Based on advancements in modern medical research regarding the intricate connection between the endocrine and exocrine functions of the pancreas， as well as the relationship between pancreatic functions and traditional Chinese medicine （TCM） spleen system， this paper discussed the categorization of the pancreas. It is proposed that the pancreas is neither a true zang organ nor a fu organ， but possessed the attributes of an extraordinary fu-organ and can be classified under the spleen. The spleen governs transportation and transformation， ascent of the clear and dispersion of essence， which encompasses the endocrine and exocrine functions， and pancreatic enzymes and glucose-regulating hormones form the material basis for the spleen's function of dispersing essence. Diseases of the pancreas exhibit characteristics of both zang-organ deficiency and fu-organ excess， so treatment should simultaneously supplement zang-organ disease and regulate fu-organ disease when pancreas showing endocrine and exocrine co-morbidities， with focus on restoring the pancreas （spleen）'s dispersing essence function. Therapeutic strategies include supplementing spleen qi， nourishing spleen yin to strengthen spleen earth， unblocking spleen collaterals， raising spleen yang， and removing spleen turbidity to support the spleen's dispersing essence function， so as to replenish the essential qi of zang-fu organs， ensure their distribution throughout the body， and improve the endocrine and exocrine functions of the pancreas.

ObjectiveTo establish the specific chromatogram and quantitative analysis of multi-components by single-marker（QAMS） based on linear calibration using two reference substances（LCTRS）， explore the consistency between Hedyotis Herba dispensing granules and standard decoction， and evaluate the quality of the dispensing granules. MethodsHigh performance liquid chromatography（HPLC） specific chromatogram was established based on 15 batches of Hedyotis Herba standard decoction and 10 batches of the dispensing granules， and LCTRS was used to locate chromatographic peaks. The actual retention times of 7 characteristic peaks in the specific chromatogram was measured on 24 different types of C₁₈ columns， taking deacetyl asperulosidic acid and asperulosidic acid as the dual standard compounds， the retention times of the other 5 characteristic peaks were predicted and validated. Based on this， QAMS was developed to determine the contents of four components（deacetyl asperulosidic acid， deacetyl asperulosidic acid methyl ester， asperulosidic acid， and p-coumaric acid）. Then， the relative correction factors of deacetyl asperulosidic acid， deacetyl asperulosidic acid methyl ester and p-coumaric acid were calculated using the reference peak of asperulosidic acid in the dual standard compounds， and each component was quantified accordingly. Finally， the consistency between the dispensing granules and standard decoction was assessed by taking extract rate of the standard decoction， consistency of the specific chromatograms， contents and transfer rates of the indicator components as indexes， and the quality of the dispensing granules was evaluated. ResultsThere were 7 common peaks in the characteristic chromatogram of samples of Hedyotis Herba standard decoction and the dispensing granules， and four of them were identified by reference standards， namely deacetyl asperulosidic acid（peak 1）， deacetyl asperulosidic acid methyl ester（peak 3）， asperulosidic acid（peak 6） and p-coumaric acid（peak 7）. The similarity between the dispensing granules and the standard decoction was >0.9. The absolute deviation in the predicted retention time for each component by LCTRS was lower than that of the relative retention time method. The extract rate of the 15 batches of Hedyotis Herba standard decoction ranged from 7.89% to 14.60%， the contents of deacetyl asperulosidic acid， deacetyl asperulosidic acid methyl ester， asperulosidic acid and p-coumaric acid were 6.62-19.70， 3.83-17.99， 1.57-6.69， 1.62-4.52 mg·g^-1， and the transfer rates of these components from decoction pieces to the standard decoction were 22.89%-39.60%， 34.03%-62.24%， 24.25%-43.70%， and 40.58%-73.71%， respectively. The extract rate， index component contents and transfer rates from decoction pieces to the three batches of Hedyotis Herba dispensing granules（P1-P3）， produced by manufacturer A， were similar to those of the standard decoction prepared from the same batch of decoction pieces， and all fell within the specified range. The contents of the 4 indicator components in 7 batches of the dispensing granules（P4-P10） from manufacturers B-E were all within the range of the content converted from the standard decoction based on the quantity of the dispensing granules. ConclusionThe established specific chromatogram and QAMS based on LCTRS are reasonable and reliable. Based on the evaluation indicators of standard decoction yield， consistency of specific chromatograms， contents and transfer rates of the four index components， the 10 batches of Hedyotis Herba dispensing granules from various manufacturers have exhibited good consistency with the standard decoction， indicating that the current production process is relatively reasonable.

Objective: The study aims to investigate the impact of moderate intensity gymnastics on the development of executive function in children aged 5-6, thereby providing a theoretical foundation for exercise interventions targeting executive function. Methods: A total of 63 preschool children, randomly seleted from 3 senior classes in a private kindergarten in Shangqiu, were randomly allocated to the intervention group ( n =31) and control group ( n =32). Children in the intervention group participated in 60 minute gymnastics at a moderate intensity, three times per week, for a total duration of 12 weeks. Concurrently, myzone technology was utilized to monitor exercise intensity throughout the entire intervention period. Children in the control group maintained their regular activities. Inhibitory control (Flanker task), working memory (Empty house task), and cognitive flexibility (Dots task) were assessed before and after the experiment. Results: There was no statistically significant difference in the performance of inhibitory control, working memory, and cognitive flexibility tasks between the two groups of children before intervention ( P >0.05) .The results of covariance analysis revealed significant differences in reaction time [(782.88±24.29，805.13±23.74；719.90±119.99， 833.55± 177.87；1 042.39±72.75，1 091.29±49.42) ms] and accuracy[(73.86±7.26)%，(67.02±8.22)%;(86.36±7.63)%，( 80.50± 9.39 )%;(76.45±9.48)%，(69.59±7.66)%] across inhibitory control, working memory, and cognitive flexibility between the intervention group and the control group ( F =6.84, 4.50，4.87, 6.11, 3.74 , 5.06 , P <0.05). The intervention effect exhibited modest effects( d =0.17-0.74). Conclusions Moderate intensity gymnastics can make modest or moderate effect on improving children s executive function. Brain imaging technology can be incorporated into future research designs to investigate the underlying mechanisms of gymnastics impact on the brain structure and executive function in young children.

Idiopathic oligoasthenospermia （IO） has been increasingly emphasized in the diagnosis and treatment of male infertility. Oxidative stress damage directly affects sperm quality and spermatogenesis， constituting a major causative factor of IO. Firstly， due to its high content of polyunsaturated fatty acids， the sperm plasma membrane is highly sensitive to reactive oxygen species （ROS）， leading to lipid peroxidation accumulation and even inducing ferroptosis. Secondly， deficient downstream key proteins in the base excision repair pathway render sperm unable to repair extensive DNA oxidative damage under oxidative stress. Simultaneously， under oxidative stress， the apoptotic pathway of sperm is cascade-activated， causing rapid loss of motility. ROS further disrupts the hypothalamic-pituitary-gonadal axis， inhibiting testosterone production and ultimately affecting spermatogenesis. Wuzi Yanzongwan，in line with traditional Chinese medicine theory of treating IO through "nourishing kidney essence and harmonizing Yin and Yang"， clinically demonstrates its ability to improve sperm morphology， count， and motility， thereby enhancing male fertility. The research on the pharmacological constituents of Wuzi Yanzongwan primarily involves establishing a characteristic spectrum of Chinese medicine to achieve quality control and exploring the pharmacology of effective components. Studies have found that its main active ingredients consist of flavonoids and phenylpropanoids. Specifically， compounds such as hyperin， acteoside， kaempferol， and schisandrin A are identified as the primary active substances and quality control components. These compounds exhibit strong antioxidant activity and have been partly applied in research related to reproductive endocrine disorders. Tripterygium glycoside is primarily used for modeling of oxidative stress-induced IO. It leads to the accumulation of various lipid peroxides in testicular tissues and concurrently compromises the body's antioxidant capacity. Mechanistic studies have found that Wuzi Yanzongwan can inhibit elevated ROS levels in IO models and enhance the body's antioxidant capacity， thereby ameliorating inflammation， suppressing cell apoptosis， promoting testosterone production， and ultimately alleviating the decline in sperm quality and spermatogenesis caused by oxidative stress.

Objective To investigate the bacterial community diversity in human Demodex mites, so as to provide insights into unraveling the role of human Demodex mites in them caused infectious diseases. Methods From June to July 2023, Demodex mites were collected from the faces of college students in a university in Wuhu City using the adhesive tape method, and the V4 region of 16S ribosomal RNA (16S rRNA) gene and the internal transcribed spacer (ITS) gene of nuclear ribosomal DNA were amplified on an Illumina PE250 high-throughput sequencing platform. Sequencing data were spliced according to the overlapping relations and filtered to yield effective sequences, and operational taxonomic units (OTUs) was clustered. The diversity index of obtained OUTs was analyzed, and the structure of the bacterial community was analyzed at various taxonomic levels. Results A total of 57 483 valid sequences were obtained using 16S rRNA gene sequencing, and 159 OUTs were classified according to similarity. Then, OUTs at a 97% similarity were included for taxonomic analyses, and the bacteria in Demodex mites belonged to 14 phyla, 20 classes, 51 orders, 72 families, and 94 genera. Proteobacteria was the dominant phylum, and Vibrio, Bradyrhizobium and Variovorax were dominant genera. A total of 56 362 valid sequences were obtained using ITS gene sequencing, and 147 OTUs were obtained, which belonged to 5 phyla, 17 classes, 34 orders, 68 families, and 93 genera and were annotated to Ascomycota, Basidiomycota and Chytridiomycota, with Ascomycota as the dominant phylum, and Alternaria alternata, Epicoccum, Penicillium, and Sarocladium as dominant genera. Conclusions There is a high diversity in the composition of bacterial communities in human Demodex mites, with multiple types of microorganisms and high species abundance.

A GC-LSTM model is proposed based on the characteristics of global optimization of genetic algorithm.The model automatically and iteratively searches the optimal hyper-parameter configuration of the C-LSTM model through the genetic algorithm of a specific genetic strategy,and it is configured using the genetic iteration results and validated on the MIT-BIH arrhythmia database according to the classification criteria of the Association for the Advancement of Medical Instrumentation.The testing shows that the classification accuracy,sensitivity,accuracy and F1 value of GC-LSTM model are 99.37%,95.62%,95.17%and 95.39%,respectively,higher than those of the manually established model,and it is also advantageous over the existing mainstream methods.Experimental results demonstrate that the proposed method can achieve better classification performance while avoiding a large number of experimental parameters.

Purpose To investigate the clinical value of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid(Gd-EOB-DTPA)-enhanced MRI for the preoperative evaluation of colorectal cancer liver metastases(CRCLM).Materials and Methods Fifty-six CRCLM patients with 156 CRCLM lesions confirmed by surgical pathology in the First Affiliated Hospital of Henan University of Chinese Medicine from September 2019 to March 2023 were collected,and all underwent dynamic Gd-EOB-DTPA-enhanced MRI.The characteristic manifestations of T2WI,diffusion-weighted imaging(DWI),arterial phase and hepatobiliary phase(HBP)were observed,and the detection rate of each sequence was calculated,and then the signal intensity ratio of lesions to liver parenchyma on HBP and the apparent diffusion coefficient(ADC)were calculated.The ADC values of lesions with reversed target and target signs and lesions with homogeneous and heterogeneous hypointensity on HBP and the detection rate of each sequence were compared.Results Among 156 CRCLM lesions,20.51%(32/156)and 38.46%(60/156)exhibited a target appearance on T2WI,51.28%(80/156)displayed a target sign on DWI,73.72%(115/156)showed rim enhancement on the arterial phase,and 34.62%(54/156)presented a target sign on HBP.The mean ADC value of lesions with reversed target and target signs on HBP did not significantly differ from that of lesions with homogeneous and heterogeneous hypointensity on HBP[(0.98±0.43)×10-3 mm2/s vs.(1.01±0.47)×10-3 mm2/s;t=-0.340,P=0.327].Based on the size of CRCLM lesions,three groups were categorized,including<1.0 cm(41 lesions),1.0-2.0 cm(55 lesions),and>2.0 cm(60 lesions).The overall detection rate of HBP(96.79%)was the highest compared with T2WI,DWI and Gd-EOB-DTPA four-phase dynamic contrast-enhanced multiphase imaging(P<0.05).Regarding<1.0 cm lesions,the detection rate of HBP(87.80%)was superior to that of T2WI,DWI and Gd-EOB-DTPA four-phase dynamic contrast-enhanced multiphase imaging(P<0.05).Conclusion Gd-EOB-DTPA-enhanced MRI has important clinical value for the preoperative evaluation of CRCLM,especially the features of target sign or reversed target sign on HBP and the excellent efficacy of detecting microscopic lesions.

Aldehyde oxidase (AOX) is a molybdoenzyme that is primarily expressed in the liver and is involved in the metabolism of drugs and other xenobiotics. AOX-mediated metabolism can result in unexpected outcomes, such as the production of toxic metabolites and high metabolic clearance, which can lead to the clinical failure of novel therapeutic agents. Computational models can assist medicinal chemists in rapidly evaluating the AOX metabolic risk of compounds during the early phases of drug discovery and provide valuable clues for manipulating AOX-mediated metabolism liability. In this study, we developed a novel graph neural network called AOMP for predicting AOX-mediated metabolism. AOMP integrated the tasks of metabolic substrate/non-substrate classification and metabolic site prediction, while utilizing transfer learning from ¹³C nuclear magnetic resonance data to enhance its performance on both tasks. AOMP significantly outperformed the benchmark methods in both cross-validation and external testing. Using AOMP, we systematically assessed the AOX-mediated metabolism of common fragments in kinase inhibitors and successfully identified four new scaffolds with AOX metabolism liability, which were validated through in vitro experiments. Furthermore, for the convenience of the community, we established the first online service for AOX metabolism prediction based on AOMP, which is freely available at https://aomp.alphama.com.cn.

Background::The ability to generate functional hepatocytes without relying on donor liver organs holds significant therapeutic promise in the fields of regenerative medicine and potential liver disease treatments. Clustered regularly interspaced short palindromic repeats (CRISPR) activator (CRISPRa) is a powerful tool that can conveniently and efficiently activate the expression of multiple endogenous genes simultaneously, providing a new strategy for cell fate determination. The main purpose of this study is to explore the feasibility of applying CRISPRa for hepatocyte reprogramming and its application in the treatment of mouse liver fibrosis.Method::The differentiation of mouse embryonic fibroblasts (MEFs) into functional induced hepatocyte-like cells (iHeps) was achieved by utilizing the CRISPRa synergistic activation mediator (SAM) system, which drove the combined expression of three endogenous transcription factors— Gata4, Foxa3, and Hnf1a—or alternatively, the expression of two transcription factors, Gata4 and Foxa3. In vivo, we injected adeno-associated virus serotype 6 (AAV6) carrying the CRISPRa SAM system into liver fibrotic Col1a1-Cre ER; Cas9 fl/fl mice, effectively activating the expression of endogenous Gata4 and Foxa3 in fibroblasts. The endogenous transcriptional activation of genes was confirmed using real-time quantitative polymerase chain reaction (RT-qPCR) and RNA-seq, and the morphology and characteristics of the induced hepatocytes were observed through microscopy. The level of hepatocyte reprogramming in vivo is detected by immunofluorescence staining, while the improvement of liver fibrosis is evaluated through Sirius red staining, alpha-smooth muscle actin (α-SMA) immunofluorescence staining, and blood alanine aminotransferase (ALT) examination. Results::Activation of only two factors, Gata4 and Foxa3, via CRISPRa was sufficient to successfully induce the transformation of MEFs into iHeps. These iHeps could be expanded in vitro and displayed functional characteristics similar to those of mature hepatocytes, such as drug metabolism and glycogen storage. Additionally, AAV6-based delivery of the CRISPRa SAM system effectively induced the hepatic reprogramming from fibroblasts in mice with live fibrosis. After 8 weeks of induction, the reprogrammed hepatocytes comprised 0.87% of the total hepatocyte population in the mice, significantly reducing liver fibrosis. Conclusion::CRISPRa-induced hepatocyte reprogramming may be a promising strategy for generating functional hepatocytes and treating liver fibrosis caused by hepatic diseases.

Objective To investigate the effect of Porphyromonas gingivalis(Pg)infection on immune escape of oesophageal cancer cells and the role of YTHDF2 and Fas in this regulatory mechanism.Methods We examined YTHDF2 and Fas protein expressions in esophageal squamous cell carcinoma(ESCC)tissues with and without Pg infection using immunohistochemistry and in Pg-infected KYSE150 cells using Western blotting.The interaction between YTHDF2 and Fas was investigated by co-immunoprecipitation(Co-IP).Pg-infected KYSE150 cells with lentivirus-mediated YTHDF2 knockdown were examined for changes in expression levels of YTHDF2,cathepsin B(CTSB),Fas and FasL proteins,and the effect of E64(a cathepsin inhibitor)on these proteins were observed.After Pg infection and E64 treatment,KYSE150 cells were co-cultured with human peripheral blood mononuclear cells(PBMCs),and the expressions of T cell-related effector molecules were detected by flow cytometry.Results ESCC tissues and cells with Pg infection showed significantly increased YTHDF2 expression and lowered Fas expression.The results of Co-IP demonstrated a direct interaction between YTHDF2 and Fas.In Pg-infected KYSE150 cells with YTHDF2 knockdown,the expression of CTSB was significantly reduced while Fas and FasL expressions were significantly increased.E64 treatment of KYSE150 cells significantly decreased the expression of CTSB without affecting YTHDF2 expression and obviously increased Fas and FasL expressions.Flow cytometry showed that in Pg-infected KYSE150 cells co-cultured with PBMCs,the expressions of Granzyme B and Ki67 were significantly decreased while PD-1 expression was significantly enhanced.Conclusion Pg infection YTHDF2-dependently regulates the expression of Fas to facilitate immune escape of esophageal cancer and thus promoting cancer progression,suggesting the key role of YTHDF2 in regulating immune escape of esophageal cancer.