BACKGROUND:Promoting skin wound healing is a huge challenge facing global public health.To promote faster and higher-quality wound healing,it is necessary to explore more advantageous dressings to address this problem.OBJECTIVE:To investigate the hemostatic properties of acellular dermal matrix hydrogel and its effect on skin wound healing.METHODS:(1)Acellular dermal matrix hydrogel was prepared,and the differences in microscopic morphology and main components between it and acellular dermal matrix were analyzed.(2)Acellular dermal matrix hydrogel and chitosan hydrogel were used to cover the femoral artery puncture site of rats,and the bleeding quality and coagulation time were recorded.Acellular dermal matrix hydrogel and chitosan hydrogel were mixed with rat anticoagulated blood,and the coagulation index within 30 minutes was detected.(3)A full-thickness skin defect model with a diameter of 12 mm was made on the back of 18 SD rats,and they were randomly divided into 3 groups,with 6 rats in each group:the model group used PBS to clean the wound,and the control group and the experimental group used chitosan hydrogel and acellular dermal matrix hydrogel to cover the wound,respectively.The hydrogel dressing was changed every day,and the treatment was continued for 14 days,and the wound healing was observed.On day 3 after modeling,immunofluorescence staining of inducible nitric oxide synthase(M1 macrophages)and CD206(M2 macrophages)was performed on the wound surface.On day 14 after modeling,hematoxylin-eosin staining,Masson staining,and CD31 immunohistochemical staining were performed on the wound surface.RESULTS AND CONCLUSION:(1)Scanning electron microscopy revealed that the acellular dermal matrix hydrogel had a porous structure,and the Fourier transform infrared spectrum showed that it had the same main components as the acellular dermal matrix.(2)Both acellular dermal matrix hydrogel and chitosan hydrogel had obvious hemostatic ability in vivo.In the in vitro coagulation experiments,the coagulation index of acellular dermal matrix hydrogel was significantly higher than that of chitosan hydrogel.(3)In the rat skin full-thickness defect model,both acellular dermal matrix hydrogel and chitosan hydrogel could improve the wound healing rate.Hematoxylin-eosin and Masson staining results showed that acellular dermal matrix hydrogel could reduce the infiltration of inflammatory cells in the center of the wound.Both acellular dermal matrix hydrogel and chitosan hydrogel could decrease scar width and increase collagen deposition rate.CD31 immunohistochemical staining results showed that both hydrogels could promote angiogenesis in the wound site.Immunofluorescence staining results showed that both hydrogels could reduce the proportion of M1 macrophages and increase the proportion of M2 macrophages,and the effect of acellular dermal matrix hydrogel was stronger than that of chitosan hydrogel.(4)The results show that the acellular dermal matrix hydrogel has good hemostatic properties and the ability to promote wound healing.

BACKGROUND:Promoting skin wound healing is a huge challenge facing global public health.To promote faster and higher-quality wound healing,it is necessary to explore more advantageous dressings to address this problem.OBJECTIVE:To investigate the hemostatic properties of acellular dermal matrix hydrogel and its effect on skin wound healing.METHODS:(1)Acellular dermal matrix hydrogel was prepared,and the differences in microscopic morphology and main components between it and acellular dermal matrix were analyzed.(2)Acellular dermal matrix hydrogel and chitosan hydrogel were used to cover the femoral artery puncture site of rats,and the bleeding quality and coagulation time were recorded.Acellular dermal matrix hydrogel and chitosan hydrogel were mixed with rat anticoagulated blood,and the coagulation index within 30 minutes was detected.(3)A full-thickness skin defect model with a diameter of 12 mm was made on the back of 18 SD rats,and they were randomly divided into 3 groups,with 6 rats in each group:the model group used PBS to clean the wound,and the control group and the experimental group used chitosan hydrogel and acellular dermal matrix hydrogel to cover the wound,respectively.The hydrogel dressing was changed every day,and the treatment was continued for 14 days,and the wound healing was observed.On day 3 after modeling,immunofluorescence staining of inducible nitric oxide synthase(M1 macrophages)and CD206(M2 macrophages)was performed on the wound surface.On day 14 after modeling,hematoxylin-eosin staining,Masson staining,and CD31 immunohistochemical staining were performed on the wound surface.RESULTS AND CONCLUSION:(1)Scanning electron microscopy revealed that the acellular dermal matrix hydrogel had a porous structure,and the Fourier transform infrared spectrum showed that it had the same main components as the acellular dermal matrix.(2)Both acellular dermal matrix hydrogel and chitosan hydrogel had obvious hemostatic ability in vivo.In the in vitro coagulation experiments,the coagulation index of acellular dermal matrix hydrogel was significantly higher than that of chitosan hydrogel.(3)In the rat skin full-thickness defect model,both acellular dermal matrix hydrogel and chitosan hydrogel could improve the wound healing rate.Hematoxylin-eosin and Masson staining results showed that acellular dermal matrix hydrogel could reduce the infiltration of inflammatory cells in the center of the wound.Both acellular dermal matrix hydrogel and chitosan hydrogel could decrease scar width and increase collagen deposition rate.CD31 immunohistochemical staining results showed that both hydrogels could promote angiogenesis in the wound site.Immunofluorescence staining results showed that both hydrogels could reduce the proportion of M1 macrophages and increase the proportion of M2 macrophages,and the effect of acellular dermal matrix hydrogel was stronger than that of chitosan hydrogel.(4)The results show that the acellular dermal matrix hydrogel has good hemostatic properties and the ability to promote wound healing.

BACKGROUND: Pancreatic cancer is a lethal malignancy prone to gemcitabine resistance. The single-strand selective monofunctional uracil DNA glycosylase (SMUG1), which is responsible for initiating base excision repair, has been reported to predict the outcomes of different cancer types. However, the function of SMUG1 in pancreatic cancer is still unclear. METHODS: Gene and protein expression of SMUG1 as well as survival outcomes were assessed by bioinformatic analysis and verified in a cohort from Fudan University Shanghai Cancer Center. Subsequently, the effect of SMUG1 on proliferation, cell cycle, and migration abilities of SMUG1 cells were detected in vitro . DNA damage repair, apoptosis, and gemcitabine resistance were also tested. RNA sequencing was performed to determine the differentially expressed genes and signaling pathways, followed by quantitative real-time polymerase chain reaction and Western blotting verification. The cancer-promoting effect of forkhead box Q1 (FOXQ1) and SMUG1 on the ubiquitylation of myelocytomatosis oncogene (c-Myc) was also evaluated. Finally, a xenograft model was established to verify the results. RESULTS: SMUG1 was highly expressed in pancreatic tumor tissues and cells, which also predicted a poor prognosis. Downregulation of SMUG1 inhibited the proliferation, G1 to S transition, migration, and DNA damage repair ability against gemcitabine in pancreatic cancer cells. SMUG1 exerted its function by binding with FOXQ1 to activate the Protein Kinase B (AKT)/p21 and p27 pathway. Moreover, SMUG1 also stabilized the c-Myc protein via AKT signaling in pancreatic cancer cells. CONCLUSIONS SMUG1 promotes proliferation, migration, gemcitabine resistance, and c-Myc protein stability in pancreatic cancer via protein kinase B signaling through binding with FOXQ1. Furthermore, SMUG1 may be a new potential prognostic and gemcitabine resistance predictor in pancreatic ductal adenocarcinoma.
Humans ; Pancreatic Neoplasms/pathology* ; Forkhead Transcription Factors/genetics* ; Signal Transduction/genetics* ; Animals ; Cell Line, Tumor ; Proto-Oncogene Proteins c-akt/metabolism* ; Cell Proliferation/physiology* ; Mice ; Uracil-DNA Glycosidase/genetics* ; Female ; Male ; Gemcitabine ; Mice, Nude ; Apoptosis/physiology* ; Deoxycytidine/analogs & derivatives* ; Cell Movement/genetics*

OBJECTIVE To evaluate the influence of pharmaceutical quality control on the efficiency and outcomes of standardized medication therapy management （MTM） services for patients with coronary heart disease by using Economic， Clinical and Humanistic Outcomes （ECHO） model. METHODS This study collected case data of coronary heart disease patients who received MTM services during January-March 2023 （pre-quality control implementation group， n＝96） and June-August 2023 （post-quality control implementation group， n＝164）. Using propensity score matching analysis， 80 patients were selected from each group. The study subsequently compared the economic， clinical， and humanistic outcome indicators of pharmaceutical services between the two matched groups. RESULTS There were no statistically significant differences in baseline data between the two groups after matching （P＞0.05）. Compared with pre-quality control implementation group， the daily treatment cost （16.26 yuan vs. 24.40 yuan， P＜0.001）， cost-effectiveness ratio [23.12 yuan/quality-adjusted life year （QALY） vs. 32.32 yuan/QALY， P＜0.001]， and the incidence of general adverse drug reactions （2.50% vs. 10.00%， P＝0.049） of post-quality control implementation group were decreased significantly； the utility value of the EuroQol Five-Dimensional Questionnaire （0.74± 0.06 vs. 0.71±0.07， P＝0.003）， the reduction in the number of medication related problems （1.0 vs. 0.5， P＜0.001）， the medication adherence score （[ 6.32±0.48） points vs. （6.10±0.37） points， P＝0.001]， and the satisfaction score （[ 92.56±1.52） points vs. （91.95±1.56） points， P＝0.013] all showed significant improvements. Neither group experienced serious adverse drug reactions. There was no statistically significant difference in the incidence of new adverse reactions between the two groups （1.25% vs. 3.75%， P＝0.310）. CONCLUSIONS Pharmaceutical quality control can improve the quality of pharmaceutical care， and the ECHO model can quantitatively evaluate the effect of MTM services， making pharmaceutical care better priced and more adaptable to social needs， thus being worthy of promotion.

ObjectiveTo investigate the possible mechanism of action of Xibining Formula （膝痹宁） for cartilage damage in knee osteoarthritis （KOA） through the cyclic guanosine-adenosine monophosphate synthase （cGAS）- stimulator of interferon genes （STING） signaling pathway. MethodsFifty C57BL/6J mice were randomly divided into five groups （10 per group）， sham operation group， KOA model group， low-dose Xibining Formula group， high-dose Xibining Formula group， and high-dose Xibining Formula + agonist group. The KOA models were constructed using the destabilization of the medial meniscus （DMM） method in all groups but the sham surgery group. Two weeks after surgery， the low- and high-dose Xibining Formula groups were administered Xibining Formula at doses of 3.58 g/（kg·d） and 14.32 g/（kg·d） respectively via gavage. The high-dose Xibining Formula + agonist group received 14.32 g/（kg·d） of Xibining Formula via gavage followed by an intraperitoneal injection of Vadimezan （DMXAA） at 25 mg/kg. The sham surgery group and the KOA model group mice were given an equivalent volume of normal saline at 5 ml/（kg·d） via gavage， once daily for four consecutive weeks. Serum levels of tumor necrosis factor-alpha （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6） were measured by ELISA； pathological changes in cartilage tissue were observed using hematoxylin-eosin （HE） staining and Safranin O-Fast Green staining. Pathological changes were scored according to the Mankin scoring system； the levels of cartilage tissue matrix regulation-related indicators such as matrix metalloproteinase 3 （MMP3）， matrix metalloproteinase 13 （MMP13）， a disintegrin and metalloproteinase with thrombospondin motifs 5 （ADAMTS）， type-Ⅱ collagen （CⅡ） and aggregated proteoglycan （Aggrecan）， and also cGAS-STING pathway-related protein and mRNA expression levels were detected by Western blot and qPCR methods. ResultsCompared with the sham surgery group， the KOA model group showed severe cartilage edge destruction， significantly increased Mankin scores， significantly decreased protein and mRNA expression levels of COLⅡ and Aggrecan， and significantly increased protein and mRNA expression levels of cGAS， STING， MMP3， MMP13， and ADAMTS5 （P＜0.01）. Compared with the control group， serum level of IL-6， IL-1β， TNF-α in all the intervented groups decreased （P＜0.01）， while compared with high-dose Xibining Formula group， level of IL-6， IL-1β， and TNF-α in low-dose Xibining Formula group and high-dose Xibining Formula + agonist group increased （P＜0.01）. Compared with the KOA model group， all the intervention groups exhibited alleviated cartilage pathological changes， signi-ficantly reduced Mankin scores， significantly increased protein and mRNA expression levels of COLⅡ and Aggrecan， and significantly decreased protein and mRNA expression levels of cGAS， STING， MMP3， MMP13， and ADAMTS5 （P＜0.01）. Compared with high-dose Xibining Formula group， high-dose Xibining Formula + agonist group showed cartilage edge destruction， significantly increased Mankin scores， significantly decreased protein and mRNA expression levels of COLⅡ and Aggrecan， and increased protein and mRNA expression levels of cGAS， STING， MMP3， MMP13， and ADAMTS5 （P＜0.01）. ConclusionXibining Formula may improve KOA cartilage damage by inhibiting the cGAS-STING signaling pathway， decreasing matrix degradation-related proteins， and elevating matrix composition-related proteins.

Objective:To investigate the current situation of water-borne endemic fluorosis in Anhui Province, and provide basic data for the adjusting the prevention and control measures.Methods:Using cross-sectional survey method, all villages in the water-borne endemic fluorosis areas were investigated in Anhui Province from 2019 to 2022. In water-borne endemic fluorosis village, the situation of water improvement project and the fluoride level of drinking water were investigated, and dental fluorosis of all children aged 8 - 12 was examined. The criteria for determining the achievement of control targets for water-borne endemic fluorosis in affected counties were based on the "Evaluation Measures for Control and Elimination of Key Endemic Diseases (2019 Edition)".Results:From 2019 to 2022, the rate of water improvement village in water-borne endemic fluorosis areas were 88.47% (1 527/1 726), 100% (1 726/1 726), 100% (1 726/1 726) and 100% (1 726/1 726), respectively. The qualified proportion of water fluoride in water-borne endemic fluorosis villages was 33.84% (584/1 726), 63.09% (1 089/1 726), 70.74% (1 221/1 726) and 74.33% (1 283/1 726), respectively. The prevalence rates of dental fluorosis in children aged 8 - 12 were 25.48% (45 461/178 440), 15.78% (27 959/177 200), 13.68% (23 505/171 880) and 12.66% (23 315/184 200), respectively. The proportion of affected counties that had achieved the control target of water-borne endemic fluorosis was 16% (4/25), 60% (15/25), 36% (9/25) and 40% (10/25), respectively.Conclusions:The water-borne endemic fluorosis areas in Anhui Province have improved the water fluoride qualification rate and reduced the incidence of fluorosis in children through prevention and control measures such as water improvement and fluoride reduction. However, the prevention and control efforts in key areas and counties need to be further improved.

Breast cancer remains a substantial threat to women's health and is one of the most prevalent malignant tumors in women.Because breast cancer onset is closely associated with female physiological characteristics,this article proposes that breast cancer be classified as a"women's miscellaneous diseases"and that its treatment be explored from this perspective.Drawing from Chapter 8 on Golden Chamber of Prescriptions for Miscellaneous Diseases in Women of Synopsis of Golden Chamber,the initial pathogenesis of breast cancer is associated with"emotional stress,improper lifestyle,deficiency,cold,and stagnation."The fundamental mechanism behind its formation is"blood cold accumulation and hardened masses."Specifically,emotional imbalance and improper lifestyle habits contribute to the combined invasion of the uterus by"deficiency,""accumulated cold,"and"stagnant qi."Over time,"cold-blood stasis accumulates at the uterine ostium,"and the cold and the stasis ascends from the uterus along the thoroughfare and conception vessels,obstructing the breast collaterals.This combination of yang qi stagnation and yin cold congealment,ultimately leads to the development of breast cancer.The treatment principle should focus on"activating yang and dispersing cold."A therapeutic approach centered on Wenjing Decoction combined with Xiaoyao Powder can be adapted based on the stage and type of breast cancer while also considering the dynamic interplay between pathogenic factors and healthy qi,along with shifts in deficiency and excess patterns of disease.By adhering to the principles of consistency and flexibility and integrating disease and syndrome differentiation,the goal is to develop precise and personalized treatment strategies to improve clinical outcomes.

Based on the previous transcriptomic experimental data of Trichinella spiralis(T.spira-lis)in this study,the larval stage specific gene TP12446 was screened and its identity in the ubiq-uitin ligase RNF family was predicted.In the study,bioinformatics methods were used to analyze its physicochemical properties and its activity to lay the foundation for further exploring the func-tion of TP12446 gene.The physicochemical properties and protein structure of TP12446 protein were predicted by bioinformatics.Its ubiquitin ligase activity was also verified by ubiquitination re-actions in vitro.The expression characteristics of TP12446 protein in different stage of T.spiralis infection were analyzed by qPCR and Western blot.Bioinformatics analysis showed that TP12446 protein was composed of 453 amino acids and its molecular weight was 51.48 kDa.The protein had a transmembrane structure and contained signal peptides.The results indicated that it was a secre-tory protein and mainly located in the cytoplasmic membrane.The protein structure analysis re-vealed that the protein contained RING and PA domain,its secondary structure was mainly com-posed of α-helix and irregular crimp and there were 10 B cell epitopes on TP12446 protein.The prediction of glycosylation and phosphorylation sites indicated that TP12446 protein contained 38 potential phosphorylation sites.Results of PPI interaction protein prediction showed that TP12446 protein had strong interaction with Usp8,Tmem37,Otub1,Otub2,Ubox5 and CD151.The results of qPCR and Western blot showed that TP12446 gene expression was the highest in the larva stage of T.spiralis,the activity of ubiquitin ligase was verified by ubiquitination reaction in vitro.TP12446 protein was a secretory hydrophobic protein with E3 ubiquitin ligase activity,which was involved in regulating cell cycle and apoptosis.

As an important structure for maintaining the homeostasis of the central nervous system, the meningeal lymphatic vessels can clear abnormal proteins and metabolic wastes from the brain. Numerous studies have shown that meningeal lymphatic vessel dysfunction is closely related to the pathological process of Alzheimer′s disease. Enhancing the drainage function of meningeal lymphatic vessels may provide an innovative strategy for the treatment of the disease. This article systematically expounds the structure, function and "space-dependent differences" of meningeal lymphatic vessels, deeply explores their role in the pathogenesis of Alzheimer′s disease, and investigates the intervention measures to improve the function of meningeal lymphatic vessels, aiming to open up new ideas for the prevention and treatment of Alzheimer′s disease.