Background: and Purpose Guillain–Barré syndrome (GBS) is an autoimmune-mediated disorder characterized by demyelinating or axonal injury of the peripheral nerve. Our aim is to determine whether serum amyloid A (SAA) is a biomarker of demyelinating injury and disease severity in patients with GBS. Methods: This study retrospectively enrolled 40 patients with either the demyelinating or axonal GBS and sex- and age-matched controls with other neurological diseases as well as healthy subjects. The demographic and clinical features at entry were collected. The serum levels of the SAA isoforms SAA1, SAA2, and SAA4 were determined in the patients with GBS and the controls using the enzyme-linked immunosorbent assay and analyzed for the associations between levels of different SAA isoforms and the clinical features of the patients. Results: The levels of SAA2 and SAA4 were significantly higher in patients with GBS than in both the other neurological disease controls and the healthy subjects (p<0.05 for all). The level of SAA1 did not differ between patients with GBS and the controls. The level of SAA2 was considerably higher in GBS patients with antecedent infection than in those without infection (p=0.020). The levels of different SAA isoforms were not associated with the disease severity or other clinical features of patients with GBS (p>0.05 for all). Conclusions Increased levels of SAA2 and SAA4 may only represent the acute inflammatory status and so cannot be utilized as biomarkers of the disease severity or demyelinating injury in patients with GBS.

Background: and Purpose Guillain–Barré syndrome (GBS) is an autoimmune-mediated disorder characterized by demyelinating or axonal injury of the peripheral nerve. Our aim is to determine whether serum amyloid A (SAA) is a biomarker of demyelinating injury and disease severity in patients with GBS. Methods: This study retrospectively enrolled 40 patients with either the demyelinating or axonal GBS and sex- and age-matched controls with other neurological diseases as well as healthy subjects. The demographic and clinical features at entry were collected. The serum levels of the SAA isoforms SAA1, SAA2, and SAA4 were determined in the patients with GBS and the controls using the enzyme-linked immunosorbent assay and analyzed for the associations between levels of different SAA isoforms and the clinical features of the patients. Results: The levels of SAA2 and SAA4 were significantly higher in patients with GBS than in both the other neurological disease controls and the healthy subjects (p<0.05 for all). The level of SAA1 did not differ between patients with GBS and the controls. The level of SAA2 was considerably higher in GBS patients with antecedent infection than in those without infection (p=0.020). The levels of different SAA isoforms were not associated with the disease severity or other clinical features of patients with GBS (p>0.05 for all). Conclusions Increased levels of SAA2 and SAA4 may only represent the acute inflammatory status and so cannot be utilized as biomarkers of the disease severity or demyelinating injury in patients with GBS.

Background: and Purpose Guillain–Barré syndrome (GBS) is an autoimmune-mediated disorder characterized by demyelinating or axonal injury of the peripheral nerve. Our aim is to determine whether serum amyloid A (SAA) is a biomarker of demyelinating injury and disease severity in patients with GBS. Methods: This study retrospectively enrolled 40 patients with either the demyelinating or axonal GBS and sex- and age-matched controls with other neurological diseases as well as healthy subjects. The demographic and clinical features at entry were collected. The serum levels of the SAA isoforms SAA1, SAA2, and SAA4 were determined in the patients with GBS and the controls using the enzyme-linked immunosorbent assay and analyzed for the associations between levels of different SAA isoforms and the clinical features of the patients. Results: The levels of SAA2 and SAA4 were significantly higher in patients with GBS than in both the other neurological disease controls and the healthy subjects (p<0.05 for all). The level of SAA1 did not differ between patients with GBS and the controls. The level of SAA2 was considerably higher in GBS patients with antecedent infection than in those without infection (p=0.020). The levels of different SAA isoforms were not associated with the disease severity or other clinical features of patients with GBS (p>0.05 for all). Conclusions Increased levels of SAA2 and SAA4 may only represent the acute inflammatory status and so cannot be utilized as biomarkers of the disease severity or demyelinating injury in patients with GBS.

Objective Zinc finger protein 335 (Zfp335) plays a crucial role in the early development of thymic T cells and the differentiation of peripheral T cell subpopulations. The objective of this study is to investigate the role and underlying mechanisms of Zfp335 in the regulation of regulatory T cell (Treg) within tumor immunity. Methods The Zfp335 gene was specifically knocked out in Treg using tamoxifen (Zfp335^fl/fl FOXP3^creERT2), and the MC38 tumor model was established. On the 7th day after tumor inoculation, tumor size was observed and measured. Tumor size was monitored and recorded daily starting from day 7 post-inoculation. On day 12, tumors were harvested, and the proportions of CD4⁺ T cells, CD8⁺ T cells, and Treg were analyzed by flow cytometry. Additionally, the mitochondrial function of effector regulatory T cell (eTreg) was assessed. Results From day 10 post-tumor inoculation, tumor volume in the Zfp335^CKO group was significantly reduced compared to that of the wild-type (WT) group. Furthermore, the infiltration of CD4⁺ and CD8⁺ T cells, along with their respective effector cells, was significantly higher in the Zfp335^CKO group than in the WT group. The proportions of CD4⁺ and CD8⁺ T cells producing interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) were also significantly increased in the Zfp335^CKO group compared to that of the WT group. In addition, the percentage of CD8⁺ T cells secreting granzyme B (GzmB) was significantly higher in the Zfp335^CKO group than that in the WT group. In contrast, the proportion of Treg and inducible T cell co-stimulator (ICOS)⁺ Treg in the Zfp335^CKO group was significantly lower than that in the WT group. Finally, the expression level of Mitotracker Deep Red in eTreg from the Zfp335^CKO group was significantly reduced compared to that in the WT group. Conclusion During tumorigenesis, the specific deletion of Zfp335 impairs Treg activation, which is related to decreased mitochondrial function in eTreg. In Zfp335^CKO mice. Tumors exhibit increased infiltration of effector T cells, accompanied by elevated levels of cytotoxic cytokines, ultimately enhancing resistance to tumor progression.
Animals ; T-Lymphocytes, Regulatory/metabolism* ; Mice ; CD8-Positive T-Lymphocytes/immunology* ; Neoplasms/genetics* ; Cell Line, Tumor ; Mice, Inbred C57BL ; Mice, Knockout ; DNA-Binding Proteins/genetics* ; Female

Synthetic biology is an emerging interdisciplinary field at the convergence of biology, engineering, and computer science. It employs a bottom-up approach to progressively design biological parts, devices, and circuits, aiming to create artificial biological systems not found in nature or to redesign existing biological systems for specific purposes. With the rapid development of the synthetic biology industry, there is an increasing demand for large complex genetic circuits. However, the traditional trial-and-error methods, heavily reliant on empirical knowledge, have limited efficiency and success rates of parts/circuits construction, thereby impeding the innovation and technology translation for synthetic biology. These limitations have prompted a paradigm shift from labor-intensive, experience-driven trial-and-error models towards standardized, intelligent engineering approaches. Machine learning, capable of uncovering hidden structures and relationships within biological data, offers robust support for the intelligent design of synthetic biological parts and genetic circuits. Here, we review commonly used machine learning algorithms and analyze their typical applications in designing biological parts (e.g., synthetic promoters, RNA regulatory elements, and transcription factors) and simple genetic circuits. Additionally, we discuss the primary challenges in machine learning-aided design and propose potential solutions. Lastly, we envision the future trend of integrating machine learning with synthetic biological system design, highlighting the importance of interdisciplinary collaboration.
Synthetic Biology/methods* ; Machine Learning ; Gene Regulatory Networks ; Algorithms

AIM: To evaluate the changes in corneal epithelial thickness(CET)and corneal optical density(CD)after smart pulse technology(SPT)-assisted transepithelial photorefractive keratectomy(TPRK)and analyze their correlation.METHODS: The prospective study included 60 patients(120 eyes)with myopia and myopic astigmatism who underwent SPT-TPRK in the ophthalmology department at the First Affiliated Hospital of Xinxiang Medical University between February and August 2023. Changes in CET and CD were evaluated preoperatively and at 1 wk, 1 and 3 mo postoperatively.RESULTS: A total of 14 cases(28 eyes)were lost to follow-up, and 3 patients(6 eyes)with postoperative haze were excluded from this study, resulting in a final inclusion of 43 patients(86 eyes). At 1 wk after SPT-TPRK, CET had statistically significantly thickened compared to preoperative levels(P<0.05), particularly in the CET at 0-2 mm central corneal area(P<0.05). At 1 mo after SPT-TPRK, the CET at 0-2 mm area had statistically significantly decreased(P<0.05). At 3 mo after SPT-TPRK, the CET at 0-2 mm had essentially reached preoperative levels. Postoperative CD values increased, with a positive correlation between CET in the 0-2 mm area and CD in the whole 0-2 mm area(r=0.256, P<0.05), and a positive correlation between CET in the 2-5 mm area and CD in the anterior 2-6 mm area(r=0.319, P<0.05).CONCLUSION: Corneal epithelial remodeling takes 3 mo in areas within 2 mm of the central cornea; areas with thinner CET have faster postoperative corneal epithelial remodeling and greater thickening in the early postoperative period; CD increases in the early postoperative period compared to the preoperative value, and in some areas, there is a positive correlation between CET and CD value.

【Objective】 To analyze the serological characteristics and molecular mechanism of a novel B subtype allele 803delC. 【Methods】 ABO blood group was detected by serological method. Sequence-specific primer polymerase chain reaction (PCR-SSP) was used to detect ABO blood group genes. The coding region of exon 1-7 of ABO gene was detected by Sanger sequencing to determine the mutation site. 【Results】 Serological identification of patients was with forward O-type and reverse B-type. The result of PCR-SSP genotyping was A/O. There was A gene, which was not consistent with serological results. Further Sanger double-strand sequencing revealed that the C-base was deleted at position 803 of exon 7 on the basis of ABO^*B. 01/ABO^*O. 01.01. The mutation eventually leads to the amino acid substitution of p. Ala268Gly and p. Phe269Ser and the production of new open reading frame starting at position 269, with the new open reading frame No.20 amino acid being stop codon, resulted in the termination of B gene expression. Further single-strand sequencing of the ABO gene revealed that the mutation was located in the ABO^*B. 01 gene. The mutation was submitted to the NCBI database with the number OR343908. 【Conclusion】 A new ABO allele leading to B variant has been found in Chinese population. Genetic detection can be used to identify the ambiguous blood group with discrepancy between forward and reverse blood grouping.

【Objective】 To statistically analyze the relationship between homologous recombination repair deficiency (HRD) score and clinicopathological characteristics, genomic mutations in patients with high-risk and metastatic hormone-sensitive prostate cancer (mHSPC) and the prognostic predictive value in mHSPC. 【Methods】 A total of 127 patients diagnosed with high-risk prostate cancer and mHSPC, treated at the Department of Urology of Chinese PLA General Hospital during Dec.2021 and Nov.2023 were enrolled.Homologous recombination repair (HRR) gene sequencing was performed, and the genomic scar score (GSS) algorithm were conducted to calculate the HRD score.The relationship between HRD scores and clinicopathological features, genomic alterations, and prognosis were analyzed. 【Results】 The median HRD score was 1.6(0.8, 5.2), 30(23.6%) patients’ HRD scores ≥10, and 11(8.7%) patients’ HRD scores ≥20.Clinicopathological features, including ISUP classification ≥4 (P=0.044) and metastatic status (P=0.008) were associated with high HRD score.Patients with mutations in the BRCA, TP53 and MYC systems had significantly higher HRD score than those with wild-type genes (P<0.05).In mHSPC, the risk of biochemical recurrence was 12.836 times higher in patients with HRD score ≥20 than in those with <20 [OR:12.836 (1.332-124.623), P=0.028]. 【Conclusion】 Baseline HRD score was lower in patients with high-risk prostate cancer and mHSPC.Patients with high HRD score may have higher histological grading (ISUP≥4) and later clinical stage.Further investigation is needed to determine the threshold of HRD scores as biochemical markers suggestive of a poor prognosis.

Objective:To explore the distribution and characteristics of microbiota in the lower reproductive tract of patients with cervical squamous cell carcinoma infected by human papilloma virus (HPV) 16 subtype.Methods:A prospective, cross-sectional study was conducted. A total of 6 patients with HPV16 single subtype positive cervical squamous cell carcinoma admitted to the Cancer Hospital of Chinese Academy of Medical Sciences from August 2019 to June 2020 were selected as cervical carcinoma group, and 6 healthy women who did not indicate abnormalities in thin-based layer cytology test (TCT) during the same period among the physical examination population and had HPV negative test result were selected as the healthy control group. A sterile cotton swab was used to collect secretions from the posterior cervical fornix in patients before antitumor treatment and healthy controls during physical examination. The high variable region of the 16S rRNA gene V1-V2 of the bacteria was amplified by using next generation sequencing (NGS), and then the distribution and characteristics of the bacteria were analyzed.Results:The age of cervical cancer group and the healthy control group was (51±8) years and (48±3) years, respectively, and the difference in age between the both groups was statistically significant ( t= 0.63, P= 0.540). The patients of both groups had reproductive history and no smoking experience. Alpha diversity analysis showed that compared with the healthy control group, the sobs ( t= 3.25, P= 0.009) and chao ( t= 2.91, P= 0.016) indexes were higher in cervical cancer group, and the differences were statistically significant. The shannon index was higher ( t= 2.07, P= 0.065) and simpson index was lower ( t= 1.74, P= 0.113) in cervical cancer group, while the difference was not statistically different. Data dimensionality reduction analysis in principal coordinate analysis (PCoA) based on bray-curtis distance showed that the difference in Beta diversity between the healthy control group and cervical cancer group was statistically significant ( R2= 0.154, P = 0.018). At the phylum level, the proportion of Firmicutes in cervical cancer group was lower than that in the healthy control group (30.21% vs. 68.28%), while the proportion of Bacteroidetes in cervical cancer group decreased slightly (6.87% vs. 8.11%); and the proportion of Actinobacteria (26.91% vs. 14.42%) and Proteobacteria (27.33% vs. 0.67%) had an increase in cervical cancer group. At the genus level, compared with the healthy control group, the proportion of Lactobacillus and Corynebacterium decreased in cervical cancer group, and loss of dominant flora could be detected; while Rhodococcus, Klebsiella and Aerococcus increased significantly in cervical cancer group. The bacteria species in cervical cancer group was increased compared with the healthy control group. Linear discriminant analysis (LDA) showed that Rhodococcus (LDA = 5.04), Klebsiella (LDA = 4.71), Enterobacter (LDA = 4.29), Ralstonia (LDA = 4.28), Ochrobactrum (LDA = 4.23) and Veillonella (LDA = 4.14) were the distinctive microbiota of cervical cancer group at the genus level. At the phylum level, Firmicutes (LDA = 5.23) in the healthy control group could be considered as a marker species. At the species level, the proportions of Rhodococcus ( P = 0.025), Ralstonia ( P = 0.045), Veillonella ( P = 0.044), Paraburkholderia ( P = 0.045), Pseudomonas ( P = 0.043) in cervical cancer group were increased compared with the healthy control group, and the differences were statistically significant. Conclusions:HPV16 single positive patients with cervical squamous cell carcinoma show the characteristics such as the increased diversity and richness of the lower reproductive tract microbiota compared with the healthy controls, while the abundance of Lactobacillus decreases. Rhodococcus and Klebsiella could serve as symbolic microbial in the lower reproductive tract. However, further studies still need to be verified.

Objective To explore the mechanism of butylphthalide(NBP)in regulating microglia acti-vation and inflammatory cytokine expression in the hippocampus of the mouse model of delayed encephalopathy af-ter carbon monoxide poisoning(DEACMP).Methods Wild-type C57 adult mice with normal cognitive function were selected,and DEACMP was modeled by static inhalation of carbon monoxide.The mice were randomized in-to three groups:DEACMP,control,and NBP.The NBP group was administrated with NBP suspension at 6 mg/kg by gavage for 21 days,and the DEACMP and control groups were administrated with the same amount of vegeta-ble oil by gavage.The hippocampal injury was observed by HE staining.The protein level of ionized calcium-bind-ing adapter molecule 1(IBA1)was determined by Western blotting,and the levels of downstream inflammatory cytokines were measured by ELISA.Results Compared with the control group,the DEACMP and NBP groups showed prolonged escape latency(P=0.001,P=0.029),reduced nerve cells(P=0.001,P=0.035),up-regulated expression of IBA1(P=0.001,P=0.042),increased mean fluorescence intensity of IBA1(P=0.001,P=0.021),and elevated levels of tumor necrosis factor-α(TNF-α)(P=0.002,P=0.024),inter-leukin(IL)-6(P=0.001,P=0.015),and IL-1β(P=0.001,P=0.023).Compared with the DEACMP group,the NBP group showed shortened escape latency(P=0.025),increased nerve cells(P=0.039),down-regulated expression of IBA1(P=0.035),decreased average fluorescence intensity of IBA1(P=0.031),and lowered levels of TNF-α(P=0.028),IL-6(P=0.037),and IL-1 β(P=0.034).Conclusion NBP can inhibit the activation of microglia and reduce the expression of inflammatory factors,thereby alleviating cog-nitive dysfunction and brain tissue damage caused by DEACMP.