Optimized new Shengmai powder inhibits myocardial fibrosis in heart failure by regulating the rat sarcoma/rapidly accelerated fibrosarcoma/mitogen-activated protein kinase kinase/extracellular regulated protein kinases signaling pathway.

OBJECTIVE: Exploring the effect of Optimized New Shengmai powder (, ONSMP) on myocardial fibrosis in heart failure (HF) based on rat sarcoma (RAS)/rapidly accelerated fibrosarcoma (RAF)/mitogen-activated protein kinase kinase (MEK)/extracellular regulated protein kinases (ERK) signaling pathway. METHODS: Randomized 70 Sprague-Dawley rats into sham (n = 10) and operation (n = 60) groups, then established the HF rat by ligating the left anterior descending branch of the coronary artery. We randomly divided the operation group rats into the model, ONSMP [including low (L), medium (M), and high (H) dose], and enalapril groups. After the 4-week drug intervention, echocardiography examines the cardiac function and calculates the ratios of the whole/left heart to the rat's body weight. Finally, we observed the degree of myocardial fibrosis by pathological sections, determined myocardium collagen (COL) I and COL Ⅲ content by enzyme-linked immunosorbent assay, detected the mRNA levels of COL I, COL Ⅲ, α-smooth muscle actin (α-SMA), and c-Fos proto-oncogene (c-Fos) by universal real-time, and detected the protein expression of p-RAS, p-RAF, p-MEK1/2, p-ERK1/2, p-ETS-like-1 transcription factor (p-ELK1), p-c-Fos, α-SMA, COL I, and COL Ⅲ by Western blot. RESULTS: ONSMP can effectively improve HF rat's cardiac function, decrease cardiac organ coefficient, COL volume fraction, and COL I/Ⅲ content, down-regulate the mRNA of COL I/Ⅲ, α-SMA and c-Fos, and the protein of p-RAS, p-RAF, p-MEK1/ 2, p-ERK1/2, p-ELK1, c-Fos, COL Ⅰ/Ⅲ, and α-SMA. CONCLUSIONS: ONSMP can effectively reduce myocardial fibrosis in HF rats, and the mechanism may be related to the inhibition of the RAS/RAF/MEK/ERK signaling pathway.

Metaplastic regeneration in the mouse stomach requires a reactive oxygen species pathway.

In pyloric metaplasia, mature gastric chief cells reprogram via an evolutionarily conserved process termed paligenosis to re-enter the cell cycle and become spasmolytic polypeptide-expressing metaplasia (SPEM) cells. Here, we use single-cell RNA sequencing (scRNA-seq) following injury to the murine stomach to analyze mechanisms governing paligenosis at high resolution. Injury causes induced reactive oxygen species (ROS) with coordinated changes in mitochondrial activity and cellular metabolism, requiring the transcriptional mitochondrial regulator Ppargc1a (Pgc1α) and ROS regulator Nf2el2 (Nrf2). Loss of the ROS and mitochondrial control in Ppargc1a-/- mice causes the death of paligenotic cells through ferroptosis. Blocking the cystine transporter SLC7A11(xCT), which is critical in lipid radical detoxification through glutathione peroxidase 4 (GPX4), also increases ferroptosis. Finally, we show that PGC1α-mediated ROS and mitochondrial changes also underlie the paligenosis of pancreatic acinar cells. Altogether, the results detail how metabolic and mitochondrial changes are necessary for injury response, regeneration, and metaplasia in the stomach.

Gastric intestinal metaplasia: progress and remaining challenges.

Most gastric cancers arise in the setting of chronic inflammation which alters gland organization, such that acid-pumping parietal cells are lost, and remaining cells undergo metaplastic change in differentiation patterns. From a basic science perspective, recent progress has been made in understanding how atrophy and initial pyloric metaplasia occur. However, pathologists and cancer biologists have long been focused on the development of intestinal metaplasia patterns in this setting. Arguably, much less progress has been made in understanding the mechanisms that lead to the intestinalization seen in chronic atrophic gastritis and pyloric metaplasia. One plausible explanation for this disparity lies in the notable absence of reliable and reproducible small animal models within the field, which would facilitate the investigation of the mechanisms underlying the development of gastric intestinal metaplasia (GIM). This review offers an in-depth exploration of the current state of research in GIM, shedding light on its pivotal role in tumorigenesis. We delve into the histological subtypes of GIM and explore their respective associations with tumor formation. We present the current repertoire of biomarkers utilized to delineate the origins and progression of GIM and provide a comprehensive survey of the available, albeit limited, mouse lines employed for modeling GIM and engage in a discussion regarding potential cell lineages that serve as the origins of GIM. Finally, we expound upon the myriad signaling pathways recognized for their activity in GIM and posit on their potential overlap and interactions that contribute to the ultimate manifestation of the disease phenotype. Through our exhaustive review of the progression from gastric disease to GIM, we aim to establish the groundwork for future research endeavors dedicated to elucidating the etiology of GIM and developing strategies for its prevention and treatment, considering its potential precancerous nature.

Single-cell sequencing of ascites fluid illustrates heterogeneity and therapy-induced evolution during gastric cancer peritoneal metastasis.

Peritoneal metastasis is the leading cause of death for gastrointestinal cancers. The native and therapy-induced ascites ecosystems are not fully understood. Here, we characterize single-cell transcriptomes of 191,987 ascites cancer/immune cells from 35 patients with/without gastric cancer peritoneal metastasis (GCPM). During GCPM progression, an increase is seen of monocyte-like dendritic cells (DCs) that are pro-angiogenic with reduced antigen-presenting capacity and correlate with poor gastric cancer (GC) prognosis. We also describe the evolution of monocyte-like DCs and regulatory and proliferative T cells following therapy. Moreover, we track GC evolution, identifying high-plasticity GC clusters that exhibit a propensity to shift to a high-proliferative phenotype. Transitions occur via the recently described, autophagy-dependent plasticity program, paligenosis. Two autophagy-related genes (MARCKS and TXNIP) mark high-plasticity GC with poorer prognosis, and autophagy inhibitors induce apoptosis in patient-derived organoids. Our findings provide insights into the developmental trajectories of cancer/immune cells underlying GCPM progression and therapy resistance.

Unique ghost surface phonon polaritons in biaxially hyperbolic materials.

We predicted peculiar ghost surface phonon polaritons in biaxially hyperbolic materials, where the two hyperbolic principal axes lie in the plane of propagation. We took the biaxially-hyperbolic α-MoO3 as one example of the materials to numerically simulate the ghost surface phonon polaritons. We found three unique ghost surface polaritons to appear in three enclosed wavenumber-frequency regions, respectively. These ghost surface phonon polaritons have different features from the surface phonon polaritons found previously, i.e., they are some hybrid-polarization surface waves composed of two coherent evanescent branch-waves in the α-MoO3 crystal. The interference of branch-waves leads to that their Poynting vector and electromagnetic fields both exhibit the oscillation-attenuation behavior along the surface normal, or a series of rapidly attenuated fringes. We found that the in-plane hyperbolic anisotropy and low-symmetric geometry of surface are the two necessary conditions for the existence of these ghost surface polaritons.

Unique surface polaritons and their transitions in metamaterials.

We investigated surface polaritons in a metamaterial composed of polar-crystal layers and antiferromagnetic layers. In a specific geometry, two surface polaritons were predicted, which are a unique ghost surface polariton (GSP) and surface hybrid-polarization polariton (SHP). The two surface polaritons occupy different segments of one smooth dispersion curve and are magnetically tunable. An external magnetic field along the antiferromagnetic easy axis can bring about the switch or transition between the two surface polaritons and meanwhile performs the necessary condition for the existence of two surface polaritons. In the metamaterial, either surface polariton consists of two branch waves. The branch waves of the GSP are coherent and have the same amplitude and different phases, but those of the SHP are not coherent and have different amplitudes and phases. The main characteristic of the GSP is that its fields oscillate and attenuate with the distance away from the metamaterial surface and exhibit interferent fringes on the plane normal to the surface.

Spin angular momentum and nonreciprocity of ghost surface polariton in antiferromagnets.

We investigated the spin angular momentum (SAM) and nonreciprocity of ghost surface polariton (GSP) at the surface of an antiferromagnet (AF) in the normal geometry, where the AF easy axis and external field (H0) both are normal to the AF surface. We found that the dispersion equation is invariant when the inversions of wavevector and external magnetic field, k→-k and H0→-H0, are taken. However, its polarization and SAM are nonreciprocal. The SAM is vertical to the propagation direction of GSP, and consists of two components. We analytically found that the in-plane component is locked to H0, or it is changed in sign due to the inversion of H0. The out-plane one is locked to k since it is changed in sign as the inversion of k is taken. Either component contains an electric part and a magnetic part. Above the AF surface, the two electric parts form the left-handed triplet with the wavevector k, but the two magnetic parts form the right-handed triplet with k. In the AF, the chirality of the SAM changes with the distance from the surface. The SAM is very large on or near the surface and it may be very interesting for the manipulation of micron and nano particles on the AF surface. These are obviously different from the relevant features of conventional surface polaritons. The SAM also is field-tunable.

The Efficacy and Safety of Celecoxib in Addition to Standard Cancer Therapy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

The purpose of this meta-analysis was to evaluate the efficacy and safety of celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, in addition to standard anticancer therapy. Randomized controlled trials (RCTs) that evaluated the efficacy and safety of celecoxib-combined cancer therapy were systematically searched in PubMed and Embase databases. The endpoints were overall survival (OS), progression-free survival (PFS), disease-free survival (DFS), objective response rate (ORR), disease control rate (DCR), pathological complete response (pCR), and adverse events (AEs). The results of 30 RCTs containing 9655 patients showed limited benefits in celecoxib-combined cancer therapy. However, celecoxib-combined palliative therapy prolonged PFS in epidermal growth factor receptor (EGFR) wild-type patients (HR = 0.57, 95%CI = 0.35-0.94). Moreover, despite a slight increase in thrombocytopenia (RR = 1.35, 95%CI = 1.08-1.69), there was no increase in other toxicities. Celecoxib combined with adjuvant therapy indicated a better OS (HR = 0.850, 95%CI = 0.725-0.996). Furthermore, celecoxib plus neoadjuvant therapy improved the ORR in standard cancer therapy, especially neoadjuvant therapy (overall: RR = 1.13, 95%CI = 1.03-1.23; neoadjuvant therapy: RR = 1.25, 95%CI = 1.09-1.44), but not pCR. Our study indicated that adding celecoxib to palliative therapy prolongs the PFS of EGFR wild-type patients, with good safety profiles. Celecoxib combined with adjuvant therapy prolongs OS, and celecoxib plus neoadjuvant therapy improves the ORR. Thus, celecoxib-combined cancer therapy may be a promising therapy strategy.

Mesoscopic structural damage and permeability evolution of Shale subjected to freeze-thaw treatment.

To study the mesoscopic damage and permeability evolution characteristics of rock under freeze-thaw (F-T) cycles, freeze-thaw cycle experiments were carried out of shale under different F-T temperatures and numbers of cycles, and nuclear magnetic resonance (NMR) and permeability experiments of shale were conducted thereafter. On the basis of these experiments, the pores and permeability of the F-T shale were analyzed, and the existing permeability model is modified and improved; Therefore, the mesoscopic damage evolution characteristics and permeability evolution law of the F-T shale are obtained. It was found that with increasing number of cycles, the pore structure of the rock samples changed as the pore size expanded and the number of pores increased, and the average porosity also increased correspondingly. The influence of the F-T cycle temperature on the shale permeability was not as notable as that of the number of F-T cycles. Based on the SDR-REV permeability model, the spectral area ratio parameters of large pores and fractures in the T2 spectrum were considered for correction, and a direct relationship between the permeability, F-T temperature and number of cycles was obtained via regression analysis. Compared to the experimental results, it was found that the modified model achieved a good applicability. The damage and permeability characteristics of shale under different F-T conditions were analysed from a microscopic perspective, which could yield an important reference for engineering construction in frozen soil areas.

Survival landscape of different tumor regression grades and pathologic complete response in rectal cancer after neoadjuvant therapy based on reconstructed individual patient data.

BACKGROUND: Neoadjuvant therapy can lead to different tumor regression grades (TRG) in rectal cancer after neoadjuvant therapy. The purposes of this study are to investigate the relationships among TRG, pathologic complete response (pCR) and long-term survival, on the basis of reconstructed individual patient data (IPD). METHODS: The PubMed, Embase, Ovid and Cochrane CENTRAL databases were searched. The primary endpoint was to evaluate the survival landscape of different TRGs after neoadjuvant therapy and the secondary endpoint was to evaluate the associations between pCR and survival. IPD were reconstructed with Kaplan-Meier curves. RESULTS: The 10-year overall survival (OS) and 5-year disease-free survival (DFS) were clearly higher in the pCR group than in the non-pCR (npCR) group (80.5% vs. 48.3, 90.1% vs. 69.8%). Furthermore, the OS and DFS increased with improvement in tumor regression after neoadjuvant therapy. According to the IPD, the pCR group had longer OS (HR = 0.240, 95% CI = 0.177-0.325, p < 0.001) and DFS (HR = 0.274, 95% CI = 0.205-0.367, p < 0.001) than the npCR group. Better tumor regression was associated with better survival outcomes (p < 0.005). Direct calculation of published HR values yielded similar results. CONCLUSIONS: Our results indicate a positive relationship between better tumor regressions and improved survival benefits among the npCR group and patients with rectal cancer achieving pCR had much longer OS and DFS than patients achieving npCR, presenting a survival landscape of different TRGs and pCR in rectal cancer after neoadjuvant therapy.

Spin-splitting in a reflective beam off an antiferromagnetic surface.

A linearly-polarized radiation can be considered as the superposition of two circularly-polarized components with the same propagating direction and opposite spins. We investigated the splitting between the two spin-components in the reflective beam off the antiferromagnetic surface. The gyromagnetism and surface impedance mismatch cause the difference between the spatial shifts of the two spin-components, i.e., the spin-splitting. We analytically achieved the in- and out-plane shift-expressions of either spin-component for two typical linearly-polarized incident beams (i.e., the p- and s-incidences). In the case of no gyromagnetism, we obtained very simple shift-expressions, which indicate a key role played by the gyromagnetism or the surface impedance-mismatch in spin-splitting. Based on a FeF2 crystal, the spin-splitting distance was calculated. The spin-splitting distance is much longer for the p-incidence than the s-incidence, and meanwhile the in-plane splitting distance is much larger than the out-plane one. The gyromagnetism plays a key role for the in-plane spin-splitting and the surface impedance-mismatch is a crucial factor for the out-plane spin-splitting distance. The results are useful for the manipulation of infrared radiations and infrared optical detection.

Postoperative Adjuvant Treatment Strategy for Locally Advanced Rectal Cancer after Neoadjuvant Treatment.

BACKGROUND: Neoadjuvant (chemo) radiotherapy is used as a standard treatment for locally advanced rectal cancer (LARC), but there is no general consensus on either the efficacy of postoperative adjuvant chemotherapy in patients with LARC after neoadjuvant treatment and surgery, or whether the addition of oxaliplatin to adjuvant chemotherapy provides survival benefits. METHODS: We performed a meta-analysis of data from the PubMed and Embase databases. We included patients with LARC who received neoadjuvant (chemo) radiotherapy and curative surgery. Overall survival (OS), disease-free survival (DFS), toxicity, and compliance were analyzed in the oxaliplatin/fluorouracil- (OX/FU-) based group compared with the FU-based group, and in the chemotherapy group compared with the observation group. RESULTS: Twenty studies were included in the analysis. Our results indicated that adjuvant chemotherapy prolonged OS (hazard ratio [HR] = 0.78, 95%CI = 0.67-0.91) in patients with LARC treated with neoadjuvant (chemo) radiotherapy and surgery compared with those in the observation group. Subgroup analysis showed the same results in both the ypStage II and ypStage III groups. Compared with those in the observation group, patients in the chemotherapy group also showed an increase in DFS (HR = 0.75, 95%CI = 0.60-0.93). No significant increase was observed in OS (HR = 1.04, 95%CI = 0.87-1.24) or DFS (HR = 0.98, 95%CI = 0.76-1.27) when oxaliplatin was added to FU-based adjuvant chemotherapy, as compared with the FU-based treatment, and subgroup analysis also indicated no survival benefits in the clinical stage II, clinical stage III, ypStage II, and ypStage III groups. CONCLUSIONS: For patients with LARC who have already received neoadjuvant (chemo) radiotherapy and curative surgery, adjuvant chemotherapy improves OS over that in the observation group. Adding oxaliplatin to FU-based adjuvant chemotherapy does not confer survival benefits beyond those from FU-based adjuvant chemotherapy.

Large spatial shifts of reflective beam at the surface of graphene/hBN metamaterials.

We theoretically studied the Goos-Hänchen (GH) and Imbert-Fedorov (IF) shifts of reflective beam at the surface of graphene/hBN metamaterials. The results show that the GH-shift is significantly enhanced and also possesses the large reflectivity when the light beam is incident at the critical angle near the Brewster angle. We found that the IF-shift is the largest when the reflective beam is a special polarized-beam or the reflective coefficients satisfy the conditions |rs | = |rp | and φs - φp = 2jπ (j is an integer). By changing the chemical potential, filling ratio and tilted angle, the position and width of frequency windows obtaining the maximum values of shifts can be effectively adjusted. The large and tunable GH- and IF-shifts with the higher reflectivity provide an alternative scheme to develop new nano-optical devices.

Continuous Wound Infiltration with Local Anesthetic Is an Effective and Safe Postoperative Analgesic Strategy: A Meta-Analysis.

INTRODUCTION: Postoperative pain management is an essential module for perioperative care, especially for enhanced recovery after surgery programs. Continuous wound infiltration (CWI) with local anesthetic may be a promising postoperative analgesic strategy. However, its analgesic efficacy and safety remain debatable. METHODS: Embase and PubMed databases were systematically searched for relevant randomized controlled trials (RCTs). RCTs assessing the analgesic efficacy and safety of CWI with local anesthetic for postoperative analgesia were selected. The outcomes contained pain scores during rest and mobilization, total opioid consumption, time to the first request of rescue analgesia, length of hospital stay, satisfaction with analgesia, time to return of bowel function, postoperative nausea and vomiting, total complication, wound infection, hypotension, and pruritus. The weighted mean difference and risk ratio were used to pool continuous and dichotomous variables, respectively. RESULTS: A total of 121 RCTs were included. CWI with local anesthetic reduced postoperative pain during rest and mobilization at different time points, increased satisfaction with analgesia, shortened recovery of bowel function, and reduced postoperative nausea and vomiting compared with the placebo group, especially for laparotomy surgery. There were no significant differences in these clinical outcomes compared to epidural and intravenous analgesia. CWI with local anesthetic reduced the total opioid consumption and hypotension risk and did not increase total complications, wound infection, or pruritus. CWI with local anesthetic had a better analgesic efficacy without increased side effects for sternotomy surgery. However, CWI with local anesthetic did not translate into favorable analgesic benefits in laparoscopic surgery. CONCLUSION: CWI with local anesthetic is an effective postoperative analgesic strategy with good safety profiles in laparotomy and sternotomy surgery, and thus CWI with local anesthetic may be a promising analgesic option enhancing recovery after surgery programs for these surgeries.

Continuous wound infiltration (CWI) with local anesthetic may be a promising postoperative analgesic strategy, but its effect remains debatable. We performed this meta-analysis based on 121 high-quality articles (RCTs) to evaluate the analgesic efficacy and safety of CWI with local anesthetic. We found that CWI with local anesthetic could reduce postoperative pain, increase satisfaction with analgesia, shorten recovery of bowel function, and reduce postoperative nausea and vomiting, especially for laparotomy surgery. However, CWI with local anesthetic did not show favorable analgesic benefits in laparoscopic surgery.

Goos-Hänchen and Imbert-Fedorov shifts on hyperbolic crystals.

We investigated Goos-Hänchen (GH) and Imbert-Fedorov (IF) shifts on a uniaxial hyperbolic crystal, where a circularly-polarized beam was incident on the crystal from the free space. The GH- and IF-shifts were analytically obtained and numerically calculated for the hexagonal boron nitride. Our results demonstrate that the GH- and IF-shift spectra are complicated and completely different in and out the hyperbolic frequency-bands (the reststrahlen bands in the infrared region). At the critical or Brewster angle, concisely analytical expressions of GH-shift was found, which explicitly state the optical-loss dependence of GH-shift at these special angles. We found the GH-shifts are very large at the critical and Brewster angles. It is very necessary to know these effects since hyperbolic materials are usually applied in the nano- and micro-optics or technology fields.

Unusual spin and angular momentum of Dyakonov waves at the hyperbolic-material surface.

Three Dyakonov-like polaritons (DLPs) exist at the interface between a hyperbolic material (HM) and a covering medium (CM). Each DLP is a hybridized-polarization surface polariton composed of two evanescent waves on both sides of the interface. We investigated their spin and angular momentum. We analytically found that any DLP carries two spins producing mutually orthogonal spin angular-momentum (SAM) components. The spins and angular-momentum have different features on both sides of the interface, and further differences among the three DLPs are very obvious. For the interface structure formed by hexagonal boron nitride (hBN) and air, the SAM mainly distributes in the air for DLP-I, the SAM is approximately transverse to the propagating direction for DLP-II, and it is surprisingly large in the hBN for DLP-III and can reach several ten times that in the usual situation. There is the spin-k locking for every DLP, but the spin-k locking is different for different DLPs. These properties do not exist for traditional surface polaritons or ordinary evanescent waves. The above unique results can support some potential applications in the fields of nano- and micro-photonics, optoelectronics and mechanics, as well as relevant technologies.

Efficacy and Prognostic Factors for PARP Inhibitors in Patients With Ovarian Cancer.

Background: The prognostic factors for efficacy of poly(ADP-ribose) polymerase (PARP) inhibitors in ovarian cancer remain unknown. The purpose of this study is to evaluate the efficacy of PARP inhibitors and to explore their prognostic factors in ovarian cancer. Methods: PubMed, Embase, and conference databases were searched for relevant prospective clinical trials. The primary outcomes included overall survival (OS), progression-free survival (PFS), and their prognostic factors. Secondary outcomes included PFS2, time to first subsequent therapy (TFST), time to second subsequent therapy (TSST), chemotherapy-free interval (CFI), and their prognostic factors. Hazard ratio (HR) with a 95% confidence interval (CI) was used as an effect measure. Results: PARP inhibitors significantly prolonged PFS in patients with ovarian cancer regardless of their BRCA and HRD status (HR = 0.44, 95% CI = 0.36-0.55). BRCA mutation, HRD-positive status, and sensitivity to platinum represented effective prognostic factors for PFS (Pinteraction < 0.01 and within-trial interaction HR < 1). Other clinicopathological factors did not predict the benefit of PFS (Pinteraction > 0.10). Moreover, PARP inhibitors significantly increased PFS2, TFST, TSST, and CFI, with significant BRCA-related differences. However, HRD-related differences could not be evaluated due to the lack of eligible studies. Furthermore, PARP inhibitors did not translate into prolonged OS, although there was a benefit associated with OS (HR = 0.84, 95% CI = 0.70-1.02). PARP inhibitors used as maintenance therapy after first or subsequent line therapy improved OS (HR = 0.77, 95% CI = 0.63-0.93). Conclusions: PARP inhibitors can significantly prolong PFS, PFS2, TFST, TSST, and CFI in ovarian cancer patients. BRCA mutation, HRD-positive status, and sensitivity to platinum are effective prognostic factors for the efficacy of PARP inhibitors. However, despite the PFS improvement, this does not translate into prolonged OS for patients.

Protein acetylation in mitochondria plays critical functions in the pathogenesis of fatty liver disease.

BACKGROUND: Fatty liver is a high incidence of perinatal disease in dairy cows caused by negative energy balance, which seriously threatens the postpartum health and milk production. It has been reported that lysine acetylation plays an important role in substance and energy metabolism. Predictably, most metabolic processes in the liver, as a vital metabolic organ, are subjected to acetylation. Comparative acetylome study were used to quantify the hepatic tissues from the severe fatty liver group and normal group. Combined with bioinformatics analysis, this study provides new insights for the role of acetylation modification in fatty liver disease of dairy cows. RESULTS: We identified 1841 differential acetylation sites on 665 proteins. Among of them, 1072 sites on 393 proteins were quantified. Functional enrichment analysis shows that higher acetylated proteins are significantly enriched in energy metabolic pathways, while lower acetylated proteins are significantly enriched in pathways related to immune response, such as drug metabolism and cancer. Among significantly acetylated proteins, many mitochondrial proteins were identified to be interacting with multiple proteins and involving in lipid metabolism. Furthermore, this study identified potential important proteins, such as HADHA, ACAT1, and EHHADH, which may be important regulatory factors through modification of acetylation in the development of fatty liver disease in dairy cows and possible therapeutic targets for NAFLD in human beings. CONCLUSION: This study provided a comprehensive acetylome profile of fatty liver of dairy cows, and revealed important biological pathways associated with protein acetylation occurred in mitochondria, which were involved in the regulation of the pathogenesis of fatty liver disease. Furthermore, potential important proteins, such as HADHA, ACAT1, EHHADH, were predicted to be essential regulators during the pathogenesis of fatty liver disease. The work would contribute to the understanding the pathogenesis of NAFLD, and inspire in the development of new therapeutic strategies for NAFLD.

Efficacy of immune checkpoint inhibitors and age in cancer patients.

Aim: To evaluate the impact of age on the efficacy of immune checkpoint inhibitors (ICI) in cancer patients. Materials & methods: The primary outcomes included overall survival (OS) and progression-free survival (PFS). Subgroup, meta-regression analysis and within-trial interaction HR were conducted. Results: A total of 34 studies containing 20,511 cancer patients were included. ICI could improve the OS and PFS in patient aged <65 and ≥65 years. Patients aged <75 years treated with ICI also had favorable OS and PFS compared with the control groups. Conclusion: ICI has comparable efficacy in cancer patients aged <65 and ≥65 years. Cancer patients aged ≥75 years need more attention in the future clinical trials.