Objective:To construct fused cancer cell/neutrophil membrane-coated polydopamine nanoparticles chelated with manganese ions (Ⅱ) (PMNP@FMs) and explore the potential for targeted pancreatic cancer fluorescence imaging and MRI.Methods:Cancer cell membranes fused with neutrophil membranes were encapsulated on the surface of polydopamine nanoparticles chelated with manganese ions (Ⅱ) (PMNPs) to prepare PMNP@FMs. The morphology, structure, and MRI performance of the product were characterized. The cytotoxicity of PMNP@FMs towards human pancreatic cancer cells (PANC-1) and normal human pancreatic ductal epithelial cells (hTERT-HPNE) was evaluated using cell counting kit (CCK)-8, and in vivo toxicity was assessed in healthy mice. PANC-1 pancreatic cancer xenograft nude mouse models were established for in vivo fluorescence imaging and MRI. Data were analyzed using the independent-sample t test, repeated measures analysis of variance and the least significance difference method. Results:PMNP@FMs exhibited a core-shell structure with a diameter of (112.81±8.64) nm, negative surface charge, and good dispersibility. The T 1 relaxivity of PMNPs was 18.81±0.22, which was 4.1 times higher than that of gadopentetate dimeglumine (Gd-DTPA) (4.55±0.24; t=75.54, P<0.001). Co-culture of PMNPs and PMNP@FMs with hTERT-HPNE and PANC-1 cells for 24 h resulted in cell viability above 90% within the concentration range of 0-500 μg/ml. PMNP@FMs did not affect mouse survival and showed no apparent organ damage. In vivo fluorescence imaging and MRI revealed that PMNP@FMs accumulated highly in tumors and reached the peak 24 h post intravenous administration (relative MR signal: 1.35±0.01, fluorescence intensity: (1.20±0.25)×10 10), surpassing the peak observed in the control group (1.22±0.01, (3.87±0.50)×10 9;F values: 11.03-188.01, t values: 18.20, 5.64, all P<0.05), with hepatic metabolism being the primary route of clearance. Conclusion:PMNP@FMs demonstrate a potential for targeted pancreatic cancer fluorescence imaging and MRI, offering promising prospect for precise diagnosis of early-stage pancreatic cancer.

Objective: To investigate the factors affecting carotid plaques among perimenopausal women, so as to provide the basis for the prevention and early intervention of cardiovascular diseases in perimenopausal women. Methods: Perimenopausal women aged 40-60 who underwent health check-ups at Xingtai People's Hospital from January 2022 to January 2023 were selected as subjects by convenient sampling method. Demographic information, lifestyle, waist-to-hip ratio, and blood biochemical indicators were collected through questionnaire surveys, physical examinations, and laboratory tests. Carotid plaques were detected using a Doppler ultrasound diagnostic instrument. Factors affecting carotid plaques among perimenopausal women were identified using a multivariable logistic regression model. Results: Totally 2 146 perimenopausal women were surveyed, with an age of (50.04±5.82) years. Carotid plaques were detected in 525 cases, with a detection rate of 24.46%. Multivariable logistic regression analysis showed that older age (45-<50 years old, OR=1.474, 95%CI: 1.062-2.047; 55-60 years old, OR=1.779, 95%CI: 1.276-2.481), residing in urban areas (OR=1.601, 95%CI: 1.079-2.376), drinking (OR=1.805, 95%CI: 1.108-2.941), hypertension (OR=1.815, 95%CI: 1.290-2.553), abnormal waist-to-hip ratio (OR=2.479, 95%CI: 1.982-3.101), and abnormal atherogenic index of plasma (OR=1.325, 95%CI: 1.064-1.650) were associated with a higher risk of carotid plaques. College degree or above (college, OR=0.659, 95%CI: 0.502-0.865; bachelor's degree or above, OR=0.517, 95%CI: 0.397-0.673), physical exercise (OR=0.621, 95%CI: 0.494-0.781) were associated with a lower risk of carotid plaques. Conclusion The carotid plaques among perimenopausal women mainly affected by age, place of residence, educational level, alcohol consumption, physical exercise, hypertension, waist-to-hip ratio and atherogenic index of plasma.

Objective:To construct fused cancer cell/neutrophil membrane-coated polydopamine nanoparticles chelated with manganese ions (Ⅱ) (PMNP@FMs) and explore the potential for targeted pancreatic cancer fluorescence imaging and MRI.Methods:Cancer cell membranes fused with neutrophil membranes were encapsulated on the surface of polydopamine nanoparticles chelated with manganese ions (Ⅱ) (PMNPs) to prepare PMNP@FMs. The morphology, structure, and MRI performance of the product were characterized. The cytotoxicity of PMNP@FMs towards human pancreatic cancer cells (PANC-1) and normal human pancreatic ductal epithelial cells (hTERT-HPNE) was evaluated using cell counting kit (CCK)-8, and in vivo toxicity was assessed in healthy mice. PANC-1 pancreatic cancer xenograft nude mouse models were established for in vivo fluorescence imaging and MRI. Data were analyzed using the independent-sample t test, repeated measures analysis of variance and the least significance difference method. Results:PMNP@FMs exhibited a core-shell structure with a diameter of (112.81±8.64) nm, negative surface charge, and good dispersibility. The T 1 relaxivity of PMNPs was 18.81±0.22, which was 4.1 times higher than that of gadopentetate dimeglumine (Gd-DTPA) (4.55±0.24; t=75.54, P<0.001). Co-culture of PMNPs and PMNP@FMs with hTERT-HPNE and PANC-1 cells for 24 h resulted in cell viability above 90% within the concentration range of 0-500 μg/ml. PMNP@FMs did not affect mouse survival and showed no apparent organ damage. In vivo fluorescence imaging and MRI revealed that PMNP@FMs accumulated highly in tumors and reached the peak 24 h post intravenous administration (relative MR signal: 1.35±0.01, fluorescence intensity: (1.20±0.25)×10 10), surpassing the peak observed in the control group (1.22±0.01, (3.87±0.50)×10 9;F values: 11.03-188.01, t values: 18.20, 5.64, all P<0.05), with hepatic metabolism being the primary route of clearance. Conclusion:PMNP@FMs demonstrate a potential for targeted pancreatic cancer fluorescence imaging and MRI, offering promising prospect for precise diagnosis of early-stage pancreatic cancer.

The correlation between hearing loss (HL) and physical performance in patients receiving maintenance hemodialysis (MHD) remains poorly investigated. This study explored the association between HL and physical performance in patients on MHD. Methods: This multicenter cross-sectional study was conducted between July 2020 and April 2021 in seven hemodialysis centers in Shanghai and Suzhou, China. The hearing assessment was performed using pure-tone average (PTA). Physical performance was assessed using the Timed Up and Go Test (TUGT), handgrip strength, and gait speed. Results: Finally, 838 adult patients (male, 516 [61.6%]; 61.2 ± 2.6 years) were enrolled. Among them, 423 (50.5%) had mild to profound HL (male, 48.6% and female, 53.4%). Patients with HL had poorer physical performance than patients without HL (p < 0.001). TUGT was positively correlated with PTA (r = 0.265, p < 0.001), while handgrip strength and gait speed were negatively correlated with PTA (r = –0.356, p < 0.001 and r = –0.342, p < 0.001, respectively). Physical performance in patients aged <60 years showed significant dose-response relationships with HL. After adjusting for confounders, the odds ratios (95% confidence intervals) for HL across the TUGT quartiles (lowest to highest) were 1.00 (reference), 1.15 (0.73–1.81), 1.69 (1.07–2.70), and 2.87 (1.69–4.88) (p for trend = 0.005). Conclusion: Lower prevalence of HL was associated with a faster TUGT and a stronger handgrip strength in patients on MHD.

Phage therapy is one of the most important tools for the treatment of infections with multi-drug resistant bacteria. Such phages are usually isolated from hospital effluents, however, no systematic study on the distribution of phages in hospital effluents has been conducted so far. The aim of this study was to isolate the corresponding phages of common pathogenic bacteria isolated in the clinic as hosts, so as to assess the ecological distribution of phages in hospital wastewater and to provide a reference for the isolation and application of phages of drug-resistant bacteria in the clinic. A cross-sectional study design was used in this study. The 125 pathogenic bacteria (belonging to 16 different strains) isolated from the clinical microbiology laboratory of Qilu Hospital of Shandong University from May to June 2023 were selected as the target strains, and the phages corresponding to these strains were isolated and purified from the hospital wastewater by using the double-layer plate sandwich method. At the same time, the distribution of pathogenic bacteria in the same batch of wastewater was analyzed with the help of mNGS sequencing technology, so as to preliminarily investigate the abundance correspondence between pathogenic bacteria and phages in wastewater. The results showed that a total of 56 phage strains were isolated from 125 clinical pathogens as hosts, corresponding to six pathogens, including Acinetobacter baumannii, Klebsiella pneumoniae, Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, and Stenotrophomonas maltophilia. All six pathogenic bacteria contained strains with different degrees of drug resistance, with a higher percentage of multi-drug resistant strains in A. baumannii, Escherichia coli and P. aeruginosa. The phage acquisition rates of these six pathogens were, in descending order, Escherichia coli (80%), Stenotrophomonas maltophilia (75%), Pseudomonas aeruginosa (70%), Klebsiella pneumoniae (66.67%), Acinetobacter baumannii (36.36%) and Staphylococcus aureus (12.5%). Preliminary mNGS sequencing results showed that the pathogenic bacteria with higher abundance in the batch of effluent were Enterococcus faecalis, Klebsiella pneumoniae, Escherichia coli, Enterococcus faecalis, Acinetobacter baumannii, Klebsiella aerogenes, Klebsiella michiganensis and Pseudomonas aeruginosa. In conclusion, phages of most common clinical Gram-negative pathogens were isolated from hospital wastewater with high isolation rates; however, phages of Gram-positive pathogens were isolated at lower rates, and only phages corresponding to Staphylococcus aureus were isolated in this study. The corresponding mNGS sequencing results showed that the distribution of Gram-negative pathogens in sewage may had a positive correlation with the ecological distribution of phages.

Phage therapy is one of the most important tools for the treatment of infections with multi-drug resistant bacteria. Such phages are usually isolated from hospital effluents, however, no systematic study on the distribution of phages in hospital effluents has been conducted so far. The aim of this study was to isolate the corresponding phages of common pathogenic bacteria isolated in the clinic as hosts, so as to assess the ecological distribution of phages in hospital wastewater and to provide a reference for the isolation and application of phages of drug-resistant bacteria in the clinic. A cross-sectional study design was used in this study. The 125 pathogenic bacteria (belonging to 16 different strains) isolated from the clinical microbiology laboratory of Qilu Hospital of Shandong University from May to June 2023 were selected as the target strains, and the phages corresponding to these strains were isolated and purified from the hospital wastewater by using the double-layer plate sandwich method. At the same time, the distribution of pathogenic bacteria in the same batch of wastewater was analyzed with the help of mNGS sequencing technology, so as to preliminarily investigate the abundance correspondence between pathogenic bacteria and phages in wastewater. The results showed that a total of 56 phage strains were isolated from 125 clinical pathogens as hosts, corresponding to six pathogens, including Acinetobacter baumannii, Klebsiella pneumoniae, Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, and Stenotrophomonas maltophilia. All six pathogenic bacteria contained strains with different degrees of drug resistance, with a higher percentage of multi-drug resistant strains in A. baumannii, Escherichia coli and P. aeruginosa. The phage acquisition rates of these six pathogens were, in descending order, Escherichia coli (80%), Stenotrophomonas maltophilia (75%), Pseudomonas aeruginosa (70%), Klebsiella pneumoniae (66.67%), Acinetobacter baumannii (36.36%) and Staphylococcus aureus (12.5%). Preliminary mNGS sequencing results showed that the pathogenic bacteria with higher abundance in the batch of effluent were Enterococcus faecalis, Klebsiella pneumoniae, Escherichia coli, Enterococcus faecalis, Acinetobacter baumannii, Klebsiella aerogenes, Klebsiella michiganensis and Pseudomonas aeruginosa. In conclusion, phages of most common clinical Gram-negative pathogens were isolated from hospital wastewater with high isolation rates; however, phages of Gram-positive pathogens were isolated at lower rates, and only phages corresponding to Staphylococcus aureus were isolated in this study. The corresponding mNGS sequencing results showed that the distribution of Gram-negative pathogens in sewage may had a positive correlation with the ecological distribution of phages.

Myotonic dystrophy type 1(DM1)is a multisystem trinucleotide repeat expansion disorder usually referred to the department of neurology with complaints of progressive muscle weakness and myotonia.This article reported a 33-year-old female patient with DM1 presenting with acute respiratory failure.Muscle bi-opsy in vastus lateralis showed significantly increased internal nuclei.Genetic test show CTG repeat expansions with the size of(847±76)in dystrophia myotonica protein kinase(DMPK)gene on chromosome 19.This case report broadens the clinician's understanding of the atypical clinical manifestations of DM1,so as to avoid missed diagnosis and misdiagnosis.

Objective:To investigate the effect and role of the hepatitis B virus (HBV) on the expression of inhibin (PHB) in the proliferation and survival of hepatocellular carcinoma (HCC) cells.Methods:The expression of PHB in 13 pairs of HBV-infected livers, normal livers and HepG2.2.15 and HepG2 cells was detected by real-time fluorescent quantitative PCR and Western blot. Liver tissues were collected from seven patients with chronic hepatitis B before and after antiviral (tenofovir) treatment, and the expression of PHB was detected by RT-PCR and Western blot. HepG2.2.15 cells were transfected with Pcmv6-AC-GFP-PHB, and control vectors were collected. DNA content was analyzed by flow cytometry. The proliferation level of each cell group was detected using the EdU cell proliferation assay. HepG2.2.15 cells transfected with Pcmv6-AC-GFP-PHB and the control vector were cultured in serum-free medium for 6 days. Apoptosis was measured at the indicated time points using fluorescence-activated cell sorting (FACS)-based Annexin-V/PI double staining.Results:Compared with normal liver tissue, the expression of PHB in HBV-infected liver tissue was down-regulated ( P < 0.01). Compared with HepG2 cells, the expression of PHB in HepG2.2.15 cells was significantly decreased ( P < 0.01). The expression level of PHB in liver tissue after antiviral treatment (tenofovir) was significantly higher than that before treatment ( P < 0.01). Compared with the control vector, the proliferation rate of HepG2.2.15 cells transfected with Pcmv6-AC-GFP-PHB was significantly lower than that of the control vector, and the apoptosis rate of HepG2.2.15 cells transfected with the Pcmv6-AC-GFP-PHB vector was significantly higher than the control vector ( P < 0.01). Conclusion:HBV down-regulates the expression of inhibin to promote the proliferation and survival of hepatocellular carcinoma cells.

Objective To analyze the microflora structure and abundance of ileum and colon of SPF male SD rats by high-throughput sequencing technique. MethodsThe ileal and colonic lumen contents of 30 SPF male SD rats were collected, the total bacterial DNA in the contents was extracted and amplified by PCR. The V3-V4 region of bacterial 16S rRNA in the samples was sequenced using Illumina NovaSeq sequencing platform. Then the species structure and abundance of the intestinal flora were analyzed at the phylum and genus level based on validated data. The diversity and differences between ileal and colonic flora were analyzed using the QIIME software (amplicon) analysis tool. The Tax4Fun program was applied to predict the dominant gene enrichment pathways of ileal and colonic flora. ResultsAt the phylum level, the dominant microflora in the ileum of male SD rats were Firmicutes and Actinobacteria, accounting for more than 98%. The dominant colonic microbial community were mainly Firmicutes and Bacteroidetes, accounting for more than 95%. At the genus level, Lactobacillus and Alistipes were the predominant bacteria in the ileum. The colon was dominated by Lactobacillus and Romboutsia. In terms of flora diversity, the alpha diversity of colonic flora including richness index (Chao1 index) and diversity index (Shannon index) were significantly higher than those of ileum (P < 0.01), and the structural variability of the composition of its flora species was smaller than that of ileum; the ileal flora with significant structural variability were mainly of the phylum Firmicutes, Romboutsia, Peptostreptococcaceae, while the colonic flora had significant structural differences in Bacteroidales. In terms of flora function, the ileal flora dominant genes were significantly enriched in lipid-like metabolism, polyketide metabolism, membrane transport, biodegradation and other pathways, while the colonic flora dominant genes were significantly enriched in glycan biosynthesis metabolism, energy metabolism, biosynthesis of cofactor and vitamins and other products, and other pathways. ConclusionThere are significant differences in structure and abundance between the ileal and colonic flora of SPF male SD rats, and the abundance and diversity of colonic flora are higher than those of ileal flora.

Objective::This study aimed to determine the likelihood of gestational diabetes mellitus (GDM) in subsequent pregnancy among women without GDM history and to identify risk factors for GDM in subsequent pregnancy.Methods::This retrospective cohort study involved participants who delivered twice in same hospital of 18 research centers when delivered the second baby from January 2018 to December 2018. Finally 6204 women were enrolled and 5180 women without GDM history were analyzed further. Women were categorized as non-GDM or GDM based on the blood glucose values of the subsequent pregnancy, and the characteristics and GDM risk of these groups were compared. A univariate analysis of potential risk factors was performed using the Chi-squared test and/or t-test for qualitative or quantitative variables, respectively. Associations with P values <0.1 were chosen to be included in the multivariate binary logistic regression model. Results::In primary analysis of 6204 women, the incidence of GDM in subsequent pregnancy is 48.9% (490/1002) in women with GDM history and 16.1% (835/5202) in women without GDM history. In a further analysis for 5180 women without GDM at index pregnancy, compared with the non-GDM group, the GDM group had a significantly higher age, prepregnancy body mass index, and blood glucose value at each oral glucose tolerance test (OGTT) timepoint (fasting, 1 h and 2 h) during the index and subsequent pregnancies, as well as higher weight retention during the interval between the two pregnancies ( P<0.001). Age above 35 years in subsequent pregnancy (odds ratio ( OR)=1.540, 95% confidence interval ( CI) = 1.257-1.886, P<0.001), macrosomia in index pregnancy ( OR=1.749, 95% CI=1.277-2.395, P=0.001), OGTT blood glucose values in index pregnancy (fasting, OR=2.487, 95% CI=1.883-3.285, P<0.001; 1 h, OR=1.142, 95% CI=1.051-1.241, P=0.002; 2 h, OR=1.290, 95% CI=1.162-1.432, P<0.001) and weight retention ( OR=1.052, 95% CI=1.035-1.068, P<0.001) were independent risk factors for GDM in subsequent pregnancy. Conclusion::For women without GDM history, GDM risk factors including age, macrosomia history, OGTT value, and weight retention, these can be evaluated before a subsequent pregnancy. Early warning and interventions are needed for women at high risk.