Effect of resistance exercise on physical fitness, quality of life, and fatigue in patients with cancer: a systematic review.

Objective: The purpose of this study is to conduct a systematic review to assess the effects of different forms of resistance exercises (resistance exercise, resistance exercise combined with aerobic exercise, and resistance exercise combined with other exercises) on physical fitness, quality of life (QOL), and fatigue of patients with cancer. Methods: We conducted a systematic review using the Cochrane Handbook for Systematic Reviews of Interventions guidelines. We searched PubMed, Web of Science, and Scopus databases for the studies from the establishment of the database to September 2023, including randomized controlled trials and clinical trials that evaluated the effects of different resistance exercise on physical fitness, QOL, and fatigue in all patients with cancer. Two reviewers independently assessed the quality of all the included studies using the Cochrane Handbook for Systematic Reviews of Interventions and MINORS scale. We divided the intervention into three types: resistance exercise, resistance exercise combined with aerobic exercise, and resistance exercise combined with other exercises. Results: In total, 48 studies (3,843 participants) met the inclusion criteria. The three exercise intervention forms have significant effects on physical fitness and QOL, but the improvement effect on fatigue is not clear. A total of 34 studies reported significant and beneficial effects of resistance exercise on physical fitness across all types of cancer. There were 28 studies that reported significant or borderline improvement effects of resistance on QOL, and only 10 studies reported significant effects of resistance exercise interventions on fatigue improvement in patients with cancer. Conclusions: Resistance exercise, resistance exercise combined with aerobic exercise, and resistance exercise combined with other exercises all have a positive effect on improving fitness and QOL in patients with cancer. Resistance exercise has an advantage in improving muscle strength, while combined resistance exercise has an advantage in improving QOL; however, there are no consistent findings in improving fatigue, although low-intensity resistance exercise is effective. Systematic review registration: www.inplasy.com, identifier INPLASY2023110034.

Appendicitis tends to be complicated during the COVID-19 epidemic: A multicentre retrospective study.

Background: In past studies, non-medical factors in the social-healthcare-patient triad associated with the prevalence of COVID-19 have led to delays in the presentation of patients with acute appendicitis and an increase in complications. However, as research progresses, there is increasing evidence of a clinical association between COVID-19 and the development of acute appendicitis. Methods: The effect of COVID-19 prevalence and associated factors on acute appendicitis in the control (2016-2019) and exposed (2020-2023) groups was derived from a retrospective study of 3070 patients with acute appendicitis from 2016 to 2023. Results: After the implementation of the restrictions, the rate of acute appendicitis visits in the exposed group compared to the control group dropped sharply in the initial period (P = 0.047) and recovered gradually with the relaxation of the restrictions. Similar changes occurred in the number of acute complicated appendicitis visits. In addition, after the lifting of restrictions and the COVID-19 outbreak, the proportion of acute complicated appendicitis in the exposed group increased significantly (P < 0.001) and an increase in the number of complicated appendicitis visits was observed (P < 0.001) compared with the control group. In addition, the age distribution of acute appendicitis during this period showed an ageing trend (P = 0.001). Conclusion: COVID-19 infections may be more likely to progress to complicated appendicitis after an episode of appendicitis, even if they have been cured for the same period of time. In addition, the proportion of elderly patients with appendicitis increased after the COVID-19 epidemic.

Effects of high-intensity intermittent exercise on glucose and lipid metabolism in type 2 diabetes patients: a systematic review and meta-analysis.

Objective: To evaluate the effects of high-intensity interval training (HIIT) on glycolipid metabolism among type 2 diabetes patients. Methods: HIIT is consistent with an exercise program (65%-90%VO2max or 75%-95% HRmax; exercise cycle≥2 weeks; frequency ≥ 2 times/week). A meta-analysis was conducted utilizing the random effects model to synthesize the data. Results: A total of 22 RCT studies with 1034 diabetic patients were included. Compared to moderate-intensity aerobic exercise or conventional controls, HIIT yields noteworthy effects on FBG (MD: -0.55; 95% CI: -0.85- -0.25, Hedges' g =0.98), 2h-PG (MD: -0.36; 95% CI: -0.57- -0.14, Hedges' g =1.05), FINS (MD: -0.41; 95% CI: -0.79- -0.03, Hedges' g =1.07), HbA1c (MD: -0.60; 95% CI: -0.84- -0.36, Hedges' g =2.69), TC (MD: -0.58; 95% CI: -0.80- -0.36, Hedges' g =2.36), TG (MD: -0.50; 95% CI: -0.86- -0.14, Hedges' g =1.50), HDL (MD: 0.62; 95% CI: 0.29-0.95, Hedges' g =1.19) and LDL (MD: -0.31; 95% CI: -0.56- -0.08, Hedges' g =0.91), all of the above p<0.01. Conclusions: HIIT has been shown to improve glucose and lipid metabolism in patients with type 2 diabetes, especially in HbA1c, TC, TG, and HDL. For patients between the ages of 40 and 60 with less than 5 years of disease, exercise programs of moderate to longer duration or moderate to high intensity will produce more favorable results.

Comparing efficacy and safety of mirabegron, tamsulosin, and solifenacin in ureteral stent-related symptoms: outcomes from a network meta-analysis.

Background: Although ureteral stents are a well-established and commonly used method for renal drainage, the ureteral stent-related symptoms (SRSs) they cause in patients cannot be ignored. It is currently unclear whether mirabegron has a place in the treatment of SRSs. Our study aims to systematically evaluate the efficacy and safety of mirabegron in treating SRSs in adult patients. Methods: Through a systematical search of multiple scientific databases before August 2023, we performed a systematic review and meta-analysis of the primary outcomes of interest according to the PRISMA. Analysis was performed under multivariate random-effects network models and effects of drugs was ranked with surface under the cumulative ranking curves (SUCRA) probabilities. Results: Sixteen studies involving 2,002 patients were included. All regimens (including mirabegron, solifenacin, and tamsulosin) were significantly better than placebo in urinary symptoms. Solifenacin was associated with more adverse drug events than mirabegron and tamsulosin. The SUCRA values showed that mirabegron was the best in the outcomes of body pain (71.5%), sexual matters (76.4%), and adverse events (70.5%). Solifenacin was the best in the outcomes of urinary symptoms (73.1%), general health (81.0%), and work performance (85.1%). Tamsulosin had the lowest rate of all outcomes. Conclusions: Compared with traditional drugs for relieving SRSs, mirabegron performs best in terms of alleviating body pain, sexual matters, and adverse events, with little difference in urinary symptoms and general health. Further high-quality prospective double-blinded randomized controlled trials (RCTs) are required to provide sufficient evidence supporting our observations.

Cluster-Based Strategy for Maximizing the Sum-Rate of a Distributed Reconfigurable Intelligent Surface (RIS)-Assisted Coordinated Multi-Point Non-Orthogonal Multiple-Access (CoMP-NOMA) System.

This article proposes a distributed intelligent Coordinated Multi-Point Non-Orthogonal Multiple-Access (CoMP-NOMA) collaborative transmission model with the assistance of reconfigurable intelligent surfaces (RISs) to address the issues of poor communication quality, low fairness, and high system power consumption for edge users in multi-cellular networks. By analyzing the interaction mechanisms and influencing factors among RIS signal enhancement, NOMA user scheduling, and multi-point collaborative transmission, the model establishes RIS-enhanced edge user grouping and coordinates NOMA user clusters based on this. In the multi-cell RIS-assisted JT-CoMP NOMA downlink transmission, joint optimization of the power allocation (PA), user clustering (UC), and RIS phase-shift matrix design (PS) poses a challenging Mixed-Integer Non-Linear Programming (MINLP) problem. The original problem is decomposed by optimizing the formulas into joint sub-problems of PA, UC, and PA and PS, and solved using an alternating optimization approach. Simulation results demonstrate that the proposed scheme effectively reduces the system's power consumption while significantly improving the system's throughput and rates.

Cancer­associated fibroblasts under therapy­induced senescence in the tumor microenvironment (Review).

Current cancer treatments target tumor cells; however, the tumor microenvironment (TME) induces therapeutic resistance, tumor development and metastasis, thus rendering these treatments ineffective. Research on the TME has therefore concentrated on nonmalignant cells. Cancer-associated fibroblasts (CAFs) are a major TME component, which contribute to cancer progression due to their diverse origins, phenotypes and functions, including cancer cell invasion and migration, extracellular matrix remodeling, tumor metabolism modulation and therapeutic resistance. Standard cancer treatment typically exacerbates the senescence-associated secretory phenotype (SASP) of senescent cancer cells and nonmalignant cells that actively leak proinflammatory signals in the TME. Therapy-induced senescence may impair cancer cell activity and compromise treatment responsiveness. CAFs and SASP are well-studied in the formation and progression of cancer. The present review discusses the current data on CAF senescence caused by anticancer treatment and assesses how senescence-like CAFs affect tumor formation. The development of senolytic medication for aging stromal cells is also highlighted. Combining cancer therapies with senolytics may boost therapeutic effects and provide novel possibilities for research.

Association between transcutaneous oxygen saturation within 24 h of admission and mortality in critically ill patients with non-traumatic subarachnoid hemorrhage: a retrospective analysis of the MIMIC-IV database.

Background: In critically ill patients, transcutaneous oxygen saturation (SpO2) upon admission is typically associated with in-hospital mortality. Nevertheless, the available information for patients with non-traumatic subarachnoid hemorrhage (SAH) is limited. In our study, our objective was to assess the correlation between SpO2 levels and mortality among patients diagnosed with severe SAH. Methods: In this study, we extracted data from the Medical Information Marketplace in Intensive Care (MIMIC-IV) database, which comprises information on critically ill patients. By employing matching ICD-9 and ICD-10 codes, we identified 3,328 patients diagnosed with SAH. Every individual who was admitted to the intensive care unit (ICU) had their SpO2 data and various covariates, including age, sex, diagnosis, and duration of stay, recorded upon admission. Subsequently, the patients were categorized into three distinct groups according to their SpO2 levels: low (≤95%), moderate (95-98%), and high (≥98%). To investigate the association between percutaneous oxygen saturation and mortality in patients with severe SAH, logistic regression, and cubic spline models were utilized. The main outcomes of interest were 28- and 90-day mortality rates. Additionally, subgroup analyses were conducted to evaluate these correlations and assess the consistency of interactions. Results: A cohort of 864 patients diagnosed with non-traumatic SAH was included in this study. The correlation between SpO2 and mortality displayed a U-shaped curve when utilizing a finite cubic spline function (non-linearity < 0.001), with the nadir in the probability of in-hospital death at 96%. Mortality at 28 and 90 days showed an inverse correlation with SpO2 < 96% (adjusted odds ratio [OR], 0.8; 95% confidence interval [CI], 0.67-0.95, and 0.76; 95% CI, 0.6-0.96). Conversely, there was a positive correlation between percutaneous oxygen saturation (SpO2) levels of ≥96% and mortality rates at both 28 and 90 days (adjusted OR, 1.17; 95% CI, 1.02-1.35 and 1.2; 95% CI, 1.05-1.39). Conclusion: In patients with severe subarachnoid hemorrhage, the association between SpO2 and mortality at 28 and 90 days demonstrated a U-shaped pattern. When SpO2 levels were between 95 and 98%, both short- and long-term mortality rates were at their lowest. Patients with significant subarachnoid hemorrhage had a lower chance of survival when their SpO2 values were either high or low.

Association between serum sodium levels within 24 h of admission and all-cause mortality in critically ill patients with non-traumatic subarachnoid hemorrhage: a retrospective analysis of the MIMIC-IV database.

Objective: The study aimed to evaluate the relationship between serum sodium and mortality in critically ill patients with non-traumatic subarachnoid hemorrhage. Methods: This is a retrospective investigation of critically ill non-traumatic patients with subarachnoid hemorrhage (SAH) utilizing the MIMIC-IV database. We collected the serum sodium levels at admission and determined the all-cause death rates for the ICU and hospital. We employed a multivariate Cox proportional hazard regression model and Kaplan-Meier survival curve analysis to ascertain the relationship between serum sodium and all-cause mortality. In order to evaluate the consistency of correlations, interaction and subgroup analyses were also conducted. Results: A total of 864 patients with non-traumatic SAH were included in this study. All-cause mortality in the ICU and hospital was 32.6% (282/864) and 19.2% (166/864), respectively. Sodium levels at ICU admission showed a statistically significant J-shaped non-linear relationship with ICU and hospital mortality (non-linear P-value < 0.05, total P-value < 0.001) with an inflection point of ~141 mmol/L, suggesting that mortality was higher than normal serum sodium levels in hypernatremic patients. Multivariate analysis after adjusting for potential confounders showed that high serum sodium levels (≥145 mmol/L) were associated with an increased risk of all-cause mortality in the ICU and hospital compared with normal serum sodium levels (135-145 mmol/L), [hazard ratio (HR) = 1.47, 95% CI: 1.07-2.01, P = 0.017] and (HR = 2.26, 95% CI:1.54-3.32, P < 0.001). Similarly, Kaplan-Meier (K-M) survival curves showed lower survival in patients with high serum sodium levels. Stratified analysis further showed that the association between higher serum sodium levels and hospital all-cause mortality was stronger in patients aged < 60 years with a hospital stay of <7 days. Conclusion: High serum sodium levels upon ICU admission are related to higher ICU and hospital all-cause mortality in patients with non-traumatic SAH. A new reference is offered for control strategies to correct serum sodium levels.

Establishment of 11-dehydro-thromboxane B2 time-resolved immunoassay and application in membranous nephropathy.

BACKGROUND: 11-Dehydro-thromboxane B2 (11-dehydro-TXB2) is the final stable metabolite of thromboxane A2 (TXA2) and is involved in thrombus formation. Patients with membranous nephropathy (MN) are prone to thromboembolism events. METHODS: Time-resolved fluorescence immunoassay (TRFIA) for 11-dehydro-TXB2 was established by indirect competitive method. The coated 11-dehydro-TXB2-BSA conjugate was used to bind the 11-dehydro-TXB2 antibody competitively to the 11-dehydro-TXB2 antigen in the samples, followed by Eu3+-labeled goat anti-mouse IgG antibody, to detect 11-dehydro-TXB2. This study measured 11-dehydro-TXB2 concentrations in serum samples from healthy individuals and patients with MN. RESULTS: The linear range of TRFIA was 16.38-2000 pg/mL, the sensitivity was 4.70 pg/mL, the average coefficients of variation from intra-assay and inter-assay were 3.50% and 4.95%, respectively, and the recovery was 99.38%. The serum level of 11-dehydro-TXB2 in patients with MN was significantly higher than that in healthy subjects (P < 0.05). The serum 11-dehydro-TXB2 concentration detected by TRFIA was highly consistent with that by ELISA (ρ = 0.900). DISCUSSION: This study successfully established a new highly sensitive method for the detection of 11-dehydro-TXB2 in serum. 11-Dehydro-TXB2 has great potential in evaluating the risk of thromboembolic events in patients with MN and is expected to be applied to other thromboembolic-related diseases.

Synergistic analysis of performance, microbial community, and metabolism in aerobic granular sludge under polyacrylonitrile microplastics stress.

Aerobic granular sludge (AGS) has proved to be a promising biotechnology for microplastics wastewater treatment. However, polyacrylonitrile microplastics (PAN MPs), the most widely used plastic in textile materials, have not been investigated. Therefore, the effect of the neglected PAN MPs on AGS at different concentrations (1, 10, and 100 mg/L) was evaluated. The results indicated that PAN MPs with 1 and 10 mg/L concentrations had no obvious effect on granular stability and nutrient removal performance, but greatly promoted the secretion of EPS. Remarkably, the granule structure was severely damaged under 100 mg/L PAN MPs. Moreover, microbial community analysis showed that phylum Proteobacteria played a dominant role in resistance to PAN MPs. Metabolic analysis further revealed that genes related to denitrification pathway (nasA, nirK, nirS and norB) and membrane transport were significantly inhibited under PAN MPs stress. This study may provide additional information on the treatment of microplastics wastewater using AGS.

Cardiac Amyloidosis: A Rare TTR Mutation Found in an Asian Female.

BACKGROUND: Transthyretin cardiac amyloidosis (ATTR) is a life-threatening, debilitating disease caused by abnormal formation and deposit of transthyretin (TTR) protein in multiple tissues, including myocardial extracellular matrix. It can be challenging to diagnose due to the myriad of presenting signs and symptoms. Additionally, numerous TTR mutations exist in certain ethnicities. Interestingly, our patient was discovered to have a very rare Gly67Ala TTR mutation typically not found in individuals of Asian descent. Recent advances in cardiovascular imaging techniques have allowed for earlier recognition and, therefore, management of this disease. Although incurable, there are now new, emerging treatments that are available for symptom control of cardiac amyloidosis, making early diagnosis vital for these patients, specifically their quality of life. CASE SUMMARY: We outline a case of a 50-year-old Asian female who was initially hospitalized for nausea and vomiting and persistent orthostatic hypotension. She underwent a multitude of laboratory and imaging tests, resulting in a diagnosis of cardiac amyloidosis, which was confirmed to be due to a rare TTR mutation via genetic testing. CONCLUSIONS: Our objective is to describe various TTR mutations, existing diagnostic imaging modalities, and available treatments, as well as highlight the importance of early screening and awareness of cardiac amyloidosis, allowing for quicker diagnosis and treatment of this disease.

Study on Quality Control of Compound Anoectochilus roxburghii (Wall.) Lindl. by Liquid Chromatography-Tandem Mass Spectrometry.

Compound Anoectochilus roxburghii (Wall.) Lindl. (A. roxburghii) oral liquid (CAROL) is a hospital preparation of A. roxburghii and Ganoderma lucidum (G. lucidum), which have hepatoprotective effects. Eight active components (five nucleosides/nucleobases and three triterpenoid acids) in CAROL, A. roxburghii, and G. lucidum were simultaneously detected by high-performance liquid chromatography−tandem mass spectrometry (LC−MS/MS). The multiple reaction monitoring (MRM) mode was applied for the detection of analytes. These eight compounds were separated well within 12 min and quantified using the internal standard working curve method. The method showed good linearity (R2 > 0.9935) and high sensitivity (limit of detection = 0.29 ng/mL). The analyte recovery ranged from 85.07% to 97.50% (relative standard deviation < 3.31%). The content of the target analytes in four batches of CAROL, and the raw materials of G. lucidum and A. roxburghii from the five regions was determined using this method. The contents of guanosine and ganoderic acid A in four batches of oral liquid were high and stabilized and could be recommended as quality markers (Q-marker) for CAROL. Simultaneous qualitative and quantitative analysis of nucleosides and triterpenoid acids in CAROL, A. roxburghii, and G. lucidum by LC−MS/MS based on the MRM model was reported for the first time. The proposed method provides a sensitive, rapid, and reliable approach for the quality control of Chinese medicinal products.

First-Principles Calculations of Two-Dimensional CdO/HfS2 Van der Waals Heterostructure: Direct Z-Scheme Photocatalytic Water Splitting.

Using two-dimensional (2D) heterostructure as photocatalyst for water splitting is a popular strategy for the generation of hydrogen. In this investigation, the first-principles calculations are explored to address the electronic performances of the 2D CdO/HfS2 heterostructure formed by van der Waals (vdW) forces. The CdO/HfS2 vdW heterostructure has a 1.19 eV indirect bandgap with type-II band alignment. Importantly, the CdO/HfS2 vdW heterostructure possesses an intrinsic Z-scheme photocatalytic characteristic for water splitting by obtaining decent band edge positions. CdO donates 0.017 electrons to the HfS2 layer in the heterostructure, inducing a potential drop to further separate the photogenerated electrons and holes across the interface. The CdO/HfS2 vdW heterostructure also has excellent optical absorption capacity, showing a promising role as a photocatalyst to decompose the water.

Development and External Validation of a Nomogram for Predicting Overall Survival in Stomach Cancer: A Population-Based Study.

OBJECTIVE: The study was to develop and externally validate a prognostic nomogram to effectively predict the overall survival of patients with stomach cancer. METHODS: Demographic and clinical variables of patients with stomach cancer in the Surveillance, Epidemiology, and End Results (SEER) database from 2007-2016 were retrospectively collected. Patients were then divided into the Training Group (n = 4,456) for model development and the Testing Group (n = 4,541) for external validation. Univariate and multivariate Cox regressions were used to explore prognostic factors. The concordance index (C-index) and the Kolmogorov-Smirnov (KS) value were used to measure the discrimination, and the calibration curve was used to assess the calibration of the nomogram. RESULTS: Prognostic factors including age, race, marital status, TNM stage, surgery, chemotherapy, grade, and the number of regional nodes positive were used to construct a nomogram. The C-index was 0.790 and the KS value was 0.45 for the Training Group, and the C-index was 0.789 for the Testing Group, all suggesting the good performance of the nomogram. CONCLUSION: We have developed an effective nomogram with ten easily acquired prognostic factors. The nomogram could accurately predict the overall survival of patients with stomach cancer and performed well on external validation, which would help improve the individualized survival prediction and decision-making, thereby improving the outcome and survival of stomach cancer.

Discovery of a cinnamyl piperidine derivative as new neddylation inhibitor for gastric cancer treatment.

Targeting neddylation pathway has been recognized as an attractive anticancer therapeutic strategy, thus discovering potent and selective neddylation inhibitors is highly desirable. Our work reported the discovery of novel cinnamyl piperidine compounds and their antitumor activity in vitro and in vivo. Among these compounds, compound 4g was identified as a novel neddylation inhibitor and decreased the neddylation levels of cullin 1, cullin 3 and cullin 5. Mechanistic studies demonstrated that compound 4g could inhibit the migration ability of gastric cancer cells and induce apoptosis partly mediated by the Nrf2-Keap1 pathway. Furthermore, in vivo anti-tumor studies showed that 4g effectively inhibited tumor growth without obvious toxicity. Collectively, the cinnamyl piperidine derivatives could serve as new lead compounds for developing highly effective neddylation inhibitors for gastric cancer therapy.

Establishment and application of an immunoassay for the simultaneous detection of IgG and its subtype IgG4 autoantibodies against M-type phospholipase A2 receptor.

BACKGROUND: The renal biopsy is an accurate and reliable gold standard for membranous nephropathy (MN) diagnosis. However, it is an invasive procedure involving the risk of hemorrhage or infection. Thus, an alternative approach that can facilitate the effective diagnosis and treatment monitoring of idiopathic membranous nephropathy (IMN) is urgently needed. METHODS: We established a dual-labeled time-resolved fluoroimmunoassay (TRFIA) to simultaneously detect phospholipase A2 receptor (PLA2R)-IgG4 and PLA2R-IgG antibodies. Utilizing this assay, we determined the ratio of autoantibodies in the serum of patients with different kidney diseases and normal controls. RESULTS: The sensitivity of TRFIA for detecting anti-PLA2R-IgG and anti-PLA2R-IgG4 was 0.12 µg/mL and 0.001 µg/mL, respectively. Human IgA did not interfere with the assay. Compared to anti-PLA2R-IgG alone, the positive rate of IMN could be increased from 86.5 % to 91.7 % through the combined use of anti-PLA2R-IgG4 and the PLA2R-IgG4/IgG ratio. In contrast, the false-positive rates for the detection of IgA nephropathy, lupus nephropathy, diabetic nephropathy, and minimal change nephropathy decreased from 25 to 50 % to 0 %. CONCLUSIONS: The dual-labeled PLA2R-IgG4/IgG-TRFIA for simultaneous detection of anti-PLA2R-IgG4 and anti-PLA2R-IgG will contribute to improved accuracy of IMN diagnosis.

Humanized anti­TLR4 monoclonal antibody ameliorates lipopolysaccharide­related acute kidney injury by inhibiting TLR4/NF­κB signaling.

A humanized anti­Toll­like receptor 4 (TLR4) monoclonal antibody (mAb) was previously produced using phage antibody library technology, and it was found that the mAb could effectively ameliorate lipopolysaccharide (LPS)­induced damage in macrophages. The present study investigated the protective effects exerted by the humanized anti­TLR4 mAb against LPS­induced acute kidney injury (AKI), as well as the underlying mechanisms. Female C57BL/6 mice were randomly divided into four groups (n=8 per group): i) Control; ii) LPS; iii) LPS + humanized anti­TLR4 mAb (1 µg/g); and iv) LPS + humanized anti­TLR4 mAb (10 µg/g). Serum creatinine, blood urea nitrogen, IL­6, TNFα and IL­1ß levels were then examined, followed by renal pathology assessment, immunohistochemical staining, reverse transcription­quantitative PCR and western blotting to assess apoptosis/survival/inflammation­related molecules and kidney injury molecule (KIM)­1. The humanized anti­TLR4 mAb successfully ameliorated LPS­induced AKI and renal pathological damage. The humanized anti­TLR4 mAb also dose­dependently suppressed LPS­induced elevations in serum IL­6, TNFα and IL­1ß, and decreased the renal expression levels of myeloid differentiation primary response 88 (MyD88), IKKα/ß, IκB, p65 and KIM­1. Compared with the LPS group, renal Bax and KIM­1 expression levels were significantly downregulated, and Bcl­2 expression was notably upregulated by the humanized anti­TLR4 mAb. Moreover, the humanized anti­TLR4 mAb also significantly decreased the protein expression levels of MyD88, phosphorylated (p)­IKKα/ß, p­IκB and p­p65 in the renal tissues compared with the LPS group. Therefore, the present study indicated that the anti­inflammatory effects of the humanized anti­TLR4 mAb against LPS­related AKI in mice were mediated via inhibition of the TLR4/NF­κB signaling pathway.

The protective role of protocatechuic acid against chemically induced liver fibrosis in vitro and in vivo.

Liver fibrosis is the result of long-term liver injury and has a high incidence worldwide. Protocatechuic acid (PCA) is ubiquitous in vegetables, nuts, brown rice and herbal medicines, which is reported to possess anti-asthmatic, anti-cancer, and anti-oxidation properties. Our research aimed to investigate the effect of PCA on liver fibrosis. In vitro, TNF-α-induced hepatic stellate cell (HSC) model was used to assess the anti-fibrosis effects of PCA. In vivo, mice were treated with thioacetamide (TAA) to develop liver fibrosis. Body weight, organ index, histological changes, and proteins alteration of factors associated with TGF-ß signaling pathway were used to assess the anti-fibrosis effects of PCA. Our results showed that PCA not only inhibited cell viability in TNF-α activated HSC-T6 cells in vitro, but also efficiently mitigated TAA-induced liver damage and fibrosis in vivo. Further experiments indicated that PCA played a protective role in liver fibrosis through regulation of the TGF-ß signaling pathway downregulating the protein expression of p-Smad2, p-ERK, c-Jun. In summary, our findings provide a pharmacological justification for the clinical application of PCA in preventing or treating liver fibrosis.

Industrial kinetic resolution of d,l-pantolactone by an immobilized whole-cell biocatalyst.

Immobilized whole-cells of Pichia pastoris harboring recombinant d-lactonase were entrapped in calcium alginate gels and used as an efficient biocatalyst for catalytic kinetic resolution of d,l-pantolactone. The immobilized whole-cell biocatalyst exhibited good catalytic stability, which was applied for stereospecific hydrolysis of d-pantolactone for up to 56 repeated batch reactions without obvious loss in the catalytic activity and enantioselectivity.

The signaling pathways and targets of traditional Chinese medicine and natural medicine in triple-negative breast cancer.

ETHNOPHARMACOLOGICAL RELEVANCE: Triple-negative breast cancer (TNBC) has a poorer prognosis than other subtypes due to its strong invasion and higher risk of distant metastasis. Traditional Chinese medicine (TCM) and natural medicine have the unique advantages of multitargets and small side-effects and may be used as long-term complementary and alternative therapies. AIM OF THE REVIEW: The present article summarizes the classical signaling pathways and potential targets by the action of TCM and natural medicine (including extracts, active constituents and formulas) on TNBC and provides evidence for its clinical efficacy. METHODS: The literature information was acquired from the scientific databases PubMed, Web of Science and CNKI from January 2010 to June 2020, and it was designed to elucidate the internal mechanism and role of TCM and natural medicine in the treatment of TNBC. The search key words included "Triple negative breast cancer" or "triple negative breast carcinoma", "TNBC" and "traditional Chinese medicine" or "Chinese herbal medicine", "medicinal plant", "natural plant", and "herb". RESULTS: We described the antitumor activity of TCM and natural medicine in TNBC based on different signaling pathways. Plant medicine and herbal formulas regulated the related gene and protein expression via pathways such as PI3K/AKT/mTOR, MAPK and Wnt/ß-catenin, which inhibit the growth, proliferation, migration, invasion and metastasis of TNBC cells. CONCLUSION: The inhibitory effect of TCM and natural medicine on tumors was reflected in multiple levels and multiple pathways, providing reasonable evidence for new drug development. To make TCM and natural medicine widely and flexibly used in clinical practice, the efficacy, safety and mechanism of action need more in-depth experimental research.