A 71-year-old male presented with esophageal cancer and severe aortic valve regurgitation. Treatment strategies for such patients are controversial. Considering the risks of cardiopulmonary bypass and potential esophageal cancer metastasis, we successfully performed transcatheter aortic valve implantation and minimally invasive three-incision thoracolaparoscopy combined with radical resection of esophageal cancer (McKeown) simultaneously in the elderly patient who did not require neoadjuvant treatment. This dual minimally invasive procedure took 6 hours and the patient recovered smoothly without any surgical complications.

Objective To describe the significance of the pretreatment inflammatory indicators in predicting the prognosis of patients with esophageal squamous cell carcinoma (ESCC) after undergoing radical radiotherapy. Methods The data of 246 ESCC patients who underwent radical radiotherapy were retrospectively collected. Receiver operating characteristic (ROC) curves were drawn to determine the optimal cutoff values for platelet-lymphocyte ratio (PLR), neutrophil-lymphocyte ratio (NLR), and systemic immune-inflammation index (SII). The Kaplan-Meier method was used for survival analysis. We conducted univariate and multivariate analyses by using the Cox proportional risk regression model. Software R (version 4.2.0) was used to create the nomogram of prognostic factors. Results The results of the ROC curve analysis showed that the optimal cutoff values of PLR, NLR, and SII were 146.06, 2.67, and 493.97, respectively. The overall response rates were 77.6% and 64.5% in the low and high NLR groups, respectively (P<0.05). The results of the Kaplan-Meier survival analysis revealed that the prognosis of patients in the low PLR, NLR, and SII group was better than that of patients in the high PLR, NLR, and SII group (all P<0.05). The results of the multivariate Cox regression analysis showed that gender, treatment modalities, T stage, and NLR were independent factors affecting the overall survival (OS). In addition, T stage and NLR were independent factors affecting the progression-free survival (PFS) (all P<0.05). The nomogram models of OS and PFS prediction were established based on multivariate analysis. The C-index values were 0.703 and 0.668. The calibration curves showed excellent consistency between the predicted and observed OS and PFS. Conclusion The pretreatment values of PLR, NLR, and SII are correlated with the prognosis of patients with ESCC who underwent radical radiotherapy. Moreover, NLR is an independent factor affecting the OS and PFS of ESCC patients. The NLR-based nomogram model has a good predictive ability.

ObjectiveTo explore the mechanism of Shouhui Tongbian capsules in treating constipation based on the research foundation of its active components combined with network pharmacology and animal experiments. MethodsThe drug components were imported into SwissTargetPrediction to predict the targets of Shouhui Tongbian capsules， and constipation-related targets were collected from disease databases. A protein-protein interaction （PPI） network was constructed for the common targets shared by Shouhui Tongbian capsules and constipation to screen key targets， which was followed by gene ontology （GO） function and Kyoto encyclopedia of genes and genomes （KEGG） pathway enrichment analyses. A "bioactive component-target-pathway" network was constructed， and the core components of Shouhui Tongbian capsules in treating constipation were screened based on the topological parameters of this network. Molecular docking was employed to predict the binding affinity of core components to key targets. A mouse model of constipation was constructed to screen the key pathways and targets of the drug intervention in constipation. ResultsThe PPI network revealed six key constipation-related targets： protein kinase B （Akt1）， B-cell lymphoma-2 （Bcl-2）， glycogen synthase kinase-3β （GSK-3β）， cyclooxygenase-2 （PTGS2）， estrogen receptor 1 （ESR1）， and epidermal growth factor receptor （EGFR）. The KEGG pathway analysis showed that the phosphatidylinositol 3-kinase （PI3K）/Akt signaling pathway was the most enriched. The topological parameter analysis of the "bioactive component-target-pathway" network screened out the top 10 core components： auranetin， isosinensetin， naringin， diosmetin， quercetin， apigenin， luteolin， hesperidin， isorhapontigenin， and chrysophanol. Molecular docking results showed that the 10 core components had strong binding affinity with the 6 key targets. Animal experiments showed that after intervention with different doses of Shouhui Tongbian capsules， the time to the first black stool excretion was reduced and the fecal water content and small intestine charcoal propulsion rate of mice were improved. After treatment with Shouhui Tongbian capsules， the colonic mucosal injury and glandular arrangement were alleviated， and the muscle layer thickness was increased. Western blot results showed that Shouhui Tongbian capsules recovered the expression of apoptosis-related molecules mediated by the PI3K/Akt pathway in the colonic tissue of constipated mice. Terminal-deoxynucleotidyl transferase-mediated nick end labeling （TUNEL） results showed that the cell apoptosis rate of the colon significantly reduced after intervention with Shouhui Tongbian capsules. ConclusionThe results of network pharmacology and animal experiments confirmed that Shouhui Tongbian capsules can treat constipation through multiple targets and pathways. The capsules can effectively intervene in loperamide-induced constipation in mice by regulating the constipation indicators and reducing cell apoptosis in the colon tissue via activating the PI3K/Akt signaling pathway.

ObjectiveThis study aimed to investigate the effects of 4-week high-intensity interval training (HIIT) on synaptic plasticity in the prefrontal cortex (PFC) of rats exposed to chronic unpredictable mild stress (CUMS), and to explore its potential mechanisms. MethodsA total of 48 male Sprague-Dawley rats were randomly divided into 4 groups: control (C), model (M), control plus HIIT (HC), and model plus HIIT (HM). Rats in groups M and HM underwent 8 weeks of CUMS to establish depression-like behaviors, while groups HC and HM received HIIT intervention beginning from the 5th week for 4 consecutive weeks. The HIIT protocol consisted of repeated intervals of 3 min at high speed (85%-90% maximal training speed, S_max) alternated with one minute at low speed (50%-55% S_max), with 3 to 5 sets per session, conducted 5 d per week. Behavioral assessments and tail-vein blood lactate levels were measured at the end of the 4th and 8th weeks. After the intervention, rat PFC tissues were collected for Golgi staining to analyze synaptic morphology. Enzyme-linked immunosorbent assays (ELISA) were employed to detect brain-derived neurotrophic factor (BDNF), monocarboxylate transporter 1 (MCT1), lactate, and glutamate levels in the PFC, as well as serotonin (5-HT) levels in serum. Additionally, Western blot analysis was conducted to quantify the expression of synaptic plasticity-related proteins, including c-Fos, activity-regulated cytoskeleton-associated protein (Arc), and N-methyl-D-aspartate receptor 1 (NMDAR1). ResultsCompared to the control group (C), the CUMS-exposed rats (group M) exhibited significant reductions in sucrose preference rates, number of grid crossings, frequency of upright postures, and entries into and duration spent in open arms of the elevated plus maze, indicating marked depressive-like behaviors. Additionally, the group M showed significantly reduced dendritic spine density in the PFC, along with elevated levels of c-Fos, Arc, NMDAR1 protein expression, and increased concentrations of lactate and glutamate. Conversely, BDNF and MCT1 contents in the PFC and 5-HT levels in serum were significantly decreased. Following HIIT intervention, rats in the group HM displayed considerable improvement in behavioral indicators compared with the group M, accompanied by significant elevations in PFC MCT1 and lactate concentrations. Furthermore, HIIT notably normalized the expression levels of c-Fos, Arc, NMDAR1, as well as glutamate and BDNF contents in the PFC. Synaptic spine density also exhibited significant recovery. ConclusionFour weeks of HIIT intervention may alleviate depressive-like behaviors in CUMS rats by increasing lactate levels and reducing glutamate concentration in the PFC, thereby downregulating the overexpression of NMDAR, attenuating excitotoxicity, and enhancing synaptic plasticity.

The analysis of ammonia nitrogen in real water samples is challenging due to matrix interferences and difficulties for rapid on-site analysis.On the basis of the standard method,i.e.water quality-determination of ammonia nitrogen-salicylic acid spectrophotometry(HJ 536-2009),a simple device for online detecting ammonia nitrogen was developed using a sequential injection analysis(SIA)system in this work.The ammonia nitrogen transformation system,color reaction system,and detection system were built in compatible with the SIA system,respectively.In particular,the detection system was assembled by employing light-emitting diode as the light source,photodiode as the detector,and polyvinylchloride tube as the cuvette,thus significantly reducing the volume,energy consumption and fabricating cost of the detection system.As a result,the accurate analysis of ammonia nitrogen in complex water samples was achieved.A quantitative detection of ammonia nitrogen in water sample was obtained in 12 min,along with linear range extending to 1000 μmol/L,precisions(Relative standard deviation,RSD)of 4.3%(C=10 μmol/L,n=7)and 4.2%(C=500 μmol/L,n=7),and limit of detection(LOD)of 0.65 μmol/L(S/N=3,n=7).The results of interfering experiments showed that the detection of ammonia nitrogen by the developed device was not interfered by the common coexisting ions and components,therefore the environmental water could be directly analyzed,such as reservoir water,domestic sewage,sea water and leachate of waste landfill.The analytical results were consistent with those obtained by the environmental protection standard method(Water quality determination of ammonia nitrogen-salicylic acid spectrophotometry,HJ 536-2009).In addition,the spiking recoveries were in the range of 92.3%-98.1%,further confirming the accuracy and practicality of the developed device.

Chronic constipation （CC） is one of the common and frequent functional gastrointestinal diseases in clinic. At present， the overall therapeutic effect of CC is still not satisfactory in China and abroad， which seriously affects the quality of life of patients. The pathophysiological mechanism of constipation has not been fully elucidated， and studies have mainly focused on the dysfunction of the enteric nervous system （ENS）， abnormalities of Cajal interstitial cells （ICCs）， alterations in mucosal immune function （low-grade intestinal inflammation， intestinal barrier damage， and immune activation）， abnormalities of gastrointestinal hormones， dysregulation of intestinal flora， and dysfunctions of intestinal dynamics. Traditional Chinese medicine （TCM） is a unique and precious resource in China with good efficacy and safety. TCM and its active ingredients can effectively treat constipation， and its mechanism of action needs to be further investigated. Signaling pathways are involved in the development of constipation， which is one of the main targets in the study of pathological mechanisms of constipation and the pharmacological study of therapeutic drugs. Therefore， the authors searched PubMed， China National Knowledge Infrastructure （CNKI）， and other literature databases with the keywords of ''constipation''， ''signaling pathway''， and ''traditional Chinese medicine'' to systematically summarize the signaling pathways related to constipation regulated by TCM. The comprehensive analysis shows that TCM mainly plays a role in regulating autophagy， apoptosis， and proliferation and ensuring anti-oxidative stress， anti-inflammation， and protection of intestinal barrier of ICCs by modulating signaling pathways such as stem cell factor/tyrosine kinase receptor （SCF/c-kit）， phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt）， 5-hydroxytryptophan （5-HT）， mitogen-activated protein kinases （MAPK）， and Toll-like receptors （TLRs）. TCM regulates neurotransmitter secretion and intestinal water metabolism to improve constipation. This demonstrates the advantages of multi-level， multi-target， and multi-level effects of TCM， and in-depth research can provide new ideas for exploring the pathogenesis of constipation and developing new drugs.

OBJECTIVE: To investigate the effects of Danmu Extract Syrup (DMS) on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice and explore the mechanism. METHODS: Seventy-two male Balb/C mice were randomly divided into 6 groups according to a random number table (n=12), including control (normal saline), LPS (5 mg/kg), LPS+DMS 2.5 mL/kg, LPS+DMS 5 mL/kg, LPS+DMS 10 mL/kg, and LPS+Dexamethasone (DXM, 5 mg/kg) groups. After pretreatment with DMS and DXM, the ALI mice model was induced by LPS, and the bronchoalveolar lavage fluid (BALF) were collected to determine protein concentration, cell counts and inflammatory cytokines. The lung tissues of mice were stained with hematoxylin-eosin, and the wet/dry weight ratio (W/D) of lung tissue was calculated. The levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-1 β in BALF of mice were detected by enzyme linked immunosorbent assay. The expression levels of Claudin-5, vascular endothelial (VE)-cadherin, vascular endothelial growth factor (VEGF), phospho-protein kinase B (p-Akt) and Akt were detected by Western blot analysis. RESULTS: DMS pre-treatment significantly ameliorated lung histopathological changes. Compared with the LPS group, the W/D ratio and protein contents in BALF were obviously reduced after DMS pretreatment (P<0.05 or P<0.01). The number of cells in BALF and myeloperoxidase (MPO) activity decreased significantly after DMS pretreatment (P<0.05 or P<0.01). DMS pre-treatment decreased the levels of TNF-α, IL-6 and IL-1 β (P<0.01). Meanwhile, DMS activated the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) pathway and reversed the expressions of Claudin-5, VE-cadherin and VEGF (P<0.01). CONCLUSIONS DMS attenuated LPS-induced ALI in mice through repairing endothelial barrier. It might be a potential therapeutic drug for LPS-induced lung injury.
Mice ; Male ; Animals ; Proto-Oncogene Proteins c-akt/metabolism* ; Lipopolysaccharides ; Phosphatidylinositol 3-Kinases/metabolism* ; Interleukin-1beta/metabolism* ; Vascular Endothelial Growth Factor A/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Claudin-5/metabolism* ; Acute Lung Injury/chemically induced* ; Lung/pathology* ; Interleukin-6/metabolism* ; Drugs, Chinese Herbal

Chronic constipation （CC） is one of the most common functional gastrointestinal diseases. At present， the overall therapeutic effect of CC is still not satisfactory worldwide， which seriously affects the quality of life and social function of patients. The etiology and pathophysiological mechanism of constipation are still unclear. It involves comprehensive factors such as heredity， social psychology， diet， intestinal flora imbalance， intestinal motility disorder， visceral sensitivity change， pelvic floor muscle group dysfunction and enteric nervous system （ENS） disorder. Among them， the abnormal factors of the brain-gut-microbiome axis are particularly significant. The brain-gut-microbiome axis is a complex network of interactions between the intestine and the brain， integrating and coordinating the physiological functions and pathological processes of the gastrointestinal tract. Microorganisms in the intestinal lumen play an important role in it， and can communicate with the intestinal tract and the central nervous system through nerve， endocrine and immune pathways. As a key brain-gut peptide in the regulation pathway of the brain-gut-microbiome axis， 5-hydroxytryptamine （5-HT） is involved in the regulation of gastrointestinal motility， sensation and secretion. The abnormal conduction of the 5-HT signaling pathway is closely related to the occurrence and development of constipation. Traditional Chinese medicine（TCM） is a unique precious resource in China， which has good curative effects and safety. In recent years， it has received extensive attention in the treatment of constipation. TCM and active ingredients， acupuncture and massage specifically regulate 5-HT signal transmission， so that the expressions of related molecules tend to be suitable for individual disease state levels to effectively improve constipation symptoms， with unique advantages. Therefore， this study used ''constipation''， ''intestinal flora''， ''5-HT''， and ''traditional Chinese medicine'' as the keywords to search PubMed， China National Knowledge Infrastructure （CNKI） and other literature databases. The correlation between 5-HT and constipation as well as brain-gut-microbiome axis and the research progress of TCM intervention in the 5-HT signaling pathway in the treatment of constipation were reviewed in order to explore the potential therapeutic value of 5-HT system in this disease and provide references for subsequent research.

Background and aim:Hepatic ischemia-reperfusion injury(IRI)is a significant challenge in liver trans-plantation,trauma,hypovolemic shock,and hepatectomy,with limited effective interventions available.This study aimed to investigate the role of leukocyte cell-derived chemotaxin 2(LECT2)in hepatic IRI and assess the therapeutic potential of Lect2-short hairpin RNA(shRNA)delivered through adeno-associated virus(AAV)vectors. Materials and methods:This study analyzed human liver and serum samples from five patients under-going the Pringle maneuver.Lect2-knockout and C57BL/6J mice were used.Hepatic IRI was induced by clamping the hepatic pedicle.Treatments included recombinant human LECT2(rLECT2)and AAV-Lect2-shRNA.LECT2 expression levels and serum biomarkers including alanine aminotransferase(ALT),aspartate aminotransferase(AST),creatinine,and blood urea nitrogen(BUN)were measured.Histological analysis of liver necrosis and quantitative reverse-transcription polymerase chain reaction were performed. Results:Serum and liver LECT2 levels were elevated during hepatic IRI.Serum LECT2 protein and mRNA levels increased post reperfusion.Lect2-knockout mice had reduced weight loss;hepatic necrosis;and serum ALT,AST,creatinine,and BUN levels.rLECT2 treatment exacerbated weight loss,hepatic necrosis,and serum biomarkers(ALT,AST,creatinine,and BUN).AAV-Lect2-shRNA treatment significantly reduced weight loss,hepatic necrosis,and serum biomarkers(ALT,AST,creatinine,and BUN),indicating thera-peutic potential. Conclusions:Elevated LECT2 levels during hepatic IRI increased liver damage.Genetic knockout or shRNA-mediated knockdown of Lect2 reduced liver damage,indicating its therapeutic potential.AAV-mediated Lect2-shRNA delivery mitigated hepatic IRI,offering a potential new treatment strategy to enhance clinical outcomes for patients undergoing liver-related surgeries or trauma.

Objective To explore the clinical characteristics of patients with alcoholic liver disease(ALD)of various traditional Chinese medicine(TCM)syndrome types.Methods A retrospective analysis was conducted in 129 patients with alcoholic liver disease who met the inclusion and exclusion criteria in Foshan Hospital of Traditional Chinese Medicine from 2018 to 2022.The general data of the patients as well as their TCM syndrome types and clinical information of liver and kidney function,blood lipid,liver transient elastography during the hospital visit were collected.The distribution of TCM syndrome types in ALD patients was analyzed,and the clinical characteristics of the ALD patients with various TCM syndrome types were explored.Results(1)Of the 129 patients,128(99.22%)were male and only one(0.78%)was female,the average age was(48.71±11.50)years old,and the average body mass index(BMI)was(23.82±3.98)kg·m-2.(2)Damp-heat accumulation syndrome was most common syndrome type in ALD patients,with a total of 70 cases(54.26%),and then came liver depression and spleen deficiency syndrome(24 cases,18.60%),internal obstruction of phlegm-damp syndrome(22 cases,17.05%),liver-kidney sufficiency syndrome(7 cases,5.43%),phlegm interweaved with blood stasis syndrome(3 cases,2.33%),and internal accumulation of blood stasis syndrome(3 cases,2.33%).(3)The analysis of clinical characteristics by non-parametric rank sum test showed that there were no statistically significant differences in BMI,alcohol consumption,aspartate aminotransferase(AST),gamma-glutamyltransferase(GGT),total bilirubin(TBIL),alkaline phosphatase(ALP),triglyceride(TG),liver stiffness measurement(LSM),and controlled attenuation parameter(CAP)which reflects the fat content of liver in ALD patients with various TCM syndrome types(P＜0.05 or P＜0.01).The prominent features were as follows:patients with the 4 types of liver depression and spleen deficiency,internal obstruction of phlegm-damp,phlegm interweaved with blood stasis,and internal accumulation of blood stasis had a BMI exceeding the standard(＞24 kg·m-2),whereas patients with damp-heat accumulation syndrome and liver-kidney deficiency syndrome,which accounted for 54.26%of the sample size,had a BMI within the normal range(23.03 kg·m-2 and 21.42 kg·m-2,respectively),and the BMI of these two types differed from that(26.44 kg·m-2)of the internal obstruction of phlegm-damp syndrome(P＜0.01),suggesting that more than half of the ALD patients had the normal BMI;moreover,the patients with internal obstruction of phlegm-damp also had the highest values of serum TG(2.69 mmol/L)and CAP(292 db/m)except for the highest BMI,indicating that patients with internal obstruction of phlegm-damp syndrome had a more serious degree of obesity and hepatic fat infiltration than those with other syndrome types;the levels of AST and GGT,which separately reflect the chronic inflammatory injury of liver and bile duct cell injury,were significantly increased in the patients with damp-heat accumulation syndrome and liver-kidney deficiency syndrome,and the LSM value of these two types of patients was also the highest in all of the syndrome types,the differences being all statistically significant(P＜0.05 or P＜0.01).Conclusion Damp-heat accumulation syndrome is the main TCM syndrome type of ALD patients,the degree of fatty infiltration of the liver and overweight of ALD patients are not corresponded to the severity of illness,and there are some differences in the clinical indicators of ALD patients with various TCM syndrome types.However,with cross reference to the data of the four diagnostic examinations of TCM and the clinical indicators,the accuracy of the TCM diagnosis of ALD is expected to be increased.