Objectives:To analyze the disease burden and trends of ischemic stroke attributable to major metabolic risk factors in China from 1990 to 2021,and provide a basis for disease prevention and management.Methods:Based on the Global Burden of Disease(GBD)2021 data,we compared the age-standardized mortality rate(ASMR)and age-standardized disability-adjusted life year rate(ASDR)of ischemic stroke attributable to major metabolic risk factors(including overweight/obesity,hypertension,elevated low-density lipoprotein cholesterol,low bone density,hyperglycemia,and impaired renal function)in China and globally,and estimated their time trends through estimated annual percentage change(EAPC).We also analyzed the number of deaths,mortality rate,disability adjusted life year(DALY),and DALY rate of ischemic stroke attributable to major metabolic risk factors in China from 1990 to 2021,and compared the epidemiological differences among different gender and age groups.Results:From 1990 to 2021,the disease burden of ischemic stroke attributable to major metabolic risk factors in China showed a slight upward trend(1990 to 2005)and then gradually decreased,with a relatively small overall decline.,while the global disease burden showed a decreasing trend.In 2021,the ASMR and ASDR of ischemic stroke attributable to major metabolic risk factors in China were 48.11/100 000 and 898.35/100 000(EAPC[95%CI]were-0.24%[-1.13%to 0.66%]and-0.25%[-1.00%to 0.51%]),respectively,both higher than the global average levels(33.96/100 000 and 651.46/100 000,EAPC[95%CI]were-1.75%[-2.03%to 1.47%]and-1.49%[-1.74%to-1.23%],respectively).Compared with 1990,the actual mortality rate and DALY rate of ischemic stroke attributable to major metabolic risk factors in China increased by 139.60%and 110.53%respectively in 2021.There are gender differences in the disease burden of ischemic stroke attributable to major metabolic risk factors in China,with significantly higher death numbers,mortality rates,DALY,and DALY rates in males compared to females.At the age level,DALY and DALY rates were both higher in individuals aged 15-49,DALY increased but DALY rates decreased in individuals aged 50-69.DALY surged in individuals aged 70 and above,male DALY rates showed increasing trend and female DALY rates showed slightly decreasing trend.Conclusions:The disease burden of ischemic stroke in China is significantly affected by metabolic risk factors.Although prevention and control have achieved certain positive results,the overall disease burden in China is higher than that of the world,and precise intervention strategies need to be developed for different genders and ages in China.

Objective:To establish a digital reverse transcription polymerase chain reaction（dRT-PCR）detection method for hepatitis E virus（HEV）using nanoplates，and to provide technical reference for HEV monitoring in shellfish by combining virus enrichment pretreatment methods.Methods:The annealing temperature，primer and probe concentrations of HEV dRT-PCR were optimized，and the specificity of the method was evaluated；the sensitivity of this method for detecting HEV in water samples and oyster extracts was compared. The inhibition rate and recovery rate of HEV detection in artificially contaminated oyster samples were calculated，commercially available oyster samples were tested，and compare them with real-time fluorescence quantitative RT-PCR（qRT-PCR）method.Results:The optimized annealing temperature for HEV dRT-PCR was determined to be 60 ℃，and the final concentrations of primers and probes were 0.4 μmol/L，0.4 μmol/L，and 0.2 μmol/L，respectively，indicating good specificity. The sensitivity of both methods for detecting HEV RNA in water samples was higher than that in oyster extracts. The recovery rates of HEV in oyster specimens contaminated with HEV fecal suspension by dRT-PCR and qRT-PCR were 18.76% and 18.36%，respectively，with no statistically significant difference（ P>0.05）；the inhibition rates were 17.26% and 9.58%，respectively，with statistically significant differences（ P<0.05）；55 commercially available oyster samples were tested，and both methods detected HEV RNA positivity in the same sample. Conclusion:The dRT-PCR method established in this study，combined with “proteinase K digestion，PEG/NaCl precipitation，and chloroform/n-butanol extraction” pretreatment，has a good recovery effect on HEV in shellfish food containing a large amount of PCR inhibitors，and can achieve absolute quantification. It has certain application value in monitoring and risk assessment of HEV in shellfish food.

Objective:To establish a digital reverse transcription polymerase chain reaction（dRT-PCR）detection method for hepatitis E virus（HEV）using nanoplates，and to provide technical reference for HEV monitoring in shellfish by combining virus enrichment pretreatment methods.Methods:The annealing temperature，primer and probe concentrations of HEV dRT-PCR were optimized，and the specificity of the method was evaluated；the sensitivity of this method for detecting HEV in water samples and oyster extracts was compared. The inhibition rate and recovery rate of HEV detection in artificially contaminated oyster samples were calculated，commercially available oyster samples were tested，and compare them with real-time fluorescence quantitative RT-PCR（qRT-PCR）method.Results:The optimized annealing temperature for HEV dRT-PCR was determined to be 60 ℃，and the final concentrations of primers and probes were 0.4 μmol/L，0.4 μmol/L，and 0.2 μmol/L，respectively，indicating good specificity. The sensitivity of both methods for detecting HEV RNA in water samples was higher than that in oyster extracts. The recovery rates of HEV in oyster specimens contaminated with HEV fecal suspension by dRT-PCR and qRT-PCR were 18.76% and 18.36%，respectively，with no statistically significant difference（ P>0.05）；the inhibition rates were 17.26% and 9.58%，respectively，with statistically significant differences（ P<0.05）；55 commercially available oyster samples were tested，and both methods detected HEV RNA positivity in the same sample. Conclusion:The dRT-PCR method established in this study，combined with “proteinase K digestion，PEG/NaCl precipitation，and chloroform/n-butanol extraction” pretreatment，has a good recovery effect on HEV in shellfish food containing a large amount of PCR inhibitors，and can achieve absolute quantification. It has certain application value in monitoring and risk assessment of HEV in shellfish food.

Objective To investigate the distribution and antimicrobial resistance profiles of clinically isolated Haemophilus influenzae and Moraxella catarrhalis in hospitals across China from 2015 to 2021,and provide evidence for rational use of antimicrobial agents.Methods Data of H.influenzae and M.catarrhalis strains isolated from 2015 to 2021 in CHINET program were collected for analysis,and antimicrobial susceptibility testing was performed by disc diffusion method or automated systems according to the uniform protocol of CHINET.The results were interpreted according to the CLSI breakpoints in 2022.Beta-lactamases was detected by using nitrocefin disk.Results From 2015 to 2021,a total of 43 642 strains of Haemophilus species were isolated,accounting for 2.91％of the total clinical isolates and 4.07％of Gram-negative bacteria in CHINET program.Among the 40 437 strains of H.influenzae,66.89％were isolated from children and 33.11％were isolated from adults.More than 90％of the H.influenzae strains were isolated from respiratory tract specimens.The prevalence of β-lactamase was 53.79％in H.influenzae strains.The H.influenzae strains isolated from children showed higher resistance rate than the strains isolated from adults.Overall,779 strains of H.influenzae did not produce β-lactamase but were resistant to ampicillin(BLNAR).Beta-lactamase-producing strains showed significantly higher resistance rates to these antimicrobial agents than the β-lactamase-nonproducing strains.Of the 16 191 M.catarrhalis strains,80.06％were isolated from children and 19.94％isolated from adults.M.catarrhalis strains were mostly susceptible to both amoxicillin-clavulanic acid and cefuroxime,evidenced by resistance rate lower than 2.0％.Conclusions The emergence of antibiotic-resistant H.influenzae due to β-lactamase production poses a challenge for clinical anti-infective treatment.Therefore,it is very important to implement antibiotic resistance surveillance for H.influenzae and guide rational antibiotic use.All local clinical microbiology laboratories should actively improve antibiotic susceptibility testing and strengthen antibiotic resistance surveillance for H.influenzae.

Objective To investigate the distribution and antimicrobial resistance profiles of clinically isolated Haemophilus influenzae and Moraxella catarrhalis in hospitals across China from 2015 to 2021,and provide evidence for rational use of antimicrobial agents.Methods Data of H.influenzae and M.catarrhalis strains isolated from 2015 to 2021 in CHINET program were collected for analysis,and antimicrobial susceptibility testing was performed by disc diffusion method or automated systems according to the uniform protocol of CHINET.The results were interpreted according to the CLSI breakpoints in 2022.Beta-lactamases was detected by using nitrocefin disk.Results From 2015 to 2021,a total of 43 642 strains of Haemophilus species were isolated,accounting for 2.91％of the total clinical isolates and 4.07％of Gram-negative bacteria in CHINET program.Among the 40 437 strains of H.influenzae,66.89％were isolated from children and 33.11％were isolated from adults.More than 90％of the H.influenzae strains were isolated from respiratory tract specimens.The prevalence of β-lactamase was 53.79％in H.influenzae strains.The H.influenzae strains isolated from children showed higher resistance rate than the strains isolated from adults.Overall,779 strains of H.influenzae did not produce β-lactamase but were resistant to ampicillin(BLNAR).Beta-lactamase-producing strains showed significantly higher resistance rates to these antimicrobial agents than the β-lactamase-nonproducing strains.Of the 16 191 M.catarrhalis strains,80.06％were isolated from children and 19.94％isolated from adults.M.catarrhalis strains were mostly susceptible to both amoxicillin-clavulanic acid and cefuroxime,evidenced by resistance rate lower than 2.0％.Conclusions The emergence of antibiotic-resistant H.influenzae due to β-lactamase production poses a challenge for clinical anti-infective treatment.Therefore,it is very important to implement antibiotic resistance surveillance for H.influenzae and guide rational antibiotic use.All local clinical microbiology laboratories should actively improve antibiotic susceptibility testing and strengthen antibiotic resistance surveillance for H.influenzae.

Objectives:To analyze the disease burden and trends of ischemic stroke attributable to major metabolic risk factors in China from 1990 to 2021,and provide a basis for disease prevention and management.Methods:Based on the Global Burden of Disease(GBD)2021 data,we compared the age-standardized mortality rate(ASMR)and age-standardized disability-adjusted life year rate(ASDR)of ischemic stroke attributable to major metabolic risk factors(including overweight/obesity,hypertension,elevated low-density lipoprotein cholesterol,low bone density,hyperglycemia,and impaired renal function)in China and globally,and estimated their time trends through estimated annual percentage change(EAPC).We also analyzed the number of deaths,mortality rate,disability adjusted life year(DALY),and DALY rate of ischemic stroke attributable to major metabolic risk factors in China from 1990 to 2021,and compared the epidemiological differences among different gender and age groups.Results:From 1990 to 2021,the disease burden of ischemic stroke attributable to major metabolic risk factors in China showed a slight upward trend(1990 to 2005)and then gradually decreased,with a relatively small overall decline.,while the global disease burden showed a decreasing trend.In 2021,the ASMR and ASDR of ischemic stroke attributable to major metabolic risk factors in China were 48.11/100 000 and 898.35/100 000(EAPC[95%CI]were-0.24%[-1.13%to 0.66%]and-0.25%[-1.00%to 0.51%]),respectively,both higher than the global average levels(33.96/100 000 and 651.46/100 000,EAPC[95%CI]were-1.75%[-2.03%to 1.47%]and-1.49%[-1.74%to-1.23%],respectively).Compared with 1990,the actual mortality rate and DALY rate of ischemic stroke attributable to major metabolic risk factors in China increased by 139.60%and 110.53%respectively in 2021.There are gender differences in the disease burden of ischemic stroke attributable to major metabolic risk factors in China,with significantly higher death numbers,mortality rates,DALY,and DALY rates in males compared to females.At the age level,DALY and DALY rates were both higher in individuals aged 15-49,DALY increased but DALY rates decreased in individuals aged 50-69.DALY surged in individuals aged 70 and above,male DALY rates showed increasing trend and female DALY rates showed slightly decreasing trend.Conclusions:The disease burden of ischemic stroke in China is significantly affected by metabolic risk factors.Although prevention and control have achieved certain positive results,the overall disease burden in China is higher than that of the world,and precise intervention strategies need to be developed for different genders and ages in China.

Background Previous research on chlorinated paraffins (CPs) in fine particulate matter (PM_2.5) has predominantly focused on short- and medium-chain chlorinated paraffins (SCCPs and MCCPs), and few studies could simultaneously determine short-, medium-, and long-chain chlorinated paraffins (LCCPs). Simultaneous extraction and determination of SCCPs, MCCPs, and LCCPs in PM_2.5 could provide technical support for their environmental monitoring and human health risk assessment. Objective To establish a method based on QUEChERS pretreatment method in conjunction with ultra-performance liquid chromatography-quadrupole/orbitrap high resolution mass spectrometry for simultaneously determining the levels of SCCPs, MCCPs, and LCCPs in PM_2.5. Methods The extraction solvents, extraction salts, and extraction steps of a QuEChERS method were optimized. The extraction efficiencies of the target substances were compared under 4 extraction solvents [acetonitrile, dichloromethane, and n-hexane solvents in sequence; acetonitrile: dichloromethane: n-hexane = 1: 1: 2 (v/v/v) mixed solvent; 1% acetic acid-acetonitrile: dichloromethane: n-hexane = 1: 1: 1 (v/v/v) mixed solvent; acetonitrile: dichloromethane: n-hexane = 1: 1: 1 (v/v/v) mixed solvent], 2 dehydrated salts (anhydrous MgSO₄+NaCl and anhydrous Na₂SO₄+NaCl), 2 purification salts (C18 and PSA), and 4 vortex time (5, 7.5, 10, and 12.5 min) conditions. Then internal standard was utilized to estimate linear range and detection limit of the refined QuEChERS approach. Results The linearities of SCCPs, MCCPs, and LCCPs were good in the range of 10~1000 ng·mL⁻¹ with the correlation coefficients all greater than 0.96. The method detection limits (MDLs) ranged from 0.01 to 0.29 ng·m⁻³. The spiked recoveries of SCCPs, MCCPs, and LCCPs at the low, medium, and high concentrations were 77.38%-81.64%, 93.11%-99.78%, and 87.41%-101.39%, respectively, and the relative standard deviations (RSDs) were 2.90%-12.84%. This method was used to determine the CPs levels in 11 PM_2.5 samples from Shijiazhuang. The positive rates of ∑SCCPs, ∑MCCPs, and ∑LCCPs were all 100%, the concentration ranges were 0.24-2.18 ng·m⁻³ (mean 0.84 ng·m⁻³), 0.17-1.67 ng·m⁻³ (mean 0.70 ng·m⁻³), and 0.01-0.16 ng·m⁻³ (mean 0.04 ng·m⁻³), respectively, and the percentages to ΣCPs were 52.95%, 44.39%, and 2.66%, respectively. Conclusion The method established in this study is simple, time-saving, solvent saving, and can simultaneously detect SCCPs, MCCPs, and LCCPs in PM_2.5, which is suitable for the determination of PM_2.5 samples in large quantities, and can also provide a reference for the detection methods of other halogenated organic compounds in PM_2.5.

Based on the metabolomics, this paper systematically analyzed the metabolic substance basis of Zuogui Pills and Yougui Pills in syndrome differentiation and treatment of diminished ovarian reserve(DOR), so as to provide a scientific basis for the traditional Chinese medicine(TCM) syndrome differentiation and treatment of DOR. Patients with DOR of kidney-Yin deficiency syndrome were collected from outpatient department of hospitals and treated with Zuogui Pills for 12 weeks. And kidney-Yang deficiency syndrome were treated with Yougui Pills for 12 weeks. Based on the non-targeted metabolomic research techniques, the potential biomarkers of Zuogui Pills and Yougui Pills in the treatment of DOR with kidney-Yin deficiency and kidney-Yang deficiency, respectively, were screened out, and metabolic pathways of biomarkers were analyzed. The pregnancy rate, basic serum hormone levels [basal follicle-stimulating hormone(bFSH), basal-luteinizing hormone(bLH), basal-estradiol(bE_2), and anti-Müllerian hormone(AMH)], TCM syndrome type score, and Kupperman score were recorded and statistically analyzed after treatment. The results showed that 23 patients with DOR of kidney-Yin deficiency syndrome and 25 patients of kidney-Yang deficiency syndrome were collected. Twenty-six differential metabolites, including L-carnitine, acetyl-CoA, coenzyme A, and coenzyme Q_(10)(CoQ10), were mapped to 12 metabolic pathways in patients with kidney-Yin deficiency treated with Zuogui Pills. Twenty-two differential metabolites, such as adipoyl-CoA, L-lysine, lysine arginine, and α-tocopherol, were mapped to 11 metabolic pathways in patients with kidney-Yang deficiency. After treatment, bFSH and bLH of patients with DOR were significantly lower than those before treatment(P<0.05). Although the comparison of bE_2 and AMH had no significant differences, there was a improvement trend. The TCM syndrome type score and Kupperman score of patients with DOR after TCM treatment were significantly lower than those before treatment(P<0.05).

OBJECTIVE: To explore the influence of lymphocyte-to-monocyte ratio (LMR) and neutrophil-to-lymphocyte ratio (NLR) on the prognosis of patients with extranodal NK/T cell lymphoma (ENKTL). METHODS: The clinical data of 203 patients with ENKTL admitted to the First Affiliated Hospital of Zhengzhou University from January 2011 to January 2020 were retrospectively analyzed. The ROC curve determined the limit values of LMR and NLR; Categorical variables were compared using a chi-square test, expressed as frequency and percentage (n,%). Continuous variables were expressed as medians and extremes and compared with the Mann-Whitney U test; Progression-free survival (PFS) and overall survival (OS) of different grouped LMR and NLR patients were analyzed using Kaplan-Meier curves and compared with log-rank tests. The COX proportional risk regression model was used to perform one-factor and multi-factor analysis of PFS and OS. RESULTS: The optimal critical values of LMR and NLR were determined by the ROC curve, which were 2.60 and 3.40, respectively. LMR≤2.60 was more likely to occur in patients with bone marrow invasion (P=0.029) and higher LDH (P=0.036), while NLR≥3.40 was more likely to occur in patients with higher ECOG scores (P=0.002), higher LDH (P=0.008), higher blood glucose (P=0.024), and lower PLT (P=0.010). Kaplan-Meier survival analysis showed that PFS and OS of patients in the high LMR group were significantly better than the low LMR group, while PFS and OS in the low NLR group were significantly better than the high NLR group. The results of multivariate COX analysis showed that EBV-DNA positive (P=0.047), LMR≤2.60 (P=0.014), NLR≥3.40 (P=0.023) were independent risk factors affecting PFS in patients with ENKTL. LMR≤2.60 (P<0.001), NLR≥3.40 (P=0.048), and high β2-MG (P=0.013) were independent risk factors affecting OS in patients with ENKTL. CONCLUSION Low LMR and high NLR before treatment are associated with poor prognosis in patients with ENKTL, which also can be used as an easily testable, inexpensive, and practical prognostic indicator in the clinic.
Humans ; Monocytes/pathology* ; Neutrophils ; Lymphoma, Extranodal NK-T-Cell/pathology* ; Retrospective Studies ; Lymphocytes ; Prognosis

Objective: To observe the platinum drugs resistance effect of N-acetyltransferase 10 (NAT10) overexpression in breast cancer cell line and elucidate the underlining mechanisms. Methods: The experiment was divided into wild-type (MCF-7 wild-type cells without any treatment) group, NAT10 overexpression group (H-NAT10 plasmid transfected into MCF-7 cells) and NAT10 knockdown group (SH-NAT10 plasmid transfected into MCF-7 cells). The invasion was detected by Transwell array, the interaction between NAT10 and PARP1 was detected by co-immunoprecipitation. The impact of NAT10 overexpression or knockdown on the acetylation level of PARP1 and its half-life was also determined. Immunostaining and IP array were used to detect the recruitment of DNA damage repair protein by acetylated PARP1. Flow cytometry was used to detect the cell apoptosis. Results: Transwell invasion assay showed that the number of cell invasion was 483.00±46.90 in the NAT10 overexpression group, 469.00±40.50 in the NAT10 knockdown group, and 445.00±35.50 in the MCF-7 wild-type cells, and the differences were not statistically significant (P>0.05). In the presence of 10 μmol/L oxaliplatin, the number of cell invasion was 502.00±45.60 in the NAT10 overexpression group and 105.00±20.50 in the NAT10 knockdown group, both statistically significant (P<0.05) compared with 219.00±31.50 in wild-type cells. In the presence of 10 μmol/L oxaliplatin, NAT10 overexpression enhanced the binding of PARP1 to NAT10 compared with wild-type cells, whereas the use of the NAT10 inhibitor Remodelin inhibited the mutual binding of the two. Overexpression of NAT10 induced PARP1 acetylation followed by increased PARP1 binding to XRCC1, and knockdown of NAT10 expression reduced PARP1 binding to XRCC1. Overexpression of NAT10 enhanced PARP1 binding to LIG3, while knockdown of NAT10 expression decreased PARP1 binding to LIG3. In 10 μmol/L oxaliplatin-treated cells, the γH2AX expression level was 0.38±0.02 in NAT10 overexpressing cells and 1.36±0.15 in NAT10 knockdown cells, both statistically significant (P<0.05) compared with 1.00±0.00 in wild-type cells. In 10 μmol/L oxaliplatin treated cells, the apoptosis rate was (6.54±0.68)% in the NAT10 overexpression group and (12.98±2.54)% in the NAT10 knockdown group, both of which were statistically significant (P<0.05) compared with (9.67±0.37)% in wild-type cells. Conclusion: NAT10 overexpression enhances the binding of NAT10 to PARP1 and promotes the acetylation of PARP1, which in turn prolongs the half-life of PARP1, thus enhancing PARP1 recruitment of DNA damage repair related proteins to the damage sites, promoting DNA damage repair and ultimately the survival of breast cancer cells.
Breast Neoplasms/enzymology* ; Cell Line, Tumor ; Drug Resistance, Neoplasm ; Female ; Humans ; MCF-7 Cells ; N-Terminal Acetyltransferases/metabolism* ; Organoplatinum Compounds/pharmacology* ; Oxaliplatin/pharmacology* ; X-ray Repair Cross Complementing Protein 1