Esophageal cancer （EC） is a highly prevalent malignant tumor in China. The phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway， as one of the key oncogenic pathways， can promote the cell cycle progression， proliferation， migration， and invasion， induce chemoresistance， and inhibit apoptosis and autophagy of EC cells. Traditional Chinese medicine （TCM）， with the advantages of targeting multiple points with multiple components to delay cancer progression， can target the PI3K/Akt signaling pathway for EC treatment. This article preliminarily discusses the molecular mechanism and role of the PI3K/Akt signaling pathway in EC and elaborates on the specific targets and efficacy of TCM in treating EC through intervention in the PI3K/Akt signaling pathway in the past five years. TCM materials and extracts inhibiting the PI3K/Akt signaling pathway in EC include Borneolum， spore powder of Ganoderma lucidum without spore coat， extract of Celastrus orbiculatus， root extract of Taraxacum， and Bruceae Fructus oil emulsion. TCM active ingredients exerting the effect include flavonoids， terpenoids， saponins， phenols， polysaccharides， alkaloids， and other compounds. TCM compound prescriptions with such effect include Qige San， Huqi San， Xuanfu Daizhetang， Tongyoutang and its decomposed prescriptions， Liujunzi Tang， and Xishenzhi Formula. In addition， TCM injections such as Compound Kushen Injection and Kang'ai injection also inhibit the PI3K/Akt signaling pathway in EC. This paper summarizes the role of the PI3K/Akt signaling pathway in EC and the TCM interventions， aiming to provide reference for the research and clinical application of new drugs for EC.

ObjectiveTo construct a multifunctional liposomal delivery system by replacing cholesterol（Chol） in conventional liposomes with saikosaponin D（SSD） and modifying with poloxamer 407（P407） for co-delivery of curcumin（Cur）. The system was evaluated for in vivo tumor targeting and inhibitory effects on mouse subcutaneous solid tumors. MethodsSingle-factor and orthogonal tests combined with information entropy weighting were used to optimize the formulation process of the liposome with encapsulation efficiency and absolute Zeta potential as indexes， and validation studies and liposomal characterization were performed. A subcutaneous solid tumor model was established by injecting H22 hepatocellular carcinoma cells subcutaneously into the dorsal surface of the right forelimb of mice. DiR-loaded traditional Chol liposomes（P407-DiR-Chol-LPs， PDCL） and novel SSD-based liposomes（P407-DiR-SSD-LPs， PDSL） were prepared by the optimized formulation process， and tail vein injection was performed to investigate the impact of SSD on liposome tumor targeting with small animal in vivo imaging. Mice were randomly divided into eight groups， including blank group， model group， free doxorubicin（DOX） group（2 mg·kg^-1）， free Cur group（8 mg·kg^-1）， free SSD group（10 mg·kg^-1）， P407-Cur-Chol-LPs（PCCL） group， P407-SSD-LPs（PSL） group， and P407-Cur-SSD-Lps（PCSL） group. Treatments were administered intraperitoneally every other day for seven doses. Antitumor efficacy and biocompatibility were evaluated by monitoring body weight change， organ indices， tumor volume and mass， relative tumor proliferation rate（T/C）， and tumor growth inhibition rate（TGI）. Histopathological analysis of liver， kidney， and tumor tissues was performed using hematoxylin-eosin（HE） staining. Serum levels of aspartate aminotransferase（AST）， alanine aminotransferase （ALT）， blood urea nitrogen（BUN）， and creatinine（Crea）in mice were quantified by fully automated biochemical analyzer. ResultsOrthogonal test yielded optimal ratios of Cur， SSD， and P407 to soybean phosphatidylcholine（SPC） as 1∶25， 1∶20， and 1∶4. The optimized PCSL exhibited spherical morphology with a particle size of 179.15 nm， a Zeta potential of -47.25 mV， and an encapsulation efficiency of 96.40%. Its in vitro release profile conformed to first-order kinetics， demonstrating excellent storage stability and hemocompatibility. In vivo imaging revealed that the fluorescence signal in tumor tissues and the fluorescence intensity ratio between tumors and organs were significantly higher in the PDSL group than in the PDCL group（P<0.05， P<0.01）. Among the treatment groups， PCSL group showed superior efficacy over free Cur group， free SSD group， PCCL group， and PSL group， with TGI>40% and T/C<60%， indicating pronounced anti-hepatocellular carcinoma effects（P<0.05， P<0.01）. Histopathology and serum biochemistry indicated minimal hepatorenal toxicity and improved hepatic and renal function in PCSL-treated mice. ConclusionReplacing Chol with SSD in preparing multifunctional drug delivery systems not only stabilizes liposomes but also yields superior anti-hepatocellular carcinoma efficacy， achieving the effect of drug-excipient integration. Co-delivery of Cur via this system can be used for treating subcutaneous solid tumors in hepatocellular carcinoma， providing new insights and technical approaches for anti-hepatocellular carcinoma research and the meridian-guiding and messenger-directing theory in traditional Chinese medicine.

From the perspective of state differentiation and treatment， it is believed that the pathogenesis of acute respiratory distress syndrome （ARDS） is that evil poisons injured the lungs， and the lung qi suddenly collapsed， then blocked and exhausted， and the qi failure to control blood and liquid， then the fluids overflow outside the vessels， and damp phlegm， stasis， and toxins became knotted up in the body， which ultimately leads to qi dysfunction， and a series of symptom arise， so qi impairment is the principal mechanism of ARDS. A combination of Chinese and Western medicine was proposed to treat ARDS by combining tangible qi and intangible qi， using Chinese herbal medicine to boost qi and relieve collapse， percolate and drain dampness with bland medicinals， resolve toxins and dissolve stasis， and regulate qi， and combining with Western medicine to assist qi circulation to improve qi's consolidation， propulsion， and transformation， so as to make the evil qi go away， the positive qi restored， the viscera qi circulated， qi， blood， yin， and yang connected， and the activities of life maintained， and thus to achieve the goal of treating ARDS by integrated Chinese medicine and Western medicine.

Background:Previous studies have proved that neutrophil gelatinase-associated lipocalin(NGAL)plays an important role in the progression of Crohn's disease(CD),and may serve as a potential biomarker for disease activity prediction,severity assessment,treatment response evaluation and prognosis monitoring.However,the diagnostic value of NGAL in perianal fistulizing Crohn's disease(pfCD)is still unclear.Aims:To investigate the serum level of NGAL and its diagnostic value in patients with active pfCD.Methods:A total of 66 patients diagnosed as pfCD from July 2021 to June 2023 at Longhua Hospital,Shanghai University of Traditional Chinese Medicine were enrolled,including 36 active pfCD patients and 30 inactive pfCD patients.The disease activity and perianal fistula activity were assessed by Crohn's disease activity index(CDAI)and perianal disease activity index(PDAI),respectively.Serum NGAL,fecal calprotectin(FC),C-reactive protein(CRP),erythrocyte sedimentation rate(ESR),as well as CDAI score and PDAI score were compared between the active and inactive pfCD patients,and the correlations of NGAL with the other parameters in active pfCD patients were analyzed.ROC curve was drawn to evaluate the values of serum NGAL,FC,CRP and ESR for diagnosis of active pfCD.Results:The serum NGAL,FC,CRP,ESR,CDAI score and PDAI score in active pfCD patients were significantly higher than those in inactive pfCD patients(all P＜0.001).NGAL was positively correlated with FC(r=0.64,P＜0.001),CRP(r=0.55,P＜0.001),ESR(r=0.53,P＜0.001),CDAI score(r=0.59,P＜0.001)and PDAI score(r=0.54,P＜0.001)in active pfCD patients.The optimal cut-off values of NGAL,FC,CRP and ESR were 220.5 μg/L,146.0 μg/g,7.9 mg/L and 23.5 mm/h,respectively,for the diagnosis of active pfCD,and the area under the curve were 0.922(95％CI:0.850-0.995),0.888(95％CI:0.806-0.970),0.853(95％CI:0.763-0.944)and 0.830(95％CI:0.731-0.930),respectively.Conclusions:Serum NGAL level is associated with the disease activity of pfCD,and can be used as a non-invasive biomarker for the clinical diagnosis of active pfCD.

Objective To investigate the effect of trehalose(Tre)H9C2 cardiomyocytes under oxy-gen-glucose deprivation/reoxygenation(OGD/R)injury and its mechanism of action with the cel-lular model simulating the process of myocardial ischemia/reperfusion injury.Methods H9C2 cells were divided control group,OGD/R group,Tre group(OGD/R+Tre),and combination group(OGD/R+Tre+ML385).MTT assay was used to observe cell proliferation,and lactate de-hydrogenase(LDH)release and Hoechst/propidium iodide staining were employed to evaluate cell membrane damage.Western blot analysis was utilized to detect the expression of nuclear fac-tor erythroid 2-related factor 2(Nrf2)and its downstream related proteins.The generation of re-active oxygen species(ROS)and mitochondrial membrane potential(MMP)were measured to quantify the level of oxidative stress.The expression of apoptosis-related proteins was determined by Western blot analysis.Results In comparison to the control group,the OGD/R group exhibi-ted a significantly reduced cell viability.When compared with the OGD/R group,the intervention of varying concentrations of Tre obviously improved cell viability in a dose-dependent manner(P＜0.01),increased MMP,and up-regulated the expression of glutathione(GSH),Nrf2,hemeo-xygenase 1,and nicotinamide adenine dinucleotide phosphate quinone oxidoreductase 1(NQO1),Bcl-2,and cysteinyl aspartate specific proteinase 3(Caspase-3)(P＜0.05,P＜0.01),and decreased the production of ROS and MDA and the expression of responding element binding protein 1,Bax,Bax/Bcl-2,and cleaved Caspase-3(P＜0.05,P＜0.01).What's more,the combined group ex-hibited significantly higher production of ROS,MDA,increased mRNA levels of TNF-α,IL-1β,and IL-6,and reduced MMP and GSH levels(P＜0.05,P＜0.01),as well as,enhanced expression of Bax,Bax/Bcl-2,and cleaved Caspase-3(1.77±0.08 vs 1.20±0.20,3.41±1.45 vs 0.99±0.15,4.10±1.05 vs 1.79±0.52,P＜0.01),and decreased expression of Bcl-2 and Caspase-3(0.58±0.21 vs 1.23±0.25,0.87±0.25 vs 1.45±0.31,P＜0.01)in comparison with the Tre group.Conclusion Tre can be regarded as an Nrf2 activator that inhibits oxidative stress and apoptosis by activating Nrf2,and thereby ameliorates OGD/R-induced cardiomyocyte injury.

Objective:To evaluate the effect of trehalose on oxygen-glucose deprivation and restoration (OGD/R) injury in H9C2 cells and the role of solute carrier family 7 member 11- (SLC7A11)-glutathione peroxidase 4 (GPX4) signaling pathway.Methods:Well-grown H9C2 cells were divided into 4 groups ( n=24 each) by the random number table method: control group (group C), OGD/R group (group O), OGD/R+ trehalose group (group OT) and OGD/R+ trehalose+ erastin group (group OTE). The cells were normally cultured in group C. In O, OT and OTE groups, the DMEM medium was replaced with EBSS medium, the cells were exposed to 5% CO 2-95% N 2 in an incubator at 37 ℃ for 6 h, and then the medium was replaced with DMEM medium supplemented with 6% fetal bovine serum to restore oxygen and glucose supply for 24 h. In group OT, trehalose at a final concentration of 50 mmol/L was added during restoration of oxygen and glucose supply. In group OTE, the SLC7A11 inhibitor erastin at a final concentration of 10 μmol/L was added at 8 h before oxygen-glucose deprivation, and trehalose at a final concentration of 50 mmol/L was added during restoration of oxygen and glucose supply. The cell viability, lactic dehydrogenase (LDH) activity, contents of glutathione (GSH), malondialdehyde (MDA) and iron, and reactive oxygen species (ROS) levels were measured at 24 h of restoration of oxygen and glucose supply. The expression of SLC7A11, GPX4, long-chain fatty acyl coenzyme A synthetase 4 (ACSL4), and ferritin heavy chain 1 (FTH1) was detected by Western blot. The structure of the mitochondrial morphology was observed with a transmission electron microscope. Results:Compared with group C, the cell viability and GSH content were significantly decreased, the LDH activity, contents of MDA and iron, and ROS level were increased, the expression of SLC7A11, GPX4 and FTH1 was down-regulated, and the expression of ACSL4 was up-regulated in group O ( P<0.05). Compared with group O, the cell viability and GSH content were significantly increased, the LDH activity, contents of MDA and iron, and ROS level were decreased, the expression of SLC7A11, GPX4 and FTH1 was up-regulated, and the expression of ACSL4 was down-regulated in group OT ( P<0.05). Compared with group OT, the cell viability and GSH content were significantly decreased, the LDH activity, contents of MDA and iron, and ROS levels were increased, the expression of SLC7A11, GPX4 and FTH1 was down-regulated, and the expression of ACSL4 was up-regulated in group OTE ( P<0.05). Conclusions:Trehalose can inhibit ferroptosis by activating the SLC7A11-GPX4 signaling pathway, thereby attenuating OGD/R injury in H9C2 cells.

Here,a styrene-based polymer monolithic column poly(VBS-co-TAT-co-AHM)with reversed-phase/hydrophilic interaction liquid chromatography(RPLC/HILIC)bifunctional separation mode was success-fully prepared for capillary electrochromatography by the in situ polymerization of sodium p-styrene sulfonate(VBS)with cross-linkers 3-(acryloyloxy)-2-hydroxypropyl methacrylate(AHM)and 1,3,5-triacryloylhexahydro-1,3,5-triazine(TAT).The preparation conditions of the monolith were optimized.The morphology and formation of the poly(VBS-co-TAT-co-AHM)monolith were confirmed by scanning electron microscopy(SEM)and Fourier transform infrared spectroscopy(FT-IR).The separation perfor-mances of the monolith were evaluated systematically.It should be noted that the incorporation of VBS functional monomer can provide π-π interactions,hydrophilic interactions,and ion-exchange in-teractions.Hence,the prepared poly(VBS-co-TAT-co-AHM)monolith can achieve efficient separation of thiourea compounds,benzene series,phenol compounds,aniline compounds and sulfonamides in RPLC or HILIC separation mode.The largest theoretical plate number for N,N'-dimethylthiourea reached 1.7×105 plates/m.In addition,the poly(VBS-co-TAT-co-AHM)monolithic column showed excellent reproducibility and stability.This novel monolithic column has great application value and potential in capillary electrochromatography(CEC).

Objective:To verify the efficacy and safety of daily oral minodronate in postmenopausal women with established osteoporosis.Methods:In this randomized, double-blinded, placebo-controlled trial, 262 postmenopausal women were enrolled. Patients were randomized to receive daily oral minodronate 1 mg with supplements of 500 mg calcium and 200 U vitamin D 3 ( n=130) or placebo ( n=132) with daily supplements of 500 mg calcium and 200 U vitamin D 3, for 48 weeks. The primary endpoint was the average bone mineral density (BMD) change in the lumbar vertebrae 48 weeks post-treatment. Secondary outcome measures was the incidence of vertebral fractures. Safety assessments included the rate of adverse events. Results:At the end of 48 weeks treatment, the average BMD change rate from baseline were: full analysis set results: (3.52±4.82)% in the minodronate group and (2.00±5.74)% in the placebo group; per-protocol set results: (3.99±5.05)% in the minodronate group and (2.07±6.20)% in the placebo group; the differences were all significant (all P<0.05). Vertebral fracture occured in 3 patients (2.3%, 3/132) in the placebo group, and 1 case (0.8%, 1/130) in the minodronate group ( P>0.05). The incidence of adverse events was 71.5% (93/130) in the minodronate group and 78.0% (103/132) in the placebo group ( P>0.05). Conclusion:Minodronate is effective and safe in the treatment of postmenopausal osteoporosis without severe side effects.

Objective:To analyze the clinical characteristics of adult Chinese patients with syncope.Methods:This is a cross-sectional survey study. Patients with preliminary diagnosis of syncope in the Emergency Department, Geriatrics and Cardiology Outpatient Department, or Syncope Unit of 37 hospitals in 19 provinces, autonomous regions and the Hong Kong Special Administrative Region from June 2018 to March 2021 were included in this study. The clinical features of these patients with syncope were analyzed.Results:A total of 4 950 consecutive patients with syncope were included in this study. The age was (56.3±16.8)years, and 2 604 cases (52.6%) were male. The most common type of syncope was neurally mediated syncope (2 345 (47.4%)), followed by cardiac syncope (1 085 (21.9%)), orthostatic hypotensive syncope (311 (6.3%)), and unexplained syncope accounted for nearly one third (1 155 (23.3%)). Predisposing syncope was more common in patients under 65 years of age(2 066(72.4%) vs. 786(27.6%),χ 2=136.5, P<0.001). Presyncope was more common in patients with neurally mediated syncope (1 972(79.0%) vs.1 908(73.9%), χ 2=17.756, P<0.001). Premonitory symptoms were more common in women(1 837(80.0%) vs. 1 863(73.0%),χ 2=33.432, P<0.001). Presyncope syndrome was more common in patients under 65 years of age (2 482(77.8%) vs. 1 218(73.4%),χ 2=17.523, P=0.001). Cyanosis was more common in ≥65 years old patients (271(18.2%) vs. 369(12.7%), χ 2=23.235, P<0.001). Urinary incontinence was more common in old patients aged ≥65 years(252(15.2%) vs. 345(10.8%), χ 2=19.313, P<0.001). Family history was more common in patients with cardiogenic syncope compared with other types of syncope (264(24.3%) vs. 754(19.5%), χ 2=11.899, P=0.001). Hypertention(1 480(30.5%)), coronary heart disease(1 057(21.4%)), atrial flutter and atrial fibrillation(359(7.2%)), second degree atrioventricular block(236(4.8%)) were common complications of syncope. The proportion of patients with coronary heart disease was significantly higher in cardiac syncope than that of other types of syncope(417(38.4%) vs. 640(16.6%), χ 2=241.376, P<0.001). Other common complications included cerebrovascular diseases (551 (11.1%)) and diabetes mellitus (632(12.8%)). Conclusions:Neurally mediated syncope is the most common syncope in adult Chinese population. Patients with predisposing conditions and premonitory conditions are younger. Presyncope is more common in women. The proportion of family history and coronary heart disease is higher in patients with cardiogenic syncope.

Recently, deep neural networks (DNNs) have been widely used in the field of electrocardiogram (ECG) signal classification, but the previous models have limited ability to extract features from raw ECG data. In this paper, a deep residual network model based on pyramidal convolutional layers (PC-DRN) was proposed to implement ECG signal classification. The pyramidal convolutional (PC) layer could simultaneously extract multi-scale features from the original ECG data. And then, a deep residual network was designed to train the classification model for arrhythmia detection. The public dataset provided by the physionet computing in cardiology challenge 2017(CinC2017) was used to validate the classification experiment of 4 types of ECG data. In this paper, the harmonic mean of classification accuracy and recall was selected as the evaluation indexes. The experimental results showed that the average sequence level ( ) of PC-DRN was improved from 0.857 to 0.920, and the average set level ( ) was improved from 0.876 to 0.925. Therefore, the PC-DRN model proposed in this paper provided a promising way for the feature extraction and classification of ECG signals, and provided an effective tool for arrhythmia classification.
Arrhythmias, Cardiac ; Disease Progression ; Electrocardiography ; Humans ; Neural Networks, Computer