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.

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.

Objective: To determine the heterogeneity for caries prevention service preferences among children in Anhui Province, so as to provide reference for the promotion and popularization of caries prevention services for school age children. Methods: Based on a discrete selection experiment, a face to face questionnaire survey was administered using a multi stage sampling method among 785 parents with children 3-12 years of age who were hospitalized in the stomatology clinics of 7 prefectures and cities in Anhui Province from October 2021 to October 2022. A mixed Logit model was used to evaluate caries prevention service preferences for children. Results: Four discrete choice experiment attributes included in the study were statistically significant for choice preference ( P <0.05). Compared with the control group, parents with a high school education or above preferred caries prevention services with 70%-<80% preventive effectiveness, 2-<5 and <2 km from the service point, and a high service cost ( β =0.38, 1.66, 1.64, 0.00); female parents preferred preventive services with 70%-<80% preventive effectiveness and a high service cost ( β =0.35, 0.01 ); parents of children <7 years of age preferred services with 70%-<80% preventive effectiveness ( β =0.75); parents of children with oral health preferred preventive services during winter and summer vacations ( β =-0.28); parents of children with caries preferred preventive services with a high cost per denticle ( β =0.00)( P <0.05). Conclusions Parents with different education levels, gender, child age, and oral health status have heterogeneity in dental caries prevention service preferences. The provision of targeted and precise services can improve the participation and coverage of caries prevention services for school age 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 evaluate the changes in cognitive function in overweight and obese adolescents,and explore the association between cognitive function and fibroblast growth factor 21(FGF21).Methods·A total of 175 adolescents from a senior high school in Shanghai were divided into normal weight group(n=50),overweight group(n=50)and obese group(n=75)based on their body mass index(BMI).General information,anthropometric data and laboratory testing indicators of the adolescents were collected and compared.The cognitive function of the three groups of adolescents was assessed by using the accuracy(ACC)and reaction time of Flanker task and n-back task.Enzyme-linked immunosorbent assay(ELISA)was used to detect the serum FGF21 level of the three groups of adolescents.Partial correlation analysis and multiple linear regression model were used to evaluate the correlation between cognitive task performance and anthropometric data and laboratory testing indicators.Results·Compared with the normal weight group,systolic blood pressure,diastolic blood pressure,and the levels of fasting plasma glucose,glycosylated hemoglobin and triacylglycerol in the obese group were higher(all P<0.05).Under congruent or incongruent stimulus conditions in the Flanker task,there was no significant difference in ACC between any two groups;compared with the normal weight and overweight groups,the reaction time of the adolescents in the obese group was prolonged(all P<0.05).In the n-back task,there were no significant differences in ACC between any two groups,while the obese group had longer reaction time in the 1-back and 2-back tasks compared to the normal weight and overweight groups(all P<0.05).Compared with the normal weight group,serum FGF21 levels of the adolescents in the obese group were higher(P=0.000).Partial correlation analysis showed that the reaction time of the adolescents in Flanker and n-back tasks was correlated with their BMI,body fat mass,waist circumference,waist-to-hip ratio and FGF21 level(all P<0.05).Multiple linear regression analysis further confirmed that BMI was associated with prolonged reaction time in cognitive-related behavioral tasks in the adolescents(all P<0.05),and FGF21 level was associated with ACC in the 2-back task(P=0.000)and reaction time in the incongruent stimulus condition(P=0.048).Conclusion·Overweight and obese adolescents have cognitive impairments,and BMI and serum FGF21 levels are associated with changes in their cognitive function.

Objective To analyze the CT signs of acute blunt or penetrating intestinal injury,and to improve the diagnostic accuracy of multi spiral CT for intestinal injury.Methods The CT and clinical data of 63 patients with intestinal injury confirmed by clinical surgical exploration who underwent emergency CT scan were collected,and the CT findings and surgical findings were comparatively analyzed.Results There were 63 cases of intestinal injury,of which 26 cases were complicated with mesenteric injury.The direct CT signs of intestinal injury included intestinal wall thickening sign and intestinal discontinuity sign,which accounted for 64%(40/63)and 17%(10/63),respectively.The indirect CT signs of intestinal injury included intraperitoneal/retroperitoneal gas sign,intraperitoneal/retroperitoneal effusion sign,intramural air,and portal venous gas,which accounted for 72%(45/63),88%(55/63),7%(5/63)and 5%(3/63),respectively.Conclusion Recognizing the CT signs of intestinal injury,such as intestinal wall thickening sign,intestinal discontinuity sign,intraperitoneal/retroperitoneal gas sign,intraperitoneal/retroperitoneal effusion sign,intramural air,and portal venous gas can help to make the early and correct diagnosis of intestinal injury if combined with clinical practice.

BACKGROUND:The treatment for bacterial biofilms after internal fixation surgery is a very difficult problem in clinic.It is a great significance to establish an animal model of irrigation for treating bacterial biofilms in the early stage after internal fixation surgery. OBJECTIVE:To establish an animal model for treating bacterial biofilms with different drugs through irrigation in early stage after internal fixation surgery. METHODS:Six New Zealand white rabbits were selected.Bilateral femoral surfaces were exposed and drilled holes were made,and bone plates colonized with Pseudomonas aeruginosa(experimental group)and blank bone plates(blank control group)were implanted around the drilled holes on one side,and two drainage tubes were retained and fixed to serve as the"inlet"and"outlet,"respectively.The model was immersed for a certain period of time after simulated perfusion before rinsing.After the simulated irrigation,the plates were soaked for a certain time before washing.At 5 days postoperatively,the rabbits were observed for body temperature,wound condition,bacterial culture of drainage fluid,and crystalline violet staining and scanning electron microscopy of the bone plate. RESULTS AND CONCLUSION:Six rabbits had difficulty in moving the affected limbs after surgery and showed elevated body temperature at 2-4 days after surgery.Local swelling could be touched at some wounds in the experimental group,and the wounds in the blank control group healed well.The results of bacterial culture of drainage fluid showed that Pseudomonas aeruginosa diffused or spread in the experimental group.At 5 days after surgery,the plate in the experimental group became purple shown by crystalline violet staining,and the absorbance value at 570 nm detected by the microplate reader was 2.621±0.088,indicating the presence of bacteria.Scanning electron microscopy at 5 days after surgery showed that a large number of bacterial microcolonies appeared on the surface of the plate in the experimental group,forming a highly inhomogeneous three-dimensional structure similar to the"mushroom-like"and"tower-like"structures,with filamentous water channels connecting the"mushroom-like"structures,which were typical biofilm structures with high densities,while no obvious colonies were seen in the blank control group.Overall,this animal model simulates the state of infected biofilm formation due to early infection after internal fixation and provides an available method of irrigation with different drugs.

BACKGROUND:Ferroptosis and pyroptosis may play a role in the development of postmenopausal osteoporosis.There may be relevant biomarkers for the diagnosis of postmenopausal osteoporosis. OBJECTIVE:To search for the key genes related to ferroptosis and pyroptosis in postmenopausal osteoporosis using bioinformatics so as to further elucidate their biological mechanisms. METHODS:The data sets GSE56815 and GSE7429 of postmenopausal osteoporosis were downloaded from the GEO database,the national comprehensive gene expression database of the United States,and the two data sets were preprocessed.The differential expression analysis of the data was carried out by the limma package of R software,and the enrichment analysis was performed by DIVID and KOBAS.The protein-protein interaction network was mapped by STRING and Cytoscape,the Hub gene was selected by CytoHubba,and the key genes were screened by the ferroptosis database and pyroptosis database.The CIBERSORT package was used to determine the immune infiltration of postmenopausal osteoporosis samples and to analyze the correlation between key genes and immune cells RESULTS AND CONCLUSION:A total of 30 differential genes of postmenopausal osteoporosis were screened in the experimental samples,of which 9 genes were up-regulated and 21 genes were down-regulated.The enrichment of GO and KEGG pathways showed that the differences were mainly in"serine-type endopeptidase activity,""innate immune response,""special particle lumen,"and"renin secretion."The protein-protein interaction network showed the correlation of differential genes and the top 10 Hub genes with"Degree"value were selected using CytoHubba.Hub gene was intersected with the FerrDb database and cell pyroptosis dataset to obtain key genes ELANE and LCN2.Receiver operating characteristic curve and box diagram showed that the expression of ELANE and LCN2 in serum samples of postmenopausal osteoporosis was significantly lower than that in normal samples,indicating a good diagnostic value.Immune infiltration analysis showed that ELANE may be related to memory resting CD4+ T cells,M0 and M2 macrophages.LCN2 may be related to M0 macrophages.

Objective To elucidate the role of programmed cell death factor 4(PDCD4)in mitochondrial dysfunction caused by sepsis-related vascular endothelial damage.Methods Cultured human umbilical vein endothelial cells(HUVECs)and mouse vascular endothelial cells(C166 cells)were transfected with a small interfering RNA targeting PDCD4 followed by treatment with lipopolysaccharide(LPS)alone or in combination with carbonyl cyanide 3-chlorophenylhydrazone(FCCP).The proteomic changes in the cells after PDCD4 knockdown were analyzed using LC-MS/MS technique.The mRNA expressions of PDCD4 and the genes associated with cell inflammation and apoptosis were detected with RT-PCR,and the expressions of FIS1,DRP1 and OPA1 proteins key to mitochondrial fission and fusion were determined using Western blotting.JC-1 and MitoSOX fluorescent probes were used to observe the changes in mitochondrial membrane potential and mitochondrial reactive oxygen species levels under by a laser confocal microscope.Results LPS stimulation of the cells significantly increased the mRNA expressions of interleukin-6(IL-6),tumor necrosis factor-α(TNF-α)and monocyte chemoattractant protein 1(MCP1)and enhanced the cellular expression of PDCD4(P<0.05).Proteomic analysis suggested a correlation between PDCD4 knockdown and changes in mitochondrial dynamics in the cells.LPS treatment significantly increased the expressions of mitochondrial fission proteins FIS1 and DRP1 and lowered the expression of the fusion protein OPA1 in the cells(P<0.05),causing also mitochondrial oxidative stress and reduction of the mitochondrial membrane potential(P<0.05).In HUVECs,treatment with FCCP significantly attenuated the protective effect of PDCD4 knockdown,which inhibited LPS-induced inflammation and oxidative stress and restored the balance between mitochondrial fission and fusion.Conclusion PDCD4 knockdown protects vascular endothelial cells against LPS-induced damages by repressing mitochondrial fission and oxidative stress,promoting mitochondrial fusion,and maintaining normal mitochondrial function.