored the abnormal levels of Plin4, Fe2⁺ and testosterone in environmental stress-treated Leydig cells. Collectively, these results suggest that Plin4 exacerbates environmental stress-decreased testosterone level via inducing ferroptosis in testicular Leydig cells.

Pervaporation Dehydration Mechanism and Performance of High-Aluminum ZSM-5 Zeolite Membranes for Organic Solvents.

Membrane-based pervaporation (PV) for organic solvent dehydration is of great significance in the chemical and petrochemical industries. In this work, high-aluminum ZSM-5 zeolite membranes were synthesized by a fluoride-assisted secondary growth on α-alumina tubular supports using mordenite framework inverted (MFI) nanoseeds (~110 nm) and a template-free synthesis solution with a low Si/Al ratio of 10. Characterization by XRD, EDX, and SEM revealed that the prepared membrane was a pure-phase ZSM-5 zeolite membrane with a Si/Al ratio of 3.8 and a thickness of 2.8 µm. Subsequently, two categories of PV performance parameters (i.e., flux versus separation factor and permeance versus selectivity) were used to systematically examine the effects of operating conditions on the PV dehydration performance of different organic solvents (methanol, ethanol, n-propanol, and isopropanol), and their PV mechanisms were explored. Employing permeance and selectivity effectively disentangles the influence of operating conditions on PV performance, thereby elucidating the inherent contribution of membranes to separation performance. The results show that the mass transfer during PV dehydration of organic solvents was mainly dominated by the adsorption-diffusion mechanism. Furthermore, the diffusion of highly polar water and methanol molecules within membrane pores had a strong mutual slowing-down effect, resulting in significantly lower permeance than other binary systems. However, the mass transfer process for water/low-polar organic solvent (ethanol, n-propanol, and isopropanol) mixtures was mainly controlled by competitive adsorption caused by affinity differences. In addition, the high-aluminum ZSM-5 zeolite membrane exhibited superior PV dehydration performance for water/isopropanol mixtures.

Will greenhouse gas emissions increase with mining depth in coal mines? An analysis of gas occurrence under varying in-situ stress conditions.

The rapid development of the economy leads to the high demand for deep coal resources, which further poses the potential problem of deep gas (or methane) emissions. The clarification of deep gas occurrence law for coal mines provides theoretical and data support for methane emission predictions, and assists industrial and mining enterprises in planning targeted emission reduction measures. This study defined and verified the existence of a critical depth for the deep gas occurrence in coal mines based on a multiple-scale case study of how the gas occurrence is associated with depth and stress status changes in the Pingdingshan No.8 Coal Mine. In addition, 882 sets of gas content data from 7 major mining areas in China were collected and their gas content distributions among various depths were statistically analyzed to prove the universal existence of critical depth. The results show that the critical depth of Pingdingshan No.8 Coal Mine is 509 m, and the critical depth of other Chinese areas is about 400 to 1000 m. Significant differences were observed in the pore space, surface, and gas desorption characteristics for coal samples with different depths and stress states. The pore structure in the critical depth area is relatively developed, and gas is easily accumulated. The gas occurrence of both normal and abnormal gas gradually increases with the depth's increase in areas above the critical depth, whereas the gas occurrence gradually decreases for areas below the critical depth, showing that the existence of critical depth lead to significant deviations in gas emission predictions. The results provide a fundamental reference for gas emission prediction, greenhouse effect assessment, and carbon emission factor calculation and indicate that using the traditional linear method may be misleading for evaluating deep gas occurrence and emission.

Thermal self-crosslink after etching for regulated preparation of Ti3C2 type MXene membrane and its preliminary gas separation.

We present an innovative methodology for the synthesis of MXene membranes through a dual-stage process involving etching and subsequent thermal self-crosslinking. A molar ratio of 1 (Al3+):9 (F-) using HCl/LiF was employed to convert raw Ti3AlC2 (MAX phase) into MXene within 48 h at 40 °C. This procedure predominantly yielded monolayers distinguished by diameters exceeding 500 nm, elevated crystallinity and a high overall yield. Advanced characterization techniques, including FESEM, TEM, HRTEM, AFM, XPS, and FTIR, were utilized. Instrumental analysis confirmed the formation of MXene exhibiting a single-flake morphology with diameters exceeding 500 nm. These monolayers were intact and continuous, with smooth peripheries and a uniform thickness of 2.1 nm. The surfaces were predominantly composed of carbon (C), oxygen (O), and titanium (Ti) atoms, interconnected by chemical bonds such as C-Ti-O, C-Ti-OH, C-C, C-O, and Ti-O. In the subsequent phase, vacuum filtration facilitated the assembly of a self-supporting MXene membrane. Thermal treatment at 170 °C for 30 h resulted in the reinforcement of C-Ti-O bonds within the nanosheets, increasing their prevalence to 43.14 % and 19.47 %, respectively. This thermal regulation reduced the interlayer d-spacing from 4.33 to 3.54 Å, which significantly improved the gas separation efficiency beyond the Knudsen diffusion limit, as demonstrated by the αH2/CF4 value exceeding 23.0.

Current landscape of preoperative neoadjuvant therapies for initial resectable colorectal cancer liver metastasis.

Colorectal cancer liver metastasis (CRLM) presents a clinical challenge, and optimizing treatment strategies is crucial for improving patient outcomes. Surgical resection, a key element in achieving prolonged survival, is often linked to a heightened risk of recurrence. Acknowledging the potential benefits of preoperative neoadjuvant chemotherapy in managing resectable liver metastases, this approach has gained attention for its role in tumor downsizing, assessing biological behavior, and reducing the risk of postoperative recurrence. However, the use of neoadjuvant chemotherapy in initially resectable CRLM sparks ongoing debates. The balance between tumor reduction and the risk of hepatic injury, coupled with concerns about delaying surgery, necessitates a nuanced approach. This article explores recent research insights and draws upon the practical experiences at our center to address critical issues regarding considerations for initially resectable cases. Examining the criteria for patient selection and the judicious choice of neoadjuvant regimens are pivotal areas of discussion. Striking the right balance between maximizing treatment efficacy and minimizing adverse effects is imperative. The dynamic landscape of precision medicine is also reflected in the evolving role of gene testing, such as RAS/BRAF and PIK3CA, in tailoring neoadjuvant regimens. Furthermore, the review emphasizes the need for a multidisciplinary approach to navigate the complexities of CRLM. Integrating technical expertise and biological insights is crucial in refining neoadjuvant strategies. The management of progression following neoadjuvant chemotherapy requires a tailored approach, acknowledging the diverse biological behaviors that may emerge. In conclusion, this review aims to provide a comprehensive perspective on the considerations, challenges, and advancements in the use of neoadjuvant chemotherapy for initially resectable CRLM. By combining evidence-based insights with practical experiences, we aspire to contribute to the ongoing discourse on refining treatment paradigms for improved outcomes in patients with CRLM.

Multigenerational paternal obesity enhances the susceptibility to male subfertility in offspring via Wt1 N6-methyladenosine modification.

There is strong evidence that obesity is a risk factor for poor semen quality. However, the effects of multigenerational paternal obesity on the susceptibility to cadmium (a reproductive toxicant)-induced spermatogenesis disorders in offspring remain unknown. Here, we show that, in mice, spermatogenesis and retinoic acid levels become progressively lower as the number of generations exposed to a high-fat diet increase. Furthermore, exposing several generations of mice to a high fat diet results in a decrease in the expression of Wt1, a transcription factor upstream of the enzymes that synthesize retinoic acid. These effects can be rescued by injecting adeno-associated virus 9-Wt1 into the mouse testes of the offspring. Additionally, multigenerational paternal high-fat diet progressively increases METTL3 and Wt1 N6-methyladenosine levels in the testes of offspring mice. Mechanistically, treating the fathers with STM2457, a METTL3 inhibitor, restores obesity-reduced sperm count, and decreases Wt1 N6-methyladenosine level in the mouse testes of the offspring. A case-controlled study shows that human donors who are overweight or obese exhibit elevated N6-methyladenosine levels in sperm and decreased sperm concentration. Collectively, these results indicate that multigenerational paternal obesity enhances the susceptibility of the offspring to spermatogenesis disorders by increasing METTL3-mediated Wt1 N6-methyladenosine modification.

Enhanced Electrical Properties and Impact Strength of Phenolic Formaldehyde Resin Using Silanized Graphene and Ionic Liquid.

In this study, to improve the electrical properties and impact strength of phenolic formaldehyde (PF) resin, PF-based composites were prepared by mixing graphene and the ionic liquid 3-decyl-bis(1-vinyl-1H-imidazole-3-ium-bromide) (C10[VImBr]2) via hot blending and compression-curing processes. The graphene surface was modified using a silane coupling agent. The synergistic effect of graphene and C10[VImBr]2 on the electrical properties, electromagnetic shielding efficiency, thermal stability, impact strength, and morphology of PF/graphene and PF/graphene/C10[VImBr]2 composites was then investigated. It was found that the electrical conductivity of the composites significantly increased from 2.3 × 10-10 to 4.14 × 10-3 S/m with an increase in the graphene content from 0 to 15 wt %, increasing further to 0.145 S/m with the addition of 5 wt % C10[VImBr]2. The electromagnetic shielding efficiency of the composite increased from 4.70 to 28.64 dB with the addition of 15 wt % graphene, while the impact strength of the composites rose significantly from 0.59 to 1.13 kJ/m2 with an increase in the graphene content from 0 to 15 wt %, reaching 1.53 kJ/m2 with the addition of 5 wt % C10[VImBr]2. Scanning electron microscopy images of the PF/GNP/C10[VImBr]2 composites revealed a rough morphology with numerous microcracks.

High-Performance FAU Zeolite Membranes Derived from Nano-Seeds for Gas Separation.

In this study, high-performance FAU (NaY type) zeolite membranes were successfully synthesized using small-sized seeds of 50 nm, and their gas separation performance was systematically evaluated. Employing nano-sized NaY seeds and an ultra-dilute reaction solution with a molar composition of 80 Na2O: 1Al2O3: 19 SiO2: 5000H2O, the effects of synthesis temperature, crystallization time, and porous support (α-Al2O3 or mullite) on the formation of FAU membranes were investigated. The results illustrated that further extending the crystallization time or increasing the synthesis temperature led to the formation of a NaP impurity phase on the FAU membrane layer. The most promising FAU membrane with a thickness of 2.7 µm was synthesized on an α-Al2O3 support at 368 K for 8 h and had good reproducibility. The H2 permeance of the membrane was as high as 5.34 × 10-7 mol/(m2 s Pa), and the H2/C3H8 and H2/i-C4H10 selectivities were 183 and 315, respectively. The C3H6/C3H8 selectivity of the membrane was as high as 46, with a remarkably high C3H6 permeance of 1.35 × 10-7 mol/(m2 s Pa). The excellent separation performance of the membrane is mainly attributed to the thin, defect-free membrane layer and the relatively wide pore size (0.74 nm).

Index of consciousness monitoring during general anesthesia may effectively enhance rehabilitation in elderly patients undergoing laparoscopic urological surgery: a randomized controlled clinical trial.

BACKGROUND: Based on electroencephalogram (EEG) analysis, index of consciousness (IoC) monitoring is a new technique for monitoring anesthesia depth. IoC is divided into IoC1 (depth of sedation) and IoC2 (depth of analgesia). The potential for concurrent monitoring of IoC1 and IoC2 to expedite postoperative convalescence remains to be elucidated. We investigated whether combined monitoring of IoC1 and IoC2 can effectively enhances postoperative recovery compared with bispectral index (BIS) in elderly patients undergoing laparoscopic urological surgery under general anesthesia. METHODS: In this prospective, controlled, double-blinded trail, 120 patients aged 65 years or older were arbitrarily assigned to either the IoC group or the control group (BIS monitoring). All patients underwent blood gas analysis at T1 (before anesthesia induction) and T2 (the end of operation). The Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) were administered to all patients at T0 (1 day before surgery) and T4 (7 days after surgery). Serum concentrations of C-reactive protein (CRP) and glial fibrillary acid protein (GFAP) were assessed at T1, T2, and T3 (24 h after surgery). Postoperative complications and the duration of hospitalization were subjected to comparative evaluation. RESULTS: The incidence of postoperative cognitive dysfunction (POCD) was notably lower in the IoC group (10%) than in the control group (31.7%) (P = 0.003). Postoperative serum CRP and GFAP concentrations exhibited significant differences at time points T2 (CRP: P = 0.000; GFAP: P = 0.000) and T3 (CRP: P = 0.003; GFAP: P = 0.008). Postoperative blood glucose levels (P = 0.000) and the overall rate of complications (P = 0.037) were significantly lower in Group IoC than in Group control. CONCLUSION: The employment of IoC monitoring for the management of elderly surgical patients can accelerate postoperative convalescence by mitigating intraoperative stress and reducing peripheral and central inflammatory injury. TRIAL REGISTRATION: Chinese Clinical Trial Registry Identifier: ChiCTR1900025241 (17/08/2019).

Incidence, prevention, risk factors, and prediction of venous thromboembolism in Chinese patients after colorectal cancer surgery: a prospective, multicenter cohort study.

BACKGROUND: Venous thromboembolism (VTE) is a common and serious complication after colorectal cancer (CRC) surgery. Few large-sample studies have reported VTE incidence and management status after CRC surgery in China. This study aimed to investigate the incidence and prevention of VTE in Chinese patients after CRC surgery, identify risk factors for developing VTE, and construct a new scoring system for clinical decision-making and care planning. METHODS: Participants were recruited from 46 centers in 17 provinces in China. Patients were followed up for 1 month postoperatively. The study period was from May 2021 to May 2022. The Caprini score risk stratification and VTE prevention and incidence were recorded. The predictors of the occurrence of VTE after surgery were identified by multivariate logistic regression analysis, and a prediction model (CRC-VTE score) was developed. RESULTS: A total of 1836 patients were analyzed. The postoperative Caprini scores ranged from 1 to 16 points, with a median of 6 points. Of these, 10.1% were classified as low risk (0-2 points), 7.4% as moderate risk (3-4 points), and 82.5% as high risk (≥5 points). Among these patients, 1210 (65.9%) received pharmacological prophylaxis, and 1061 (57.8%) received mechanical prophylaxis. The incidence of short-term VTE events after CRC surgery was 11.2% (95% CI 9.8-12.7), including deep venous thrombosis (DVT) (11.0%, 95% CI 9.6-12.5) and pulmonary embolism (PE) (0.2%, 95% CI 0-0.5). Multifactorial analysis showed that age (≥70 years), history of varicose veins in the lower extremities, cardiac insufficiency, female sex, preoperative bowel obstruction, preoperative bloody/tarry stool, and anesthesia time at least 180 min were independent risk factors for postoperative VTE. The CRC-VTE model was developed from these seven factors and had good VTE predictive performance ( C -statistic 0.72, 95% CI 0.68-0.76). CONCLUSIONS: This study provided a national perspective on the incidence and prevention of VTE after CRC surgery in China. The study offers guidance for VTE prevention in patients after CRC surgery. A practical CRC-VTE risk predictive model was proposed.

Prophylactic and therapeutic potential of magnolol-loaded PLGA-PEG nanoparticles in a chronic murine model of allergic asthma.

Magnolol is a chemically defined and active polyphenol extracted from magnolia plants possessing anti-allergic activity, but its low solubility and rapid metabolism dramatically hinder its clinical application. To improve the therapeutic effects, magnolol-encapsulated polymeric poly (DL-lactide-co-glycolide)-poly (ethylene glycol) (PLGA-PEG) nanoparticles were constructed and characterized. The prophylactic and therapeutic efficacy in a chronic murine model of OVA-induced asthma and the mechanisms were investigated. The results showed that administration of magnolol-loaded PLGA-PEG nanoparticles significantly reduced airway hyperresponsiveness, lung tissue eosinophil infiltration, and levels of IL-4, IL-13, TGF-ß1, IL-17A, and allergen-specific IgE and IgG1 in OVA-exposed mice compared to their empty nanoparticles-treated mouse counterparts. Magnolol-loaded PLGA-PEG nanoparticles also significantly prevented mouse chronic allergic airway mucus overproduction and collagen deposition. Moreover, magnolol-encapsulated PLGA-PEG nanoparticles showed better therapeutic effects on suppressing allergen-induced airway hyperactivity, airway eosinophilic inflammation, airway collagen deposition, and airway mucus hypersecretion, as compared with magnolol-encapsulated poly (lactic-co-glycolic acid) (PLGA) nanoparticles or magnolol alone. These data demonstrate the protective effect of magnolol-loaded PLGA-PEG nanoparticles against the development of allergic phenotypes, implicating its potential usefulness for the asthma treatment.

Determining the safety and effectiveness of Tai Chi: a critical overview of 210 systematic reviews of controlled clinical trials.

BACKGROUND: This overview summarizes the best available systematic review (SR) evidence on the health effects of Tai Chi. METHODS: Nine databases (PubMed, Cochrane Library, EMBASE, Medline, Web of Science, China National Knowledge Infrastructure (CNKI), Chinese Scientific Journal Database (VIP), Sino-Med, and Wanfang Database) were searched for SRs of controlled clinical trials of Tai Chi interventions published between Jan 2010 and Dec 2020 in any language. Effect estimates were extracted from the most recent, comprehensive, highest-quality SR for each population, condition, and outcome. SR quality was appraised with AMSTAR 2 and overall certainty of effect estimates with the GRADE method. RESULTS: Of the 210 included SRs, 193 only included randomized controlled trials, one only included non-randomized studies of interventions, and 16 included both. Common conditions were neurological (18.6%), falls/balance (14.7%), cardiovascular (14.7%), musculoskeletal (11.0%), cancer (7.1%), and diabetes mellitus (6.7%). Except for stroke, no evidence for disease prevention was found; however, multiple proxy-outcomes/risks factors were evaluated. One hundred and fourteen effect estimates were extracted from 37 SRs (2 high, 6 moderate, 18 low, and 11 critically low quality), representing 59,306 adults. Compared to active and/or inactive controls, 66 of the 114 effect estimates reported clinically important benefits from Tai Chi, 53 reported an equivalent or marginal benefit, and 6 an equivalent risk of adverse events. Eight of the 114 effect estimates (7.0%) were rated as high, 43 (37.7%) moderate, 36 (31.6%) low, and 27 (23.7%) very low certainty evidence due to concerns with risk of bias (92/114, 80.7%), imprecision (43/114, 37.7%), inconsistency (37/114, 32.5%), and publication bias (3/114, 2.6%). SR quality was often limited by the search strategies, language bias, inadequate consideration of clinical, methodological, and statistical heterogeneity, poor reporting standards, and/or no registered SR protocol. CONCLUSIONS: The findings suggest Tai Chi has multidimensional effects, including physical, psychological and quality of life benefits for a wide range of conditions, as well as multimorbidity. Clinically important benefits were most consistently reported for Parkinson's disease, falls risk, knee osteoarthritis, low back pain, cerebrovascular, and cardiovascular diseases including hypertension. For most conditions, higher-quality SRs with rigorous primary studies are required. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021225708.

Effects of thoracic paravertebral block combined with s-ketamine on postoperative pain and cognitive function after thoracoscopic surgery.

Objectives: To assess the effects of thoracic paravertebral block and s-ketamine on postoperative pain and perioperative neurocognitive disorder (PND) in video-assisted thoracoscopic surgery. Methods: Patients (n = 120) aged 45-65 undergoing video-assisted thoracoscopic surgery were allocated randomly into the following three groups: patients in the C group received general anaesthesia; patients in the thoracic paravertebral block group, i.e. the TP group, received general anaesthesia and ultrasound-guided paravertebral block; and patients in the s-ketamine combined with ultrasound-guided thoracic paravertebral nerve block group, i.e. the TS group, received combined anaesthesia, which was administered as follows: general anaesthesia + ultrasound-guided paravertebral block + perioperative s-ketamine (a bolus of 0.3 mg/kg, followed by an infusion of 0.2 mg/kg/h until 30 min before the end of the surgical procedure). Results: Cognitive function was measured using the Mini-Mental State Examination 1 day preoperatively, 1 day postoperatively, and 3 months postoperatively. Z-score was used to determine the incidence of PND. Postoperative pain was assessed using the visual analogue scale at 0.5 and 24 h postoperatively. The use of opioid drugs, intraoperative vital signs, and other secondary outcomes were also recorded. The final analysis included a total of 110 patients. The intraoperative heart rate and mean arterial pressure in the TS and TP groups were lower than that for group C (P＜0.05). After surgery, patients in the TS group exhibited significantly lower pain scores at 0.5 h and 24 h (P＜0.001 and P = 0.004,respectively) as well as significantly lower rates of postoperative nausea, vomiting, and pulmonary complications (P＜0.05). The incidence of PND in the TP and TS groups was lower than those who received general anaesthesia. However, there was no significant difference in the incidence of PND between the TP and TS groups (P＞0.05). Conclusions: Ultrasound-guided paravertebral nerve block combined with s-ketamine decreased acute postoperative pain and improved the quality of recovery. However, perioperative s-ketamine did not improve cognitive function in patients under general anaesthesia with thoracic paravertebral block.

Chinese herbal injections versus intrapleural cisplatin for lung cancer patients with malignant pleural effusion: A Bayesian network meta-analysis of randomized controlled trials.

Background: Malignant pleural effusion (MPE) is a common complication in patients with advanced lung cancer that can severely compromise the quality of life and limit life expectancy. Randomized controlled trials (RCTs) have shown that Chinese herbal injections (CHIs) may be beneficial in improving quality of life. This network meta-analysis (NMA) aims to explore several CHIs used for lung cancer patients with MPE. Methods: Seven databases were systematically searched for eligible RCTs from inception to November 2021. The primary outcome was the clinical effective rate. Secondary outcomes were the improvement rate of Karnofsky performance status (KPS) score and incidence of adverse events (AEs). The Cochrane risk of bias 2 tool was used to assess the quality of included studies. Data analysis was performed using STATA 16.0 and R software 4.1.0. Both pairwise meta-analysis and Bayesian NMA were conducted. Competing interventions were ranked using the surface under the cumulative ranking (SUCRA) probabilities. Evidence grading was evaluated using the Confidence in Network Meta-Analysis online software (https://cinema.ispm.unibe.ch/). Results: A total of 44 studies involving 2,573 patients were included. The combined Huachansu injection (HCS) with intrapleural cisplatin (cis-diamminedichloro-platinum, DDP) had the highest probability of improving the clinical effective rate (SUCRA, 84.33%). The Kangai injection (KA) combined with DDP had the most improvement rate of KPS score (SUCRA, 80.82%), while the Fufangkushen injection (FFKS) alone was more likely to reduce AEs including gastrointestinal reactions (SUCRA, 89.92%), leukopenia (SUCRA, 91.85%), and chest pain (SUCRA, 98.17%). FFKS combined with DDP ranked the best in reducing the incidence of fever (SUCRA, 75.45%). Conclusions: Our NMA showed that CHIs alone or combined with DDP could improve clinical effectiveness and quality of life and reduce AEs, compared to DDP alone. HSC and KA, combined with DDP, may be the most effective considering clinical effective rate and improvement of KPS score, respectively. FFKS, either used alone or in combination therapy with DDP, may be the best in reducing AEs. However, high-quality RCTs with larger sample sizes are needed to further support the evidence. Systematic review registration: PROSPERO https://www.crd.york.ac.uk/prospero/, identifier CRD42021285275.

Single medium-sized hepatocellular carcinoma treated with sequential conventional transarterial chemoembolization (cTACE) and microwave ablation at 4 weeks versus cTACE alone: a propensity score.

BACKGROUND: Microwave ablation (MWA) is a potentially curative treatment for unresectable patients with hepatocellular carcinoma (HCC) ≤ 3 cm, while its therapeutic efficacy decreases significantly for HCC > 3cm. Previous studies have demonstrated that conventional transarterial chemoembolization (cTACE) combined with MWA (cTACE-MWA) may improve local tumor control rate and reduce the recurrence rate for HCC > 3cm. However, there have been few study designs to analyze the clinical efficacy of cTACE-MWA for medium-sized HCC (3-5cm). Therefore, this study aims to compare the clinical efficacy and safety of cTACE-MWA with cTACE alone for a single medium-sized HCC of 3-5 cm in diameter. METHODS: We retrospectively investigate the data of 90 patients with a single medium-sized HCC who were referred to our hospital and underwent cTACE-MWA or cTACE alone from December 2017 to March 2020. Then, patients were identified with propensity score-matched (1:1). The local tumor response to treatment and time to progression (TTP) were compared using mRECIST criteria between the cTACE-MWA group and the cTACE group. RESULTS: A total of 42 patients were included after matching (cTACE-MWA: 21; cTACE: 21). Comparing with cTACE, cTACE-MWA demonstrate significantly better local tumor control (ORR: 95.2% vs 61.9%, p = 0.02; DCR: 95.2% vs 66.7%, p = 0.045) and TTP (median 19.8 months vs 6.8 months, p < 0.001). The 1- and 2-year cumulative probabilities of OS were 100% and 95% in the cTACE-MWA group, which were significantly higher than those in the cTACE group (95% and 76%) (p = 0.032). Multivariate Cox regression analysis illustrates that cTACE-MWA was associated with better TTP (hazard ratio, 0.28; 95% CI: 0.1, 0.76; p = 0.012), but tumor size was associated with worse TTP (hazard ratio, 1.71; 95% CI: 1.01, 2.89; p = 0.045). CONCLUSIONS: cTACE followed by MWA improved TTP and OS in patients with a single medium-sized HCC, and no major complication was observed in this study.

Knockdown of PDX1 enhances the osteogenic differentiation of ADSCs partly via activation of the PI3K/Akt signaling pathway.

BACKGROUND: Osteoporosis (OP) is a systemic bone disease manifested as low bone mass, destruction of bone microstructure, increased bone fragility and fracture risk. The purpose of this study was to explore the role and mechanism of PDX1 for osteogenic differentiation of adipose derived stem cells (ADSCs). METHODS: GSE37329 dataset was retrieved from NCBI Gene Expression Omnibus (GEO) database and performed bioinformatic analyses. ADSCs were incubated with normal medium, osteogenic induction medium (OIM) and OIM+si-PDX1. Then, alkaline phosphatase (ALP) staining and Alizarin Red Staining (ARS) were performed to assess the role of PDX1 for osteogenesis of ADSCs. PI3K inhibitor, LY294002 was then added to further explore the mechanism of PDX1 for osteogenic differentiation of ADSCs. Western blot assay was used to assess the osteogenic-related markers. Graphpad software was used to perform statistically analysis. RESULTS: A total of 285 DEGs were obtained from analysis of the dataset GSE37329, of which 145 were upregulated and 140 were downregulated genes. These differentially expressed genes mainly enriched in cell differentiation and PI3K/Akt signaling pathway. Moreover, PDX1 was decreased in osteogenic induced ADSCs. Knockdown of PDX1 significantly increased osteogenic differentiation capacity and p-PI3K and p-Akt protein levels. Administration with LY294002 could partially reversed the promotion effects of si-PDX1. CONCLUSION: In conclusion, knockdown of PDX1 promotes osteogenic differentiation of ADSCs through the PI3K/Akt signaling pathway.

Propofol suppresses cell proliferation in gastric cancer cells through NRF2-mediated polyol pathway.

Propofol, a widely used short-acting intravenous sedative agent, has gradually gained attention due to the tumour-suppressing role and non-anaesthetic effect. Dysfunction of metabolic reprogramming has been recognised as a well-documented factor for tumour progression. The aim of this study is to explore the effect of propofol on the polyol pathway in gastric cancer cells. In this study, we found that propofol treatment led to a significant downregulation of cell proliferation in BGC823 and GES-1 cells, which was attributed to the decreased AR-mediated polyol pathway. Both aldo-keto reductase family 1, member B1 (AKR1B1) and AKR1B10 were significantly reduced in BGC823 and GES-1 cells in response to propofol stimulation, leading to decreased AR activity and sorbitol level. Addition of sorbitol could reverse the inhibitory effect of propofol on cell proliferation. Mechanically, propofol treatment drastically inhibited phosphorylation and nuclear translocation of nuclear factor (erythroid-derived 2)-like 2 (NRF2), subsequently decreased the binding of NRF2 to AR promoter. Overexpression of NRF2 resulted in the recovery of AR expression in gastric cancer cell with propofol treatment. Taken together, these finding showed that propofol suppressed cell proliferation in BGC823 and GES-1 cell through NRF2-mediated polyol pathway, which would aid the selection of sedation for patients with gastric cancer.

Inhibition of Inflammation and Regulation of AQPs/ENaCs/Na+-K+-ATPase Mediated Alveolar Fluid Transport by Total Flavonoids Extracted From Nervilia fordii in Lipopolysaccharide-induced Acute Lung Injury.

Aims: The occurrence of vascular permeability pulmonary edema in acute lung injury (ALI) is related to the imbalance of alveolar fluid transport. Regulating the active transport of alveolar fluid by aquaporins (AQPs), epithelial sodium channels (ENaCs), and Na+-K+-ATPase can effectively reduce the edema fluid in the alveolar cavity and protect against ALI. We evaluated the therapeutic effects of total flavonoids, extracted from Nervilia fordii (TFENF), and investigated its potential mechanisms of alveolar fluid transport in a rat ALI model. Materials and methods: A model of lipopolysaccharide (LPS, 5 mg/kg)-induced ALI was established in Sprague-Dawley (SD) rats through the arteriae dorsalis penis. SD rats were divided into six groups, including the vehicle, LPS model, TFENF (6 mg/kg, 12 mg/kg, 24 mg/kg), and dexamethasone group (DEX group, 5 mg/kg). The wet-to-dry (W/D) lung weight ratio, oxygenation index, and histopathological observation were used to evaluate the therapeutic effect of TFENF. The mRNA expression of AQPs, ENaCs, and pro-inflammatory cytokines was determined using real-time polymerase chain reaction, whereas protein expression was determined using immunohistochemistry. The Na + -K + -ATPase activity was assessed using enzyme-linked immunosorbent assay. Results: LPS significantly stimulated the production of inflammatory mediators including tumor necrosis factor (TNF)-α and interleukin (IL)-1ß, and disrupted the water transport balance in the alveolar cavity by inhibiting AQPs/ENaCs/Na + -K + -ATPase. Pretreatment with TFENF reduced the pathological damage and W/D ratio of the lungs and ameliorated the arterial blood oxygen partial pressure (PaO2) and oxygenation index. TFENF further decreased the mRNA level of TNF-α and IL-1ß; increased the expression of AQP-1, AQP-5, αENaC, and ßENaC; and increased Na + -K + -ATPase activity. Moreover, the regulation of AQPs, ßENaC, and Na + -K + -ATPase and the inhibition of TNF-α and IL-1ß by TFENF were found to be dose dependent. Conclusion: TFENF protects against LPS-induced ALI, at least in part, through the suppression of inflammatory cytokines and regulation of the active transport capacity of AQPs/ENaCs/Na + -K + -ATPase. These findings suggest the therapeutic potential of TFENF as phytomedicine to treat inflammation and pulmonary edema in ALI.

The traditional herbal formulation, Jianpiyifei II, reduces pulmonary inflammation induced by influenza A virus and cigarette smoke in mice.

Chronic obstructive pulmonary disease (COPD) is a worldwide chronic inflammatory lung disease, and influenza A virus (IAV) infection is a common cause of acute exacerbations of COPD (AECOPD). Therefore, targeting viral infections represents a promising strategy to prevent the occurrence and development of inflammatory flare ups in AECOPD. Jianpiyifei II (JPYFII) is a traditional herbal medicine used in China to treat patients with COPD, and its clinical indications are not well understood. However, investigation of the anti-inflammatory effects and underlying mechanism using an animal model of smoking have been reported in a previous study by our group. In addition, some included herbs, such as Radix astragali and Radix aupleuri, were reported to exhibit antiviral effects. Therefore, the aim of the present study was to investigate whether JPYFII formulation relieved acute inflammation by clearing the IAV in a mouse model that was exposed to cigarette smoke experimentally. JPYFII formulation treatment during smoke exposure and IAV infection significantly reduced the number of cells observed in bronchoalveolar lavage fluid (BALF), expression of proinflammatory cytokines, chemokines, superoxide production, and viral load in IAV-infected and smoke-exposed mice. However, JPYFII formulation treatment during smoke exposure alone did not reduce the number of cells in BALF or the expression of Il-6, Tnf-a, and Il-1ß. The results demonstrated that JPYFII formulation exerted an antiviral effect and reduced the exacerbation of lung inflammation in cigarette smoke (CS)-exposed mice infected with IAV. Our results suggested that JPYFII formulation could potentially be used to treat patients with AECOPD associated with IAV infection.

Rabeprazole inhibits inflammatory reaction by inhibition of cell pyroptosis in gastric epithelial cells.

BACKGROUND: Helicobacter pylori (H. pylori) is a common pathogen in development of peptic ulcers with pyroptosis. Rabeprazole, a critical component of standard triple therapy, has been widely used as the first-line regimen for H. pylori infectious treatment. The aim of this study to explore the function of Rabeprazole on cell pyroptosis in vitro. METHODS: The clinical sample from patients diagnosed with or without H. pylori-infection were collected to analyze by Immunohistochemistry (IHC). Real-time quantitative PCR (qPCR), western blot (WB) and enzyme linked immunosorbent assay (Elisa) were performed to analyze the effect of Rabeprazole on cell pyroptosis, including LDH, IL-1ß and IL-18. RESULTS: In this study, we showed that Rabeprazole regulated a phenomenon of cell pyroptosis as confirmed by lactate dehydrogenase (LDH) assay. Further results showed that Rabeprazole inhibited cell pyroptosis in gastric epithelial cells by alleviating GSDMD-executed pyroptosis, leading to decrease IL-1ß and IL-18 mature and secretion, which is attributed to NLRP3 inflammasome activation inhibition. Further analysis showed that ASC, NLRP3 and Caspase-1, was significantly repressed in response to Rabeprazole stimulation, resulting in decreasing cleaved-caspase-1 expression. Most important, NLRP3 and GSDMD is significantly increased in gastric tissue of patients with H. pylori infection. CONCLUSION: These findings revealed a critical role of Rabeprazole in cell pyroptosis in patients with H. pylori infection, suggesting that targeting cell pyroptosis is an alternative strategy in improving H. pylori treatment.