Objective To address the challenges of poor performance and lack of interpretability in existing models,the SHAP algorithm is used to develop an interpretable machine learning model that offers a novel approach to wound age estimation,Methods Based on the previous discovery of the expression of 35 wound age healing-related genes in contused skeletal muscle,the woun age estimaton model was constructed using four algorithms,namly,Multilayer Perceptron(MLP),Random Forest(RF),LightGBM(LGBM),and Support Vector Machine(SVM).The SHAP(Shapley Additive Explanation)algorithm was used to rank the importance of genetic features,eliminate redundant attributes,and optimize the model for accurate wound age estimation.the genetic features of the optimal model were analyzed using SHAP's local interpretation capabilities.Results The best results were obtained using model of MLP(area under the curve(AUC)=0.99)The wound ages were classified into four categories:4～12 h,16～24 h,28～36 h,and 40～48 h,using only 15 gene features.According to SHAP analysis,Fam210a was identified as the most relevant gene.Local analysis revealed that high expression of Fam210a contributed to an increase in the predicted probability of 4 h～12 h,while high expression of Rae1 contributed to an increase in the predicted probability of 16 h～24 h.Additionally,low expression of Tbx18 contributed to an increase in the predicted probability of 28 h～36 h,whereas high expression of Tbx18 contributed to an increase in the predicted probability of 40 h～48 h.Conclusions The combined MLP and SHAP model can be used to predict wound age.Using the SHAP interpreter can better understand the degree of contribution of feature genes to the model prediction,and lay the foundation for further in-depth study of wound age estimation.

The comparison between traditional Chinese medicine Jinzhen oral liquid (JZOL) and Western medicine in treating children with acute bronchitis (AB) showed encouraging outcomes. This trial evaluated the efficacy and safety of the JZOL for improving cough and expectoration in children with AB. 480 children were randomly assigned to take JZOL or ambroxol hydrochloride and clenbuterol hydrochloride oral solution for 7 days. The primary outcome was time-to-cough resolution. The median time-to-cough resolution in both groups was 5.0 days and the antitussive onset median time was only 1 day. This randomized controlled trial showed that JZOL was not inferior to cough suppressant and phlegm resolving western medicine in treating cough and sputum and could comprehensively treat respiratory and systemic discomfort symptoms. Combined with clinical trials, the mechanism of JZOL against AB was uncovered by network target analysis, it was found that the pathways in TRP channels like IL-1β/IL1R/TRPV1/TRPA1, NGF/TrkA/TRPV1/TRPA1, and PGE2/EP/PKA/TRPV1/TRPA1 might play important roles. Animal experiments further confirmed that inflammation and the immune regulatory effect of JZOL in the treatment of AB were of vital importance and TRP channels were the key mechanism of action.

Vigabatrin-associated brain abnormalities on magnetic resonance imaging (VABAM) is a relatively rare side effect of vigabatrin, most of which are asymptomatic. However, there will be extremely rare cases with hyperkinetic disorders, myoclonus, tremor, and acute encephalopathy under certain circumstances. VABAM is often underappreciated by physicians and its accurate incidence remains unclear. A female infant who was diagnosed with infantile spasms and required adrenocorticotropic hormone therapy accompanied by various antiseizure medicines was reported. Unfortunately, she became lethargic and her spasm deteriorated gradually after vigabatrin exposure. Her brain magnetic resonance imaging revealed abnormal signals bilaterally in the dorsal midbrain, thalamus, and rostral part of the pallidum. She had a seizure amelioration and became lively as a result of vigabatrin withdrawal. In the meanwhile, magnetic resonance imaging returned to normal. Attempts were made to discover the risk factors of VABAM and potential pathogenesis. Further understanding of the disease should contribute to decreasing misdiagnosis and making precise decisions.

BACKGROUND: Sweat secreted by eccrine sweat glands is transported to the skin surface through the lumen. The eccrine sweat gland develops from the initial solid bud to the final gland structure with a lumen, but how the lumen is formed and the mechanism of lumen formation have not yet been fully elucidated. This study aimed to investigate the mechanism of lumen formation of eccrine gland organoids (EGOs). METHODS: Human eccrine sweat glands were isolated from the skin for tissue culture, and the primary cultured cells were collected and cultured in Matrigel for 14 days in vitro. EGOs at different development days were collected for hematoxylin and eosin (H&E) staining to observe morphological changes and for immunofluorescence staining of proliferation marker Ki67, cellular motility marker filamentous actin (F-actin), and autophagy marker LC3B. Western blotting was used to detect the expression of Ki67, F-actin, and LC3B. Moreover, apoptosis was detected using a terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) apoptosis assay kit, and the expression of poly (ADP-ribose) polymerase and Caspase-3 was detected by Western blot. In addition, 3-methyladenine (3MA) was used as an autophagy inhibitor to detect whether the formation of sweat glands can be effectively inhibited. RESULTS: The results showed that a single gland cell proliferated rapidly and formed EGOs on day 4. The earliest lumen formation was observed on day 6. From day 8 to day 14, the rate of lumen formation in EGOs increased significantly. The immunofluorescence and Western blot analyses showed that the expression of Ki67 gradually decreased with the increase in days, while the F-actin expression level did not change. Notably, the expression of autophagy marker LC3B was detected in the interior cells of EGOs as the apoptosis signal of EGOs was negative. Compared with the control group, the autophagy inhibitor 3MA can effectively limit the formation rate of the lumen and reduce the inner diameter of EGOs. CONCLUSION Using our model of eccrine gland 3D-reconstruction in Matrigel, we determined that autophagy rather than apoptosis plays a role in the lumen formation of EGOs.
Apoptosis ; Autophagy ; Eccrine Glands ; Epithelial Cells ; Humans ; Organoids

Ovarian cancer is the most malignant gynecologic malignancy. In recent years, histone modifying enzymes (HMEs) have been widely studied as an important part of epigenetic modifi-cations in ovarian cancer. Histone modifying enzymes, including histone methyltransferases and demethylases, histone acetyltransferases and deacetylases, play an important role in the prolif-eration and migration of ovarian cancer cells by modifying histone and non-histone proteins, and can regulate the development of chemoresistance. Inhibitors of various histone modifying enzymes play good anti-tumor effects in ovarian cancer by promoting cell growth arrest and apoptosis, inhibi¬ting tumor cell invasion, and increasing chemo¬therapy sensitivity, and are expected to be a new strategy for precision treatment of ovarian cancer. Therefore, this paper will review the mechanism of action and therapeutic potential of histone modifying enzymes involved in methylation and acetylation processes in ovarian cancer.

Over the past decade, traditional Chinese medicine (TCM) has widely embraced systems biology and its various data integration approaches to promote its modernization. Thus, integrative pharmacology-based traditional Chinese medicine (TCMIP) was proposed as a paradigm shift in TCM. This review focuses on the presentation of this novel concept and the main research contents, methodologies and applications of TCMIP. First, TCMIP is an interdisciplinary science that can establish qualitative and quantitative pharmacokinetics-pharmacodynamics (PK-PD) correlations through the integration of knowledge from multiple disciplines and techniques and from different PK-PD processes

Objective To analyze serotype distribution, drug resistance, quinolone resistance gene carrying status and genetic relationship of foodborne Salmonella and human Salmonella isolates in Changzhou from 2012 to 2018, to provide scientific basis for the prevention and control of Salmonella. Methods The serum type was identified by serum agglutination and liquid chip. The antibiotic sensitivity was determined by micro broth dilution method. The quinolone antibiotic resistance gene was determined by gene sequencing method. The multilocus sequence typing ( MLST ) typing was performed on quinolone-resistant Salmonella, and the genetic relationship was analyzed by BioNumerics 8.0. Results A total of 10 and 36 serotypes were detected in 46 foodborne Salmonella strains and 152 human Salmonella strains, respectively. The dominant serotypes were Indiana Salmonella and Salmonella typhimurium. Erythromycin resistance rate was the highest in both Salmonella strains, and the proportion of multidrug-resistant bacteria was 93.47 % ( 43 / 46 ) and 80.92 % ( 123 / 152 ), respectively. 38 strains of quinolone-resistant foodborne Salmonella GyrA subunit mainly occurred double mutations Asp87Asn, Ser83Phe, ParC subunit mainly occurred single mutation Ser80Arg, 119 strains of quinolone-resistant human Salmonella qnrS gene detection rate was higher, reached 68.1 % ( 81 / 119 ) ; The dominant ST types of quinolone-resistant Salmonella from two sources were ST17 and ST19, respectively. Conclusions The antibiotic sensitivity of the two Salmonella resistant strains from Changzhou was the same ; Synergistic drug resistance, but both quinolone resistance genemutations and carry inconsistent ; The ST type distribution of quinolone resistant strains isalso inconsistent, and the genetic relationship is far. It is suggested that the probability of Salmonella resistant bacteria infection caused by food transmission in our region is small, and the treatment of the two should be differentiated.

Objective To probe into the feasibility and applicability of the foodborne food risk monitoring and sentinel hospital foodborne disease surveillance on the Salmonella serotype identification by liquid phase suspension array. Methods The serotyping of Salmonella isolates was performed by traditional glass agglutination test. Meanwhile, the liquid phase suspension array was operated to analyze the antigen O, H and AT for classification identification. Results From 2012 to 2019, a total of 215 strains of Salmonella were collected divided into 38 serotypes, 96% of them could be analyzed by SSA kit. The results of xMAP were in accordance with the traditional agglutination. 8 of the 11 strains which cannot be checked out by glass agglutination seemed to be easy detected by liquid phase suspension array. Conclusion The liquid phase suspension array has advantages of high throughput, high sensitivity and high specificity. It is able to detect the Salmonella serotype rapidly during a short time. Compared with the traditional serum agglutination method, the liquid phase suspension array has obvious advantages in detection time. It can be useful and important in the break out of foodborne disease caused by Salmonella spp.

Objective Take frizzled class receptor 4(FZD4) as an example for exploring whether the transmembrane receptor protein is a suitable marker for wound age estimation. Methods A total of 78 Sprague-Dawley rats were divided randomly into the control group and the contusion groups of 4h, 8h, 12h, 16h, 20h, 24h, 28h, 32h, 36h, 40h, 44h, and 48h after injury (n=6). Using a drop-ball technique, a contusion was produced in the right lamb of rats. The samples were dissected from injury zones. Then the expression of FZD4 was detected using immunofluorescence, real-time PCR and western blot, respectively. Results FZD4 was located on the membrane of skeletal muscle cells. Compared to the control group, FZD4 mRNA showed a signiifcant increase (over 2-fold) in 8h, 12h, 36h, and 40h after injury by Real-time PCR (P<0.05), and FZD4 protein showed a statistical up-regulation (less than 2-fold) in 8h, 36h, 40h, 44h, and 48h post contusion by western blotting (P<0.05). Conclusion The expression of FZD4 mRNA and protein are both time-dependent during contused skeletal muscle repair. To some degree, FZD4 mRNA was more suitable than corresponding protein for determining wound age.

Objective T o investigate the relation betw een injury tim e and the expression of cytochrom e c oxidase subunitⅥc (COX6C) m R N A in skeletal m uscle of rat after contusion. Methods A total of fifty-four SD rats w ere divided into the control group and the contusion groups (0.5,1,6,12,18, 24, 30, and 36 h after contusion), random ly. T he contusion m odel w as established by free fall drop of gravity ham-m er. A t corresponding tim e point after contusion, the regular histology w as exam ined and expression level of COX6C m R N A w as tested by real-tim e PC R after extraction of total R N A from the tissues. Results T he m ain pathological features of 6 h after injury included edem a and hem orrhage in m yocytes w ith no inflam m atory cells found. A fter 6 hours, the findings included m yocyte degeneration and necro-sis, inflam m atory cells infiltration, and fibrous connective tissue proliferation in the contused zone. T he expression level of COX6C m R N A w as higher than that of the control group w ithin 6 h after contusion. T he expression level w as low er than that of the control group from 6-36 h after contusion. Conclusion T he level of COX6C m R N A expresses in a regular w ay after contusion. It m ay be useful for estim ating w ound age in com bination w ith the results of pathological features.