Objective:To investigate the effect of intestinal air cavity on dose distribution of volumetric intensity modulated arc therapy (VMAT) for cervical cancer.Methods:A total of 10 patients who underwent radiotherapy for cervical cancer at Suzhou Municipal Hospital from January to May 2021 were retrospectively analyzed. For each patient, the same optimization parameters were used to design both a normal full-arc plan and a field avoidance-region plan. The intestinal air cavity identified on computed tomography (CT) imaging was outlined as a separate structure. The dose distribution of the two plans were compared before and after changing the CT value (the electron density of the intestinal air cavity) to 0, using a paired t-test. Additionally, consecutive three-week cone beam CT (CBCT) images were collected for each patient. The intestinal air cavities from the three-week CBCT images were mapped onto the original CT, and the dose distributions of both plans were calculated on the CBCT images. The differences in dose distributions compared to the original plan were analyzed to assess plan robustness. Results:The 105% prescription dose coverage of the target volume ( V105) [(43.62±5.18)%)] within the target area for the field avoidance-region plan was greater than that for the normal full-arc plan [(36.38±10.20)%], with a statistically significant difference ( P<0.05). After modifying the electron density of the intestinal air cavity, the dose distribution in the target area worsened for both plans. However, the V100 and V105 for the field avoidance-region plan [(?0.64±0.58)%, (?2.16±1.66)%] were smaller than those for the normal full-arc plan [(?2.52±1.91)%, (?6.79±2.02)%], with a statistically significant difference (both P<0.05).The V30 for the small intestine in the field avoidance-region plan [(40.28±4.77)%] was lower than that in the normal full-arc plan [(42.63±4.82)%]. The V40 for the rectum [(61.70±15.39)%] and the V20 [(36.32±3.09)%, (35.06±5.32)%] and V30 [(17.76±3.05)%, (16.67±8.14)%] for the left and right femoral heads were higher than those in the normal full-arc plan {(59.72±15.13)%, [(31.36±3.97)%, (27.00±7.79%)] and [(12.99±4.55)%, (11.11±7.20)%]}, respectively, with a statistically significant differences (all P<0.05). The changes in V105 on the weekly CBCT images [(3.27±2.91)%, (2.07±2.93)%, (2.14±2.08)%] and V100 on the second and third weeks′ images [(0.44±0.54)%, (0.54±0.50)%] for the field avoidance-region plan were smaller than those for the normal full-arc plan [(8.22±5.87)%, (5.31±3.97)%, (6.91±3.34)% and (1.70±1.53)%, (2.22±1.97)%], with a statistically significant difference (all P<0.05). Conclusions:The field avoidance-region plan demonstrates higher robustness and better small bowel protection than the normal full-arc plan. The influence of intestinal air cavities on dose distribution should be considered during VMAT planing for cervical cancer to guide optimal plan selection.

Hallux valgus is a common disorder of the forefeet,and its diagnosis and treatment have always drawn the attention of the practitioners.This article introduced the minimally-invasive diagnosis and treatment system for hallux valgus of integrated traditional Chinese and western medicine,which was established by Professor WEN Jian-Min after more than 40 years of in-depth clinical practice and research based on the theory of yin-yang balance and theory of tendons and bones in traditional Chinese medicine(TCM)and through the combination of modern surgical experience.The minimally-invasive diagnosis and treatment system for hallux valgus embodies the principles of balancing yin and yang,laying equal stress on tendons and bones,unifying the fixation and functional exercises,and treating the fractures and the whole body simultaneously,and includes the key technologies such as minimally-invasive osteotomy for the first metatarsal bone,curtain-wrapped external fixation,perioperative Chinese medicine therapy based on syndrome differentiation,and rehabilitation and nursing of TCM.The system will provide a systematic guide for the standardized minimally-invasive treatment of hallux valgus,and will supply an important approach to the treatment of other orthopedic diseases with integrated traditional Chinese and western medicine.The minimally-invasive diagnosis and treatment system for hallux valgus reflects the scientific research achievements and clinical experience of Professor WEN Jian-Min,which exerts high significance of reference and application value.

Flagella are the main motility structure of Clostridioides difficile that affects the adhesion, colonization, and virulence of C. difficile in the human gastrointestinal tract. The FliL protein is a single transmembrane protein bound to the flagellar matrix. This study aimed to investigate the effect of the FliL encoding gene flagellar basal body-associated FliL family protein (fliL) on the phenotype of C. difficile. The fliL gene deletion mutant (ΔfliL) and its corresponding complementary strains (: : fliL) were constructed using allele-coupled exchange (ACE) and the standard molecular clone method. The differences in physiological properties such as growth profile, antibiotic sensitivity, pH resistance, motility, and spore production ability between the mutant and wild-type strains (CD630) were investigated. The ΔfliL mutant and the : : fliL complementary strain were successfully constructed. After comparing the phenotypes of strains CD630, ΔfliL, and : : fliL, the results showed that the growth rate and maximum biomass of ΔfliL mutant decreased than that of CD630. The ΔfliL mutant showed increased sensitivity to amoxicillin, ampicillin, and norfloxacin. Its sensitivity to kanamycin and tetracycline antibiotics decreased, and the antibiotic sensitivity partially returned to the level of CD630 strain in the : : fliL strain. Moreover, the motility was significantly reduced in the ΔfliL mutant. Interestingly, the motility of the : : fliL strain significantly increased even when compared to that of the CD630 strain. Furthermore, the pH tolerance of the ΔfliL mutant significantly increased or decreased at pH 5 or 9, respectively. Finally, the sporulation ability of ΔfliL mutant reduced considerably compared to the CD630 strain and recovered in the : : fliL strain. We conclude that the deletion of the fliL gene significantly reduced the swimming motility of C. difficile, suggesting that the fliL gene is essential for the motility of C. difficile. The fliL gene deletion significantly reduced spore production, cell growth rate, tolerance to different antibiotics, acidity, and alkalinity environments of C. difficile. These physiological characteristics are closely related to the survival advantage in the host intestine, which is correlated with its pathogenicity. Thus, we suggested that the function of the fliL gene is closely related to its motility, colonization, environmental tolerance, and spore production ability, which consequently affects the pathogenicity of C. difficile.
Humans ; Clostridioides/metabolism* ; Clostridioides difficile/metabolism* ; Bacterial Proteins/metabolism* ; Virulence ; Anti-Bacterial Agents/metabolism*

PURPOSE: High explosives are used to produce blast waves to study their biological effects. The lungs are considered as the critical target organ in blast-effect studies. The degree of lung hemorrhaging is related to both the explosive power and the increased lung weight. We studied the characteristics of the biological effects from an air explosion of a thermobaric bomb in a high-altitude environment and the lethality and lung injury severity of goats in different orientations and distances. METHODS: Goats were placed at 2.5, 3, 4, and 5 m from the explosion center and exposed them to an air blast at an altitude of 4700-meter. A group of them standing oriented to the right side and the other group seated facing the explosion center vertically. The lung injuries were quantified according to the percentage of surface area contused, and using the pathologic severity scale of lung blast injury (PSSLBI) to score the 4 injury categories (slight, moderate, serious and severe) as 1, 2, 3, and 4, respectively. The lung coefficient (lung weight [g]/body weight [kg]) was the indicator of pulmonary edema and was related to lung injury severity. Blast overpressure data were collected using blast test devices placed at matching locations to represent loadings to goats. All statistical analyses were performed using SPSS, version 26.0, statistical software (SPSS, Inc., Chicago, IL, USA). RESULTS: In total, 127 goats were involved in this study. Right-side-standing goats had a significantly higher mortality rate than those seated vertical-facing (p < 0.05). At the 2.5 m distance, the goat mortality was nearly 100%, whereas at 5 m, all the goats survived. Lung injuries of the right-side-standing goats were 1 - 2 grades more serious than those of seated goats at the same distances, the scores of PSSLBI were significantly higher than the seated vertical-facing goats (p < 0.05). The lung coefficient of the right-side-standing goats were significantly higher than those of seated vertical-facing (p < 0.05). Mortality, PSSLBI, and the lung coefficient results indicated that the right-side-standing goats experienced severer injuries than the seated vertical-facing goats, and the injuries were lessened as the distance increased. The blast overpressure was consistent with these results. CONCLUSION The main killing factors of the thermobaric bomb in the high-altitude environment were blast overpressure, blast wind propulsions and burn. The orientation and distances of the goats significantly affected the blast injury severity. These results may provide a research basis for diagnosing, treating and protecting against injuries from thermobaric explosions.
Animals ; Lung Injury/etiology* ; Blast Injuries ; Goats ; Explosions ; Lung/pathology*

Objective To investigate the role of ATP citrate lyase(ACLY)in the development of hepatocellular carcinoma(HCC)and the impact of this enzyme on the immune microenvironment of HCC.Methods We utilized the University of Alabama at Birmingham Cancer Data Analysis Portal and the Gene Expression Profiling Interactive Analysis to identify the changes in ACLY expression and prognosis across different tumor types from The Cancer Genome Atlas.With HCC as the disease model,we analyzed the ACLY expression in HCC samples from the gene expression database.Furthermore,we collected the clinical specimens from HCC patients to verify the mRNA and protein levels of ACLY.In addition,we conducted transcriptome sequencing after knocking down the expression of ACLY to analyze the differentially expressed genes and investigated the impact of ACLY expression interference on cell proliferation and other functions.Finally,we explored the correlations of ACLY with immune cells and immune infiltration in the tumor microenvironment,new antigens,and immune checkpoint genes.Results ACLY expression was significantly up-regulated in solid tumors including HCC(all P<0.05),and high ACLY expression was associated with overall survival rate in HCC(P=0.005).Furthermore,high ACLY expression affected the presence of immune cells(e.g.,tumor-associated fibroblasts)and the expression of genes involved in lipid metabolism(all P<0.05).Conclusions ACLY is closely related to the occurrence and development of HCC and lipid metabolism abnormalities.Moreover,it has a specific impact on the immune microenvironment of HCC.
Humans ; ATP Citrate (pro-S)-Lyase/metabolism* ; Carcinoma, Hepatocellular ; Clinical Relevance ; Lipid Metabolism ; Liver Neoplasms ; Tumor Microenvironment

Twelve compounds were isolated from Liquidambaris Resina by silica gel column chromatography and thin layer chromatography. Their structures were identified on the basis of spectral data, electron capture detector data, and physicochemical properties as(2'R, 3'R)-2',3'-dihydroxy-hydrocinnamyl-(E)-cinnamate(1),(E)-cinnamyl-(E)-cinnamate(2), cinnamic acid(3), 28-norlup-20(29)-en-3-one-17β-hydroperoxide(4), erythrodiol(5), 13β,28-epoxy-30-hydroxyolean-1-en-3-one(6),(3β)-olean-12-ene-3,23-diol(7), 2α,3α-dihydroxy-olean-12-en-28-oic acid(8), 28-hydroxyolean-12-en-3-one(9), 3-epi-oleanolic acid(10), 3-oxo-oleanolic acid(11), and hederagenin(12). Compound 1 was a new cinnamic acid ester derivative and compounds 2-4,6-8, and 12 were isolated from Liquidambaris Resina for the first time. Compounds 4, 5, 10, and 12 exerted inhibitory effects on the proliferation of human umbilical vein endothelial cells(HUVEC) with the IC_(50) values of(17.43±2.17),(35.32±0.61),(27.50±0.80), and(46.30±0.30) μmol·L~(-1), respectively.
Humans ; Oleanolic Acid ; Endothelial Cells ; Esters ; Cinnamates ; Triterpenes/chemistry* ; Molecular Structure

Objective To investigate the role of MLLT1 in hepatocellular carcinoma (HCC)and its impact on the tumor immune microenvironment. Methods Multivariate Cox regression analysis and tumor gene analysis tools such as GEPIA and UALCAN were used to explore the expression of the MLLT1 gene and its prognostic significance in different tumors. Real-time PCR, Western blotting, and immunohistochemistry were used to investigate the differential expression of MLLT1 between HCC tumor tissue and normal tissue. MTT assay and cell cycle analysis were performed to assess the effect of MLLT1 knockdown on cell proliferation and cell cycle. The correlation between MLLT1 and immune cells, as well as immune infiltrates in the tumor microenvironment, and their correlation with immune neoantigens, immune checkpoints, tumor mutation burden, and microsatellite instability were also explored. Results The MLLT1 gene was found to be aberrantly expressed in various solid tumors including HCC, and its high expression was associated with poor prognosis in HCC. Knockdown of MLLT1 inhibited HCC cell proliferation and blocked the cell cycle. High expression of MLLT1 was found to affect the content of multiple immune cells, including CD4

Objective: Comparative analyses of wild-type Clostridioides difficile 630 (Cd630) strain and pathogenicity locus (PaLoc) knockout mutant (ΔPaLoc) by using RNA-seq technology. Analysis of differential expression of Cd630 wild-type strain and ΔPaLoc mutant strain and measurement of its cellular virulence changes. Lay the foundation for the construction of an toxin-attenuated vaccine strain against Clostridioides difficile. Methods: Analysis of Cd630 and ΔPaLoc mutant strains using high-throughput sequencing (RNA-seq). Clustering differentially expressed genes and screening differentially expressed genes by DESeq software. Further analysis of differential genes using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment. Finally, cytotoxicity assays of ΔPaLoc and Cd630 strains were performed in the African monkey kidney epithelial cell (Vero) and the human colonic cell (Caco-2) lines. Results: The transcriptome data showed that the ΔPaLoc mutant toxin genes tcdA and tcdB were not transcribed. Compared to the wild-type strain, CD630_36010, CD630_020910,CD630_02080 and cel genes upregulated 17.92,11.40,8.93 and 7.55 fold, respectively. Whereas the hom2 (high serine dehydrogenase), the CD630_15810 (spore-forming protein), CD630_23230 (zinc-binding dehydrogenase) and CD630_23240 (galactitol 1-phosphate 5-dehydrogenase) genes were down-regulated by 0.06, 0.075, 0.133 and 0.183 fold, respectively. The GO and KEGG enrichment analyses showed that the differentially transcribed genes in ΔPaLoc were enriched in the density-sensing system, ABC transport system, two-component system, phosphotransferase (PTS) system, and sugar metabolism pathway, as well as vancomycin resistance-related pathways. Cytotoxicity assays showed that the ΔPaLoc mutant strain lost its virulence to Vero and Caco-2 cells compared to the wild-type Cd630 strain. Conclusion: Transcriptional sequencing analysis of the Cd630 and ΔPaLoc mutant strains showed that the toxin genes were not transcribed. Those other differential genes could provide a reference for further studies on the physiological and biochemical properties of the ΔPaLoc mutant strain. Cytotoxicity assays confirmed that the ΔPaLoc mutant lost virulence to Vero and Caco-2 cells, thus laying the foundation for constructing an toxin-attenuated vaccine strain against C. difficile.
Bacterial Proteins/metabolism* ; Bacterial Toxins/metabolism* ; Caco-2 Cells ; Clostridioides ; Clostridioides difficile/genetics* ; Humans ; Oxidoreductases/metabolism* ; Transcriptome ; Vaccines, Attenuated

Testicular endothelial cells have been found to play an important role in spermatogenesis and fertility, but their mechanism is obscure. Exosomes released by various cells are recognized as cell-cell communication mediators during the initiation and progression of many diseases. Therefore, the current study aimed to investigate the protein and miRNA components of human testicular endothelial cell-derived exosomes (HTEC-Exos) and to explore their potential effects on spermatogenesis. In this study, HTEC-Exos were first isolated by the ultracentrifugation method, and then identified by nanoparticle tracking analysis, transmission electron microscopy (TEM), and western blotting. The characteristics of HTEC-Exos were examined by liquid chromatography-mass spectrometry and microRNA (miRNA) chip analysis. Bioinformatics analysis was performed to explore the potential role of the exosomal content on spermatogenesis. A total of 945 proteins were identified, 11 of which were closely related to spermatogenesis. A total of 2578 miRNAs were identified. Among them, 30 miRNAs demonstrated potential associations with male reproductive disorders, such as azoospermia, and spermatogenesis disorders. In particular, 11 out of these 30 miRNAs have been proven to be involved in spermatogenesis based on available evidence. This study provides a global view of the proteins and miRNAs from HTEC-Exos, suggesting that HTEC-Exos may function as potential effectors during the process of spermatogenesis.
Endothelial Cells ; Exosomes ; Humans ; Male ; MicroRNAs ; Proteomics ; Spermatogenesis

Objective To investigate the role of phosphoglycerate kinase 1 (PGK1) in tumorigenesis and its potential post-translational modification sites were investigated by bioinformatics method and molecular biology experimental techniques, in order to provide evidence for PGK1 as a hepatocellular carcinoma ( HCC) diagnostic biomarker and therapeutic target. Methods From pan-cancer's point of view, 10 967 samples were obtained from the cancer genome database TCGAs, and the expression of PGK1 in different tumors was explored by using cBioPortal and UALCAN analysis tools; Focusing on HCC, the expression differences of PGK1 in hepatocellular carcinoma tumor tissues and normal tissues were further analyzed by using GEO database analysis, Real-time PCR, Western blotting and cell invasion assay;The String database was used to analyze the protein-protein interaction network and gene set enrichment analysis; The CSS-Palm database and bioinformatics method were used to predict protein post-translational modification sites on PGK1. Results The PGK1 gene was abnormally amplified and overexpressed in various solid tumors, including hepatocellular carcinoma, and overexpression of PGK1 was correlated with a poor prognosis in hepatocellular carcinoma. Multiple novel posttranslational modifications were existed on PGK1. Conclusion PGK1 is closely related to the occurrence and development of various cancers including HCC and glycolytic metabolism abnormalities. Epigenetic modifications can regulate PGK1 and affect its cellular function in HCC.