Whole-course quality of tuberculosis (TB) care in rural China: a retrospective study based on chart abstraction.

OBJECTIVES: The aim of this study was to assess the quality of tuberculosis (TB) care for the whole course and assess factors that affect completing treatment. DESIGN: This is an observational retrospective study using chart abstraction for the whole course of TB care conducted at two underserved provinces in China. SETTING: The study was conducted from June 2021 to July 2021. All medical records (outpatient and inpatient) for the whole course (6-8 months) of patients with TB newly registered from July 2020 to December 2020 were reviewed and abstracted using predetermined checklists. PARTICIPANTS: A total of 268 outpatient medical records and 126 inpatient records were included. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome included diagnostic quality, treatment quality and management quality. The secondary outcome was completing treatment. RESULTS: For diagnostic quality, 94.2% of the diagnosis were based on adequate evidence. For treatment quality, 240 (91.6%) outpatients and 100 (85.5%) inpatients took the standard chemotherapy regimens. 234 (87.3%) patients completed treatment. 85.1% of the inpatients prescribed with second-line drugs were inappropriate. For management quality, 128 (47.9%) patients received midterm assessments, but only 47 (19.7%) received sufficient services for the whole course. Patients with TB symptoms were 1.8 times more likely to complete treatment (p=0.011). CONCLUSION: Patients with TB received high-quality diagnosis and treatment services, but low-quality whole-course management. Integration of medical and public health services should be strengthened to improve whole-course quality.

Cost-Effectiveness of First-Line Atezolizumab versus Chemotherapy in Non-Small-Cell Lung Cancer Patients Ineligible for Platinum-Containing Regimens.

Purpose: The IPSOS study provided evidence supporting the efficacy and tolerability of first-line atezolizumab compared to single-agent chemotherapy for non-small-cell lung cancer (NSCLC) patients ineligible for treatment with a platinum-containing regimen. This study aimed to assess the cost-effectiveness of atezolizumab specifically in this population, considering the perspective of the Chinese healthcare system. Patients and Methods: In this analysis, a three-state Markov model was utilized. The survival data were derived from the IPSOS clinical trial. Direct medical costs and utility values were collected from national authoritative database and published literature. The primary outcomes were costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratio (ICER). To ensure the robustness of our model, both one-way and probabilistic sensitivity analyses were conducted. Results: Atezolizumab monotherapy led to an increase in costs of $4139.23 compared to single-agent chemotherapy. Additionally, it resulted in a gain of 0.14 QALYs, leading to an ICER of $29,365.79 per QALY, which was below the willingness-to-pay threshold of $36,066 per QALY used in the model. One-way sensitivity analyses revealed cost of atezolizumab and utility of progressive disease (PD) as major influencing factors for ICER. Furthermore, probabilistic sensitivity analyses confirmed our base-case results. Conclusion: From the perspective of the Chinese healthcare system, atezolizumab emerges as a cost-effective choice for the first-line treatment of NSCLC patients ineligible for platinum-based chemotherapy.

An integrated multi-omics analysis reveals osteokines involved in global regulation.

Bone secretory proteins, termed osteokines, regulate bone metabolism and whole-body homeostasis. However, fundamental questions as to what the bona fide osteokines and their cellular sources are and how they are regulated remain unclear. In this study, we analyzed bone and extraskeletal tissues, osteoblast (OB) conditioned media, bone marrow supernatant (BMS), and serum, for basal osteokines and those responsive to aging and mechanical loading/unloading. We identified 375 candidate osteokines and their changes in response to aging and mechanical dynamics by integrating data from RNA-seq, scRNA-seq, and proteomic approaches. Furthermore, we analyzed their cellular sources in the bone and inter-organ communication facilitated by them (bone-brain, liver, and aorta). Notably, we discovered that senescent OBs secrete fatty-acid-binding protein 3 to propagate senescence toward vascular smooth muscle cells (VSMCs). Taken together, we identified previously unknown candidate osteokines and established a dynamic regulatory network among them, thus providing valuable resources to further investigate their systemic roles.

Preparation and adjuvanticity against PCV2 of Viola philippica polysaccharide loaded in Chitosan-Gold nanoparticle.

The present Porcine circovirus type 2 virus (PCV2) vaccine adjuvants suffer from numerous limitations, such as adverse effects, deficient cell-mediated immune responses, and inadequate antibody production. In this study, we explored the potential of a novel nanoparticle (CS-Au NPs) based on gold nanoparticles (Au NPs) and chitosan (CS) that modified Viola philippica polysaccharide (VPP) as efficient adjuvants for PCV2 vaccine. The characterization demonstrated that CS-Au-VPP NPs had a mean particle size of 507.42 nm and a zeta potential value of -21.93 mV. CS-Au-VPP NPs also exhibited good dispersion and a stable structure, which did not alter the polysaccharide properties. Additionally, the CS-Au-VPP NPs showed easy absorption and utilization by the organism. To investigate their immune-enhancing potential, mice were immunized with a mixture of CS-Au-VPP NPs and PCV2 vaccine. The evaluation of relevant immunological indicators, including specific IgG antibodies and their subclasses, cytokines, and T cell subpopulations, confirmed their immune-boosting effects. The in vivo experiments revealed that the medium-dose CS-Au-VPP NPs significantly elevated the levels of specific IgG antibodies and their subclasses, cytokines, and T cell subpopulations in PCV2-immunized mice. These findings suggest that CS-Au-VPP NPs can serve as a promising vaccine adjuvant due to their stable structure and immunoenhancement capabilities.

The effect of canagliflozin on gut microbiota and metabolites in type 2 diabetic mice.

BACKGROUND: Sodium glucose cotransporter 2 inhibitor (SGLT2i) represent a new type of hypoglycemic medicine that can cause massive loss of glucose from the urine, which have several benefits of reducing body weight and improving the prognosis of cardiovascular and kidney diseases. Although they are oral medicated hypoglycemic agents, their effects on the gut microbiome and function have been unclear. OBJECTIVE: In order to describe the effects of canagliflozin on intestinal flora and metabolites, diabetic mice were randomized to receive canagliflozin or isoconcentration carboxymethylcellulose sodium by gavage for 8 weeks. Feces were collected for 16 S rRNA gene and LC-MS/MS analysis and enriched metabolic pathways through Kyoto Encyclopedia of Genes and Genomes (KEGG). Liver, muscle, intestinal, fat were collected for qRT-PCR according to KEGG enriched metabolic pathways. RESULTS: Our results showed that canagliflozin significantly increased GLP-1 level and impacted on the composition of gut microbiota and metabolites. It mainly increased Muribaculum, Ruminococcaceae_UCG_014, Lachnospiraceae-UCG-001, decreased ursodeoxycholic acids (UDCA) and hyodeoxycholic acids (HDCA), and increased fatty acids metabolites in feces. CONCLUSION: In conclusion, we analyzed the changes of intestinal microbial composition and metabolites in diabetic mice after canagliflozin intervention and found that canagliflozin influenced intestinal fatty acid and bile acid (BA) metabolism. This study will provide reference for subsequent SGLT2i and intestinal related research.

Discovery of metal-binding proteins by thermal proteome profiling.

Metal-binding proteins (MBPs) have various and important biological roles in all living species and many human diseases are intricately linked to dysfunctional MBPs. Here, we report a chemoproteomic method named 'metal extraction-triggered agitation logged by thermal proteome profiling' (METAL-TPP) to globally profile MBPs in proteomes. The method involves the extraction of metals from MBPs using chelators and monitoring the resulting protein stability changes through thermal proteome profiling. Applying METAL-TPP to the human proteome with a broad-spectrum chelator, EDTA, revealed a group of proteins with reduced thermal stability that contained both previously known MBPs and currently unannotated MBP candidates. Biochemical characterization of one potential target, glutamine-fructose-6-phosphate transaminase 2 (GFPT2), showed that zinc bound the protein, inhibited its enzymatic activity and modulated the hexosamine biosynthesis pathway. METAL-TPP profiling with another chelator, TPEN, uncovered additional MBPs in proteomes. Collectively, this study developed a robust tool for proteomic discovery of MBPs and provides a rich resource for functional studies of metals in cell biology.

Sleeve gastrectomy with one anastomosis bipartition versus one anastomosis gastric bypass: A pilot study.

BACKGROUND: One anastomosis gastric bypass (OAGB) is a new recognized metabolic surgery, but the problem that we cannot screen the excluded stomach is a troubling issue in China. The emergence of sleeve gastrectomy plus one anastomosis bipartition (SG + OAB) makes us see a hope to solve this problem. OBJECTIVES: By comparing the efficacy of the two surgical methods, to evaluate whether SG + OAB surgery can solve the dilemma faced by OAGB that the excluded stomach cannot be screened. METHODS: A retrospective study to compare the patients who underwent OAGB and SG + OAB was conducted. The main outcome measures were (1) operation risk, (2) weight loss, and (3) diabetes remission at 6 months. RESULTS: This study was conducted in the bariatric/metabolic surgical center. From November 2021 to February 2022, a total of 30 patients with obesity who received SG + OAB surgery were recruited. Another matched 60 patients undergoing OAGB were recruited as control group. There was no difference in preoperative age (32.15 ± 9.02 vs. 34.47 ± 7.22; p = .224), female ratio (83% vs. 85%; p = .837), and BMI (36.18 ± 5.30 vs. 34.68 ± 5.58; p = .217) between the two groups. OAGB had a shorter mean operation time (121.67 ± 20.41 vs. 143.50 ± 25.07 min; p < .001) and a lower intraoperative blood loss (21.92 ± 12.35 vs. 32.43 ± 22.01 mL; p = .005), but a longer postoperative flatus passage (2.13 ± 0.43 vs. 1.87 ± 0.43 days; p = .007) compared with the SG + OAB group. Two patients (6.7%) developed major surgical complication in SG + OAB group but no major complication developed in OAGB group. At 6 months after surgery, SG + OAB had a higher %total weight loss than OAGB (31.05 ± 3.12 vs. 28.14 ± 5.43%; p = .015), but diabetes remission rate was similarly high in both groups. CONCLUSIONS: SG + OAB operation had a non-inferior or even better weight loss than OAGB, with a similar glycemic control efficacy. However, the high complication rate of SG + OAB is the major drawback that needs attention.

Autophagy inhibition mediated by trillin promotes apoptosis in hepatocellular carcinoma cells via activation of mTOR/STAT3 signaling.

Apoptosis and autophagy have been shown to act cooperatively and antagonistically in self-elimination process. On the one side, apoptosis and autophagy can act as partners to induce cell death in a coordinated or cooperative manner; on the flip side, autophagy acts as an antagonist to block apoptotic cell death by promoting cell survival. Our previous research indicated that trillin could induce apoptosis of PLC/PRF/5 cells, but the effects of trillin on autophagy as well as its functional relationship to apoptosis have not been elucidated. Here, the running study aims to investigate the function and molecular mechanism of trillin on autophagy with hepatocellular carcinoma (HCC) cells. The objective of this study is to investigate the molecular mechanism of trillin on autophagy in HCC cells. Protein levels of autophagy markers beclin1, LC3B, and p62 were detected by western blotting. 6-Hydroxyflavone and stattic were used to test the role of trillin regulation of autophagy via serine threonine kinase (AKT)/extracellular-regulated protein kinases (ERK) 1/2/mammalian target of rapamycin (mTOR)/signal transducer and activator of transcription 3 (STAT3) signaling pathway. Flow cytometry was used to detect caspase 3 activity and apoptosis in PLC/PRF/5 cells treated with trillin for 24 h with or without rapamycin, stattic, and 6-hydroxyflavone. The protein level of autophagy marker beclin1 was decreased, whilst the protein level of p62 was significantly increased by trillin treatment, indicating trillin treatment led to inhibition of autophagy in HCC cells. Trillin treatment could reduce the protein levels of p-AKT and p-ERK1/2, but enhance the protein levels of mTOR and p-mTOR, suggesting that trillin could inhibit AKT/ERK rather than mTOR. The AKT/ERK activator 6-hydroxyflavone could reverse the loss of AKT and ERK1/2 phosphorylation induced by trillin, implying that trillin impairs autophagy through activated mTOR rather than AKT/ERK. STAT3 and p-STAT3 were significantly upregulated by the trillin treatment with an increase in dose from 0 to 50 µM, suggesting that autophagy inhibition is mediated by trillin via activation of STAT3 signaling. The STAT3 inhibitor stattic significantly reversed the increased STAT3 phosphorylation at tyrosine 705 induced by trillin. The mTOR signaling inhibitor rapamycin reversed the trillin-induced mTOR phosphorylation enhancement but exerted no effects on total mTOR levels, suggesting trillin treatment led to inhibition of autophagy in HCC cells through activating mTOR/STAT3 pathway. Furthermore, caspase 3 activities and the total rate of apoptosis were increased by trillin treatment, which was reversed by rapamycin, stattic, and 6-hydroxyflavone, proving that trillin promotes apoptosis via activation of mTOR/STAT3 signaling. Trillin induced autophagy inhibition and promoted apoptosis in PLC/PRF/5 cells via the activation of mTOR/STAT3 signaling. Trillin has the potential to be a viable therapeutic option for HCC treatment.

A cell transcriptomic profile provides insights into adipocytes of porcine mammary gland across development.

BACKGROUND: Studying the composition and developmental mechanisms in mammary gland is crucial for healthy growth of newborns. The mammary gland is inherently heterogeneous, and its physiological function dependents on the gene expression of multiple cell types. Most studies focused on epithelial cells, disregarding the role of neighboring adipocytes. RESULTS: Here, we constructed the largest transcriptomic dataset of porcine mammary gland cells thus far. The dataset captured 126,829 high-quality nuclei from physiological mammary glands across five developmental stages (d 90 of gestation, G90; d 0 after lactation, L0; d 20 after lactation, L20; 2 d post natural involution, PI2; 7 d post natural involution, PI7). Seven cell types were identified, including epithelial cells, adipocytes, endothelial cells, fibroblasts cells, immune cells, myoepithelial cells and precursor cells. Our data indicate that mammary glands at different developmental stages have distinct phenotypic and transcriptional signatures. During late gestation (G90), the differentiation and proliferation of adipocytes were inhibited. Meanwhile, partly epithelial cells were completely differentiated. Pseudo-time analysis showed that epithelial cells undergo three stages to achieve lactation, including cellular differentiation, hormone sensing, and metabolic activation. During lactation (L0 and L20), adipocytes area accounts for less than 0.5% of mammary glands. To maintain their own survival, the adipocyte exhibited a poorly differentiated state and a proliferative capacity. Epithelial cells initiate lactation upon hormonal stimulation. After fulfilling lactation mission, their undergo physiological death under high intensity lactation. Interestingly, the physiological dead cells seem to be actively cleared by immune cells via CCL21-ACKR4 pathway. This biological process may be an important mechanism for maintaining homeostasis of the mammary gland. During natural involution (PI2 and PI7), epithelial cell populations dedifferentiate into mesenchymal stem cells to maintain the lactation potential of mammary glands for the next lactation cycle. CONCLUSION: The molecular mechanisms of dedifferentiation, proliferation and redifferentiation of adipocytes and epithelial cells were revealed from late pregnancy to natural involution. This cell transcriptomic profile constitutes an essential reference for future studies in the development and remodeling of the mammary gland at different stages.

Highly Enhanced Mechanical, Thermal, and Crystallization Performance of PLA/PBS Composite by Glass Fiber Coupling Agent Modification.

To improve the toughness and heat resistance of polylactic acid (PLA), polybutylene succinate (PBS) was sufficiently blended with PLA as the base matrix, and the glass fiber (GF) that was modified with 3-aminopropyltriethoxysilane (KF-GF) was added as the reinforcement. The results demonstrated a noteworthy boost in both mechanical and heat resistance properties when employing KH-GF, in comparison to pristine GF. When the content of KH-GF reached 20%, the tensile, flexural, and IZOD impact strength of the composites were 65.53 MPa, 83.43 MPa, and 7.45 kJ/m2, respectively, which were improved by 123%, 107%, and 189% compared to the base matrix, respectively. This enhancement was primarily attributed to the stronger interfacial adhesion between KH-GF and the PLA/PBS matrix. Furthermore, the Vicat softening temperature of the composites reached 128.7 °C, which was a result of increased crystallinity. In summary, the incorporation of KH-GF into PLA/PBS composites resulted in notable enhancements in their mechanical properties, crystallinity, and thermal characteristics. The high performance KH-GF-reinforced PLA/PBS composite showed a broad application potential in the field of biodegradable packaging, biodegradable textiles, and biodegradable plastic bags.

Polarized Tunneling Transistor for Ultrafast Memory.

In today's information age, high performance nonvolatile memory devices have become extremely important. Despite their potential, existing devices suffer from limitations, such as low operation speed, low memory capacity, short retention time, and a complex preparation process. To overcome these limitations, advanced memory designs are required to improve speed, memory capacity, and retention time and reduce the number of preparation steps. Here, we present a nonvolatile floating-gate-like memory device based on a transistor that uses the polarization effect of ferroelectric material PZT (Pb[Zr0.2Ti0.8]O3) for regulating tunneling electrons for charging and discharging the MoS2 channel layer. The transistor is defined as a polarized tunneling transistor (PTT) and does not require a tunnel layer or a floating-gate layer. The PTT demonstrates an ultrafast programming/erasing speed of 25/20 ns and a response time of 120/105 ns, which is comparable to the ultrafast flash memories based on van der Waals heterostructures. Additionally, the PTT has a high extinction ratio of 104, a long retention time of 10 years, and a simple fabrication process. Our research provides future guidelines for the development of the next generation of ultrafast nonvolatile memory devices.

TREM2 acts as a receptor for IL-34 to suppress acute myeloid leukemia in mice.

The bone marrow microenvironment supports leukocyte mobilization and differentiation and controls the development of leukemias, including acute myeloid leukemia (AML). Here, we found that the development of AML xenotransplants was suppressed in mice with osteoclasts tuberous sclerosis 1 (Tsc1) deletion. Tsc1-deficient osteoclasts released a high level of interleukin-34 (IL-34), which efficiently induced AML cell differentiation and prevented AML progression in various preclinical models. Conversely, AML development was accelerated in mice deficient in IL-34. Interestingly, IL-34 inhibited AML independent of its known receptors but bound directly to triggering receptor expressed on myeloid cells 2 (TREM2), a key hub of immune signals. TREM2-deficient AML cells and normal myeloid cells were resistant to IL-34 treatment. Mechanistically, IL-34-TREM2 binding rapidly phosphorylated Ras protein activator like 3 and inactivated extracellular signal-regulated protein kinase 1/2 signaling to prevent AML cell proliferation and stimulate differentiation. Furthermore, TREM2 was downregulated in patients with AML and associated with a poor prognosis. This study identified TREM2 as a novel receptor for IL-34, indicating a promising strategy for overcoming AML differentiation blockade in patients with AML.

Exosome Release Delays Senescence by Disposing of Obsolete Biomolecules.

Accumulation of obsolete biomolecules can accelerate cell senescence and organism aging. The two efficient intracellular systems, namely the ubiquitin-proteasome system and the autophagy-lysosome system, play important roles in dealing with cellular wastes. However, how multicellular organisms orchestrate the processing of obsolete molecules and delay aging remains unclear. Herein, it is shown that prevention of exosome release by GW4869 or Rab27a-/- accelerated senescence in various cells and mice, while stimulating exosome release by nutrient restriction delays aging. Interestingly, exosomes isolate from serum-deprived cells or diet-restricted human plasma, enriched with garbage biomolecules, including misfolded proteins, oxidized lipids, and proteins. These cellular wastes can be englobed by macrophages, eventually, for disintegration in vivo. Inhibition of nutrient-sensing mTORC1 signaling increases exosome release and delays senescence, while constitutive activation of mTORC1 reduces exosome secretion and exacerbates senescence in vitro and in mice. Notably, inhibition of exosome release attenuates nutrient restriction- or rapamycin-delayed senescence, supporting a key role for exosome secretion in this process. This study reveals a potential mechanism by which stimulated exosome release delays aging in multicellular organisms, by orchestrating the harmful biomolecules disposal via exosomes and macrophages.

Sigma-1 Receptor Activation Improves Oligodendrogenesis and Promotes White-Matter Integrity after Stroke in Mice with Diabetic Mellitus.

Diabetes mellitus (DM) is a major risk factor for stroke and exacerbates white-matter damage in focal cerebral ischemia. Our previous study showed that the sigma-1 receptor agonist PRE084 ameliorates bilateral common-carotid-artery occlusion-induced brain damage in mice. However, whether this protective effect can extend to white matter remains unclear. In this study, C57BL/6 mice were treated with high-fat diets (HFDs) combined with streptozotocin (STZ) injection to mimic type 2 diabetes mellitus (T2DM). Focal cerebral ischemia in T2DM mice was established via injection of the vasoconstrictor peptide endothelin-1 (ET-1) into the hippocampus. Three different treatment plans were used in this study. In one plan, 1 mg/kg of PRE084 (intraperitoneally) was administered for 7 d before ET-1 injection; the mice were sacrificed 24 h after ET-1 injection. In another plan, PRE084 treatment was initiated 24 h after ET-1 injection and lasted for 7 d. In the third plan, PRE084 treatment was initiated 24 h after ET-1 injection and lasted for 21 d. The Y-maze, novel object recognition, and passive avoidance tests were used to assess neurobehavioral outcomes. We found no cognitive dysfunction or white-matter damage 24 h after ET-1 injection. However, 7 and 21 d after ET-1 injection, the mice showed significant cognitive impairment and white-matter damage. Only PRE084 treatment for 21 d could improve this white-matter injury; increase axon and myelin density; decrease demyelination; and increase the expressions of myelin regulator 2'-3'-cyclic nucleotide 3'-phosphodiesterase (CNpase) and myelin oligodendrocyte protein (MOG) (which was expressed by mature oligodendrocytes), the number of nerve/glial-antigen 2 (NG2)-positive cells, and the expression of platelet-derived growth factor receptor-alpha (PDGFRα), all of which were expressed by oligodendrocyte progenitor cells in mice with diabetes and focal cerebral ischemia. These results indicate that maybe there was more severe white-matter damage in the focal cerebral ischemia of the diabetic mice than in the mice with normal blood glucose levels. Long-term sigma-1 receptor activation may promote oligodendrogenesis and white-matter functional recovery in patients with stroke and with diabetes.

Loss of RanGAP1 drives chromosome instability and rapid tumorigenesis of osteosarcoma.

Chromothripsis is a catastrophic event of chromosomal instability that involves intensive fragmentation and rearrangements within localized chromosomal regions. However, its cause remains unclear. Here, we show that reduction and inactivation of Ran GTPase-activating protein 1 (RanGAP1) commonly occur in human osteosarcoma, which is associated with a high rate of chromothripsis. In rapidly expanding mouse osteoprogenitors, RanGAP1 deficiency causes chromothripsis in chr1q, instant inactivation of Rb1 and degradation of p53, consequent failure in DNA damage repair, and ultrafast osteosarcoma tumorigenesis. During mitosis, RanGAP1 anchors to the kinetochore, where it recruits PP1-γ to counteract the activity of the spindle-assembly checkpoint (SAC) and prevents TOP2A degradation, thus safeguarding chromatid decatenation. Loss of RanGAP1 causes SAC hyperactivation and chromatid decatenation failure. These findings demonstrate that RanGAP1 maintains mitotic chromosome integrity and that RanGAP1 loss drives tumorigenesis through its direct effects on SAC and decatenation and secondary effects on DNA damage surveillance.

Three-Dimensional Reconstruction of Conductive Filaments in HfOx -Based Memristor.

HfOx -based memristor has been studied extensively as one of the most promising memories for the excellent nonvolatile data storage and computing-in-memory capabilities. However, the resistive switching mechanism, relying on the formation and rupture of conductive filaments (CFs) during device operations, is still under debate. In this work, the CFs with different morphologies after different operations-forming, set, and reset-are clearly revealed for the first time by 3D reconstruction of conductive atomic force microscopy (c-AFM) images. Intriguingly, multiple CFs are successfully observed in HfOx -based memristor devices with three different resistive states. CFs after forming, set, and reset exhibit the typical morphologies of hourglass, inverted-cone, and short-cone, respectively. The rupture location of CFs after the reset operation is also observed clearly. These findings reveal the microscopic behaviors underlying the resistive switching, which could pave the road to design and optimize oxide-based memristors for both memory and computing applications.

Phospholipase A2 induces acute kidney injury by complement mediated mitochondrial apoptosis via TNF-α/NF-κB signaling pathway.

OBJECTIVE: Acute kidney injury (AKI) is one of common complications of wasp/bee stings. Phospholipase A2 (PLA2) is a vital pathogenic composition of wasp/bee venom. We aimed to investigate the role of complement mediated mitochondrial apoptosis in PLA2 induced AKI. MATERIALS AND METHODS: PLA2 induced AKI model was established by injecting PLA2 into via tail vein on mice. The pathological changes and the microstructural changes of kidney, complement activation, inflammation and apoptosis were detected in vitro and in vivo respectively. RESULTS: The results showed that PLA2 induced AKI models were successfully established in vivo and vitro. Compared with control, serum creatinine and urea nitrogen levels were elevated. Complement system activation and mitochondrial damage were observed. Expressions of IL-6, TNF-α, cleaved caspase-3 and cleaved caspase-9, and Bax/Bcl-2 increased in PLA2 induced AKI models. TNF-α/NF-κB signaling pathway activation in AKI models. CONCLUSION: In the present study, PLA2 induced AKI model was first successfully established to our knowledge. The role of complement mediated mitochondrial apoptosis pathway in renal tubular epithelial cells in PLA2 induced AKI were verified in vitro and vivo.

Calcium-containing versus calcium-free replacement solution in regional citrate anticoagulation for continuous renal replacement therapy: a randomized controlled trial.

BACKGROUND: A simplified protocol for regional citrate anticoagulation (RCA) using a commercial calcium-containing replacement solution, without continuous calcium infusion, is more efficient for use in continuous renal replacement therapy (CRRT). We aim to design a randomized clinical trial to compare the safety and efficacy between calcium-free and calcium-containing replacement solutions in CRRT with RCA. METHODS: Of the 64 patients receiving RCA-based postdilution continuous venovenous hemodiafiltration (CVVHDF) enrolled from 2017 to 2019 in West China Hospital of Sichuan University, 35 patients were randomized to the calcium-containing group and 29 to the calcium-free replacement solution group. The primary endpoint was circuit lifespan and Kaplan-Meier survival analysis was performed. Secondary endpoints included hospital mortality, kidney function recovery rate, and complications. The amount of 4% trisodium citrate solution infusion was recorded. Serum and effluent total (tCa) and ionized (iCa) calcium concentrations were measured during CVVHDF. RESULTS: A total of 149 circuits (82 in the calcium-containing group and 67 in the calcium-free group) and 7609 circuit hours (4335 h vs. 3274 h) were included. The mean circuit lifespan was 58.1 h (95% CI 53.8-62.4 h) in the calcium-containing group vs. 55.3 h (95% CI 49.7-60.9 h, log rank P = 0.89) in the calcium-free group. The serum tCa and iCa concentrations were slightly lower in the calcium-containing group during CRRT, whereas the postfilter iCa concentration was lower in the calcium-free group. Moreover, the mean amounts of 4% trisodium citrate solution infusion were not significantly different between the groups (171.1 ±â€Š15.9 mL/h vs. 169.0 ±â€Š15.1 mL/h, P = 0.49). The mortality (14/35 [40%] vs. 13/29 [45%], P = 0.70) and kidney function recovery rates of AKI patients (19/26, 73% vs. 14/24, 58%, P = 0.27) were comparable between the calcium-containing and calcium-free group during hospitalization, respectively. Six (three in each group) patients showed signs of citrate accumulation in this study. CONCLUSIONS: When compared with calcium-free replacement solution, RCA-based CVVHDF with calcium-containing replacement solution had a similar circuit lifespan, hospital mortality and kidney outcome. Since the calcium-containing solution obviates the need for a separate venous catheter and a large dose of intravenous calcium solution preparation for continuous calcium supplementation, it is more convenient to be applied in RCA-CRRT practice. REGISTRATION: Chinese Clinical Trial Registry (www.chictr.org.cn, ChiCTR-IPR-17012629).

Room-temperature polariton lasing in GaN microrods with large Rabi splitting.

Room-temperature polariton lasing is achieved in GaN microrods grown by metal-organic vapor phase epitaxy. We demonstrate a large Rabi splitting (Ω = 2g0) up to 162 meV, exceeding the results from both the state-of-the-art nitride-based planar microcavities and previously reported GaN microrods. An ultra-low threshold of 1.8 kW/cm2 is observed by power-dependent photoluminescence spectra, with the linewidth down to 1.31 meV and the blue shift up to 17.8 meV. This large Rabi splitting distinguishes our coherent light emission from a conventional photon lasing, which strongly supports the preparation of coherent light sources in integrated optical circuits and the study of exciting phenomena in macroscopic quantum states.

Preparation, characterization and immune activity of Codonopsis pilosula polysaccharide loaded in chitosan-graphene oxide.

The purpose of this study was to investigate the effects of chitosan graphene oxide Codonopsis pilosula polysaccharide (CS-GO-CPP) complex on the immune function of macrophage cells (RAW264.7). In this experiment, chitosan (CS) was combined with graphene oxide (GO) by electrostatic action to prepare CS-GO nanocomposites, and it was used as a carrier to load Codonopsis pilosula polysaccharide (CPP) onto CS-GO to prepare CS-GO-CPP. Using infrared spectroscopy detection, zeta potential detection, and thermogravimetric analysis, we conduct a preliminary analysis of the structure of CS-GO-CPP. Macrophages were employed to evaluate CS-GO-CPP immunomodulatory activity and the possible mechanism responsible for the activation of macrophages in vitro. The results showed that compared with CPP, CS-GO-CPP did not change the basic structure of polysaccharide, and its thermal stability was improved. 0.78- 12.5 µg·mL-1 of CS-GO-CPP could significantly promote the phagocytic activity of RAW264.7 cells (P < 0.05) and significantly increase NO content, IL-4 and IFN-γ secretion, the expression of CD40, CD86, and F4/80 (P < 0.05). CS-GO-CPP might activate the NF-κB signaling pathway and induce the nuclear translocation of NF-κB p65. In conclusion, CS-GO-CPP has a capacity to activate RAW264.7 cells for an improvement of immunomodulation activities, which might be through NF-κB signaling pathway.