The innate immune system can be boosted in response to subsequent triggers by pre-exposure to microbes or microbial products, known as “trained immunity”. Compared to classical immune memory, innate trained immunity has several different features. Firstly, the molecules involved in trained immunity differ from those involved in classical immune memory. Innate trained immunity mainly involves innate immune cells (e.g., myeloid immune cells, natural killer cells, innate lymphoid cells) and their effector molecules (e.g., pattern recognition receptor (PRR), various cytokines), as well as some kinds of non-immune cells (e.g., microglial cells). Secondly, the increased responsiveness to secondary stimuli during innate trained immunity is not specific to a particular pathogen, but influences epigenetic reprogramming in the cell through signaling pathways, leading to the sustained changes in genes transcriptional process, which ultimately affects cellular physiology without permanent genetic changes (e.g., mutations or recombination). Finally, innate trained immunity relies on an altered functional state of innate immune cells that could persist for weeks to months after initial stimulus removal. An appropriate inducer could induce trained immunity in innate lymphocytes, such as exogenous stimulants (including vaccines) and endogenous stimulants, which was firstly discovered in bone marrow derived immune cells. However, mature bone marrow derived immune cells are short-lived cells, that may not be able to transmit memory phenotypes to their offspring and provide long-term protection. Therefore, trained immunity is more likely to be relied on long-lived cells, such as epithelial stem cells, mesenchymal stromal cells and non-immune cells such as fibroblasts. Epigenetic reprogramming is one of the key molecular mechanisms that induces trained immunity, including DNA modifications, non-coding RNAs, histone modifications and chromatin remodeling. In addition to epigenetic reprogramming, different cellular metabolic pathways are involved in the regulation of innate trained immunity, including aerobic glycolysis, glutamine catabolism, cholesterol metabolism and fatty acid synthesis, through a series of intracellular cascade responses triggered by the recognition of PRR specific ligands. In the view of evolutionary, trained immunity is beneficial in enhancing protection against secondary infections with an induction in the evolutionary protective process against infections. Therefore, innate trained immunity plays an important role in therapy against diseases such as tumors and infections, which has signature therapeutic effects in these diseases. In organ transplantation, trained immunity has been associated with acute rejection, which prolongs the survival of allografts. However, trained immunity is not always protective but pathological in some cases, and dysregulated trained immunity contributes to the development of inflammatory and autoimmune diseases. Trained immunity provides a novel form of immune memory, but when inappropriately activated, may lead to an attack on tissues, causing autoinflammation. In autoimmune diseases such as rheumatoid arthritis and atherosclerosis, trained immunity may lead to enhance inflammation and tissue lesion in diseased regions. In Alzheimer’s disease and Parkinson’s disease, trained immunity may lead to over-activation of microglial cells, triggering neuroinflammation even nerve injury. This paper summarizes the basis and mechanisms of innate trained immunity, including the different cell types involved, the impacts on diseases and the effects as a therapeutic strategy to provide novel ideas for different diseases.

Objective To investigate the prevalence of Schistosoma japonicum infections in wild rodents in schistosomiasis-endemic areas of China, so as to provide insights into formulation of technical guidelines for monitoring of and the precise control strategy for S. japonicum infections in wild rodents during the elimination phase. Methods Two administrative villages where schistosomiasis was historically highly prevalent were selected each from Dongzhi County, Anhui Province, and Duchang County, Jiangxi Province as study villages. Wild rodents were captured from study villages with baited traps or cages at night in June and September, 2021. The number of rodents captured was recorded, and the rodent species was characterized based on morphologi-cal characteristics. Liver tissues were sampled from captured rodents for macroscopical observation of the presence of egg granu- lomas, and S. japonicum infection was detected simultaneously using liver tissue homogenate microscopy, examinations of mesenteric tissues for parasites, and modified Kato-Katz thick smear technique (Kato-Katz technique). A positive S. japonicum infection was defined as detection of S. japonicum eggs or adult worms by any of these methods. The rate of wild rodent capture and prevalence of S. japonicum infections in wild rodents were compared in different study villages and at different time periods, and the detection of S. japonicum infections in wild rodents was compared by different assays. Results The overall rate of wild ro- dent capture was 8.28% (237/2 861) in Dongzhi County, and the wild rodent capture rates were 9.24% (133/1 439) and 7.31% (104/1 422) in two study villages (χ² = 3.503, P = 0.061), and were 8.59% (121/1 409) and 7.99% (116/1 452) in June and September, 2021, respectively (χ² = 0.337, P = 0.561). The overall rate of wild rodent capture was 3.72% (77/2 072) in Duchang County, and the wild rodent capture rates were 6.91% (67/970) and 0.91% (10/1 102) in two study villages (χ² = 51.901, P < 0.001), and were 4.13% (39/945) and 3.37% (38/1 127) in June and September, 2021, respectively (χ² = 0.815, P = 0.365). Rattus norvegicus was the predominant rodent species captured in both counties, accounting for 70.04% (166/237) of all captured wild rodents in Dongzhi County and 88.31% (68/77) in Duchang County. No S. japonicum infection was detected in wild rodents captured in Duchang County. Nevertheless, the overall prevalence of S. japonicum infections was 51.05% (121/237) in wild rodents captured in Dongzhi County, with prevalence rates of 50.38% (67/133) and 51.92% (54/104) in two study villages (χ² = 0.098, P = 0.755), and 54.31% (63/116) and 47.93% (58/121) in September and June, 2021, respectively (χ² = 0.964, P = 0.326). Of 237 wild rodents captured in Dongzhi County, there were 140 (59.07%) rodents with visible hepatic egg granulomas, 117 (49.47%) tested positive for S. japonicum eggs by liver tissue homogenate microscopy, 34 (14.35%) tested positive for S. japonicum eggs with Kato-Katz technique; however, no adult S. japonicum worms were detected in mesenteric tissues. In addition, hepatic egg granulomas were found in all wild rodents tested positive for S. japonicum eggs with liver tissue homogenate microscopy. Conclusions The rate of wild rodent capture and prevalence of S. japonicum infection in wild rodents vary greatly in schistosomiasis-endemic areas of China, and the prevalence of S. japonicum infection is slightly higher in wild rodents captured in autumn than in summer. Liver tissue is recommended as the preferred sample for surveillance of S. japonicum infection in wild rodents, and a combination of macroscopical observation of hepatic egg granulomas and liver tissue homogenate microscopy may be a standard method for surveillance of S. japonicum infection in wild rodents.

Background Diurnal temperature range (DTR) is closely associated with cardiovascular health in the elderly, but there is a lack of research on the relationship between DTR and ischemic heart disease (IHD) in the elderly. Objective To investigate the effect of DTR on daily hospital admissions for IHD in people 65 years and older in Wuhan. Methods The study obtained data on elderly inpatients with IHD from all secondary and tertiary hospitals in Wuhan between January 1, 2017 and December 31, 2018, along with synchronous meteorological and air pollution data. Daily DTR was calculated as the difference between the maximum and minimum temperatures in a day. We employed distributed lag nonlinear models based on quasi-Poisson distribution to analyze the association between DTR and hospitalization risk in individuals aged 60 years and above. We assessed the extreme effects of DTR by selected DTR percentiles (the 1st percentile, P₁: 1.8 ℃; the 5th percentile, P₅: 2.9 ℃; the 95th percentile, P₉₅: 14.3 ℃; and the 99th percentile, P₉₉: 16.2 ℃) on hospitalization for IHD in the elderly population. Additionally, we conducted stratified analyses by gender, age (60-74 years and ≥75 years) and different subtypes (acute IHD and chronic IHD) to investigate the effects of DTR on hospitalizations for IHD across different genders, ages, and subtypes. Results This study included a total of 64212 first-time IHD hospitalizations among individuals aged 65 years and above in Wuhan from 2017 to 2018. The results showed a "J"-shaped exposure-response relationship between DTR and the cumulative risk of IHD hospitalization with a lag of 7 d; the optimal DTR was 5.0 ℃, and as DTR increased or the lag time lengthened, the risk of hospitalization for IHD in the elderly population increased. Extremely high DTR (P₉₉: 16.2 ℃) had a significant impact on the day of exposure (lag 0), with a cumulative RR of 1.58 (95%CI: 1.25, 1.99) at a lag of 7 d. The overall effects of DTR on IHD for different genders, ages, and subtypes of IHD exhibited similar patterns to the effects for overall population. High DTR had a significantly higher impact on hospitalization for chronic IHD (RR=1.46, 95%CI: 1.20, 1.79), compared to acute IHD (RR=1.29, 95%CI: 1.04, 1.61). At a cumulative lag of 7 d, elderly individuals aged 60-74 (RR=1.78, 95% CI: 1.30, 2.42) were more affected by high DTR in terms of IHD hospitalizations compared to those aged ≥75 (RR=1.35, 95% CI: 1.08, 1.70). Conclusion High DTR significantly increases the risk of hospitalization for IHD among elderly individuals. The effect of high DTR is particularly pronounced in patients with chronic IHD and elderly individuals aged 60–74 years.

Objective:To investigate the safety and effectiveness of endoscopic retrograde cholangiopancreatography (ERCP) for the diagnosis and treatment of pediatric pancreaticobiliary maljunction (PBM).Methods:Data of 40 pediatric patients under 14 with PBM diagnosed and treated by ERCP at Department of Gastroenterology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School from November 2012 to September 2022 were collected. PBM types, ERCP-related diagnosis and treatment, adverse events and prognosis were retrospectively analyzed.Results:Nineteen cases were P-B type (joining of common bile duct with pancreatic duct), 17 were B-P type (joining of pancreatic duct with common bile duct), and 4 were complex type. Forty children with PBM underwent 50 ERCP-related operations, among which 48 procedures succeeded. One case failed during cannulation of ERCP, replaced by rendezvous-assisted endoscopic retrograde pancreatography (RV-ERP) afterwards. There were no serious postoperative adverse events such as bleeding, perforation or death. Thirty-four patients (85%) were followed up successfully, among which 14 underwent further surgery and 20 continued conservative treatment.Conclusion:ERCP is the golden standard to diagnose pediatric PBM, and it is also safe and effective treatment for PBM.

Idiopathic pulmonary fibrosis （IPF）， as a progressive lung disease， has a poor prognosis and no reliable and effective therapies. IPF is mainly treated by organ transplantation and administration of chemical drugs， which are ineffective and induce side effects， failing to meet the clinical needs. Therefore， developing safer and more effective drugs has become an urgent task， which necessitates clear understanding of the pathogenesis of IPF. The available studies about the pathogenesis of IPF mainly focus on macrophage polarization， epithelial-mesenchymal transition （EMT）， oxidative stress， and autophagy， while few studies systematically explain the principles and links of the pathogeneses. According to the traditional Chinese medicine theory， Qi deficiency and blood stasis and Qi-Yang deficiency are the key pathogeneses of IPF. Therefore， the Chinese medicines or compound prescriptions with the effects of replenishing Qi and activating blood， warming Yang and tonifying Qi， and eliminating stasis and resolving phlegm are often used to treat IPF. Modern pharmacological studies have shown that such medicines play a positive role in inhibiting macrophage polarization， restoring redox balance， inhibiting EMT， and regulating cell autophagy. However， few studies report how Chinese medicines regulate the pathways in the treatment of IPF. By reviewing the latest articles in this field， we elaborate on the pathogenesis of IPF and provide a comprehensive overview of the mechanism of the active ingredients or compound prescriptions of Chinese medicines in regulating IPF. Combining the pathogenesis of IPF with the modulating effects of Chinese medicines， we focus on exploring systemic treatment options for IPF， with a view to providing new ideas for the in-depth study of IPF and the research and development of related drugs.

Jasmonic acid (JA), a plant endogenously synthesized lipid hormone, plays an important role in response to stress. This manuscript summarized the biosynthesis and metabolism of JA and its related regulatory mechanisms, as well as the signal transduction of JA. The mechanism and regulatory network of JA in plant response to biotic and abiotic stresses were systematically reviewed, with the latest advances highlighted. In addition, this review summarized the signal crosstalk between JA and other hormones in regulating plant resistance to various stresses. Finally, the problems to be solved in the study of plant stress resistance mediated by JA were discussed, and the application of new molecular biological technologies in regulating JA signaling to enhance crop resistance was prospected, with the aim to facilitate future research and application of plant stress resistance.
Signal Transduction ; Cyclopentanes ; Oxylipins ; Plant Growth Regulators

The column chromatography and semi-preparative liquid phase chromatography with several chromatographic packing materials, including macroporous adsorbent resin, silica gel, ODS, and Sephadex LH-20, were used for the separation and purification of n-butanol-soluble portion of ethanol extract of Leonurus japonicus Houtt. The structures of isolates were identified by HR-MS, IR, NMR, and acid hydrolysis reaction. Six phenylethanol glycosides were obtained from L. japonicus and identified as leonoside G (1), leonoside E (2), leonoside B (3), leonoside F (4), cistanoside G (5), and salidroside (6). Compound 1 is a new phenylethanol glycoside.

Objective To investigate the effects of probiotics combined with dietary intervention on pe-ripheral blood glucose and lipid metabolism indicators,placental tissue insulin signaling pathway proteins ex-pression and pregnant outcome in the patients with gestational diabetes mellitus(GDM).Methods A total of 83 patients with GDM in this hospital from December 2021 to December 2022 were selected as the study sub-jects and divided into the probiotics group(probiotics combined with diet intervention,43 cases)and control group(simple diet intervention,40 cases)by the random number table method.The levels of peripheral blood glucose,lipid and insulin resistance related indicators before the intervention and in 8 weeks after the interven-tion were compared between the two groups.The histological changes of placenta were observed by HE stai-ning.The pathological indicators were compared between the two groups.The expression levels of insulin re-ceptor substrate-1(IRS-1),glucose transporter 4(GLUT4)and synaptosome-associated protein of 23 kDa(SNAP23)in placental tissue were detected by immunohistochemistry.The pregnant adverse outcomes were compared between the two groups,and the clinical efficacy of probiotics was evaluated.Results Compared with the control group,the levels of fasting blood glucose(FBG),fasting insulin(FINS),serum triglyceride(TG)and low density lipoprotein cholesterol(LDL-C)in 8 weeks after intervention in the probiotics group were significantly decreased(P＜0.05),and the level of serum high density lipoprotein cholesterol(HDL-C)was significantly increased(P＜0.05).There were no significant differences in the incidence rates of poor villi maturation,thickening of dry villi arterioles and capillary filling in villi interstitial between the two groups(P＞0.05).Compared with the control group,the expression levels of IRS-1,GLUT4 and SNAP23 in placen-tal tissue of the probiotics group were significantly increased(P＜0.05).The incidence rates of neonatal hy-poglycemia and neonatal hyperbilirubinemia in the probiotics group were significantly lower than those in the control group(P＜0.05).Conclusion Compared with simple dietary intervention,probiotics combined with dietary intervention has more advantages in improving glucose and lipid metabolism of GDM patients,moreo-ver reduces the adverse events occurrence in newborns.

Objective To investigate the effects of microRNA(miR)-30a-regulated MAPK pathway on the formation of intercalation,inflammatory factors and vasoconstriction in a rat model of aortic coarctation.Methods Fifty SD rats were selected to establish the rat model of aortic coarctation,and were randomly divided into control group,model group,miR-NC group,miR-30a group and miR-30a inhibitor group,10 rats in each group.Histopathological changes in the aortic tissue and changes in the elastic fibers and collagen fibers of the aortic mesothelium were observed;The expression of miR-30a,systolic blood pressure before and after the intervention and the expression of serum inflammatory factors in each group were measured by PCR,tail artery manometry and ELISA;Matrix metalloproteinase(MMP)-6,MMP-2 protein expression and MAPK pathway were measured by Western blotting in each group.The expression of MMP-6,MMP-2 and MAPK pathway related proteins were measured by Western blotting.Results The miR-30a inhibitor group improved the degree of vessel wall tearing and disorganized internal arterial wall arrangement;The miR-30a group improved vascular remodeling;miR-30a expression was higher in the model group compared with the control group,and lower in the miR-30a group and miR-30a inhibitor group compared with the miR-NC group,P<0.05;Before the intervention,the difference in systolic blood pressure between the groups compared was not statistically significant,P>0.05;Compared with the control group,systolic blood pressure was higher in the model group,higher expression in the miR-30a group and lower expression in the miR-30a inhibitor group compared with the miR-NC group,P<0.05;compared with the control group,tumor necrosis factor(TNF)-α,interleukin(IL)-6,IL-1β expression was higher in the model group,higher expression in the miR-30a group compared with the miR-NC group,lower expression in the miR-30a inhibitor group,P<0.05;higher expression of TNF-α,MMP-6,MMP-2,Ras,Raf,P38 MAPK,ERK1/2 proteins in the model group compared with the control group,higher expression in the miR-30a group compared with the miR-NC group,lower expression in the miR-30a inhibitor group,P<0.05.Conclusion MiR-30a is involved in the process of aortic coarctation formation,inflammatory response,and regulation of aortic coarctation vascular remodeling,possibly through regulation of the MAPK signaling pathway.

Objective Based on the theory of"lung governs the skin and hair"in"Yellow Emperor's Inner Classic",this paper analyzes the medication rules of whitening and freckle-removing.The aim of this study is to provide reference for the clinical practice of traditional Chinese medicine(TCM)theory and the medication in TCM cosmetics.Methods"Chinese Medical Classics"was used to search the records of whitening and freckle-related drugs.The frequency,nature,flavor,meridian tropism and compatibility laws of TCM for whitening and freckle-removal were analyzed by statistics and association rules.The network pharmacology research was used to analyze the whitening and freckle-removing effects and mechanisms of high-frequency drugs.Then,the potential active ingredients were analyzed.The whitening and anti-freckle effect was verified through cytotoxicity experiments and melanin content detection.Results A total of 171 external prescriptions were selected in eligible articles,including 261 Chinese medicinals,most of which were pungent and belong to the lung meridian.The most frequently used Chinese medicinals was"Erbai Yixin"(EBYX,Angelicae Dahuricae Radix,Typhonii Rhizoma,Asari Radix et Rhizoma).Network pharmacological analysis showed that the core targets of EBYX for whitening and removing freckles are TP53,EGFR,ALB,etc.,which are mainly involved in oxygen perception and response,skin immune regulation,skin cell growth,differentiation,stress,inflammatory response,and other biological processes.Based on the results of molecular docking,biological analysis proved that the active ingredients of EBYX are chrysophanol,gallic acid and caffeic acid,which have inhibitory effects on the proliferation of melanoma cells and melanin production.Conclusion Most of the ancient prescriptions for whitening and removing freckles are pungent and belong to the lung meridian,which embodies the theory of"lung governs the skin and hair".The high-frequency drug EBYX may play a role by regulating skin redox,immunity and inflammation.The active ingredients of EBYX have an inhibitory effect on melanin formation.This study enriches the scientific connotation of TCM whitening and freckle-removing prescriptions based on the theory of"lung governs the skin and hair",realizes interdisciplinary integration and provides support for the modernization of TCM.