Objective To establish an efficient and stable model of pelvic inflammatory disease in rats via a non-surgical method,and to evaluate its application in pharmacodynamic testing.Methods Female Sprague-Dawley rats were divided randomly into the following groups:control group;model group with phenol for 7 d;model group with phenol for 10 d;treatment group modeled with phenol;model group with low concentration of bacteria;model group with high concentration of bacteria;and treatment group modeled with bacteria.Rats in the model and treatment groups were injected with 25%phenol gel and 2×107 or 2×108 Escherichia coli and Staphylococcus aureus mixture via a non-surgical method,to construct a rat model of pelvic inflammatory disease.Rats in the treatment groups received the Chinese patent medicine Jingangteng capsules by gavage,and rats in the control group received the same volume of solvent solution.The health status,weight changes,and uterine appearance were monitored and the uterine coefficient was calculated.Pathological changes in the uterus and fallopian tubes,endometrial thickness,and number of glands were detected by hematoxylin and eosin staining.Serum levels of interleukin(IL)-1β,IL-6,and tumor necrosis factor(TNF)-α were detected by enzyme-linked immunosorbent assay.Protein expression of the macrophage marker CD68 was detected by immunofluorescence.Expression of Toll-like receptor 4(TLR4)/nuclear factor(NF)-κB pathway-related proteins in the uterus was detected by Western blot.Results The mortality rate in the model group was only 5%.Compared with the control group,model rats showed decreased body weight,increased uterine coefficient,pathological changes in the uterus and Fallopian tubes,thinner endometrium,fewer glands,significantly higher serum levels of IL-1β,IL-6,and TNF-α and more macrophages in the uterine tissue,and activation of the TLR4/NF-κB signaling pathway.The 7 d phenol and low-concentration bacterial solution models were judged to be mild pelvic inflammatory disease models,and the 10 d phenol and high-concentration bacterial solution models were considered severe pelvic inflammatory disease models.Treatment with Jingangteng capsules relieved the pathological symptoms in the uterus and fallopian tubes,in line with the efficacy evaluation of clinical pelvic inflammatory disease.Conclusions We established rat models of pelvic inflammatory disease using phenol and a mixed bacterial solution via a non-surgical method,to simulate the different pathological states of pelvic inflammatory disease caused by different factors.These models will be suitable for evaluating drug efficacy and elucidating the pathological mechanism of pelvic inflammatory disease.

Infectious pneumonia caused by bacteria,viruses,or other pathogenic microorganisms remains a huge threat to human health.Immunocyte-derived biomimetic nano-drug delivery systems can be used for drug delivery by taking advantage of the natural anti-inflammatory effect of immune cells and thus show great potential in lung-targeted therapy.This review begins by introducing different types of immune cells in the lung.The preparation methods of immunocyte-derived biomimetic nano-drug delivery systems and their applications in bacterial pneumonia,viral pneumonia,acute respiratory distress syndrome and cytokine storms are also reviewed.The review is expected to provide data for the targeted therapy of infectious pneumonia.

Objective To conduct an analysis on objective data of tongue manifestations and complexions among college students with yang deficiency constitution and balanced constitution,thus to explore the correlation between yang deficiency constitution and the objective data of tongue manifestations and complexions among college students.Methods From August 2023 to January 2024,data collection was carried out in 325 cases of yang deficiency constitution(yang deficiency group)and 175 cases of balanced constitution(balanced group)from college students of Hunan University of Chinese Medicine,Central South University,Hunan Normal University,Hunan University and Changsha University of Science and Technology in Hunan Province.YM-MA-Ⅰ digital detection system for tongue manifestations and complexions of traditional Chinese medicine(TCM)was utilized for data collection and image analysis,and the differences in the Lab parameters of tongue color,tongue shape,tongue coating color,complexions,and lip color were compared between yang deficiency group and balanced group.Of the Lab parameters,letter"L"stands for luminance,which expresses the luminance from absolute black to absolute white,and takes the value of 0-100;letter"a"and letter"b"stand for two color channels,letter"a"represents the color from dark green to grey then to bright pink,and takes a value from-128 to 127,and letter"b"represents the color from bright blue to grey then to yellow,and also takes a value from-128 to 127.Results(1)The analysis of tongue manifestations showed that in comparison with the balanced group,enlarged tongue(72.62％),tooth-marked tongue(83.69％),and greasy coating(59.38％)were frequently seen in the yang deficiency group,and the differences were all statistically significant(P＜0.05 or P＜0.01).(2)The analysis of complexions showed that in comparison with the balanced group,lusterless complexion(79.08％)and pale lip(42.15％)were frequently seen in the yang deficiency group,with statistically significant differences(P＜0.01).(3)The yang deficiency group had higher L value of tongue color,L value of tongue coating color,L value of complexions,and L and b values of lip color than the balanced group,and the differences were all statistically significant(P＜0.05),indicating that the tongue color,complexions,and lip color of the yang deficiency group were all pale.Conclusion The objective data and image analysis of tongue manifestations and complexions can accurately identify the population of yang deficiency constitution from college students,and the results will provide approaches and references for the identification of other TCM constitutions from the population.

Objective To establish an efficient and stable model of pelvic inflammatory disease in rats via a non-surgical method,and to evaluate its application in pharmacodynamic testing.Methods Female Sprague-Dawley rats were divided randomly into the following groups:control group;model group with phenol for 7 d;model group with phenol for 10 d;treatment group modeled with phenol;model group with low concentration of bacteria;model group with high concentration of bacteria;and treatment group modeled with bacteria.Rats in the model and treatment groups were injected with 25%phenol gel and 2×107 or 2×108 Escherichia coli and Staphylococcus aureus mixture via a non-surgical method,to construct a rat model of pelvic inflammatory disease.Rats in the treatment groups received the Chinese patent medicine Jingangteng capsules by gavage,and rats in the control group received the same volume of solvent solution.The health status,weight changes,and uterine appearance were monitored and the uterine coefficient was calculated.Pathological changes in the uterus and fallopian tubes,endometrial thickness,and number of glands were detected by hematoxylin and eosin staining.Serum levels of interleukin(IL)-1β,IL-6,and tumor necrosis factor(TNF)-α were detected by enzyme-linked immunosorbent assay.Protein expression of the macrophage marker CD68 was detected by immunofluorescence.Expression of Toll-like receptor 4(TLR4)/nuclear factor(NF)-κB pathway-related proteins in the uterus was detected by Western blot.Results The mortality rate in the model group was only 5%.Compared with the control group,model rats showed decreased body weight,increased uterine coefficient,pathological changes in the uterus and Fallopian tubes,thinner endometrium,fewer glands,significantly higher serum levels of IL-1β,IL-6,and TNF-α and more macrophages in the uterine tissue,and activation of the TLR4/NF-κB signaling pathway.The 7 d phenol and low-concentration bacterial solution models were judged to be mild pelvic inflammatory disease models,and the 10 d phenol and high-concentration bacterial solution models were considered severe pelvic inflammatory disease models.Treatment with Jingangteng capsules relieved the pathological symptoms in the uterus and fallopian tubes,in line with the efficacy evaluation of clinical pelvic inflammatory disease.Conclusions We established rat models of pelvic inflammatory disease using phenol and a mixed bacterial solution via a non-surgical method,to simulate the different pathological states of pelvic inflammatory disease caused by different factors.These models will be suitable for evaluating drug efficacy and elucidating the pathological mechanism of pelvic inflammatory disease.

Aiming at the classification and lesion localization of giga-pixel pathology whole slide images of breast cancer,a bidirectional gated recurrent unit attention based multi-instance learning(ABMIL-BiGRU)model is proposed for interpretable prediction of H&E stained breast cancer lymph node metastasis images.The method uses two orthogonal bidirectional gated recurrent units to establish the long-short distance dependencies between the features in the row and column directions of the image block,thereby embedding the spatial position and context information of the image block,and then quantifies the attention score of each feature representation through attention multi-instance pooling,thereby achieving whole slide image-level feature aggregation and generating interpretable heat maps.The results show that ABMIL-BiGRU model has an average accuracy of 0.918 6 and an AUCof 0.9467 on the breast cancer metastasis dataset,realizing high-precision prediction of whole slide images and localization of regions of interest,and also providing human-interpretable features at the image block level.The proposed model solves the"accuracy-interpretability trade-off"problem to a certain extent,and its superior performance provides a new paradigm for the clinical application of computer-aided diagnosis and intelligent systems.

Aiming at the classification and lesion localization of giga-pixel pathology whole slide images of breast cancer,a bidirectional gated recurrent unit attention based multi-instance learning(ABMIL-BiGRU)model is proposed for interpretable prediction of H&E stained breast cancer lymph node metastasis images.The method uses two orthogonal bidirectional gated recurrent units to establish the long-short distance dependencies between the features in the row and column directions of the image block,thereby embedding the spatial position and context information of the image block,and then quantifies the attention score of each feature representation through attention multi-instance pooling,thereby achieving whole slide image-level feature aggregation and generating interpretable heat maps.The results show that ABMIL-BiGRU model has an average accuracy of 0.918 6 and an AUCof 0.9467 on the breast cancer metastasis dataset,realizing high-precision prediction of whole slide images and localization of regions of interest,and also providing human-interpretable features at the image block level.The proposed model solves the"accuracy-interpretability trade-off"problem to a certain extent,and its superior performance provides a new paradigm for the clinical application of computer-aided diagnosis and intelligent systems.

Objective Microcystin-leucine-arginine(MC-LR)exposure induces lipid metabolism disorders in the liver.Secreted frizzled-related protein 5(SFRP5)is a natural antagonist of winglesstype MMTV integration site family,member 5A(Wnt5a)and an anti-inflammatory adipocytokine.In this study,we aimed to investigate whether MC-LR can induce lipid metabolism disorders in hepatocytes and whether SFRP5,which has anti-inflammatory effects,can alleviate the effects of hepatic lipid metabolism by inhibiting the Wnt5a/Jun N-terminal kinase(JNK)pathway. Methods We exposed mice to MC-LR in vivo to induce liver lipid metabolism disorders.Subsequently,mouse hepatocytes that overexpressed SFRP5 or did not express SFRP5 were exposed to MC-LR,and the effects of SFRP5 overexpression on inflammation and Wnt5a/JNK activation by MC-LR were observed. Results MC-LR exposure induced liver lipid metabolism disorders in mice and significantly decreased SFRP5 mRNA and protein levels in a concentration-dependent manner.SFRP5 overexpression in AML12 cells suppressed MC-LR-induced inflammation.Overexpression of SFRP5 also inhibited Wnt5a and phosphorylation of JNK. Conclusion MC-LR can induce lipid metabolism disorders in mice,and SFRP5 can attenuate lipid metabolism disorders in the mouse liver by inhibiting Wnt5a/JNK signaling.

Objective To study the properties and antimicrobial activity of the novel self-assembled antimicrobial peptide(AMP)CR-16,and to provide experimental evidence for the treatment of bacterial infections.Methods CR-16 was designed and synthesized based on the structure of antimicrobial peptides Buforin Ⅱ and LfcinB.Dynamic light scattering(DLS),transmission electron microscopy(TEM),and X-ray diffraction(XRD)were used to characterize CR-16.Based on the results of critical micelle concentration(CMC),the self-assembled properties of CR-16 were investigated using atomic force microscopy(AFM)and circular dichroism(CD).The minimum inhibitory concentration(MIC)was used to study the inhibitory effect of CR-16 while transmission electron microscopy(TEM)was adopted to observe the interactions between CR-16 and the outer membrane of bacteria.Results AMP CR-16 was prepared as self-assemblies,which were regularly spherical in shape and stable in activity.CR-16 could inhibit both the growth of Escherichia coli and,more importantly,the growth of NDM-1-producing carbapenem-resistant Escherichia coli,promising good prospects in treating infections caused by antibiotic-resistant bacteria.Conclusion CR-16 can be self-assembled and deliver antibacterial effects against Escherichia coli.

Objective To enhance the photostability of colchicine(COL)for sustained-release COL pellets.Methods The degradation was investigated by studying the photochemical degradation kinetics of COL.The impact of such physical properties of the photostabilizers as the type,color,dosage,and position on the photostability of COL in sustained-release pellets was also evaluated.Results The contents of photochemical degradation products did not increase after 10 days of light exposure to sustained-release COL pellets with red iron oxide of 4％(w/w)as the protective layer.Conclusion The findings of this study indicate that use of iron oxide as a photostabilizer in sustained-release COL pellets can significantly reduce the photochemical degradation of COL in the pellets.

Objective:To retrospectively analyze the clinical and genetic characteristics of six patients with Acromicric dysplasia due to variants of the FBN1 gene. Methods:Six patients who had visited the Affiliated Hospital of Qingdao University between February 2018 and October 2020 were selected as the study subjects. Clinical data of the patients were collected. High-throughput sequencing was carried out. And candidate variants were verified by Sanger sequencing.Results:All of the six patients had presented with severe short stature (< 3 s), brachydactyly, short and broad hands and feet. Other manifestations included joint stiffness, facial dysmorphism, delayed bone age, liver enlargement, coracoid femoral head, and lumbar lordosis. Genetic testing revealed that all had harbored heterozygous variants of the FBN1 gene. Patient 1 had harbored a c. 5183C>T (p.A1728V) missense variant in exon 42, which had derived from his father (patient 2). Patient 3 had harbored a c. 5284G>A (p.G1762S) missense variant in exon 43, which had derived from her mother (patient 4). Patient 5 had harbored a c. 5156G>T (p.C1719F) missense variant in exon 42, which was de novo in origin. Patient 6 had harbored a c. 5272G>T (p.D1758Y) missense variant in exon 43, which was also de novo in origin. The variants carried by patients 1, 3 and 6 were known to be pathogenic. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the FBN1: c. 5156G>T was rated as a pathogenic variant (PS2+ PM1+ PM2_Supporting + PM5+ PP3). Conclusion:All of the six patients had severe short stature and a variety of other clinical manifestations, which may be attributed to the variants of the FBN1 gene.