BACKGROUND:Ischemic stroke is a serious threat to human health.After ischemia and hypoxia,astrocyte expresses lipocalin-2 in large amounts to aggravate brain injury,but the specific mechanism is not clear.Hydroxysafflor yellow A has anti-ischemia,anti-oxidation,anti-thrombosis and anti-inflammatory effects.However,whether hydroxysafflor yellow A affects the expression of lipocalin-2 in astrocytes after cerebral ischemia and hypoxia and its mechanism are not clear. OBJECTIVE:To investigate the effect and mechanism of hydroxysafflor yellow A on the expression of lipocalin-2 in astrocytes after cerebral ischemia and reperfusion. METHODS:(1)Thirty adult SD rats were randomly divided into three groups:sham operation group,middle cerebral artery occlusion and reperfusion group,and hydroxysafflor yellow A group.The middle cerebral artery occlusion and reperfusion model was established in the latter two groups,and hydroxysafflor yellow A group was intraperitoneally injected with 12 mg/kg hydroxysafflor yellow A after reperfusion.Longa score was used to evaluate the degree of neurological impairment.Infarct volume was determined by TTC staining.JAK2/STAT3 pathway and lipocalin-2 expression were detected by western blot assay and immunofluorescence.Levels of interleukin 1β,interleukin 6 and tumor necrosis factor α were detected by ELISA.(2)Astrocytes were divided into four groups:Normal group,glucose-oxygen deprivation group,hydroxysafflor yellow A group and AG490 group.In the latter three groups,glucose-oxygen deprivation and glucose-oxygen recovery models were established.Astrocytes were treated with 75 μmol/L hydroxysafflor yellow A and 10 μmol/L tyrosine phosphorylation inhibitor AG490 for 8 hours during glucose-oxygen deprivation,respectively.The mechanism of hydroxysafflor yellow A on lipocalin-2 was further verified. RESULTS AND CONCLUSION:(1)Compared with the sham operation group,cerebral infarction was significantly increased in the middle cerebral artery occlusion and reperfusion group,accompanied by aggravated neurological impairment(P<0.01).Hydroxysafflor yellow A treatment could reduce cerebral infarction volume and improve neurological function(P<0.01).(2)The expressions of p-JAK2,p-STAT3 and lipocalin-2 in the middle cerebral artery occlusion and reperfusion group were higher than those in the sham operation group(P<0.01).Hydroxysafflor yellow A treatment reduced the expressions of JAK2,STAT3 and lipocalin-2(P<0.01).(3)The expression levels of interleukin 1β,interleukin-6 and tumor necrosis factor α in the middle cerebral artery occlusion and reperfusion group were higher than those in the sham operation group(P<0.01).Hydroxysafflor yellow A inhibited the expressions of interleukin 1β,interleukin-6 and tumor necrosis factor α(P<0.01).(4)In vitro,the expressions of p-JAK2,p-STAT3 and lipocalin-2 in the glucose-oxygen deprivation group were significantly higher than those in the normal group(P<0.01).After adding AG490,the phosphorylation of JAK2 and STAT3 decreased,and the expression of lipocalin-2 was inhibited(P<0.01).The results suggest that hydroxysafflor yellow A may inhibit the expression of lipocalin-2 in astrocytes after ischemia and hypoxia by regulating the JAK2/STAT3 signaling pathway,thereby reducing brain injury.

[Objective] To explore the expression of Nectin-4 in invasive bladder urothelial carcinoma (BUC) tissue and its clinical significance, so as to provide reference for clinical diagnosis and treatment of BUC. [Methods] Nectin-4 expression in 60 cases of invasive BUC and 40 cases of chronic inflammation of bladder mucosa was detected with immunohistochemical staining (IHC) and RNAscope.The results of the two methods were analyzed and compared, and the relationship between the two methods and the clinicopathological characteristics of invasive BUC was discussed.The correlation between the protein expression of Nectin-4 in BUC tissues, human epidermal growth factor receptor 2 (Her-2) and programmed death factor ligand 1 (PD-L1) was analyzed. [Results] The positive protein expression rates of Nectin-4 detected by IHC were 78.33%(47/60) and 17.50% (7/40) in the invasive BUC group and inflammatory group, respectively, while the positive mRNA expression rates of Nectin-4 detected by RNAscope were 83.33% (50/60) and 12.50% (5/40), respectively.The Kappa values of Nectin-4 in the invasive BUC group and inflammatory group were 0.732 and 0.610, respectively, with general consistency.The protein expression of Nectin-4 in invasive BUC was correlated with muscular invasion, histological grade, vascular thrombus, lymph node metastasis and clinical stage (P<0.05). The mRNA expression of Nectin-4 in invasive BUC was correlated with max tumor diameter, muscular invasion, histological grade, vascular thrombus, lymph node metastasis and clinical stage (P<0.05). The high expression of Nectin-4 in invasive BUC was positively correlated with the expression of Her-2 (P=0.002), but not with the expression of PD-L1 (P>0.05). [Conclusion] Nectin-4 is highly expressed in invasive BUC, and is usually associated with the pathological parameters of poor prognosis.Detection of Nectin-4 expression will help to guide clinical diagnosis and treatment.

Objective:To explore the incidence and mortality of digestive system cancers, and the trend of the disease burden attributed to different risk factors in population in China.Methods:Data were obtained from the GLOBOCAN 2020 and the Global Burden of Disease Study in 2019 databases and only the data from the Chinese population were included. Using Excel 2019 and R 4.2.1 software, indicators including age-standardized incidence rate (ASIR), age-standardized mortality rate (ASMR), age-standardized disability-adjusted life year (DALY) rate and its rate of change were used to illustrate the disease burden of digestive system cancers attributed to different factors and their trends.Results:In 2020, the ASIR of digestive system cancers in China was 83.00/100 000, and the ASMR was 63.80/100 000. The numbers of digestive system cancer cases and deaths increased with age, and more cases and deaths occurred in men than in women in all age groups. The age-standardized DALY rate of esophageal cancer, gastric cancer and liver cancers showed decreasing trends in China from 1990 to 2019 (rate of change: -45.26%, -46.87%, and -65.63%, respectively), whereas the age-standardized DALY rate of pancreatic cancer, colorectal cancer and gallbladder and biliary tract cancer showed increasing trends (rate of change: 67.61%, 30.52%, and 7.21%, respectively). The trend of the mortality rate was consistent with the DALY rate. Compared with the age-standardized DALY rate attributed to behavioral factors, the annual proportion of the age-standardized DALY rate attributed to metabolic factors to the total age-standardized DALY rate of esophageal cancer, liver cancer, pancreatic cancer, and colorectal cancer increased from 1990 to 2019. There was no significant change in the rank of age-standardized DALY rate of gastric cancer, liver cancer, pancreatic cancer, and gallbladder and biliary tract cancer attributed to different risk factors in China from 1990 to 2019, but the rank of certain attributed risk factors for the age-standardized DALY rate of esophageal cancer and colorectal cancer moved ahead (esophageal cancer: high BMI; colorectal cancer: low milk intake, and low whole-grain intake).Conclusions:The incidence and mortality of digestive system cancers was serious in China in 2020, and the annual proportion of the disease burden of digestive system cancers attributed to metabolic factors increased from 1990 to 2019. The rank of attributed risk factors for several digestive system cancers changed significantly.

Objective:To understand the prevalence and characteristics of Rhinovirus (HRV) infection in influenza-like Illness (ILIs) patients in Mianyang, Sichuan province, China.Methods:Throat swabs were collected from patients of ILIs in sentinel hospitals in Mianyang during 2021—2022. Real-time fluorescence quantitative PCR was used to detect 16 common pathogens. The VP4/VP2 coding region genes of HRV positive samples were amplified by nest PCR. The phylogeny, consistency and amino acid variation of different serotypes were analyzed and compared with reference sequences from GenBank database.Results:A total of 332 ILIs′ samples were collected with a virus detection rate of 58.73% (195/332) in Mianyang. Among them, 23 samples (23/332) were HRV-positive, and 18 VP4/VP2 sequences of HRV strains were successfully amplified. It was found that 13 HRV serotypes were detected in ILIs samples in Mianyang, which belonged to three genotypes, namely HRV-A (12 strains), HRV-B (5 strains) and HRV-C (1 strain).Conclusions:HRV was one of the pathogens of ILIs cases in Mianyang during 2021—2022, with HRV-A types as the dominant strains.

Objective:To understand the status quo of self-regulating fatigue (SRF) in aged patients undergoing maintenance hemodialysis (MHD) and analyze its influencing factors.Methods:This study is a cross-sectional study. From January to June 2022, 310 aged patients undergoing MHD from the blood purification centers of three ClassⅢ Grade A hospitals in Jinan, Shandong Province, were selected by convenience sampling. Various questionnaires, including the general information questionnaire, Mini-Mental State Examination (MMSE), Self-Regulatory Fatigue Scale (SRF-S), Medical Coping Modes Questionnaire (MCMQ), General Self-Efficacy Scale (GSES), and 5-Item Geriatric Depression Scale (GDS-5), were used to investigate and analyze the factors influencing self-regulation of fatigue in aged patients undergoing MHD through univariate and multiple stepwise regression analysis.Results:The SRF-S score for the aged patients undergoing MHD was (42.26±7.86). The results of the multiple factor analysis showed that family average monthly income, depression, coping style, and self-efficacy were factors influencing SRF in these patients ( P<0.05) . Conclusions:It is urgent to pay attention to the current status of self-regulation of fatigue in aged patients undergoing MHD and take effective measures to improve their self-efficacy, promote positive coping strategies, alleviate depression, and reduce their level of SRF.

Objective:To systematically evaluate the care experience of family caregivers for amyotrophic lateral sclerosis (ALS) patients, providing guidance for home care of ALS patients.Methods:Qualitative studies on the care experience of family caregivers for ALS patients were retrieved from PubMed, American Psychological Association Psychnet, CINAHL, Web of Science, Medline, Cochrane Library, Embase, China Biology Medicine disc, WanFang Data, VIP, and China National Knowledge Infrastructure. The search period was from database establishment to October 30, 2022. The quality of literature was evaluated using the quality evaluation criteria for qualitative research of the Australia Joanna Briggs Institute Evidence-Based Health Care Center (2016 edition). The aggregative integration method was used to integrate the results using NVivo 11 software.Results:A total of 11 studies were included. A total of 22 complete and clear results were extracted and combined to form eight new categories, which were integrated into three results, namely, family caregivers facing personal development limitations and various family difficulties, experiencing complex and chaotic emotional experiences, and craving for diversified care support.Conclusions:Nursing staff should pay attention to the impact of ALS on their patient's family caregivers, provide caregiver knowledge and skill guidance, promote positive emotional experiences, and offer diversified care support to improve the quality of life of patients and family caregivers.

Ischemic stroke,with a high disability and mortality rate,seriously endangers human health.Pathological process of ischemic stoke involves participations of various cells such as microglia and astrocytes.Among them,microglia,as innate immune cells in central nervous system(CNS),play an important role whether in physiological or pathological states.Triggering receptor expressed on myeloid cells 2(TREM2)is an immunoglobulin like receptor mainly existing on microglia in CNS,and can bind to a variety of ligands,which can negatively regulate autoimmunity and inflammation.In addition,TREM2 can mainly play an important role in process of proliferation,phagocytosis,survival and expressions of inflammatory factors.This article focused on biological characteristics of TREM2 on microglia,corresponding ligands and its signaling pathways,discussing regulation of TREM2 in ischemic stroke and its potential therapeutic effects,in order to provide an new target for prevention and treatment of ischemic stroke.

Objective To explore the effects of wogonin on cognitive function and neuroinflamma-tion in VaD rats by regulating AMPK/SIRT1 pathway.Methods 90 VaD rats were randomly di-vided into model group,low-,medium-and high-dose wogonin groups(50,100,200 mg/kg),and high dose+AMPK inhibitor(20 mg/kg)group,18 animals per group.Another 18 normal rats served as sham operation group.ELISA was utilized to measure the contents of IL-1β,TNF-α and IL-6 in hippocampal tissues.Western blotting was conducted to detect the expression of Iba-1,p-AMPK,AMPK and SIRT1 in hippocampal tissues.Results Compared with the sham operation group,the model group had longer escape latency,and elevated contents of IL-1β,TNF-α and IL-6,number of Iba-1 positive cells and expression level of Iba-1 protein in hippocampal tissue,shorter stay time at original platform,and lower expression of p-AMPK/AMPK and SIRT1 in hippocampal tissues(P＜0.05).Treatment of three doses of wogonin,in a dose-dependent man-ner,reduced escape latency,and decreased levels of IL-1β,TNF-α and IL-6,number of Iba-1 posi-tive cells and expression of Iba-1 protein in hippocampal tissue,but longer stay time at original platform,and enhanced expression of p-AMPK/AMPK and SIRT1 protein in hippocampal tissue when compared with the model group(P＜0.05).The high dose+AMPK inhibitor group showed longer escape latency(47.64±5.39 s vs 26.45±3.27 s),shorter stay time at original platform(21.78±3.51 s vs 35.22±5.02 s),increased levels of IL-1β,TNF-α and IL-6,number of Iba-1 positive cells and expression of Iba-1 protein in hippocampal tissue,and lower expression levels of p-AMPK/AMPK and SIRT1 in hippocampal tissue when compared with the high-dose group(P＜0.05).Conclusion Wogonin may improve cognitive function and hippocampal tissue patho-logical damage in VaD rats by activating the AMPK/SIRT1 pathway,and inhibit neuroinflammation.

Objective:To investigate the etiology of hand, foot and mouth disease (HFMD) in Mianyang city in 2022, and to analyze the genetic characteristics of coxsackievirus A6.Methods:Pharyngeal swabs were collected from patients with HFMD in Mianyang city in 2022. Real-time fluorescence quantitative PCR was used to detect enteroviruses in the samples. Part of the VP1 gene in enterovirus-positive samples was amplified by nested PCR using enterovirus typing primers to further identify the viral types. The VP1 coding region of all CVA6-positive samples and the whole genome of some samples were amplified and sequenced by PCR. The endemic strain in Mianyang city was analyzed for phylogeny, gene homology, amino acid variation and genetic recombination.Results:A total of 151 pharyngeal swabs were collected, and 104 enterovirus-positive samples were detected by real-time fluorescence quantitative PCR, with an overall detection rate of 68.88% (104/151). The typing results showed that there were 77 cases of CVA6 infection, with a positive rate of 50.99% (77/151). The full-length VP1 genes of 77 CVA6 strains were amplified, sequenced, and successfully spliced, and phylogenetic analysis showed that all 77 strains were of the D3 genotype. There were multiple amino acid variant sites in the prevalent strains in Mianyang city compared with the reference strain. Twenty whole genome sequences were amplified, sequenced, and successfully spliced, and homology analysis showed that the nucleotide homology between the 20 positive sequences ranged from 97.0% to 99.9%. Phylogenetic tree and recombination analysis showed that no recombination occurred in the coding regions of the epidemic strains in this study.Conclusions:The predominant pathogen causing HFMD in Mianyang city in 2022 is CVA6 D3 subtype, which is consistent with the national epidemic in 2022.

OBJECTIVES: The magnesium depletion score (MDS) is considered more reliable than traditional approaches for predicting magnesium deficiency in humans. We explored the associations of MDS and dietary magnesium intake with diabetes. METHODS: We obtained data from 18,853 participants in the National Health and Nutrition Examination Survey 2011-2018. Using multivariate regression and stratified analysis, we investigated the relationships of both MDS and magnesium intake with diabetes. To compute prevalence ratios (PRs), we employed modified Poisson or log-binomial regression. We characterized the non-linear association between magnesium intake and diabetes using restricted cubic spline analysis. RESULTS: Participants with MDS ≥2 exhibited a PR of 1.26 (95% confidence interval [CI], 1.19 to 1.34) for diabetes. Per-standard deviation (SD) increase in dietary magnesium intake was associated with a lower prevalence of diabetes (PR, 0.91; 95% CI, 0.87 to 0.96). Subgroup analyses revealed a positive association between MDS ≥2 and diabetes across all levels of dietary magnesium intake, including the lowest (PR, 1.35; 95% CI, 1.18 to 1.55), middle (PR, 1.23; 95% CI, 1.12 to 1.35), and highest tertiles (PR, 1.25; 95% CI, 1.13 to 1.37; pinteraction<0.001). Per-SD increase in magnesium intake was associated with lower diabetes prevalence in participants with MDS <2 (PR, 0.92; 95% CI, 0.87 to 0.98) and those with MDS ≥2 (PR, 0.91; 95% CI, 0.84 to 0.98; pinteraction=0.030). CONCLUSIONS MDS is associated with diabetes, particularly among individuals with low magnesium intake. Adequate dietary magnesium intake may reduce diabetes risk, especially in those with high MDS.