Renal ischemia-reperfusion injury （RIRI） is a major cause of acute kidney injury during kidney transplantation and peri-operative settings， and there is still a lack of safe and effective targeted preventive and therapeutic drugs in clinical practice. Specifically， xanthohumol， luteolin， dracorhodin C， naringin， senkyunolide Ⅰ， verbascoside， and shikonin enhance antioxidant defenses， and inhibit lipid peroxidation and ferroptosis via the nuclear factor-erythroid 2-related factor 2/heme oxygenase-1 pathway. Apigenin， nobiletin， tanshinone Ⅱ A ， and salidroside activate the phosphatidylinositol 3-kinase/protein kinase B pathway to inhibit mitochondria- dependent apoptosis and facilitate renal repair. Quercetin， methyleugenol， cyanidin-3-glucoside， and platycodin D promote autophagy and improve mitochondrial homeostasis through the adenosine monophosphate-activated protein kinase（AMPK）/mTOR or AMPK/phosphatase and tensin homolog-induced kinase 1/Parkin pathways. In addition， hesperidin， curcumin， ganoderic acid， pulsatilla saponin B4， capsaicin， and diosgenin mitigate inflammatory responses and decrease renal tubular injury markers by inhibiting the Toll-like receptor 4/nuclear factor κB， high mobility group box 1， Janus kinase/signal transducer and activator of transcription pathways， thereby exerting multi-target， multi-stage renoprotective effects.

Objective To analyze clinical characteristics affecting survival outcomes in gastric adenocarcinoma(GAC)patients with second primary malignancies(SPM)and construct a predictive model with a web-based calculator.Methods Patients diagnosed with GAC between January 2010 and December 2017 in the SEER database(n=24 085)were analyzed,comparing non-SPM(n=22 963)and SPM cohorts(n=1 122).SPM patients were randomized(3:1)into training(n=842)and internal validation cohorts(n=280).Univariate/multivariate Cox regression identified prognostic factors for model construction.Model performance was evaluated via ROC curves,calibration plots,and decision curve analysis(DCA).A web-based calculator was deployed using DynNom(https://kunma697.shinyapps.io/dynnomapp-1/).External validation used 192 SPM patients diagnosed at Yantai Yuhuangding Hospital(2010-2017).Results χ2 tests revealed SPM patients had higher age(56.3%),earlier T-stage(T1:29.2%;T2:10.5%),predominant gastric cardia involvement(43.7%),fewer distant metastases(12.3%),and higher rates of radiotherapy(32.5%)and surgery(77.2%)vs.non-SPM(P<0.05).Cox analyses identified GAC primary site,T-stage,SEER stage,radiotherapy/surgery history,plus SPM grade/stage/treatment history as significant predictors(P<0.05).AUCs in the training cohort were 0.771(95%CI:0.722～0.820),0.839(95%CI:0.796～0.882),and 0.836(95%CI:0.792～0.879)for 1-/3-/5-year survival;internal validation showed 0.751(95%CI:0.700～0.801),0.746(95%CI:0.695～0.797),and 0.772(95%CI:0.723～0.821);external validation yielded 0.713(95%CI:0.648～0.778),0.805(95%CI:0.749～0.861),and 0.851(95%CI:0.801～0.901).Calibration indicated high prediction-actuality concordance;DCA confirmed clinical utility.Conclusion The model and web calculator incorporating GAC/SPM characteristics effectively predict SPM patient prognosis.

OBJECTIVE To study the effects of Phellodendron amurense polysaccharides （PAP） on improving gouty nephropathy （GN） in rats， and to investigate its mechanism primarily by interfering the p38 mitogen-activated protein kinase （p38 MAPK）/nuclear factor-κB（NF-κB）/tumor necrosis factor-α（TNF-α）. METHODS Sixty rats were randomly divided into normal group （water）， model group （water）， allopurinol group （positive control， 20 mg/kg）， PAP high-dose， medium-dose and low-dose groups （100， 50， 25 mg/kg， by raw material） after being stratified by body weight， with 10 rats in each group. Except for the normal group， the other groups were induced to construct GN model by giving 1 500 mg/kg potassium oxazinate and 100 mg/kg adenine intragastrically for 14 days. After modeling， the rats in each group were given relevant medicine/water intragastrically， once a day， for consecutive 28 days. After the last medication， the levels of biochemical parameters related to renal function [uric acid， creatinine （Cr）， blood urea nitrogen （BUN）， xanthine oxidase （XOD）] were detected in rats， and the histopathological changes in the rat kidney were observed. The protein expressions of monocyte chemoattractant protein-1（MCP-1），TNF-α and interleukin-6（IL-6） as well as the phosphorylation levels of p38 MAPK and NF-κB p65 protein were determined in renal tissue of rats. RESULTS Compared with the normal group， the model group suffered from the dilatation of renal tubules， structural damage to glomeruli， accompanied by inflammatory infiltration and fibrosis； the contents of uric acid， Cr， BUN and XOD， the protein expressions of MCP-1，TNF-α and IL-6 and the phosphorylation levels of p38 MAPK and NF-κB p65 protein were all increased significantly （P＜0.05 or P＜0.01）. Compared with the model group， the pathological symptoms of renal tissue in rats had been improved to varying degrees in different dose groups of PAP； the contents of uric acid， Cr， BUN and XOD， protein expressions of MCP-1， TNF-α and IL-6， the phosphorylation levels of p38 MAPK and NF-κB p65 protein in PAP high-dose and PAP medium-dose groups were all decreased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS PAP exhibits an anti-GN effect， the mechanism of which may be associated with inhibiting the p38 MAPK/NF-κB/TNF-α signaling pathway.

Objective:To explore the efficacy and adverse reactions of nimotuzumab combined with induction chemotherapy (IC) based on albumin-bound paclitaxel plus cisplatin (TP regimen) for patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC).Methods:Clinical data were collected from 65 patients with LA-HNSCC (stages Ⅲ/Ⅳ A/Ⅳ B; excluding nasopharyngeal carcinoma) who received 2-3 cycles of IC followed by concurrent chemoradiotherapy (CRT) in the Second Hospital of Dalian Medical University from January 2018 to June 2022. Based on the IC regimen, these patients were categorized into a nimotuzumab combined with TP (Nimo-TP) group ( n = 34) and a TP group ( n = 31), and their short-term efficacy [i.e., the objective response rate (ORR)], survival outcomes [e.g., overall survival (OS), progression-free survival (PFS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS)], and adverse reactions were compared. Additionally, factors affecting their survival outcomes were analyzed. Results:There were statistically significant differences in 1- and 2-year DMFS between both groups (90.4% vs. 69.5%, 90.4% vs. 66.0%, χ2=1.81, P < 0.05), so did the ORRs after IC and CRT of both groups (after IC: 67.6% vs. 41.9%, χ2=4.34, P = 0.037; after CRT: 88.2% vs. 67.7%, χ2=4.03, P = 0.045). However, there was no statistically significant difference in the 2-year OS, PFS, and LRFS between both groups ( P > 0.05). Multivariate analysis revealed that nimotuzumab combined with TP-based IC served as an independent prognostic factor for DMFS ( HR = 0.27, 95% CI: 0.07-0.97, P = 0.045), while complete/partial response after IC acted as an independent prognostic factor for both PFS and local relapse-free survival ( HR = 0.36, 95% CI: 0.17-0.76, P = 0.008; HR = 0.28, 95% CI: 0.11-0.69, P = 0.006). Notably, adding nimotuzumab did not aggravate the adverse reactions in the patients during IC and CRT( P > 0.05). Conclusions:Nimotuzumab combined with TP-based induction chemotherapy followed by CRT significantly improved the DMFS of LA-HNSCC patients, exhibiting high safety. However, such therapy failed to significantly improve their OS, PFS, and LRRFS, and, thus, further research is required.

Objective:Investigate the characteristics of hospitalized patients infected with parvovirus B19 (B19V) and the potential impact of B19V on disease progression and clinical outcomes in patients.Methods:The subjects of this observational retrospective study were 62 hospitalized patients who tested positive for B19V among 3 129 inpatients who visited Peking University People′s Hospital between April 1, 2022, and August 31, 2023, and underwent metagenomic next-generation sequencing (mNGS) for pathogens. Patient data regarding pathogen detection, clinical characteristics, and outcomes were collected, along with other laboratory test results, to assess hospitalization duration, incidence of mixed infections during hospitalization, and clinical outcomes within 30 days. The chi-square test was utilized to analyze differences in patient mortality rates and other relevant factors.Results:B19V infection waspobserved in patients with hematological disorders and solid organ transplant recipients (79.03%, 49/62). Additionally, B19V frequently coexists with other pathogens (40/62), with the highest rates of mixed infections involving human herpesvirus 6, cytomegalovirus, and Epstein-Barr virus, having 20, 9, and 8 cases respectively. The most common site of B19V detection is peripheral blood (χ 2=0.000 3, P<0.001), although it can also be detected in other bodily fluid samples. The 30 day mortality rate among B19V infected patients was 19.35% (12/62) 10 out of 12 deceased patients had concurrent mixed infections with other pathogens. Moreover, patients with mixed B19V infections exhibited a higher mortality rate compared to those with B19V infection alone (χ 2=4.546, P=0.033). Comparative analysis of 24 patients who underwent multiple mNGS tests revealed that patients with chronic B19V infection (12 cases) had a higher mortality rate compared to those with transient B19V infection (12 cases) (χ 2=12, P<0.001). Conclusions:Parvovirus B19 (B19V) infection is more commonly observed in patients with hematological disorders and solid organ transplant recipients, often coexisting with other pathogens. The mortality rate within 30 days of B19V infection is elevated, particularly when accompanied by concurrent mixed infections with other pathogens. Moreover, patients with chronic and persistent B19V infection face an increased risk of mortality.

OBJECTIVE: To analyze the correlation between the mRNA levels of breast cancer resistance protein (BCRP) and lung-specific X protein (LUNX) genes with pathological types and stages of patients with non-small cell lung cancer (NSCLC) and their significance for prognosis. METHODS: Eighty nine patients with NSCLC admitted to Huaihe Hospital of Henan University between June 2015 and June 2018 were recruited, with 55 patients with benign lung lesions admitted during the same period of time selected as the control group. The mRNA levels of BCRP and LUNX genes were detected in the peripheral blood samples from the two groups, and their correlation with the clinicopathological characteristics and prognosis of the patients was analyzed. RESULTS: The expression rates of BCRP and LUNX mRNA in the NSCLC group were significantly higher compared with the control group (P < 0.05). The level of BCRP mRNA of the NSCLC patients has correlated with the degree of differentiation and TNM staging (P < 0.05), but not with gender, age, smoking, pathological types and lymph node metastasis (P > 0.05). The level of LUNX mRNA of them has correlated with the degree of differentiation, TNM staging and lymph node metastasis (P < 0.05), but not with gender, age, smoking, and pathological types (P > 0.05). Compared with those with no expression, the overall survival rate of patients with BCRP and LUNX expression was significantly lower (P < 0.05). The degree of differentiation, TNM staging, lymph node metastasis, and expression of the BCRP and LUNX mRNA may all affect the prognosis of the patients. CONCLUSION The levels of BCRP and LUNX mRNA in the peripheral blood of patients with NSCLC are significantly increased. The expression of BCRP mRNA is correlated with the degree of differentiation and TNM staging, whilst the expression of LUNX mRNA is correlated with the differentiation degree, TNM staging and lymph node metastasis. Both may be used as independent predictors for the prognosis of patients with NSCLC.
Humans ; ATP Binding Cassette Transporter, Subfamily G, Member 2/genetics* ; Biomarkers, Tumor/genetics* ; Carcinoma, Non-Small-Cell Lung/pathology* ; Glycoproteins/genetics* ; Lung Neoplasms/pathology* ; Lymphatic Metastasis ; Neoplasm Proteins/genetics* ; Phosphoproteins/genetics* ; Prognosis ; RNA, Messenger/genetics*

RBM46 is a germ cell-specific RNA-binding protein required for gametogenesis, but the targets and molecular functions of RBM46 remain unknown. Here, we demonstrate that RBM46 binds at specific motifs in the 3'UTRs of mRNAs encoding multiple meiotic cohesin subunits and show that RBM46 is required for normal synaptonemal complex formation during meiosis initiation. Using a recently reported, high-resolution technique known as LACE-seq and working with low-input cells, we profiled the targets of RBM46 at single-nucleotide resolution in leptotene and zygotene stage gametes. We found that RBM46 preferentially binds target mRNAs containing GCCUAU/GUUCGA motifs in their 3'UTRs regions. In Rbm46 knockout mice, the RBM46-target cohesin subunits displayed unaltered mRNA levels but had reduced translation, resulting in the failed assembly of axial elements, synapsis disruption, and meiotic arrest. Our study thus provides mechanistic insights into the molecular functions of RBM46 in gametogenesis and illustrates the power of LACE-seq for investigations of RNA-binding protein functions when working with low-abundance input materials.
Animals ; Mice ; 3' Untranslated Regions/genetics* ; Cell Cycle Proteins/metabolism* ; Gametogenesis/genetics* ; Meiosis/genetics* ; Nuclear Proteins/genetics* ; RNA-Binding Proteins/genetics*

Renal fibrosis is the main pathological foundation of chronic kidney diseases progressing to end-stage renal diseases. With complex pathogenic factors and prolonged disease course， it threatens the quality of life of patients and brings about heavy financial burden to medical care. In the instance of intestinal flora disturbance， the internal homeostasis is broken， resulting in various "imbalances". The "combination of state and target" endows the syndrome differentiation-based treatment of renal fibrosis with new connotation from the perspective of intestinal flora reconstruction and microbial diversity restoration. In addition， traditional Chinese medicine （TCM）-targeted intervention of intestinal microecology has unique advantages under the principle of "treating different diseases with the same method"， which can guide the diagnosis and treatment of renal fibrosis. To be specific， TCM emphasizes macroscopic regulation of state and microscopic targeting. In view of the inflammatory response， accumulation of endotoxin， and excessive deposition of extracellular matrix （ECM） in the process of renal fibrosis， the strategies for treating this disease have been developed， such as alleviating dampness，removing turbid toxin， and relieving deficiency and stasis. Famous prescriptions in ancient books or compound Chinese medicine prescriptions， classical formulas， Chinese medicine monomers， or active components of Chinese medicine target intestinal microecology. Therefore， from the perspective of common pathogenic factors of renal diseases （renal fibrosis） or pathological product-intestinal microecological imbalance， this article combines TCM basic theory with modern medical pathogenesis， and summarizes the research on TCM intervention of renal fibrosis by regulating intestinal microecology and the scientific connotation of renal fibrosis， which is expected to provide ideas and methods for the product development and related preparations and in-depth molecular biological research.

In 2016, a national one million general population cohort project was set up in China for the first time in "Precision Medicine Research" Key Project, National Key Research and Development Program of China, which consists of general population cohorts in seven areas in China. As one of the seven major areas in China, northeastern China has unique climate and specific dietary patterns, and population aging is serious in this area. And the burden of chronic and non-communicable diseases ranks tops in China. Therefore, it is of great significance to establish a large general population cohort in northeastern China to explore the area specific exposure factors related to pathogenesis and prognosis of chronic and non-communicable diseases, develop new prevention strategies to reduce the burden of the diseases and improve the population health in northeastern China. In July 2018, the general population cohort study in northeastern China was launched, the study includes questionnaire survey, health examination and blood, urine and stool sample collection and detection in recruited participants. By now, the cohort has covered all age groups, and the baseline data of 115 414 persons have been collected. This paper summarizes the design and practice of the general population cohort study in northeastern China to provide reference for related research in China.

Using chemoproteomic techniques, we first identified EIF2AK2, eEF1A1, PRDX3 and VPS4B as direct targets of berberine (BBR) for its synergistically anti-inflammatory effects. Of them, BBR has the strongest affinity with EIF2AK2 via two ionic bonds, and regulates several key inflammatory pathways through EIF2AK2, indicating the dominant role of EIF2AK2. Also, BBR could subtly inhibit the dimerization of EIF2AK2, rather than its enzyme activity, to selectively modulate its downstream pathways including JNK, NF-κB, AKT and NLRP3, with an advantage of good safety profile. In EIF2AK2 gene knockdown mice, the inhibitory IL-1β, IL-6, IL-18 and TNF-α secretion of BBR was obviously attenuated, confirming an EIF2AK2-dependent anti-inflammatory efficacy. The results highlight the BBR's network mechanism on anti-inflammatory effects in which EIF2AK2 is a key target, and inhibition of EIF2AK2 dimerization has a potential to be a therapeutic strategy against inflammation-related disorders.