Targeting PD-L1 in solid cancer with myeloid cells expressing a CAR-like immune receptor.

Introduction: Solid cancers Myeloid cells are prevalent in solid cancers, but they frequently exhibit an anti-inflammatory pro-tumor phenotype that contribute to the immunosuppressive tumor microenvironment (TME), which hinders the effectiveness of cancer immunotherapies. Myeloid cells' natural ability of tumor trafficking makes engineered myeloid cell therapy an intriguing approach to tackle the challenges posed by solid cancers, including tumor infiltration, tumor cell heterogenicity and the immunosuppressive TME. One such engineering approach is to target the checkpoint molecule PD-L1, which is often upregulated by solid cancers to evade immune responses. Method: Here we devised an adoptive cell therapy strategy based on myeloid cells expressing a Chimeric Antigen Receptor (CAR)-like immune receptor (CARIR). The extracellular domain of CARIR is derived from the natural inhibitory receptor PD-1, while the intracellular domain(s) are derived from CD40 and/or CD3ζ. To assess the efficacy of CARIR-engineered myeloid cells, we conducted proof-of-principle experiments using co-culture and flow cytometry-based phagocytosis assays in vitro. Additionally, we employed a fully immune-competent syngeneic tumor mouse model to evaluate the strategy's effectiveness in vivo. Result: Co-culturing CARIR-expressing human monocytic THP-1 cells with PD-L1 expressing target cells lead to upregulation of the costimulatory molecule CD86 along with expression of proinflammatory cytokines TNF-1α and IL-1ß. Moreover, CARIR expression significantly enhanced phagocytosis of multiple PD-L1 expressing cancer cell lines in vitro. Similar outcomes were observed with CARIR-expressing human primary macrophages. In experiments conducted in syngeneic BALB/c mice bearing 4T1 mammary tumors, infusing murine myeloid cells that express a murine version of CARIR significantly slowed tumor growth and prolonged survival. Conclusion: Taken together, these results demonstrate that adoptive transfer of PD-1 CARIR-engineered myeloid cells represents a promising strategy for treating PD-L1 positive solid cancers.

Tracing the contribution and fate of synthetic nitrogen fertilizer in young apple orchard agrosystems.

Excessive synthetic nitrogen (N) inputs in intensive orchard agrosystems of developing countries are a growing concern regarding their adverse impacts on fruit production and the environment. Quantifying the distribution and contribution of fertilizer N is essential for increasing N use efficiency and minimizing N loss in orchards. A 15N tracer experiment was performed in a young dwarf apple orchard over two growing seasons to determine the fertilizer N transformation and fate. Fertilizer N primarily contributed to 25 % to 75 % of soil nitrate in the top 60 cm, but the contribution to soil microbial biomass N and fixed ammonium was <8 %, with the contribution to plant N ranging from 9 % to 19 %. In most growth periods, soil nitrate and fixed ammonium contents derived from native soil with N fertilization were higher than those not receiving N fertilizer. The N use efficiency of plants was only 2.6 % and 4.9 % in the first and second seasons, respectively, in contrast to 56.6 % and 54.0 % of N recovered in soil. Meanwhile, N assimilated into microbial biomass accounted for 0.8 %, and the proportion fixed by clay minerals was 3.5 %-5.2 %. One season after N fertilization, the nitrate below the 1 m soil layers accounted for 4.6 % of the applied N fertilizer, and the proportion increased to 22.5 % after two seasons. The N loss rate via N2O emission was 0.4 % over two years. The application of N fertilizer facilitated indigenous soil N mineralization, and abiotic ammonium fixation more efficiently retained synthetic N than microbial immobilization. These findings provide new insight into orchard N cycling, and attention should be given to the improvement of soil N retention and turnover capacity regulated by soil microbial and abiotic processes, as well as the potential environmental impacts of additional soil N mineralization resulting from prolonged chemical N fertilization.

Qingfei mixture modulates the immune responses in lung cancer through modulating mTOR signaling and gut microbiota-derived short-chain fatty acids.

Lung cancer ranks among the primary contributors to cancer-related fatalities on a global scale. Multiple research investigations have demonstrated that there exists a dysbiosis within the intestinal bacteria and short-chain fatty acids (SCFAs) is linked with immune responses in lung cancer. Qingfei mixture (QFM) has been widely used in treating lung cancer, yet the active ingredients and roles of the QFM on immune responses by targeting gut microbiota remain to be elucidated. The chemical constituents of QFM were qualitatively examined by UPLC/Q-TOF-MS. Additionally, we evaluated the therapeutic impact of the organic substance QFM on lung cancer, aiming to elucidate its mechanisms for improving the tumor-immune microenvironment. Herein, we constructed a Lewis lung carcinoma (LLC)-bearing mice model with QFM treatment to observe tumor growth and immune cell changes. Then, the feces were collected and a combinatory study using metagenomes, non-targeted metabonomics, and targeted metabonomics of SCFAs was performed. In vitro experiments have been conducted to estimate the roles of acetate and sodium propionate in CD8+ T cells. Furthermore, we treated tumor-bearing mice with QFM, QFM + MHY1485 (an mTOR activator), and QFM + an antibiotic mixture (ABX) to explore the potential therapeutic benefit of regulation of the tumor microenvironment. A total of 96 compounds were obtained from QFM by UPLC/Q-TOF-MS. Besides, the findings demonstrated that QFM exhibited significant efficacy against lung cancer, manifesting in reduced tumor growth and improved immune responses. In investigating its mechanisms, we integrated gut microbiota sequencing and fecal metabolomics, revealing that QFM effectively restored disruptions in gut microbiota and SCFAs in mice with lung cancer. QFM, acetate, or sodium propionate contributed to the up-regulation of IFN-γ, Gzms-B, perforin, IL-17, IL-6, IL-12, TNF-α expressions and decreased HDAC and IL-10 levels in vitro and in vivo. Moreover, MHY1485 and ABX weakened the effects of QFM on immunomodulation. Collectively, these results suggest that QFM may facilitate immune responses in the LLC-bearing mice via regulating the gut microbiota-derived SCFAs at least partially through targeting the mTOR signaling pathway.

Ecological niche shift and suitable area expansion of a globally invasive species Phthorimaea operculella.

Phthorimaea operculella is a major potato pest of global importance, early warning and detection of which are of significance. In this study, we analyzed the climate niche conservation of P. operculella during its invasion by comparing the overall climate niche from three dimensions, including the differences between native range (South America) and entire invaded region (excluding South America), the differences bwtween native range (South America) and five invaded continents (North America, Oceania, Asia, Africa, and Europe), as well as the differences between native region (South America) and an invaded region (China). We constructed ecological niche models for its native range (South America) and invaded region (China). The results showed that the climatic niche of the pest has expanded to varying degrees in different regions, indicating that the pest could well adapt to new environments during the invasion. Almost all areas of South America are suitable for P. operculella. In China, its suitable area is mainly concentrated in Shandong, Hebei, Tianjin, Beijing, Henan, Hubei, Yunnan, Guizhou, Sichuan, Hainan, northern Guangxi, southern Hunan, Anhui, Guangdong, Jiangsu, southern Shanxi, and southern Shaanxi. With increasing greenhouse gas emissions and global temperature, its suitable area will decrease at low latitude and increase gradually at high latitude. Specifically, the northern boundary will extend to Liaoning, Jilin, and the southeastern region of Inner Mongolia, while the western boundary extends to Sichuan and the southeast Qinghai-Tibet Plateau. The suitable area in the southeast Yunnan-Guizhou Plateau, Hainan Island, and the south of Yangtze River, will gradually decrease. The total suitable habitat area for P. operculella in China is projected to increase under future climate condition. From 2081 to 2100, under the three greenhouse gas emissions scenarios of ssp126, ssp370, and ssp585, the suitable area is expected to increase by 27.78, 165.54, and 140.41 hm2, respectively. Therefore, it is crucial to strengtehen vigilance and implement strict measures to prevent the further expansion of P. operculella.

Clinical Analysis and Mental Health Survey of Hemophilia Carriers: a Cross-sectional Study.

OBJECTIVE: Hemophilia carriers (HCs), who are heterozygous for mutations in the clotting factor VIII/clotting factor IX gene (F8 or F9), may have a wide range of clotting factor levels, from very low, similar to afflicted males, to the upper limit of normal, and may experience mental health issues. The purpose of this study was to provide genetic information on mothers of hemophilia patients and to understand the clotting factor activity and phenotype of HCs. Additionally, we aimed to investigate the mental health status of HCs in China. METHODS: A total of 127 hemophilia mothers, including 93 hemophilia A (HA) mothers and 34 hemophilia B (HB) mothers, were enrolled in this study. Long distance PCR, multiplex PCR, and Sanger sequencing were used to analyze mutations in F8 or F9. Coagulation factor activity was detected by a one-stage clotting assay. The Symptom Checklist 90 (SCL-90, China/Mandarin version) was given to HCs at the same time to assess their mental health. RESULTS: A total of 90.6% of hemophilia mothers were diagnosed genetically as carriers, with inversion in intron 22 and missense mutations being the most common mutation types in HA and HB carriers, respectively. The median clotting factor level in carriers was 0.74 IU/mL (ranging from 0.09 to 1.74 IU/mL) compared with 1.49 IU/mL (ranging from 0.93 to 1.89 IU/mL) in noncarriers, of which 14.3% of HCs had clotting factor levels of 0.40 IU/mL or below. A total of 53.8% (7/13) of HA carriers with low clotting factor levels (less than 0.50 IU/mL) had a history of bleeding, while none of the HB carriers displayed a bleeding phenotype. The total mean score and the global severity index of the SCL-90 for surveyed HCs were 171.00 (±60.37) and 1.78 (±0.59), respectively. A total of 67.7% of the respondents had psychological symptoms, with obsessive-compulsive disorder being the most prevalent and severe. The pooled estimates of all nine factors were significantly higher than those in the general population (P<0.05). CONCLUSIONS: The detection rate of gene mutations in hemophilia mothers was 90.6%, with a median clotting factor level of 0.74 IU/mL, and 14.3% of HCs had a clotting factor level of 0.40 IU/mL or below. A history of bleeding was present in 41.2% of HCs with low clotting factor levels (less than 0.50 IU/mL). Additionally, given the fragile mental health status of HCs in China, it is critical to develop efficient strategies to improve psychological well-being.

Biomimetic Nanoporous Transparent Universal Fire-Resistant Coatings.

The inherent flammability of most polymeric materials poses a significant fire hazard, leading to substantial property damage and loss of life. A universal flame-retardant protective coating is considered as a promising strategy to mitigate such risks; however, simultaneously achieving high transparency of the coatings remains a great challenge. Here, inspired by the moth eye effect, we designed a nanoporous structure into a protective coating that leverages a hydrophilic-hydrophobic interactive assembly facilitated by phosphoric acid protonated amino siloxane. The coating demonstrates robust adhesion to a diverse range of substrates, including but not limited to fabrics, foams, paper, and wood. As expected, its moth-eye-inspired nanoporous structure conferred a high visible light transparency of >97% and water vapor transmittance of 96%. The synergistic effect among phosphorus (P), nitrogen (N), and silicon (Si) largely enhanced the char-forming ability and restricted the decomposition of the coated substrates, which successfully endowed the coating with high fire-fighting performance. More importantly, for both flexible and rigid substrates, the coated samples all possessed great mechanical properties. This work provides a new insight for the design of protective coatings, particularly focusing on achieving high transparency.

Huangqin decoction attenuates spared nerve injury (SNI)-induced neuropathic pain by modulating microglial M1/M2 polarization partially mediated by intestinal nicotinamide metabolism.

BACKGROUND: The incidence of neuropathic pain is progressively increasing over time. The activation of M1-type microglia plays a crucial role in the initiation and progression of neuropathic pain. Huangqin Decoction (HQD) is traditionally used to alleviate dysentery and abdominal pain. However, it remains unclear whether HQD can effectively mitigate neuropathic pain and the underlying mechanisms. PURPOSE: The present study aims to investigate the impact of HQD on neuropathic pain induced by spared nerve injury (SNI) in mice, and to elucidate whether the analgesic effect of HQD is associated with microglia polarization. METHODS: The analgesic effect of HQD on SNI mice was investigated through assessments of mechanical pain threshold, thermal pain threshold, cold pain threshold, and motor ability. We elucidated the molecular mechanisms of HQD in alleviating SNI-induced neuropathic pain by focusing on microglia polarization and intestinal metabolite abnormalities. The expression levels of markers associated with microglia polarization (Iba-1, CD68, CD206, iNOS) was detected by immunofluorescence and Western blot, and the levels of inflammatory factors (IL-4, IL-10, IL-6, TNF-α) were assessed by ELISA. UPLC-QTOF-MS metabolomics was utilized to identify differential metabolites in the intestines of SNI mice. We screened the differential metabolites related to microglial polarization by correlation analysis, subsequently nicotinamide was selected for validation in LPS-induced BV-2 cells. RESULTS: Our findings demonstrated that HQD (20 g/kg) significantly enhanced the mechanical pain threshold, thermal pain threshold, and cold pain threshold, and protected the injured DRG neurons of SNI mice. Moreover, HQD (20 g/kg) obviously suppressed the expression of microglia M1 polarization markers (Iba-1, CD68, iNOS, IL-6, TNF-α), and promoted the expression of microglia M2 polarization markers (CD206, IL-10, IL-4) in the spinal cord of SNI mice. Additionally, HQD (20 g/kg) prominently ameliorated intestinal barrier damage by upregulating Claudin 1 and Occludin expression in the colon of SNI mice. Furthermore, HQD (20 g/kg) rectified 19 metabolite abnormalities in the intestine. Notably, nicotinamide (100 µM), an amide derivative with anti-inflammatory property, effectively suppresses microglia activation and polarization in LPS-induced BV-2 cells by downregulating IL-6 level and CD68 expression while upregulating IL-4 level and CD206 expression. CONCLUSION: In summary, HQD alleviates neuropathic pain in SNI mice by regulating the activation and polarization of microglia, partially mediated through intestinal nicotinamide metabolism.

Ruegeria marisflavi sp. nov. and Ruegeria aquimaris sp. nov., isolated from seawater of the Yellow Sea.

Two novel Gram-stain-negative, aerobic, non-motile and rod-shaped bacteria, designated as WL0004T and XHP0148T, were isolated from seawater samples collected from the coastal areas of Nantong and Lianyungang, PR China, respectively. Both strains were found to grow at 10-42 °C (optimum, 37 °C) and with 2.0-5.0 % (w/v) NaCl (optimum, 3.0 %). Strain WL0004T grew at pH 6.0-9.0 (optimum, pH 7.0-8.0), while XHP0148T grew at pH 6.0-10.0 (optimum, pH 7.0-8.0). The major cellular fatty acids (>10 %) of both strains included summed feature 8 (C18 : 1 ω6c and/or C18 : 1 ω7c). In addition, strain WL0004T contained 11-methyl C18 : 1 ω7c and strain XHP0148T contained C12 : 0 3-OH. The respiratory quinone of both strains was ubiquinone-10. The G+C content of genomic DNA of strains WL0004T and XHP0148T were 62.5 and 63.0 mol%, respectively. Strains WL0004T and XHP0148T showed the highest 16S rRNA gene sequence similarity to Ruegeria pomeroyi DSS-3T (99.4 and 99.0 %, respectively), and the 16S rRNA gene-based phylogenetic analysis indicated that the two strains were closely related to members of the genus Ruegeria. The average nucleotide identity and digital DNA-DNA hybridization values among the two strains and type strains of the genus Ruegeria were all below 95 and 70 %, respectively, and the phylogenetic tree reconstructed from the bac120 gene set indicated that the two strains are distinct from each other and the members of the genus Ruegeria. Based on this phenotypic and genotypic characterization, strains WL0004T (=MCCC 1K07523T=JCM 35565T=GDMCC 1.3083T) and XHP0148T (=MCCC 1K07543T=JCM 35569T=GDMCC 1.3089T) should be recognized as representing two novel species of the genus Ruegeria and the names Ruegeria marisflavi sp. nov. and Ruegeria aquimaris sp. nov. are proposed, respectively.

Actomonas aquatica gen. nov., sp. nov., a marine lineage in the phylum Verrucomicrobiota with genetic potential for carbon and nitrogen fixation.

A novel bacterial strain, designated WL0086T, was isolated from a marine sediment sample collected in Lianyungang city, Jiangsu province, PR China. This strain showed the highest 16S rRNA gene sequence similarity to Geminisphaera colitermitum TAV2T (92.7 %) of the family Opitutaceae, and all the unclassified cultured and uncultured isolates with similarities >95 % were from marine environments. Cells were Gram-stain-negative, aerobic, non-motile cocci with a size of 0.6-0.8 µm in diameter. Strain WL0086T was positive for both oxidase and catalase, and grew at 20-37 °C (optimum, 28 °C), with 1.5-11.0 % NaCl (w/v; optimum, 2.5-4.0 %) and at pH 5.0-9.0 (optimum, pH 7.0). The major polar lipid profile of strain WL0086T consisted of phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, and phosphatidylcholine. The major isoprenoid quinone was menaquinone-7 and the predominant fatty acids were iso-C14 : 0, anteiso-C15 : 0, C16 : 0 and C16 : 1 ω9c. The complete genome consisted of a chromosome with 6 109 182 bp. The G+C content of genomic DNA was 64.0%. Results of phylogenomic analysis based on the 16S rRNA gene sequence and the whole genome suggested that strain WL0086T formed a distinct clade closely neighbouring the members of the family Opitutaceae. On the basis of phylogenetic, phenotypic, and chemotaxonomic evidences, strain WL0086T should represent a novel genus of the family Opitutaceae, for which the name Actomonas aquatica gen. nov., sp. nov. is proposed. The type strain is WL0086T (=MCCC 1K05844T=JCM 34677T=GDMCC 1.2411T).

The highly selective and sensitive fluorescence probe for detection of copper (II) ions and its bioimaging in vitro and vivo.

We designed and developed the probe W-3 for detection of Cu2+. The results showed probe can selectively detect Cu2+, accompanied by noticeable color change. The probe can detect the Cu2+ in water samples and drinks based on absorption detection. In addition, the combination of portable test paper and the smartphone platform obtained great convenience for on-site and visual detection of Cu2+, with satisfactory sensitivity and reliability. More importantly, the fluorescence probe W-3 can be used for the detection of Cu2+ in cells and mice. Therefore, the W-3 provided potential chemical tools for detecting Cu2+ in vitro and vivo.

Long-term observation of polycaprolactone small-diameter vascular grafts with thickened outer layer and heparinized inner layer in rabbit carotid arteries.

In our previous study, the pristine bilayer small-diameterin situtissue engineered vascular grafts (pTEVGs) were electrospun from a heparinized polycaprolactone (PCL45k) as an inner layer and a non-heparinized PCL80k as an outer layer in the thickness of about 131 µm and 202 µm, respectively. However, the hydrophilic enhancement of inner layer stemmed from the heparinization accelerated the degradation of grafts leading to the early formation of arterial aneurysms in a period of 3 months, severely hindering the perennial observation of the neo-tissue regeneration, host cell infiltration and graft remodeling in those implanted pTEVGs. Herein to address this drawback, the thickness of the outer layers was increased with PCL80k to around 268 µm, while the inner layer remained unchangeable. The thickened TEVGs named as tTEVGs were evaluated in six rabbits via a carotid artery interpositional model for a period of 9 months. All the animals kept alive and the grafts remained patent until explantation except for one whose one side of arterial blood vessels was occluded after an aneurysm occurred at 6 months. Although a significant degradation was observed in the implanted grafts at 9 month, the occurrence of aneurysms was obviously delayed compared to pTEVGs. The tissue stainings indicated that the endothelial cell remodeling was substantially completed by 3 months, while the regeneration of elastin and collagen remained smaller and unevenly distributed in comparison to autologous vessels. Additionally, the proliferation of macrophages and smooth muscle cells reached the maximum by 3 months. These tTEVGs possessing a heparinized inner layer and a thickened outer layer exhibited good patency and significantly delayed onset time of aneurysms.

Presence of Spontaneous Nystagmus, Benign Paroxysmal Positional Vertigo, and Tumarkin Fall in Patients With Primary Headache and Their Responses to Caloric and Video Head Impulse Tests.

Background: Migraine, vestibular migraine (VM) and tension-type headache (TTH) are the most common disorders in dizziness and headache clinics, associated with dizziness or vertigo and postural imbalance, causing a substantial burden on the individual and the society. The objective of this research was to examine the presence of spontaneous nystagmus, comorbidity of benign paroxysmal positional vertigo (BPPV), and Tumarkin fall in patients; additionally, the study focused on assessing the patients' responses to bithermal caloric irrigation and video head impulse test (vHIT). Methods: Consecutive patients diagnosed with migraine, VM, and TTH according to the International Classification of Headache Disorders, third edition (beta version (ICHD-3ß)), who were referred to Dizziness and Headache Clinic were enrolled. BPPV and Tumarkin fall were assessed by questionnaires. The presence of BPPV was further evaluated through Dix-Hallpike or head roll maneuver, while spontaneous nystagmus was monitored using video-oculography during interictal period. Lastly, patients' responses to bithermal caloric irrigation and vHIT were analyzed. Results: There was a significantly higher incidence of spontaneous nystagmus in VM compared to both migraine and TTH. The drop attack episodes were slightly more frequent in VM than in TTH and migraine, though not statistically significant. The prevalence of BPPV was significantly higher in VM than in migraine and TTH. Unilateral vestibular paresis was more common in the VM group than in migraine and TTH. There was profound unilateral weakness (UW) in VM patients than in migraine, but no significant difference was found between VM and TTH. In VM, the percentage of saccades along with reduced vHIT gain was significantly higher than in migraine. Lastly, the percentage of abnormal response in vHIT was significantly lower than the percentage of abnormal UW in caloric irrigation across all groups. Conclusions: In VM patients, the prevalences of decompensated peripheral damage and BPPV were higher than in migraine and TTH patients as disclosed by the presence of peripheral spontaneous nystagmus and abnormal vHIT during the interictal period. Our findings suggest that the peripheral vestibular system acts as a significant mechanism in the pathogenesis of VM, and it might also be involved in migraine and TTH cases without vertigo symptoms.

Maximizing Polysaccharides and Phycoerythrin in Porphyridium purpureum via the Addition of Exogenous Compounds: A Response-Surface-Methodology Approach.

Phycoerythrin and polysaccharides have significant commercial value in medicine, cosmetics, and food industries due to their excellent bioactive functions. To maximize the production of biomass, phycoerythrin, and polysaccharides in Porphyridium purpureum, culture media were supplemented with calcium gluconate (CG), magnesium gluconate (MG) and polypeptides (BT), and their optimal amounts were determined using the response surface methodology (RSM) based on three single-factor experiments. The optimal concentrations of CG, MG, and BT were determined to be 4, 12, and 2 g L-1, respectively. The RSM-based models indicated that biomass and phycoerythrin production were significantly affected only by MG and BT, respectively. However, polysaccharide production was significantly affected by the interactions between CG and BT and those between MG and BT, with no significant effect from BT alone. Using the optimized culture conditions, the maximum biomass (5.97 g L-1), phycoerythrin (102.95 mg L-1), and polysaccharide (1.42 g L-1) concentrations met and even surpassed the model-predicted maximums. After optimization, biomass, phycoerythrin, and polysaccharides concentrations increased by 132.3%, 27.97%, and 136.67%, respectively, compared to the control. Overall, this study establishes a strong foundation for the highly efficient production of phycoerythrin and polysaccharides using P. purpureum.

Multifunctional fluorescence probe for simultaneous detection of viscosity, polarity, and ONOO- and its bioimaging in vitro and vivo.

Intracellular microenvironment (viscosity and polarity) and peroxynitrite ions (ONOO-) are involved in maintaining cell morphology, cell function, and signaling so that it is crucial to explore their level changes in vitro and vivo. In this work, we designed and synthesized a mitochondria-targeted fluorescence probe XBL for monitoring the dynamic changes of viscosity, polarity, and ONOO- based on TICT and ICT mechanism. The fluorescence spectra showed obvious changes for polarity at 500 nm as well as ONOO- and viscosity at 660 nm, respectively. The XBL can image simultaneously viscosity, polarity, and ONOO- in cells, and the results showed excess ONOO- leaded to the increase of viscosity in mitochondrial. The ferroptosis process was accompanied by increase of intracellular viscosity and ONOO- levels (or decrease of polarity), which allowed us to better understand the relevant physiological and pathological processes. The XBL can distinguish normal cells and cancerous cells by the fluorescence intensity changes in green and red channels, and image viscosity in inflamed mice. Thus, XBL can provided the chemical tool to understand the physiological and pathological mechanisms of disease by simultaneous detection of viscosity, polarity and ONOO-.

Effects of cluster nursing interventions on the prevention of pressure ulcers in intensive care units patients: A meta-analysis.

A meta-analysis was conducted to comprehensively evaluate the impact of cluster nursing interventions on the prevention of pressure ulcers (PUs) in intensive care unit (ICU) patients. Computer searches were performed in databases including Embase, Google Scholar, Cochrane Library, PubMed, Wanfang and China National Knowledge Infrastructure for randomized controlled trials (RCTs) implementing cluster nursing interventions for PUs prevention in ICU patients, with the search period covering the database inception to November 2023. Two researchers independently screened the literature, extracted data and conducted quality assessments. Stata 17.0 software was employed for data analysis. Overall, 17 RCTs involving 1463 ICU patients were included. The analysis showed that compared with conventional nursing, cluster nursing interventions significantly reduced the incidence of PUs (odds ratio: 0.24, 95% confidence intervals [CI]: 0.17-0.34, p < 0.001) and also significantly improved the levels of anxiety (standardized mean difference [SMD]: -1.39, 95% CI: -1.57 to 1.22, p < 0.001) and depression (SMD: -1.64, 95% CI: -2.02 to 1.26, p < 0.001) in ICU patients. This study indicates that the application of cluster nursing interventions in ICU patients can effectively reduce the incidence of PUs, as well as improve patients' anxiety and depression levels, thereby enhancing their quality of life, which is worth clinical promotion and application.

YKL-40 (chitinase-3-like protein 1) serum levels are associated with abdominal aortic calcification in hemodialysis patients.

BACKGROUND: Vascular calcification (VC) is highly prevalent and predicts cardiovascular mortality in dialysis patients. The mechanisms are still unclear. Inflammation is a well-known inducer of VC. YKL-40 has been suggested as a novel biomarker of inflammation and has been demonstrated to be associated with cardiovascular mortality in hemodialysis patients. This study aims to evaluate the relationship between serum YKL-40 and VC in hemodialysis (HD) patients. METHODS: A total of 109 HD patients and 31 healthy controls were enrolled in the study from September 2014 to December 2014. We evaluated the abdominal aortic calcification (AAC) score by plain X-ray films of the abdomen and measured serum YKL-40 concentrations using enzyme-linked immunosorbent assay. We also examined the relationship between YKL-40 levels and AAC scores in HD patients. RESULTS: Serum YKL-40 levels in HD patients were significantly higher than those in healthy controls [199.8 (144.8, 288.7) vs. 71.9 (52.8, 89.3) ng/ml; P < 0.001]. There was a tendency that YKL-40 levels in diabetic hemodialysis patients were higher than those in nondiabetic patients [217.8 (155.3, 335.8) vs. 192.9 (135.9, 274.4) ng/ml; P = 0.093]. A significant positive correlation was found between serum YKL-40 level and AAC score in these patients (r = 0.410, P = 0.003). Multiple regression analysis showed that Ln(YKL-40) was independently associated with AAC score in HD patients (P = 0.044). CONCLUSION: This study showed high serum YKL-40 concentrations in chronic HD patients and that YKL-40 was independently associated with increased AAC in hemodialysis patients.

Tubule-specific cyclin-dependent kinase 12 knockdown potentiates kidney injury through transcriptional elongation defects.

Direct tubular injury caused by several medications, especially chemotherapeutic drugs, is a common cause of AKI. Inhibition or loss of cyclin-dependent kinase 12 (CDK12) triggers a transcriptional elongation defect that results in deficiencies in DNA damage repair, producing genomic instability in a variety of cancers. Notably, 10-25% of individuals developed AKI after treatment with a CDK12 inhibitor, and the potential mechanism is not well understood. Here, we found that CDK12 was downregulated in the renal tubular epithelial cells in both patients with AKI and murine AKI models. Moreover, tubular cell-specific knockdown of CDK12 in mice enhanced cisplatin-induced AKI through promotion of genome instability, apoptosis, and proliferative inhibition, whereas CDK12 overexpression protected against AKI. Using the single molecule real-time (SMRT) platform on the kidneys of CDK12RTEC+/- mice, we found that CDK12 knockdown targeted Fgf1 and Cast through transcriptional elongation defects, thereby enhancing genome instability and apoptosis. Overall, these data demonstrated that CDK12 knockdown could potentiate the development of AKI by altering the transcriptional elongation defect of the Fgf1 and Cast genes, and more attention should be given to patients treated with CDK12 inhibitors to prevent AKI.

Effects of psychological intervention on negative emotions and psychological resilience in breast cancer patients after radical mastectomy.

Breast cancer (BC)is the most common malignant tumor in women, and the treatment process not only results in physical pain but also significant psychological distress in patients. Psychological intervention (PI) has been recognized as an important approach in treating postoperative psychological disorders in BC patients. It has been proven that PI has a significant therapeutic effect on post-operative psychological disorders, improving patients' negative emotions, enhancing their psychological resilience, and effectively enhancing their quality of life and treatment compliance.

Intestinal tuberculosis with small bowel stricture and hemorrhage as the predominant manifestation: Three case reports.

BACKGROUND: Intestinal tuberculosis is a chronic disease caused by Mycobacterium tuberculosis that mainly affects the ileum and cecum. Small bowel tuberculosis, characterized by predominant involvement of the small intestine, is an extremely rare condition with highly atypical clinical presentations, making diagnosis even more challenging. CASE SUMMARY: We report three cases of small intestinal tuberculosis, two of the patients presented primarily with abdominal pain, and one presented with gastrointestinal bleeding. All patients underwent blood tests and imaging examinations. Small bowel endoscopy (SBE) revealed that the main lesions in these patients were intestinal stenosis or gastrointestinal bleeding caused by small intestinal ulcers. One patient ultimately underwent surgical treatment. Following a complex diagnostic process and comprehensive analysis, all patients were confirmed to have small intestinal tuberculosis and received standard antituberculosis treatment, leading to an improvement in their condition. CONCLUSION: Patients with SBTs present with nonspecific symptoms such as abdominal pain, weight loss, and occasional gastrointestinal bleeding. Accurate diagnosis requires a thorough evaluation of clinical symptoms and various tests to avoid misdiagnosis and complications.

Clinical internship environment and caring behaviours among nursing students: A moderated mediation model.

BACKGROUND: Caring behaviour is critical for nursing quality, and the clinical internship environment is a crucial setting for preparing nursing students for caring behaviours. Evidence about how to develop nursing students' caring behaviour in the clinical environment is still emerging. However, the mechanism between the clinical internship environment and caring behaviour remains unclear, especially the mediating role of moral sensitivity and the moderating effect of self-efficacy. RESEARCH OBJECTIVE: This study aimed to examine the mediating effect of moral sensitivity and the moderating function of self-efficacy on the association between the clinical internship environment and caring behaviours. RESEARCH DESIGN: A cross-sectional design used acceptable validity scales. The hypothesised moderated mediation model was tested in the SPSS PROCESS macro. PARTICIPANTS AND RESEARCH CONTEXT: This survey collected data from 504 nursing students in an internship at a teaching hospital in Changsha, China. ETHICAL CONSIDERATIONS: This study was pre-approved by the ethics committee of the medical school (No. E2022210). Informed consent was obtained from all students. RESULTS: The clinical internship environment (B = 0.450, 95% CI = [0.371, 0.530]) and moral sensitivity (B = 1.352, 95% CI = [1.090, 1.615]) had positive direct effects on nursing students' caring behaviours. Clinical internship environment also indirectly influenced students' caring behaviours via moral sensitivity (B = 0.161, 95% CI = [0.115, 0.206]). In addition, self-efficacy played a moderating role between the clinical internship environment and caring behaviours (B = 0.019, 95% CI = [0.007, 0.031]), as well as the relationship between the clinical internship environment and moral sensitivity (B = 0.006, 95% CI = [0.003, 0.010]). CONCLUSION: Moral sensitivity mediates the effect of the clinical internship environment on caring behaviour, and self-efficacy strengthens both direct and indirect effects. This study emphasises the importance of self-efficacy in developing moral sensitivity and caring behaviours in nursing students.