Objective:To discuss the causal association between sterol esters and intrahepatic duct,biliary tract,and gallbladder malignancies using two-sample Mendelian randomization(MR)analysis,and to clarify the biological mechanisms of sterol esters,and to provide the a basis for early prevention and treatment of these malignancies.Methods:The instrumental variable data for 15 different types of sterol ester traits were obtained from the Finnish database(FinnGen).The genome-wide association study(GWAS)data for intrahepatic duct,biliary tract,and gallbladder malignancies were retrieved from the GWAS database using the keywords"sterol ester"and"intrahepatic duct,biliary tract,and gallbladder malignancies"(accession numbers:ICD-O-3 and GCST90277238-GCST9027725).The inverse-variance weighted(IVW)method,MR-Egger regression,and weighted median(WM)method were used to assess the causal association between sterol esters and the risk of these malignancies.Pleiotropy was tested using the MR-Egger intercept method;heterogeneity was evaluated using Cochran's Q test;and sensitivity analysis was performed using the leave-one-out approach to comprehensively assess the reliability and robustness of the results.Results:The IVW analysis results showed that Sterol ester(27:1/14:0)odds ratio(OR)=2.349,95%confidence interval(CI)=1.371-4.025,P=0.002),Sterol ester(27:1/16:0)(OR=1.248,95%CI=1.018-1.523,P=0.033),Sterol ester(27:1/18:2)(OR=1.361,95%CI=1.078-1.718,P=0.009),and Sterol ester(27:1/22:6)(OR=1.339,95%CI=1.001-1.791,P=0.049)were associated with an increased risk of intrahepatic duct,biliary tract,and gallbladder malignancies.The MR-Egger regression analysis results indicated that Sterol ester(27:1/18:2)(OR=2.038,95%CI=1.337-3.105,P=0.011)was a risk factor for these malignancies.The WM analysis results revealed that Sterol ester(27:1/14:0)(OR=2.786,95%CI=1.419-5.468,P=0.003)and Sterol ester(27:1/18:2)(OR=1.548,95%CI=1.148-2.088,P=0.004)were also risk factors.The MR-Egger intercept analysis and Cochran's Q test results indicated no significant horizontal pleiotropy or heterogeneity.The leave-one-out sensitivity analysis did not identify any influential outlier single nucleotide polymorphism(SNPs),confirming the reliability of the study.Conclusion:Sterol ester(27:1/14:0),Sterol ester(27:1/16:0),Sterol ester(27:1/18:2),and Sterol ester(27:1/22:6)exhibit causal associations with intrahepatic duct,biliary tract,and gallbladder malignancies and may promote their development.

Objective To investigate differential patterns of oxygenated hemoglobin concentration in prefron-tal cortical regions between major depressive disorder patients with or without psychotic symptoms during verbal flu-ency task(VFT)performance using functional near-infrared spectroscopy(fNIRS).Methods A total of 108 pa-tients with major depression who were hospitalized in the psychiatric department of the hospital from July 2023 to April 2024 were selected as the study objects.They were divided into two groups(n=60)with or without psychotic symptoms(n=48).fNIRS devices were used to measure and compare the changes in the relative concentration of cerebral hemoglobin in 52 brain channels between the two groups during VFT.Re-sults Compared with the unaccompanied group,the relative concentration of cerebral oxygenated hemoglobin in channel 13 was higher(0.003±0.001 vs.0.002±0.001),and the relative concentration of cerebral oxygen-ated hemoglobin in channel 33 was lower(0.003±0.001 vs.0.007±0.002),the difference was statistically significant(P＜0.05).There was no significant difference in the relative concentration of oxygenated hemo-globin in other brain areas between the two groups(P＞0.05).Conclusion There are abnormal oxygen activ-ity in brain functional areas associated with psychotic symptoms,and fNIRS technique is helpful for early as-sessment of cerebral aerobic function in depressed patients with psychotic symptoms.

Objective To evaluate the effect of dapagliflozin on myocardial function in early spontaneously hypertensive rats(SHR)with layer-specific global longitudinal strain(GLS).Methods A total of 45 male SHR aged 6 weeks were randomly divided into control group(normal saline),dapagliflozin group[1 mg/(kg·day)],and losartan group[10 mg/(kg·day)].Fifteen male Wistar-Kyoto(WKY)rats at same age with normal blood pressure were subjected and served as blank control group.During 8 weeks of intervention,systolic blood pressure(SBP)was measured,and conventional echocardiography and two-dimensional speckle tracking echocardiography(2DSTE)were performed and the results were collected to acquire the longitudinal strain of each layer of left ventricular(LV)myocardium.The parameters were compared among the groups.The pathological changes of myocardium were observed in each group of rats.Results Compared with the WKY group,LV ejection fraction(LVEF)and LV fraction shortening(LVFS)at week 8 were decreased in the control group(P＜0.05),but no such decreases were observed in the dapagliflozin group and the losartan group.The GLS of endo-myocardium(GLSendo)at the 6th week was decreased,and GLSendo,GLSmid and GLSepi at the 8th week were all decreased in the control group than the WKY group(all P＜0.05).But there were no statistical differences in the above 3 indicators in the dapagliflozin and losartan groups when compared with the WKY group(all P＞0.05).The pathological results showed that myocardial interstitial fibrosis was observed in the control group at the 6th week.Conclusion Dapagliflozin can effectively improve myocardial function in early SHR.

Chronic atrophic gastritis （CAG）， a common digestive system disease， has an unclear pathogenesis. Currently， it is mostly believed to be related to Helicobacter pylori （Hp） infection， immune factors， dietary factors， bile reflux， long-term use of antibiotics and anti-inflammatory drugs， and other factors. Ferroptosis is a regulated cell death mechanism that is iron-dependent and characterized by disruption of iron metabolism and accumulation of lipid peroxides. More and more studies have found that ferroptosis is closely related to the onset of CAG. Professor LI Diangui， a master of traditional Chinese medicine， first proposed the turbid toxin theory， which holds that spleen deficiency and turbid toxin is the main pathogenic mechanism of CAG. Abnormal iron metabolism regulation is a prerequisite for the accumulation of turbid toxin in CAG， and ferroptosis is in accordance with the pathogenic mechanism （spleen deficiency and turbid toxin） of CAG. This article explores the pathological mechanism of spleen deficiency and turbid toxin in CAG from the perspectives of iron metabolism， oxidative stress， and lipid peroxidation， providing theoretical support of traditional Chinese medicine for the modern research on CAG. It enriches the modern scientific connotation of the turbid toxicity theory and provides new ideas and breakthrough points for the clinical treatment of CAG.

Chronic atrophic gastritis （CAG）， a common digestive system disease， has an unclear pathogenesis. Currently， it is mostly believed to be related to Helicobacter pylori （Hp） infection， immune factors， dietary factors， bile reflux， long-term use of antibiotics and anti-inflammatory drugs， and other factors. Ferroptosis is a regulated cell death mechanism that is iron-dependent and characterized by disruption of iron metabolism and accumulation of lipid peroxides. More and more studies have found that ferroptosis is closely related to the onset of CAG. Professor LI Diangui， a master of traditional Chinese medicine， first proposed the turbid toxin theory， which holds that spleen deficiency and turbid toxin is the main pathogenic mechanism of CAG. Abnormal iron metabolism regulation is a prerequisite for the accumulation of turbid toxin in CAG， and ferroptosis is in accordance with the pathogenic mechanism （spleen deficiency and turbid toxin） of CAG. This article explores the pathological mechanism of spleen deficiency and turbid toxin in CAG from the perspectives of iron metabolism， oxidative stress， and lipid peroxidation， providing theoretical support of traditional Chinese medicine for the modern research on CAG. It enriches the modern scientific connotation of the turbid toxicity theory and provides new ideas and breakthrough points for the clinical treatment of CAG.

Objective:To compare the efficacy and safety of crisaborole ointment 2% versus pimecrolimus cream 1% in the treatment of mild to moderate atopic dermatitis in children aged 2 years or older.Methods:A multicenter, randomized, open-label, controlled clinical trial was conducted. A total of 120 pediatric patients aged 2 - 17 years with mild to moderate atopic dermatitis were enrolled from departments of dermatology of 8 hospitals in China between March 2022 and February 2023. The participants were randomly assigned in a 1∶1 ratio to the crisaborole group and the pimecrolimus group, and received the treatment with crisaborole ointment 2% and pimecrolimus cream 1% respectively, twice a day for 4 weeks. Visits were scheduled at baseline/on day 1, as well as on days 8, 15, and 29. The primary efficacy outcome was the percentage of patients achieving the Investigator's Static Global Assessment (ISGA) success (defined as clear [0] or almost clear [1] on the ISGA scale, combined with ≥ 2‐grade improvement from baseline) on day 29. The secondary efficacy outcomes included changes in the Eczema Area and Severity Index (EASI) total scores from baseline to day 29, percentages of patients achieving ISGA improvement (defined as clear [0] or almost clear [1] on the ISGA scale), as well as changes in the Peak Pruritus Numerical Rating Scale (NRS) scores, Dermatology Life Quality Index (DLQI) /Infants' Dermatology Life Quality Index (IDLQI) /Children's Dermatology Life Quality Index (CDLQI) scores, and in the Dermatitis Family Impact (DFI) scores. Drug safety was evaluated according to the incidence of adverse events. Categorical data were compared using the chi-square test. Since measurement data did not follow a normal distribution, the rank sum test was used for comparisons of measurement data between groups.Results:A total of 106 children with mild to moderate atopic dermatitis were included in the per-protocol analysis set, with 52 in the crisaborole group (26 males and 26 females) and 54 in the pimecrolimus group (27 males and 27 females). There were no significant differences in age, disease duration, ISGA and EASI scores at baseline between the two groups (all P > 0.05). On day 29, 22 patients (42.31%) in the crisaborole group and 25 (46.30%) in the pimecrolimus group achieved ISGA success, with no significant difference between the two groups ( χ2 = 0.17, P = 0.68) ; 35 patients (67.31%) in the crisaborole group and 45 (83.33%) in the pimecrolimus group achieved ISGA improvement, also with no significant difference between the two groups ( χ2 = 3.68, P = 0.06) ; additionally, there were no significant differences in the EASI, pruritus NRS, DLQI/IDLQI/CDLQI, or DFI scores between the two groups (all P > 0.05). Adverse reactions to the two topical agents were mainly local reactions such as mild to moderate pain, itching, or worsening of itching, and no obvious systemic adverse reactions occurred. The incidence of drug-related adverse reactions was 46.15% (24 cases) in the crisaborole group and 37.04% (20 cases) in the pimecrolimus group, with no significant difference between the two groups ( χ2 = 0.91, P = 0.34) . Conclusion:The efficacy of crisaborole ointment 2% was comparable to that of pimecrolimus cream 1% in the treatment of mild to moderate atopic dermatitis in children aged ≥ 2 years, and it yielded early and rapid improvement in the quality of life of patients and their families, with good safety and tolerability profiles.

Objective To develop an exercise rehabilitation program for the patients with upper limb lymphedema in order to provide standardised guidance for specialised management and nursing practice,and to promote the recovery of patients.Methods With the evidence-based methods,domestic and international literaturs were retrieved and the quality of the papers was evaluated.A research team was established to discuss and draft an initial version of the rehabilitation program for the patients with upper limb lymphedema.Delphi method was used to conduct two rounds of consultation with 15 experts in lymphedema between June and September 2023.According to the expert opinions,the exercise rehabilitation program for patients with upper limb lymphedema was finalised after screening and modification of the indicators.Results The final version of the exercise rehabilitation program for patients with upper limb lymphedema includes four tier-1 indicators(routine upper limb rehabilitation exercises,aerobic exercise,anti-resistance exercise and respiratory training),15 tier-2 indicators,and 33 tier-3 indicators.The positive response rate in both rounds of expert consultation was 100.00%,with the authority coefficient at 0.95.In the second round of expert consultation,it was founds that the importance of tier-3 indicators was from 3.93 to 5.00,with the rationality from 4.13 to 5.00 and the feasibility from 3.53 to 4.93.The coefficient of variation in tier-1 and tier-2 indicators was 0.00-0.17 and 0.07-0.23,respectively.The coefficients of variation of per tier-3 indicator in importance,rationality and feasibility were from 0.00 to 0.22,0.00 to 0.22 and 0.05 to 0.22,respectively.The Kendall's coefficient of concordance(W)for tier-1 and tier-2 indicators was 0.490 and 0.387,respectively.The Kendall's W of per tier-3 indicator in importance,rationality and feasibility was 0.427,0.311 and 0.530,respectively,with statistically significant differences(P<0.001).Conclusion The exercise rehabilitation program developed in this study is scientific,comprehensive and highly targeted.It provides a theoretical basis and practical guidance for exercise rehabilitation and nursing care of the patients with upper limb lymphedema.

The precise and rapid monitoring of multiple organ dysfunction is crucial in drug discovery. Traditional methods, such as pathological analysis, are often time-consuming and inefficient. Here, we developed a multiplexed near-infrared window two (NIR-II) fluorescent bioimaging method that allows for real-time, rapid, and quantitative assessment of multiple organ dysfunctions. Given that existing probes did not fully meet requirements, we synthesized a range of NIR-II hemicyanine dyes (HDs) with varying absorption and emission wavelengths. By modifying these dyes, we achieved high spatial and temporal resolution imaging of the liver, kidneys, stomach, and intestines. This method was further applied to investigate disorders induced by cisplatin, a drug known to cause gastric emptying issues along with liver and kidney injuries. By monitoring the metabolic rate of the dyes in these organs, we accurately quantified multi-organ dysfunction, which was also confirmed by gold-standard pathological analysis. Additionally, we evaluated the effects of five aristolochic acids (AAs) on multiple organ dysfunction. For the first time, we identified that AA-I and AA-II could cause gastric emptying disorders, which was further validated through transcriptomics analysis. Our study introduces a novel approach for the simultaneous monitoring of multi-organ dysfunction, which may significantly enhance the evaluation of drug side effects.

Computational analysis can accurately detect drug-gene interactions (DGIs) cost-effectively. However, transductive learning models are the hotspot to reveal the promising performance for unknown DGIs (both drugs and genes are present in the training model), without special attention to the unseen DGIs (both drugs and genes are absent in the training model). In view of this, this study, for the first time, proposed an inductive learning-based model for the precise identification of unseen DGIs. In our study, by integrating disease nodes to avoid data sparsity, a multi-relational drug-disease-gene (DDG) graph was constructed to achieve effective fusion of data on DDG intro-relationships and inter-actions. Following the extraction of graph features by utilizing graph embedding algorithms, our next step was the retrieval of the attributes of individual gene and drug nodes. In this way, a hybrid feature characterization was represented by integrating graph features and node attributes. Machine learning (ML) models were built, enabling the fulfillment of transductive predictions of unknown DGIs. To realize inductive learning, this study generated an innovative idea of transforming known node vectors derived from the DDG graph into representations of unseen nodes using node similarities as weights, enabling inductive predictions for the unseen DGIs. Consequently, the final model was superior to existing models, with significant improvement in predicting both external unknown and unseen DGIs. The practical feasibility of our model was further confirmed through case study and molecular docking. In summary, this study establishes an efficient data-driven approach through the proposed modeling, suggesting its value as a promising tool for accelerating drug discovery and repurposing.

OBJECTIVE To observe the characteristics of outer membrane vesicles(OMVs)of 1 strain of hypervir-ulent Klebsiella pneumoniae(hvKp)11492.METHODS The hvKp11492,one of major clones of hvKp that were i-solated from patients with bloodstream infection in the First Medical Center of Chinese PLA General Hospital,was chosen as the research subject.The strain was identified by means of matrix-assisted laser desorption/ioniza-tion time of flight mass spectrometry and whole genome sequencing.The hvKp1 1492-OMVs were separated and purified by high speed centrifugation in combination with polymer precipitation,the morphology and particle size of the hvKp11492-OMVs were identified by transmission electron microscopy(TEM)and nanoparticle tracking a-nalysis(NTA),the proteomic characteristics were analyzed through bicinchoninic acid assay(BCA)and liquid chromatography-mass spectrometry(LC-MS)series technique,and the virulence genes were detected by PCR.RESULTS The hvKp11492-OMVs were displayed differently in size,round or oval,and complete double-layer membrane vesicles on TEM.The result of NTA showed that the average particle size of the hvKp1 1492-OMVs was 270 nm.The protein content of hvKp11492-OMVs was(2.448±0.975)μg/μl.The result of subcellular lo-calization indicated that the protein included plasmosin,intracellular membrane protein,periplasmic protein,ex-tracellular membrane protein and nuclear region protein,which were found,by the annotation of GO database,to participate in the biological processes such as oxidation-reduction,interpretation,and metabolism.The hvKp11492-OMVs contained various proteins such as GDP-L-fucose synthetase,iron ion transporter protein and ferritin that were associated with pathogenicity.In addition,the hvKp1 1492-OMVs carried with iutA,iroN,iucA and rmpA virulence genes.CONCLUSIONS The morphologic characteristics,size and proteomic characteris-tics of the hvKp11492-OMVs are identified in the study.It is concluded that the hvKp11492-OMVs carry with va-rious proteins and genes that are association with the virulence and pathogenicity.