Acute liver injury (ALI) serves as a critical precursor and major etiological factor in the progression and ultimate manifestation of various hepatic disorders. The prevention and treatment of ALI is still a serious global challenge. Given the limited therapeutic options for ALI, exploring novel targeted therapeutic agents becomes imperative. The potential therapeutic efficacy of inhibiting RIPK2 is highlighted, as it may provide significant benefits by attenuating the MAPK pathway and NF-κB signaling. Herein, we propose a CMD-OPT model, a two-stage molecular optimization tool for the rapid discovery of RIPK2 inhibitors with optimal properties. Compound RP20, which targets the ATP binding site, demonstrated excellent kinase specificity, ideal oral pharmacokinetics, and superior therapeutic effects in a model of APAP-induced ALI, positioning RP20 as a promising preclinical candidate. This marks the first application of RIPK2 inhibitors in ALI treatment, opening a novel therapeutic pathway for clinical applications. These results highlight the efficacy of the CMD-OPT model in producing lead compounds from known active molecules, showcasing its significant potential in drug discovery.

Synthetic promoters are novel promoters artificially designed and do not exist in nature. They can initiate the expression of target genes with specific regulatory modes, offering advantages such as high expression efficiency, precise regulation, and modularity. These features endow synthetic promoters with significant application potential in fields such as industrial production, environmental monitoring, and disease diagnosis and treatment. This paper reviews the basic structures, functions, and classification of promoters, discusses various regulatory elements that influence promoter functions, including enhancers, signal response elements, and transcription factors. Additionally, the conventional and deep learning-based strategies for designing synthetic promoters are summarized. Finally, the theoretical significance of synthetic promoters is emphasized, which is followed by an overview of their current applications, along with a rational discussion on the challenges and future development directions of synthetic promoters. Given the critical role of promoters in gene regulation, this article provides a review and outlook on the research progress of synthetic promoters, which holds reference value for the design of cellular gene circuits.
Promoter Regions, Genetic/genetics* ; Transcription Factors/genetics* ; Synthetic Biology/methods* ; Gene Expression Regulation ; Humans ; Deep Learning

Multimodal data fusion(MDF),a data processing technology in the field of artificial intelligence,refers to a comprehensive processing technology of multimodal data such as pictures,texts,audio and videos by computer.Compared with traditional single-mode data processing,MDF has higher accuracy and reliability in the analysis of described objects.In recent years,the application of MDF in ophthalmology has made great progress,and studies have shown that this tech-nology can improve the accuracy of artificial intelligence-assisted diagnosis.This paper review the principles and advanta-ges,brief history of development,architecture and technical difficulties of MDF,as well as its application in ophthalmologic clinics and problems to be solved.

Objective To observe the clinical efficacy of Shen Shuai Ⅱ Granules combined with integrated Western medicine therapy in patients with primary chronic kidney disease(CKD)in stages 3-4 with the syndrome of spleen and kidney qi deficiency,dampness turbidity and blood stasis,and its effects on expression of serum autophagy related proteins.Methods Totally 88 patients were randomly divided into treatment group and control group,with 44 cases in each group.Both groups were given an integrated Western medicine therapy.On this basis,the treatment group was given Shen Shuai Ⅱ Granules,while the control group was given Shen Shuai Ⅱ placebo,1 bag at a time,twice a day,orally.The treatment for both groups lasted for 24 weeks.The clinical efficacy of the two groups was observed.The TCM symptom scores,serum creatinine(Scr),blood urea nitrogen(BUN),uric acid(UA),blood calcium(Ca2+),blood phosphorus(P3-),parathyroid hormone(PTH),and 24-hour urinary protein quantification(24 UPro)before and after treatment were compared in the two groups.The serum levels of autophagy related protein Beclin-1,Atg7,and LC3-Ⅱ were detected by ELISA before and after treatment in the two groups.Safety indexes of both groups were monitored.Results During the treatment,4 cases fell off in the treatment group and 4 cases in the control group.The total effective rate in the treatment group was 55％(22/40),while that in the control group was 30％(12/40).The therapeutic effect in the treatment group was better than that in the control group(P<0.01).Compared with before treatment,the TCM symptom scores in the treatment group decreased after treatment(P<0.01),the levels of Scr,BUN,UA,P3-,PTH,and 24 UPro decreased(P<0.05,P<0.01),while eGFR increased(P<0.01).The levels of Scr in the control group increased(P<0.05),while eGFR decreased(P<0.01).After treatment,the treatment group had lower various TCM symptom scores,Scr,BUN,UA,P3-,PTH,and 24 UPro levels than the control group(P<0.01,P<0.05),and higher eGFR than the control group(P<0.01).Compared with before treatment,the serum levels of Beclin-1,Atg7,and LC3-Ⅱ increased in the treatment group after treatment(P<0.01,P<0.05),while the serum level of Beclin-1 decreased in the control group after treatment(P<0.01).After treatment,the improvement of the above indicators in the treatment group were better than those in the control group(P<0.01,P<0.05).Correlation analysis showed that Beclin-1,Atg7,and LC3-Ⅱ were negatively correlated with Scr and BUN(P<0.05),and positively correlated with eGFR(P<0.05).There was no obvious adverse reaction in both groups.Conclusion The combination of Shen Shuai Ⅱ Granules and integrated Western medicine therapy for the treatment of primary CKD in stages 3-4 with the syndrome of spleen and kidney qi deficiency,dampness turbidity and blood stasis has confirmed efficacy,which can effectively alleviate clinical symptoms,improve renal function,and delay the progression of CKD.The mechanism may be related to improving the level of autophagy in renal.

Objective: To explore the predictor of lower airway inflammation among the index of nasal inflammation by investigating the expression and association of eosinophils (EOS) in the upper-lower airways and blood of patients with chronic rhinitis. Methods: A total of 162 patients with allergic rhinitis (AR), 117 patients with non-allergic rhinitis (NAR) and 104 controls were enrolled from June 2010 to December 2013 from General Hospital of Eastern Theater Command, People′s Liberation Army. All subjects were required detailed medical history collection and nasal resistance measurement. Skin prick test (SPT), blood total immunoglobin E (tIgE) and blood EOS, nasal lavage and induced sputum EOS, nasal provocation and bronchial provocation test (NPT, BPT), nasal and forced exhaled nitric oxide (NNO, FeNO) were performed in all patients. One-way analysis of variance was used for comparison between groups. LSD t test or Mann-Whitney U test was used for comparison between the two groups. Pearson or Spearman related parameter test was used for correlation analysis. Results: The nasal lavage EOS, NNO, induced sputum EOS, FeNO, blood EOS and tIgE were higher in the AR group than that in the NAR group (3.70[1.20, 14.23]/200 HP vs 1.40[0.20, 3.40]/200 HP, 673.50[466.80, 936.00] ppb vs 455.80[248.10, 705.60] ppb, 2.97[0.00, 10.63]% vs 1.00[0.23, 2.00]%, (49.28±26.37)ppb vs (34.07±19.11)ppb, 4.00[2.00, 7.00]% vs 2.00[1.00, 5.00]%, 208.01[61.70, 387.50] IU/ml vs 43.30[19.00, 122.00] IU/ml, F or χ² value was 11.442, 19.440, 70.727, 69.449, 47.453, 46.525, respectively, all P<0.05). But there was no significant difference in nasal resistance, NPT and BPT between the two groups. Nasal lavage EOS in AR group and NAR group was correlated with induced sputum EOS, FeNO, tIgE and blood EOS (r value of AR group was 0.448, 0.202, 0.159, 0.321, r value of NAR group was 0.442, 0.268, 0.268, 0.334, respectively, all P<0.05), but not with BPT. After adjustment for gender, age, height and weight, nasal EOS was positively correlated with sputum EOS. Multiple linear regression analysis showed that nasal EOS, blood EOS and SPT were factors affecting sputum EOS levels. The optimal threshold for nasal EOS to determine induced sputum EOS was 3.30/200 HP by (receiver operating characteristic,ROC) analysis. Conclusion The nasal EOS is correlated with multiple lower airway and systemic inflammatory markers, and is a risk factor for the induced sputum EOS, which can be used as an inflammation biomarker to predict the lower air inflammation.

Objective     To analyze the effect of myocardial protection between modified Del Nido cardioplegia and St. Thomas Hospital Cardioplegia in adult patients with aortic valve and mitral valve replacement. Methods     From January 2014 to June 2016, 140 patients underwent aortic valve and mitral valve replacement in our hospital. According to different cardioplegia, the patients were divided into two groups including a modified Del Nido cardioplegia group (70 patients, 37 males, 33 females at mean age of 53.13±9.52 years) and a St. Thomas cardioplegia group (70 patients, 32 males, 38 females, at age of 50.71±9.29 years). We collected clinical data of the patients before operation (T1), 2 h after aortic unclamping (T2), 24 h after operation (T3) and 48 h after operation (T4). Indexes of muscle enzymes including blood center creatine kinase (CK), creatine kinase isoenzyme (CK-MB) concentration and liver function indexes including urea nitrogen (BUN), creatinine (Cr), alanine aminotransferase (ALT), aspartate aminotransferase (AST) concentrations, and compared the postoperative and follow-up clinical data. Results     There was no statistical difference in age, weight, gender, ejection fraction baseline data between the two groups (P>0.05). All patients were successfully completed  combined valve replacement under cardiopulmonary bypass. The cardiopulmonary time was no statistical difference between the two groups (P>0.05). However, compared with St. Thomas cardioplegia group, modified Del Nido group was less in perfusion (1.19±0.39 vs. 2.99±0.75, P<0.001), shorter in aortic clamping time (P=0.003). No statistical difference was found in defibrillation rate after resuscitation between the two groups (P=0.779). Biochemical indicators were not statistically different at different time points between the two groups (P>0.05). Conclusion     Modified Del Nido cardioplegia has the same effect on myocardial protection with St. Thomas cardioplegia in adult patients. It reduces the frequency of reperfusion, and shortens the clamping time. There is no additional injury in the important organs such as liver, kidney. Modified Del Nido cardioplegia myocardial protection ability in adult heart valve surgery is feasible.

Objective: To study the mechanism of vocal mucosal barrier damage mediated by NF-κB and NF-κB-regulated signaling pathway via probing the expression of inflammatory factors and essential proteins for node of NF-κB signaling pathway. Methods: The patients suffering from vocal leukoplakia accompanied with larygopharyngeal reflux(LPR) were treated with oral administration of proton pump inhibitor(PPI). Mucosal specimens of vocal cord were collected from all patients before PPI treatment. And the mucosal specimens of vocal cord were collected from the patients with suspected recurrence at 8 weeks after PPI treatment. HE staining was used to observe the histopathological changes of the mucosa. ELISA was utilized to detect the levels of inflammatory factors including tumor necrosis factor(TNF)-α, interleukin(IL)-1 and IL-6. Western blot was used to detect the expression of p-p65, p-IKK and p-IκB. Immunofluorescence method was adopted to detect the entrance of p65 to cell nucleus.Data was analyzed by SPSS 23.0 software. Results: In PPI untreated group, the expressions of IL-1β, TNF-α and IL-6 in the specimens of 8 weeks after operation were not different significantly from those obtained during operation.But in the PPI-treated group, the expressions were down-regulated.The expression of p-p65 in the middle and high grade heterogenous hyperplasia group was higher than that of low level heterogenous hyperplasia group.The difference of p65 and p-p65 expression between 8 weeks after surgery and surgery in PPI-untreated group was statistically insignificant (P>0.05). The difference of p65 expression between PPI-treated group and PPI pre-treatment group was statistically insignificant (P>0.05). The expression of p-p65 in the PPI-treated group was lower than that of the PPI pre-treatment group (P<0.05). The expressions of IL-1β, TNF-α and IL-6 were positively related with that of NF-κB-p65. Immun of luorescence method revealed the entrance of p65 to cell nucleus in PPI pre-treatment group, which meant that NF-κB was activated. In the PPI-treated group, few activated p65 could be observed in the cell nucleu. Conclusion The possible mechanism of vocal mucosal barrier damage in vocal leukoplakia accompanied with LPR maybe the vocal mucosal inflammation mediated by NF-κB and NF-κB-regulated signaling pathway activated with refluxed materials.

[Abstract ] Objective Clinically, the necessity of acid suppression treatment in vocal leukoplakia is still controversial .This paper aims to investigate the roles of LPR in the pathogenesis and pathological process of vocal leukoplakia , and to clear the signifi-cance of acid suppression in the treatment of this disease through observing the influence of laryngopharyngeal reflux ( LPR) on the symptoms of postoperative vocal leukoplakia . Methods We collected 97 cases underwent vocal leukoplakia surgery from June 2013 to December 2015 in the Department of Otorhinolarygology Head and Neck Surgery , Nanjing General Hospital of Nanjing Military Re-gion.According to the results of ambulatory 24-hour double probe ( simultaneous esophageal and pharyngeal ) pH monitoring ( pH-me-try), the patients with vocal leukoplakia were divided into LPR group (n=26, laryngopharyngeal reflux) and non-LPR group(n=71, non-laryngopharyngeal reflux).Meanwhile, the patients in LPR group were then randomly divided into acid-suppressing group(n=13, oral esomeprazole ) and non-acid-suppressing ( n=13, oral placebo ) . All patients received evaluation and compared by electrolaryngendo-scope, voice handicap index-10 ( VHI-10), reflux symptom index ( RSI) and reflux finding score ( RFS) before operation and 8 weeks after operation, and observe the effect of laryngopharyngeal reflux and acid suppression on the symptoms of postoperative vocal leukoplakia . Results RSI and RFS after operation were significantly lower than before operation in LPR group[(13.6±5.8) vs (18.2±6.2), (9.2±2.4) vs (10.6±2.8), P<0.05].The difference of RSI and RFS between before and after operation in LPR group was higher than the non-LPR group[(5.8±1.4) vs (2.3±0.8), (1.2±0.6) vs (0.5±0.2), P<0.05].The difference of RSI and RFS between before and after operation in acid-suppressing group was higher than the non-acid-suppressing group[(6.6±1.2) vs (0.8±0.6), (2.6±0.6) vs (0.5±0.3), P<0.05].VHI-10 after operation was significantly lower than before operation in acid-suppressing group[(12.6±3.6) vs (15.2±4.2), P<0.05] Conclusion Standard PPI administration to patients suffering from vocal leukoplakia accompanied with LPR can alleviate the symptoms of LPR and improve hoarseness .

Objective Allergic rhinitis (AR) is studied extensively while nonallergic rhinitis (NAR) insufficiently in the recent years .The aim of this study is to describe the inflammation characteristics of different types of NAR . Methods Using the skin prick test , we investigated the characteristics , nasal cytokine levels , serum cytokine levels , and the proportion of peripheral blood Treg cells in 12 cases of AR, 10 cases of NAR with eosinophilia (EOS) syndrome (NARES), 12 cases of NAR without ES (NAR), and 11 control adults . Results The NARES patients had a signifi-cantly higher level of IFN-γ(28.89 [10.97-127.07] pg/mL) than the control (8.98 [7.88-14.90] pg/mL) and the NAR patients (7.92 [7.67-45.85] pg/mL) ( P<0.05) but a lower level of nasal IL-10 than the control ([3.97±0.68] vs [4.80±1.32] pg/mL, P<0.05) .The contents of nasal IL-4, serum IL-4, nasal IL-17 and ser-um IL-17 were all markedly higher in the AR and NARES groups than in the control (P<0.05).The proportion of CD4+CD25+FOXP3+Treg cells in the CD4+T cells in the peripheral blood was (4.5±1.3)%in the AR group and (4.0±1.8) %in the NARES group, both significantly lower than (6.5±1.0) %in the control group (P<0.05) and (6.5±1.0) %in the NAR group (P<0.05). Conclusion NAR was classified according to the EOS level into NARES and NAR without EOS, which had different mechanisms and manifestations of inflammation and similar inflammatory manifestations of Th 2 and Th17.The classification of rhinitis by the level of EOS has more practical significance .

Objective To explore the efficacy of group cognitive behavioral therapy for improving depressive symptoms and social functional in patients with major depressive disorder.Methods A total of 160 patients with major depressive disorder were randomly divided into intervention group (n=80) and control group (n=80).Intervention group was treated with conventional antidepressants combined with group cognitive behavioral therapy.Control group was treated with one conventional antidepressants.All participants were assessed with Hamilton Depression Scale (HAMD)and Scale of Social function of Psychosis Inpatients (SSFPI) before and 8 weeks after the treatment.Results After 8 weeks treatment,the scores of HAMD (14.76±9.48) was significantly reduced and the scores of SSFPI(30.09±4.34) were significantly increased in intervention group compared with the baseline ((37.91± 10.58),(12.40±2.56),all P＜0.01).The scores of HAMD were significantly lower and the scores of SSFPI were significantly higher in intervention group than that in control group((20.71±7.85),(22.63±3.63),all P＜0.01).Conclusion Group cognitive behavioral therapy is effective for major depressive disorder patients by reducing depressive symptom and improving social function.