Tumor microenvironment(TME)includes inflammatory,metabolic,and immune microenvironment,which interact in a complex network,influencing tumorigenesis,progression,and metastasis.Clinical studies on traditional Chinese medicine(TCM)have found that dampness pathogen plays a significant role in gastrointestinal precancerous lesions,tumorigenesis,and metastasis.It disrupts the gastrointestinal tumor's inflammatory,metabolic,and immune microenvironments,promoting tumor development through various mechanisms.Based on the theory of dampness pathogen,it is proposed to eliminate dampness combined with detoxification to regulate tumor inflammatory microenvironment;invigorate qi,warm yang,and remove dampness to regulate metabolic microenvironment;and strengthen the spleen,support vital energy,and dispel dampness to improve immunosuppressive microenvironment.Treating gastrointestinal tumors from the perspective of dampness pathogen theory can offer new insights and focus areas for clinical diagnosis and treatment,as well as directions for research into the molecular mechanisms of compound Chinese herbal formulas.

Tumor microenvironment(TME)includes inflammatory,metabolic,and immune microenvironment,which interact in a complex network,influencing tumorigenesis,progression,and metastasis.Clinical studies on traditional Chinese medicine(TCM)have found that dampness pathogen plays a significant role in gastrointestinal precancerous lesions,tumorigenesis,and metastasis.It disrupts the gastrointestinal tumor's inflammatory,metabolic,and immune microenvironments,promoting tumor development through various mechanisms.Based on the theory of dampness pathogen,it is proposed to eliminate dampness combined with detoxification to regulate tumor inflammatory microenvironment;invigorate qi,warm yang,and remove dampness to regulate metabolic microenvironment;and strengthen the spleen,support vital energy,and dispel dampness to improve immunosuppressive microenvironment.Treating gastrointestinal tumors from the perspective of dampness pathogen theory can offer new insights and focus areas for clinical diagnosis and treatment,as well as directions for research into the molecular mechanisms of compound Chinese herbal formulas.

AIM:To evaluate the agreement of corneal high-order aberrations from Topcon KR-1W, i.Profiler and OPD-Scan Ⅲ wavefront aberrometers in myopic adults.METHODS:A prospective clinical study. A total of 92 adult patients(92 eyes)with myopia in the department of optometry, the People's Hospital of Guangxi Zhuang Autonomous Region from June to August 2022 were enrolled. The third-order and fourth-order corneal aberrations at the pupil diameter of 4 and 6mm were measured by Topcon KR-1W, i.Profiler, and OPD-Scan Ⅲ, respectively. The difference and agreement of the three aberrometers were evaluated.RESULTS: The measurements at 6mm pupil diameter were all greater than those at 4mm pupil diameter. Although there were no statistical differences in the measurements of Z-44、Z-24 by the three aberrometers at 4 pupil diameter(P>0.05), there were statistical differences in other measurements(P<0.05). The aberration results measured by the three aberrometers were statistically different at the 6mm pupil diameter(P<0.05). The 95% limit of agreement(95%LoA)of the measurements of higher-order aberration, including the third-order aberrations at 4mm pupil diameter and the third-order and fourth-order aberrations at 6mm pupil diameter(except for the Z-24)were greater than 0.1μm. The concordance correlation coefficient(Pc)was lower than 0.90, indicating a poor consistency. The correlation coefficients of corneal higher-order aberrations were significantly different among the three aberrometers at 4 and 6mm pupil diameter(r4mm=0.215～0.805, P4mm<0.05; r6mm=0.561～0.916, P6mm<0.001).CONCLUSION:There were significant differences in the measurements of the third- and fourth-order corneal aberrations at 4 and 6mm pupil diameter among Topcon KR-1W, i.Profiler, and OPD-Scan Ⅲ, and the agreements were poor, so they are not interchangeably in clinical applications.

Gram-positive bacteria secrete virulence factors into host cells and cause suppurative inflammation, which leads to the emergence of diseases, therefore poses a great threat to human health. Identifying secreted proteins is beneficial to understand the secretion system and pathogenic mechanism of bacteria, and lays the foundation for further screening of pathogenic factors. Due to the lack of classical signal peptide sequence in non-classical secreted proteins, it is relatively difficult and time-consuming to identify such proteins in large-scale experiments. At present, some computational prediction methods have been proposed, but their performance in predicting non-classical secreted proteins of Gram-positive bacteria is not satisfactory. This paper proposed an ensemble learning model - SPNG+, which integrates six machine learning algorithms including naive bayes, random forest, support vector machine, two gradient promotion trees XGBoost and LightGBM, and K-nearest neighbor through stacking strategy. The results of 5-fold cross validation and independent dataset test show that the SPNG+ is superior to the single machine learning model, the simple integrated learning model and the existing prediction tools in predicting non-classical secreted proteins of Gram-positive bacteria. Compared with the predictors constructed by limited feature coding methods or single machine learning algorithms in the past, the proposed method is a useful supplement to the study of non-classical secreted proteins in Gram-positive bacteria. The source code of SPNG+ is available from https: / / github.com / weidai00 / SPNG.

A method was established for simultaneous determination of 21 active constituents including flavanols, isoflavones, flavonols, dihydroflavones, dihydroflavonols, chalcones, pterocarpan, anthocyanidins and phenolic acids in Spatholobi Caulis by ultra fast liquid chromatography with triple quadrupole linear ion trap mass spectrometry(UFLC-QTRAP-MS/MS). Then, it was employed to analyze and evaluate the dynamic accumulation of multiple bioactive constituents in Spatholobi Caulis. The chromatographic separation was performed on a XBridge®C_(18)(4.6 mm×100 mm, 3.5 μm) at 30 ℃ with a gradient elution of 0.3% formic acid aqueous solution-methanol, and the flow rate was 0.8 mL·min~(-1), using multiple-reaction monitoring(MRM) mode. A comprehensive evaluation of the multiple bioactive constituents was carried out by gray correlation analysis(GRA). The 21 target components showed good linearity(r>0.999 0) in the range of the tested concentrations. The average recovery rates of the 21 components were from 97.46% to 103.6% with relative standard deviations less than 5.0%. There were differences in the contents of 21 components in Spatholobi Caulis at diffe-rent harvest periods. Spatholobi Caulis had high quality from early November to early December, which is consistent with the local tradi-tional harvest period. This study reveals the rule of the dynamic accumulation of 21 components in Spatholobi Caulis and provides basic information for the suitable harvest time. At the same time, it provides a new method reference for the comprehensive evaluation of the internal quality of Spatholobi Caulis.
Chromatography, High Pressure Liquid ; Fabaceae/chemistry* ; Phytochemicals/isolation & purification* ; Plant Stems/chemistry* ; Plants, Medicinal/chemistry* ; Tandem Mass Spectrometry

Seventeen compounds were isolated from the 95% ethanol extract of the stems and leaves of Sapium discolor by using various chromatographic techniques,including silica gel,Sephadex LH-20,MCI,ODS,and semi-preparative HPLC. Their structures were elucidated as sapiumin F( 1),kadsulignan C( 2),ciwujiatone( 3),ethylbrevifolin carboxylate( 4),7-hydroxy-8-methoxycoumarin( 5),fraxetin( 6),fraxidin( 7),isofraxidin( 8),6,7,8-trimethoxycoumarin( 9),5,6,7,8-tetramethoxycoumarin( 10),8-hydroxy-5,6,7-trimethoxycoumarin( 11),3,3'-di-O-methylellagic acid( 12),3,3',4'-tri-O-methylellagic acid( 13),3'-methoxyellagic acid 4'-O-α-rhamnopyranoside( 14),4,5-didehydro-chebulic acid triethyl ester( 15),ent-kaurane-3-oxo-16α,17-diol( 16),and abscisic acid( 17) by spectroscopic data. Compound 1 is a new compound. Except for compounds 4,11,and 13,the remaining compounds were isolated from this plant for the first time. All the isolates were evaluated for their in vitro antineuroinflammatory activities,and the results showed that compounds 6 and 15 significantly inhibited nitric oxide production in lipopolysaccharide-induced BV-2 microglial cells,with IC50 values of 6. 06 and 6. 05 μmol·L-1,respectively.
Animals ; Cell Line ; Chromatography, High Pressure Liquid ; Mice ; Phytochemicals ; analysis ; Plant Leaves ; chemistry ; Plant Stems ; chemistry ; Sapium ; chemistry

To enhance in vitro dissolution of Cur by preparing Cur solid dispersions. The ability of HPMCAS-HF,HPMCAS-MF,HPMCAS-LF and PVPK30 to maintain supersaturated solution was investigated by supersaturation test. Amorphous solid dispersions were prepared by the solvent-evaporation method. The prepared samples were characterized using infrared spectroscopy( IR) and differential scanning calorimetry( DSC),and in vitro dissolution was investigated. DSC and IR results showed that in 1 ∶3 and 1 ∶9 solid dispersions,Cur was amorphously dispersed in the carrier,and the interaction existed between drug and carrier. The supersaturation test showed that the order of the ability of polymer to inhibit crystallization of Cur was MF>HF>LF>K30. The dissolution results showed that Cur-K30 amorphous solid dispersion had the highest drug release rate; Cur-K30 and Cur-LF amorphous solid dispersions had a quicker but not stable dissolution rate,and the drug concentration decrease after 4 h; Cur-MF and Cur-HF solid dispersions had a low dissolution,which however increased steadily,attributing to the strong ability of the polymers to inhibit the crystallization of Cur. HPMCAS could inhibit the degradation of Cur better than K30,especially MF and HF. The amorphous solid dispersions of cur significantly enhanced the dissolution of Cur and improved the chemical stability of Cur. This study can provide a basis for the rational selection of the polymer used for Cur solid dispersion.
Chemistry, Pharmaceutical ; Curcumin ; chemistry ; Drug Stability ; Methylcellulose ; analogs & derivatives ; chemistry ; Polymers ; Solubility

Background: Our previous studies have shown that regulatory factor X5 (RFX5), a classical transcription regulator of MHCII genes, was obviously overexpressed in hepatocellular carcinoma (HCC) tumors. However, the role of RFX5 in the carcinogenesis and progress of HCC remains unknown. This study aimed to reveal its biological significance and the underlying mechanism in HCC. Methods: RFX5 mRNA expression level and copy number variation in HCC tumors and cell lines were determined by analyzing deposited data sets in the Cancer Genome Atlas and Gene Expression Omnibus database. The biological significance of RFX5 in HCC was investigated by monitoring the colony formation and subcutaneous tumor growth capacity when RFX5 was silenced with lentiviral short hairpin RNA and CRISPR/Cas9 system in HCC cell lines. The downstream gene transcriptionally activated by RFX5 in HCC cells was determined by chromatin immunoprecipitation and luciferase reporter assay. The involvement of tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein theta (YWHAQ) in HCC development was further determined by performing colony formation rescue assay and subcutaneous tumor growth rescue experiment. The association of YWHAQ with recurrence-free survival of patients with HCC was assessed by Kaplan-Meier analysis. Moreover, apoptosis level and the protein level of p53 pathway were determined to reveal the mechanism of RFX5 in driving HCC development. Results: RFX5 was amplified and highly overexpressed in HCC tumor tissues compared with the corresponding non-tumor tissues. The mRNA expression level of RFX5 was significantly correlated with its DNA copy number (r = 0.4, P < 0.001). Functional study demonstrated that RFX5 was required for both clonogenic forming in vitro and subcutaneous tumor growth in vivo of HCC cells. Further study identified YWHAQ, namely 14-3-3 tau, as a key downstream transcriptional target gene of RFX5, which was tightly regulated by RFX5 in HCC. Moreover, overexpression of YWHAQ largely rescued the clonogenic growth of HCC cells that was suppressed by RFX5 knockdown. In addition, overexpression of YWHAQ in primary tumor was linked to poor prognosis of patients with HCC. These results demonstrated that YWHAQ was a downstream effector of RFX5 in HCC. Notably, RFX5-YWHAQ pathway could protect cells from apoptosis by suppressing the p53 and Bax in HCC. Conclusion RFX5 is a putative HCC driver gene that plays an important role in the development and progression of HCC by transactivating YWHAQ and suppressing apoptosis.

AIM: To study the subfoveal choroidal thickness(SFCT)and its influencing factors in children with different degree of myopia.

METHODS: This is prospective cohort study. Eighty-nine eyes of 45 school-age children aged 5-14 years old were studied, and according to the equivalent sphericity(SE)into different refractive groups. Mild, moderate and high myopia groups had 27, 42 and 20 eyes respectively, apply the enhanced depth scanning mode(EDI-OCT)of an optical coherence tomography(OCT)scanner to measure SFCT to compare choroid thickness differences among myopia groups, to find out the change rule of SFCT between myopia groups, and Pearson correlation analysis was used to analyze the related influencing factors.

RESULTS:SFCT of mild myopia, moderate myopia and high myopia respectively were(253.22±43.56)μm,(223.19±54.93)μm,(185.90±50.99)μm, SFCT differences between different refractive groups were statistically significant(P<0.05), Pearson correlation analysis found that there was a significant correlation between SFCT and SE and axial length(r=0.430, -0.499, 0.425, all P<0.001); slightly related to K1 and K2, and the correlation of AL, retinal nerve fiber layer(RNFL)thickness were better than that of SE. There were statistically significant differences in family history of myopia among the myopic groups(χ2=7.44, P<0.05).

CONCLUSION: The degree of myopia in children was deepened and SFCT became thinner. The degree of myopia in children is related to the family history of myopia.

The training of neurocritical care is an important component in standardized training of neurosurgical specialists. As a subspeciality of neurosurgery, as well as with the characteristics of critical care medicine, neurocritical care carries its own discipline features. Based on clinical training and practice experiences, the training mode and practice experience were summarized, including basic requirement, theory training, skill training, research training, humanity accomplishment improvement and evaluation stan-dard, in order to discuss the appropriate training mode of neurocritical care in standardized training of neurosurgical specialists, improve the training methods and advance the training effectiveness, and provide reference for cultivating qualified and comprehensively developed neurosurgical specialists.