This study aims to investigate the medication rules of patented traditional Chinese medi-cine(TCM)compound formulas and molecular mechanisms of core drugs for treating sepsis using data mining and network pharmacology approaches.In the present study,we first searched the PubMed database,Web of Science database,and the China National Knowledge Infrastructure(CNKI)since the establishment of the library to April 30,2024 for the relevant literature on the treatment of sepsis by traditional Chinese medicine.The prescriptions were then statistically ana-lyzed for drug frequency and association analysis to obtain the core drugs.Then we screened the ef-fective active ingredients of the core drugs by TCMSP and other database platforms,obtained sep-sis-related genes in GeneCards and other databases,and statistically intersected targets,and predic-ted the mechanism of action of the core TCMs by subjecting the intersected targets to PPI analy-sis,GO function and KEGG pathway enrichment analysis.Finally,the relationship between key tar-gets and herbal components was examined in reverse by molecular docking method.The results showed that 64 compound formulas were obtained,with a total of 150 Chinese medicines,which were mostly sweet in taste,cold in nature,and belonged to the spleen,stomach and intestinal me-ridians.According to the association rules,the core drugs were identified as"mirabilite-peach ker-nel-rheum officinale".There were 79 intersecting targets between the core drugs and sepsis,with core targets such as IL-1β,EGFR and SRC.MAPK,TNF,IL-17 and other signaling pathways are involved to mediate inflammatory responses,apoptosis and other biological processes to exert ther-apeutic effects on sepsis.The molecular docking results indicated that the docking activity of the key targets with the main components of the drug,and sennoside E_qt has the lowest binding ener-gy and the best docking activity with SRC.In conclusion,this study showed that the prescription of Chinese medicine for sepsis is mostly based on tonifying the spleen and clearing heat.The mecha-nism of action of the core drug"mirabilite-peach kernel-rheum officinale"in the treatment of sep-sis is multilevel and multifaceted,which provides a certain theoretical basis for the treatment of sepsis by traditional Chinese medicine.

This study aims to investigate the medication rules of patented traditional Chinese medi-cine(TCM)compound formulas and molecular mechanisms of core drugs for treating sepsis using data mining and network pharmacology approaches.In the present study,we first searched the PubMed database,Web of Science database,and the China National Knowledge Infrastructure(CNKI)since the establishment of the library to April 30,2024 for the relevant literature on the treatment of sepsis by traditional Chinese medicine.The prescriptions were then statistically ana-lyzed for drug frequency and association analysis to obtain the core drugs.Then we screened the ef-fective active ingredients of the core drugs by TCMSP and other database platforms,obtained sep-sis-related genes in GeneCards and other databases,and statistically intersected targets,and predic-ted the mechanism of action of the core TCMs by subjecting the intersected targets to PPI analy-sis,GO function and KEGG pathway enrichment analysis.Finally,the relationship between key tar-gets and herbal components was examined in reverse by molecular docking method.The results showed that 64 compound formulas were obtained,with a total of 150 Chinese medicines,which were mostly sweet in taste,cold in nature,and belonged to the spleen,stomach and intestinal me-ridians.According to the association rules,the core drugs were identified as"mirabilite-peach ker-nel-rheum officinale".There were 79 intersecting targets between the core drugs and sepsis,with core targets such as IL-1β,EGFR and SRC.MAPK,TNF,IL-17 and other signaling pathways are involved to mediate inflammatory responses,apoptosis and other biological processes to exert ther-apeutic effects on sepsis.The molecular docking results indicated that the docking activity of the key targets with the main components of the drug,and sennoside E_qt has the lowest binding ener-gy and the best docking activity with SRC.In conclusion,this study showed that the prescription of Chinese medicine for sepsis is mostly based on tonifying the spleen and clearing heat.The mecha-nism of action of the core drug"mirabilite-peach kernel-rheum officinale"in the treatment of sep-sis is multilevel and multifaceted,which provides a certain theoretical basis for the treatment of sepsis by traditional Chinese medicine.

Objective To investigate whether the extracts of Patrinia heterophylla(MTH)inhibits the activation of macrophages induced by lipopolysaccharide(LPS)in vitro and the inflammatory response induced in vivo by suppressing the nuclear factor kappa B(NF-κB)signaling pathway.Methods Cellular studies:RAW264.7 cells were divided into 6 groups:control group,LPS group,LPS+Dexamethasone(DEX)group and LPS+MTH(low,medium,high dose)groups.The LPS group,LPS+DEX and LPS+MTH group were induced with a final concentration of 100 ng/ml LPS.While the LPS+DEX group was additionally treated with 5.0 ng/ml DEX,the LPS+MTH group was additionally treated with MTH(final concentrations of 0.1,0.2 and 0.4 mg/ml).The cell activity was detected using CCK-8 assay,cell invasion was detected using Transwell assay,cell apoptosis was detected using flow cytometry,and interleukin-6(IL-6),interleukin-17(IL-17)and tumor necrosis factor-α(TNF-α)were detected using real-time fluorescence quantitative PCR and enzyme-linked immunosorbent assay,respectively.The expression and secretion levels of nitric oxide(NO)in cells were detected by Griess assay,total reactive oxygen species(ROS)levels were detected by flow cytometry.The phosphorylation level of p65 and inhibitor of κB(IκB)were detected by protein immunoblotting assay.The transcriptional activity was detection by luciferase reporter gene assay.Animal studies:50 rats were randomly divided into 5 groups,10 per group,namely the control group,LPS group,LPS+DEX group,LPS+MTH low-dose group(6 g/kg)and LPS+MTH high-dose group(24 g/kg).LPS was injected into the lungs of rats,and the groups were orally administered at 36 h,24 h,12 h before modeling,and 12 h,24 h after modeling.12 h after the last administration,bronchoalveolar lavage fluid was collected,and the IL-6,IL-17,TNF-α and NF-κB signaling pathway-related indicators in the bronchoalveolar lavage fluid were measured.Results Cellular studies:Compared with the control group,the cell activity,invasion,apoptosis,IL-6,IL-17 and TNF-α mRNA and protein,NO,ROS,phosphorylation level of P536 protein S536 site and IκB protein S32 site and transcription activity of NF-κB had significantly increased in the LPS group(all P＜0.05).Compared with the LPS group,the cell activity,invasion,IL-6,IL-17,and TNF-αmRNA and protein,NO,ROS,phosphorylation level of P536 protein S536 site and IκB protein S32 site and transcription activity of NF-κB had significantly decreased in 3 LPS+MTH groups(all P＜0.05),and apoptosis was significantly increased in 3 LPS+MTH groups(all P＜0.05).All of which showed a dose-dependent trend of MTH.Animal studies:Compared with the control group,the LPS group showed a significant increase in IL-6,IL-17,TNF-α and phosphorylation levels of p65 protein at S536 site and IκB protein at S32 site(all P＜0.05).Compared with the LPS group,the 2 LPS+MTH groups showed a significant decrease in IL-6,IL-17,TNF-α and phosphorylation levels of p65 protein at S536 site and IκB protein at S32 site(all P＜0.05).These indicators showed a dose-dependent trend with MTH.Conclusion MTH can inhibit the activation of mouse macrophage RAW264.7 induced by LPS and the inflammatory response in the lungs of rats induced by LPS,which may be related to the inhibition of the NF-κB signaling pathway.

Objective To explore the clinical value of models based on clinical features and enhanced MRI radiomics for predicting the occurrence of post-acute pancreatitis diabetes mellitus(PPDM-A).Methods A retrospective selection of 161 acute pancreatitis(AP)patients was conducted,comprising 99 in the non-PPDM-A group and 62 in the PPDM-A group.They were randomly divided into training set and test set in a ratio of 7∶3.Region of interest(ROI)were delineated and radiomics features were extracted on the late arterial phase MRI images.Optimal radiomics features were selected by maximum relevance and minimum redundancy(mRMR)and least absolute shrinkage and selection operator(LASSO).Support vector machine(SVM)was used to develop three predictive models.The efficacy of the models in predicting PPDM-A was evaluated,the receiver operating characteristic(ROC)curve was drawn,and the DeLong test was employed to assess the difference in predictive capability among the models.Results In the training set,the area under the curve(AUC)of the clinical model,radiomics model,and combined model were 0.702,0.810 and 0.901,respectively,and in the test set were 0.678,0.797 and 0.830,respectively.The DeLong test revealed a statistically significant difference in the predictive capability of the combined model compared to the clinical model both in the training and test sets(training set:P＜0.001;test set:P=0.019).Conclusion The combined model based on clinical features and enhanced MRI radiomics features demonstrates good predictive effi-cacy and can provide valuable insights for clinical interventions aimed at preventing PPDM-A.

Objective To evaluate the application effect of a novel hemodialysis catheter fixing strap in clinical hemodialysis. Methods A total of 199 hemodialysis patients from the Second Affiliated Hospital of Anhui Medical University between May and July 2023 were enrolled in this study. Employing the self-controlled study design, patients were initially fixed with conventional adhesive tape (fixation method A) for their dialysis tubing from May 20 to June 20, 2023. Subsequently, from June 21 to July 21, 2023, patients were transitioned to a novel hemodialysis catheter fixing belt (fixation method B) for the fixation of their dialysis tube. The incidence of puncture needle, central venous catheter displacement, the stability of fixation, and the satisfaction levels of nurses and patients were compared between the two fixation methods. Results The rate of puncture needle/central venous catheter displacement with method B was significantly lower than that with method A (P < 0.001). No statistically significant difference was observed in the puncture needle/central venous catheter displacement between the two methods (P>0.05). The stability of fixation with method B was significantly higher than that with method A (P < 0.001). Patients' satisfaction with fixation method B (in favor of mobility and comfort) was significantly higher than that with fixation method A (P < 0.001); similarly, nurses'satisfaction with fixation method B (in favor of cleaning and convenient operation) was markedly superior to that with fixation method A (P < 0.001). Conclusion Compared with the traditional adhesive tape fixation method, the novel hemodialysis catheter securing strap effectively secures the catheter with improved safety and significantly enhances the satisfaction of both nurses and patients.

Objective To investigate whether the extracts of Patrinia heterophylla(MTH)inhibits the activation of macrophages induced by lipopolysaccharide(LPS)in vitro and the inflammatory response induced in vivo by suppressing the nuclear factor kappa B(NF-κB)signaling pathway.Methods Cellular studies:RAW264.7 cells were divided into 6 groups:control group,LPS group,LPS+Dexamethasone(DEX)group and LPS+MTH(low,medium,high dose)groups.The LPS group,LPS+DEX and LPS+MTH group were induced with a final concentration of 100 ng/ml LPS.While the LPS+DEX group was additionally treated with 5.0 ng/ml DEX,the LPS+MTH group was additionally treated with MTH(final concentrations of 0.1,0.2 and 0.4 mg/ml).The cell activity was detected using CCK-8 assay,cell invasion was detected using Transwell assay,cell apoptosis was detected using flow cytometry,and interleukin-6(IL-6),interleukin-17(IL-17)and tumor necrosis factor-α(TNF-α)were detected using real-time fluorescence quantitative PCR and enzyme-linked immunosorbent assay,respectively.The expression and secretion levels of nitric oxide(NO)in cells were detected by Griess assay,total reactive oxygen species(ROS)levels were detected by flow cytometry.The phosphorylation level of p65 and inhibitor of κB(IκB)were detected by protein immunoblotting assay.The transcriptional activity was detection by luciferase reporter gene assay.Animal studies:50 rats were randomly divided into 5 groups,10 per group,namely the control group,LPS group,LPS+DEX group,LPS+MTH low-dose group(6 g/kg)and LPS+MTH high-dose group(24 g/kg).LPS was injected into the lungs of rats,and the groups were orally administered at 36 h,24 h,12 h before modeling,and 12 h,24 h after modeling.12 h after the last administration,bronchoalveolar lavage fluid was collected,and the IL-6,IL-17,TNF-α and NF-κB signaling pathway-related indicators in the bronchoalveolar lavage fluid were measured.Results Cellular studies:Compared with the control group,the cell activity,invasion,apoptosis,IL-6,IL-17 and TNF-α mRNA and protein,NO,ROS,phosphorylation level of P536 protein S536 site and IκB protein S32 site and transcription activity of NF-κB had significantly increased in the LPS group(all P＜0.05).Compared with the LPS group,the cell activity,invasion,IL-6,IL-17,and TNF-αmRNA and protein,NO,ROS,phosphorylation level of P536 protein S536 site and IκB protein S32 site and transcription activity of NF-κB had significantly decreased in 3 LPS+MTH groups(all P＜0.05),and apoptosis was significantly increased in 3 LPS+MTH groups(all P＜0.05).All of which showed a dose-dependent trend of MTH.Animal studies:Compared with the control group,the LPS group showed a significant increase in IL-6,IL-17,TNF-α and phosphorylation levels of p65 protein at S536 site and IκB protein at S32 site(all P＜0.05).Compared with the LPS group,the 2 LPS+MTH groups showed a significant decrease in IL-6,IL-17,TNF-α and phosphorylation levels of p65 protein at S536 site and IκB protein at S32 site(all P＜0.05).These indicators showed a dose-dependent trend with MTH.Conclusion MTH can inhibit the activation of mouse macrophage RAW264.7 induced by LPS and the inflammatory response in the lungs of rats induced by LPS,which may be related to the inhibition of the NF-κB signaling pathway.

ObjectiveTo review the information and clinical studies of oral Chinese patent medicines （CPMs） for chronic kidney disease （CKD）. MethodThe CPMs for treating CKD were retrieved from the Pharmacopoeia of the People's Republic of China， National Essential Drugs List， and Medicine List for National Basic Medical Insurance， Employment Injury Insurance and Maternity Insurance. China National Knowledge Infrastructure（CNKI）， VIP， Wanfang Data， SinoMed， PubMed， Embase， Cochrane， and Web of Science were searched for the clinical trials of the treatment of CKD by CPMs from their inception dates to September 25， 2022. A database was established with the collected CPMs， and then the general conditions of the clinical trials were analyzed and presented visually. ResultA total of 16 CPMs for CKD were included in this study， including 5 classical traditional Chinese medicine （TCM） prescriptions involving Rehmanniae Radix and 11 new CPMs. The indications of the TCM prescriptions did not mention the corresponding western disease names， and those of the new CPMs mainly included chronic renal insufficiency， chronic renal failure， and chronic nephritis. Four CPMs were prepared with single Chinese medicine or active components. Specifically， Bailing Preparation and Jinshuibao Preparation were mainly prepared with the powder of Cordyceps， and the main components of Haikun Shenxi capsules and Huangkui capsules were fucoidan sulfate and the flower extract of Abelmoschi Corolla， respectively. The CPMs mainly exerted tonifying and eliminating effects on the lung， spleen， and kidney. A total of 892 clinical trials were screened out， covering all the areas in China and presented an increasing trend. Bailing Preparation was the most studied， followed by Niaoduqing Preparation. Among the 892 studies， 475 focused on single CPMs without combination with other CPMs or therapies. These studies mainly compared between conventional intervention and conventional intervention + CPM， which accounted for 75.58%. The 475 studies covered different kidney diseases， such as chronic kidney disease， chronic renal failure， nephrotic syndrome， diabetic kidney disease， IgA nephropathy， and membranous nephropathy， and involved a variety of populations including the elderly and children. Thirty-six studies evaluated TCM syndromes， reflecting the characteristics and advantages of TCM treatment. ConclusionThere are abundant oral CPMs for CKD， with varied efficacy and characteristics for different kidney diseases. However， the instruction manuals of the oral CPMs are not detailed or standard. According to the clinical research evidence in this field， the research on oral CPMs for CKD is characterized by a wide scope， rich study types， and wide disease coverage， while the sample size and quality remain to be improved.

OBJECTIVE To compare the anticoagulant effectiveness and safety of new oral anticoagulants （NOACs）and warfarin after heart valve replacement ，and to provide evidence-based reference for clinical drug use. METHODS Retrieved from PubMed，Cochrane Library ，Embase，Web of Science ，CNKI，Wanfang database and VIP ，clinical studies about the use of NOACs versus warfarin after heart valve replacement were collected during the inception to July 2021. After literature screening and data extrac tion，the quality of included randomized controlled trials （RCTs）were evaluat ed by bias risk assessment tool recommended by Cochrane system evaluator manual 5.2.0. After the quality of the included cohort studies was evaluated by Newcastle-Ottawa scale （NOS），RevMan 5.3 software was used for meta-analysis and sensitivity analysis. RESULTS A E-mail：carolmeng_0813@163.com total of 9 studies involving 4 962 patients were included ，of which 7 were RCTs and 2 were cohort studie s. Results of meta-analysis showed that after biological valve replacement/repair ，the incidence of stroke and systemic embolism （SSE）[OR＝0.71，95％CI（0.52，0.97），P＝0.03]，major bleeding [OR ＝0.40，95％CI （0.30，0.54），P＜0.000 01] and intracranial hemorrhage [OR ＝0.20，95％CI（0.04，0.95），P＝0.04] in trial group were significantly lower than warfarin group ；there was no significant difference in all-cause mortality between 2 groups [OR ＝1.25，95％CI（0.88， 1.79），P＝0.22]. After mechanical valve replacement/repair ，there were no significant difference in the incidence of SSE [OR ＝1.52， 95％CI（0.04，60.29），P＝0.82] or all-cause mortality [OR ＝0.26，95％CI（0.04，1.84），P＝0.18] between 2 groups. The results of subgroup analysis according to the follow-up time showed that after biological valve replacement/repair ，the incidence of SSE in trial group was significantly lower than that in control group when the follow-up time was ≤3 months [OR ＝0.20，95％CI（0.06， 0.74），P＝0.03]；but there was no significant difference in the incidence of major bleeding between 2 groups [OR ＝0.67，95％CI （0.19，2.38），P＝0.53]；when the follow-up time was longer than 3 months，there was no statistical significance in the incidence of SSE between 2 groups [OR ＝0.74，95％CI（0.54，1.02），P＝0.07]，while the incidence of major bleeding in trial group was significantly lower than control group [OR ＝0.39，95％CI（0.29，0.52），P＜0.001]. Subgroup analysis by study type showed that after biological valve replacement/repair ，the incidence of SSE in the RCT in trial group was significantly lower than that in control group [OR ＝0.51，95％CI（0.29，0.92），P＝0.03]，but there was no significant difference in the incidence of major bleeding between 2 groups[OR＝0.58，95％CI（0.33，1.03），P＝0.06]. In cohort study ，there was no significant difference in the incidence of SSE between 2 groups [OR ＝1.03，95％CI（0.40，2.66），P＝0.95]，while the incidence of major bleeding in trial group was significantly lower than control group [OR ＝0.20，95％CI（0.06，0.74），P＜0.001]. Sensitivity analysis results showed that the results of the above-mentioned meta-analysis were relatively robust. CONCLUSIONS For the patients underwent biological valve replacement/repair，the effectiveness and safety of NOACs are better than or similar to those of warfarin ；for the patients underwent mechanical valve replacement/repair ，there is no significant difference in the effectiveness and safety between NOACs and warfarin.

Aging of craniofacial skeleton significantly impairs the repair and regeneration of trauma-induced bony defects, and complicates dental treatment outcomes. Age-related alveolar bone loss could be attributed to decreased progenitor pool through senescence, imbalance in bone metabolism and bone-fat ratio. Mesenchymal stem cells isolated from oral bones (OMSCs) have distinct lineage propensities and characteristics compared to MSCs from long bones, and are more suited for craniofacial regeneration. However, the effect of epigenetic modifications regulating OMSC differentiation and senescence in aging has not yet been investigated. In this study, we found that the histone demethylase KDM4B plays an essential role in regulating the osteogenesis of OMSCs and oral bone aging. Loss of KDM4B in OMSCs leads to inhibition of osteogenesis. Moreover, KDM4B loss promoted adipogenesis and OMSC senescence which further impairs bone-fat balance in the mandible. Together, our data suggest that KDM4B may underpin the molecular mechanisms of OMSC fate determination and alveolar bone homeostasis in skeletal aging, and present as a promising therapeutic target for addressing craniofacial skeletal defects associated with age-related deteriorations.
Aging ; Cell Differentiation ; Facial Bones/physiology* ; Humans ; Jumonji Domain-Containing Histone Demethylases/genetics* ; Mesenchymal Stem Cells/cytology* ; Osteogenesis ; Osteoporosis

Objective:To investigate the clinicopathological features of fumarate hydratase (FH) deficiency uterine leiomyoma.Methods:The data of 38 patients with FH deficiency uterine leiomyoma were screened and analyzed. The expressions of FH, S-(2-succino)-cysteine (2SC), desmin, p16, p53, CD 10 and cell proliferation associated nuclear antigen (Ki-67) proteins were detected by immunohistochemistry, and their clinicopathological features were analyzed retrospectively. Results:(1) Clinical features: the median age of the patients was (42.5±7.4) years old. Twenty-one cases (55%) of them were myomas found in physical examination, and the median maximum diameter of the tumor was 6.0 cm (range: 5.0-7.5 cm); myomectomy was performed in 23 cases (61%), total hysterectomy with or without bilateral appendages in 15 cases (39%); laparoscopic surgery in 27 cases (71%), open surgery in 11 cases (29%); none of the patients had renal cell carcinoma. (2) Histological features: atypical nuclear cells were distributed locally or diffusely, eosinophilic nucleoli and intranuclear inclusion bodies could be seen, glass like globules could be seen in the cytoplasm, nuclear division was 0-4/10 high power field (HPF), and antler like blood vessels and pulmonary edema-like changes could be seen in the stroma. Among 38 patients with FH deficiency uterine leiomyoma, FH was negative in 37 cases (97%), and positive in 1 case (3%); 2SC, desmin, p16, p53, CD 10 and Ki-67 showed focal positive expression in 38 cases (100%), including 35 cases (92%) with Ki-67 index<10% and 3 cases (8%) with Ki-67 index ≥10%. (3) Follow-up: 4 cases (11%) recurred, and there was no death. There were significant differences in age, family history, distribution of atypical nuclei and mitosis number between recurrent group and non-recurrent group (all P<0.05). Conclusions:FH deficiency uterine leiomyoma is a rare tumor, which needs pathological examination,immunohistochemical examination and clinical history. Patients younger than 43 years old, with family history, histologically atypical diffuse nuclear distribution and mitotic number ≥3/10 HPF should be alert to the risk of recurrence.