Humans ; Adsorption ; MicroRNAs/genetics* ; Cell Line, Tumor ; Colorectal Neoplasms/genetics* ; RNA, Long Noncoding ; Cell Proliferation ; Gene Expression Regulation, Neoplastic

Objective:To investigate the characteristics of anorectal dynamics in elderly patients with functional defecation disorders(FDD), and to provide a basis for their diagnosis, treatment and prevention.Methods:In this retrospective study, 226 patients with FDD receiving 3D high-resolution anorectal manometry were divided into an elderly group(93 cases)and a non-elderly group(133 cases). Results from anorectal manometry parameters were compared and analysis of patterns of anorectal pressure changes in elderly participants based on sex, the Bristol stool classification and clinical symptoms was conducted.Results:The resting anal pressure, rectal pressure and anal relaxation rate were lower( t=-3.407, -2.051, Z=2.548, P=0.001, 0.040, 0.011)and the volume of first sensation was higher( t=1.998, P=0.047)in the elderly group than in the non-elderly group.The maximum anal squeezing pressure, residual anal pressure and maximum tolerated volume were higher( t=4.589, 4.730, 2.025, all P<0.05), whereas the anal relaxation rate and anorectal pressure gradient were lower in elderly men than in elderly women( Z=4.059, t=-3.714, P<0.001 for both). Regarding the types of FDD, both the elderly group and the non-elderly group were dominated with type Ⅱ defecation disorder, with more men than women having type Ⅱ defecation disorder in the elderly group( χ2=10.343, P=0.001). In cases of paradoxical sphincter contraction during simulated defecation, the incidence in the elderly group was 80.65%(75/93), which was higher than 68.42%(91/133)in the non-elderly group( χ2=4.194, P=0.041). The volume of first sensation, volume of first defecation sensation, and maximum tolerated volume of patients in the elderly group without the urge to defecate were(59.86±23.84)ml, (96.76±34.61)ml, and(144.32±30.57)ml, respectively, higher than those of patients with the urge to defecate(46.79±17.20)ml, (75.26±28.75)ml, and(120.00±40.28)ml( t=-2.241, -2.493, -2.891, P=0.027, 0.014, 0.005). The rectal pressure(26.52±16.08)mmHg of patients with defecation dyssynergia was lower than that of patients without defecation dyssynergia(39.91±8.82)mmHg(1 mmHg=0.133 kPa)( t=-3.128, P=0.002), while the resting anal pressure of patients with defecation dyssynergia(90.60±28.44)mmHg was higher than that of patients without defecation dyssynergia(73.65±27.10)mmHg( t=-2.201, P=0.030). The resting anal pressure and maximum anal squeezing pressure in patients with anal blockage sensation[(87.11±24.64)mmHg, (149.28±48.29)mmHg]were higher than those in patients without anal blockage sensation[(72.43±20.02)mmHg, (121.76±26.35)mmHg]( t=2.954、3.066, P=0.004、0.003). There was no significant difference in values from parameters of anorectal dynamics between patients with different Bristol stool types, with and without incomplete defecation or with different degrees of abdominal distension(all P>0.05). Conclusions:Anorectal dynamics in patients with FDD are characterized by paradoxical anal sphincter movements, but older patients with FDD are mainly characterized by inadequate rectal propulsion, pelvic floor muscle dysfunction and reduced rectal sensitivity.

Humans ; Colorectal Neoplasms/genetics* ; Esophageal Neoplasms ; Genetic Predisposition to Disease ; Genotype ; Phosphoinositide Phospholipase C/genetics* ; Polymorphism, Single Nucleotide

【Objective】 To analyze the basic characteristics of whole blood donors from blood stations before and after the outbreak of COVID-19. 【Methods】 After excluding invalid data, data related to the basic characteristics of whole blood donors collected from 26 blood stations in China during 2018 to 2021 were statistically analyzed, including the trend of total whole blood donors, the number of repeated blood donors, the frequency of blood donation, the average age of donors and the recruitment of first-time blood donors. 【Results】 Affected by the epidemic, 8 out of 14 indicators were with large variations, accounting for 57%. The overall growth rate of total whole blood donors during the epidemic was higher than before the epidemic (P<0.05).The number of repeated blood donors has shown an increased trend, with a higher number during the epidemic than before (P<0.05). The frequency of blood donation was lower during the epidemic than before(P<0.05).Average ages of blood donors and female blood donors fluctuated widely during the epidemic, both higher than those before the epidemic(P<0.05).The donation rate of first-time blood donors <25 years old and ≥25 years old varied widely and irregularly during the epidemic (both P<0.05). The percentage of first-time blood donors fluctuated irregularly during the epidemic, with overall percentage lower than that before the epidemic(P<0.05). 【Conclusion】 Whole blood donors from 26 blood stations increased after the outbreak of COVID-19, and some indicators in certain areas showed significant fluctuations during the epidemic.

The production efficiency of microbial cell factory is determined by the growth performance, product synthetic capacity, and stress resistance of the strain. Strengthening the stress resistance is the key point to improve the production efficiency of microbial cell factory. Tolerance engineering is based on the response mechanism of microbial cell factory to resist stress. Specifically, it consolidates the cell wall-cell membrane barrier to enhance the defense against stress, accelerates the stress response to improve the damage repair, and creates tolerance evolutionary tools to screen industrial microorganisms with enhanced robustness. We summarize the regulation strategies and forecast the prospects of tolerance engineering, which plays an important role in the microbial cell factories for sustainable production of natural products and bulk chemicals.
Cell Membrane ; Metabolic Engineering

GC-MS metabolomics was used to investigate the effects of fudosteine on lung cancer A549 cells in an inflammatory microenvironment. Eleven metabolites (malic acid, isoleucine, lactose, galactinol, creatinine, gluconic acid, oleic acid, phosphate, S-carboxymethyl-L-cysteine, uridine and tagatose) were identified in the metabolomics results and could be used as biomarkers of fudosteine treatment. Pathway enrichment analysis showed that the metabolic pathways of amino acids including isoleucine, valine, leucine, glycine, serine and threonine were significantly altered, as were the metabolic pathways of carbohydrates such as galactose and pentose phosphate. Fudosteine significantly reduced the level of inflammatory factors in A549 cells and corrected the inflammatory microenvironment by interfering with the effects of amino acid metabolites and amino acid metabolism pathways. This study reveals that fudosteine may be able to inhibit the continuous inflammatory response and prevent the further progression of lung cancer by suppressing the inflammatory microenvironment.

Colorectal Neoplasms/genetics* ; Gene Expression ; Humans ; Polymorphism, Single Nucleotide ; RNA, Long Noncoding/genetics*

The high- and the low-molecular weight hyaluronic acids (HMW-HA and LMW-HA, respectively) showed different biological activities in inflammation. However, the role of LMW-HA in inflammatory response is controversial. In this study, we aimed to investigate the effect of bioactive hyaluronan (B-HA) on lipopolysaccharide (LPS)-induced inflammatory responses in human macrophages and mice. B-HA was produced from HA treated with glycosylated recombinant human hyaluronidase PH20. Human THP-1 cells were induced to differentiate into macrophages. THP-1-derived macrophages were treated with B-HA, LPS, or B-HA + LPS. The mRNA expression and the production of inflammatory cytokines were determined using quantitative real-time PCR and enzyme-linked immunosorbent assay. The phosphorylation levels of proteins in the nuclear factor-κB (NF-κB), mitogen-activated protein kinase (MAPK), and IRF-3 signaling pathways were measured using Western blot. The in vivo efficacy of B-HA was assessed in a mouse model of LPS-induced inflammation. Results showed that B-HA inhibited the expression of TNF-α, IL-6, IL-1, and IFN-β, and enhanced the expression of the antiinflammatory cytokine IL-10 in LPS-induced inflammatory responses in THP-1-derived macrophages and in vivo. B-HA significantly suppressed the phosphorylation of the TLR4 signaling pathway proteins p65, IKKα/β, IκBα, JNK1/2, ERK1/2, p38, and IRF-3. In conclusion, our results demonstrated that the B-HA attenuated the LPS-stimulated inflammatory response by inhibiting the activation of the TLR4 signaling pathway. B-HA could be a potential anti-inflammatory drug in the treatment of inflammatory disease.
Animals ; Cytokines ; Hyaluronic Acid ; Lipopolysaccharides ; Mice ; NF-kappa B/metabolism* ; Signal Transduction ; Toll-Like Receptor 4

OBJECTIVES: To evaluate the ability of the ForenSeq^TM DNA Signature Prep kit (ForenSeq kit) in analyzing the sequence information of STRs in Zhejiang She ethnic group and its forensic application efficacy. METHODS: A total of 50 Zhejiang She ethnic group samples were sequenced with the ForenSeq kit on the MiSeq FGx platform. The data was analyzed using ForenSeq^TM universal analysis software to obtain the motif structure and flank regions of the 58 STRs, then compared with PCR-CE typing results to test the consistency. At last, the allele frequency and population genetic parameters were calculated. RESULTS: A total of 448 sequence polymorphic alleles were detected in 50 samples of Zhejiang She ethnic group. Compared with fragment length polymorphism detected by PCR-CE, 82 alleles were increased by MPS detection based on ForenSeq kit, and 7 SNPs variation were detected in the flanking regions of 6 loci. The 22 male individuals were genotyped, and total 19 haplotypes were detected in 24 Y chromosome STRs of these 22 males. The cumulative discrimination power of the 27 autosomal STRs was 1-8.87×10^-30, the cumulative probability of exclusion of duo-testing was 0.999 999 962 640 657, the cumulative probability of exclusion of trios-testing was 0.999 999 999 999 633. CONCLUSIONS Based on MPS typing technology, using the ForenSeq kit greatly improves the detection efficiency. In addition, the 58 STRs have good genetic polymorphisms in Zhejiang She ethnic group, which are suitable for individual identification and paternity identification in forensic application.
DNA ; DNA Fingerprinting/methods* ; Ethnicity/genetics* ; Gene Frequency ; High-Throughput Nucleotide Sequencing/methods* ; Humans ; Male ; Microsatellite Repeats ; Polymorphism, Single Nucleotide ; Sequence Analysis, DNA/methods*

Objective:To assess the left ventricular (LV) systolic function in amateur marathoners by two-dimensional speckle tracking echocardiography.Methods:A total of 59 amateur marathon runners were recruited from January 2019 to June 2020 in Hangzhou and were divided into group A (>2-5 years) and group B (>5 years) based on their time of participating in marathon. Thirty-one healthy volunteers were enrolled from Affiliate Hospital of Hangzhou Normal University during the same period as a control group. Conventional echocardiography combined with two-dimensional speckle tracking imaging were applied to all the subjects to obtain interventricular septum diastolic thickness (IVSd), LV posterior wall thickness(PWd), LV end-diastolic diameter (LVEDd), relative wall thickness(RWT) and LV mass(LVM), LV end-diastolic volume(EDV), LV end-systolic volume(ESV) and stroke volume(SV), LV ejection fraction(LVEF), LV global longitudinal strain (GLS), and global circumferential strain (GCS). Pre-marathon, 1 hour and 4th day post-marathon echocardiography were performed in amateur marathon runners.Results:Compared with the control group, group A amateur marathon runners showed significant increases in IVSd, PWd, LVEDd, RWT and LVM(all P<0.05); In addition, the IVSd, PWd, LVEDd, RWT, LVM, EDV, ESV and SV in group B runners were further increased compared to those of group A runners (all P<0.01). The LVEF and pre-marathon GCS showed no statistically significant differences among the three groups (all P>0.05), while the pre-marathon GLS showed a statistically significant difference among the three groups ( P<0.01). Compared with group A runners, the pre-marathon, 1 hour and 4th day post-marathon GLS and 1 hour post-marathon GCS were significantly decreased in group B runners (all P<0.01); In intra-group comparison, 1 hour post-marathon GLS was significantly decreased in relative to pre-marathon and 4th day post-marathon GLS in both group A and B (all P<0.05). One hour post-marathon GCS was significantly decreased compared with pre-marathon GCS in group B ( P<0.05). Conclusions:Amateur runners who have participated in long time marathon have reduced LV longitudinal strains and transient post-marathon decreases in LV systolic function.