ObjectiveTo explore the effect and mechanism of Jianpi Xiaoai prescription （JPXA） in ameliorating the 5-fluorouracil （5-FU） resistance of colon cancer. MethodsA HCT116/5-FU resistant cell line was established. Different concentrations （10%， 15%， 20%） of JPXA-containing serum and drug-free serum were used for intervention， and 10% fetal bovine serum （10% FBS）， fibroblast growth factor receptor （FGFR） inhibitor （AZD4547）， and recombinant fibroblast growth factor 2 （FGF2） were set as the control groups. Sensitive HCT116 cells were used in the FGF2 group， while HCT116/5-FU cells were used in other groups. Drug resistance， the level of FGF2 in the cell culture medium， the mRNA level of FGF2 in cells， and the protein levels of FGF2/FGFR and phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） were determined. The drug-resistant cells were transplanted into the axilla of nude mice to establish a tumor model. The modeled mice were allocated into model， JPXA （15 g·kg^-1）， 5-FU （0.02 g·kg^-1）， JPXA+5-FU （15 g·kg^-1+0.02 g·kg^-1）， AZD4547 （0.012 5 g·kg^-1）， and AZD4547+5-FU （0.012 5 g·kg^-1+0.02 g·kg^-1） groups. The tumor growth and the protein levels of FGF/FGFR and PI3K/Akt in each group were observed. ResultsThe survival rate of HCT116/5-FU cells decreased in all the JPXA groups with different concentrations. The cell survival rate was decreased most obviously in the 20% JPXA group. The level of FGF2 in the cell culture medium and the mRNA level of FGF2 in cells of each JXPA group decreased， and the decrease was the most significant in the 20% group （P<0.01）. HCT116/5-FU cells showed up-regulated protein levels of FGF2 and phosphorylated fibroblast growth factor receptor 1 （p-FGFR1）， but down-regulated protein level of FGFR1 （P<0.01）. JPXA down-regulated the expression of FGF2 and p-FGFR1 and up-regulated the expression of FGFR1 （P<0.05）. In addition， JPXA down-regulated the expression levels of phosphorylated protein kinase B （p-Akt） and phosphorylated mammalian target of rapamycin （p-mTOR）， while up-regulating the expression levels of Akt and Bcl-2-asociated death promoter （Bad） （P<0.05）. Animal experiments showed that the JPXA combined with 5-FU significantly inhibited the growth of drug-resistant tumors， reduced the protein levels of FGF2， p-FGFR1， phosphorylated phosphatidylinositol-3-kinase （p-PI3K）， p-Akt， and p-mTOR， and increased the expression of Bad. It indicated that JPXA can inhibit the FGF2/FGFR1 signaling in colon cancer and regulate PI3K/Akt and downstream signaling pathways. ConclusionJPXA can ameliorate the chemotherapy resistance of colon cancer through down-regulating FGF2 expression and inhibiting the activation of the PI3K/Akt signaling pathway.

Patients with Takayasu arteritis combined with aortic valve disease often have a poor prognosis following surgical valve replacement, frequently encountering complications such as perivalvular leakage, valve detachment, and anastomotic aneurysm. This article presents a high-risk case wherein severe aortic valve insufficiency associated with Takayasu arteritis was successfully managed through transcatheter aortic valve implantation via the transapical approach. The patient had satisfactory valve function with no complications observed during the six-month postoperative follow-up. This case provides a minimally invasive and feasible alternative for the clinical management of such high-risk patients.

With the accelerating trend of population aging, the number of elderly patients with lung cancer continues to rise, and the disease burden is becoming increasingly heavy. The clinical management of these patients faces severe challenges due to their decreased physiological reserve, complex comorbidities, and significant individual heterogeneity. Consequently, under traditional diagnosis and treatment models, doctors often struggle to identify the individualized risks of elderly patients in a timely and comprehensive manner, which can easily lead to decision biases such as undertreatment or overtreatment. In view of this, this study advocates for the establishment of an umbrella decision-making model specifically tailored for elderly lung cancer patients. Grounded in a multidisciplinary team (MDT) platform, this model deeply integrates oncological indicators with the comprehensive geriatric assessment (CGA) system. By holistically considering multidimensional variables including tumor burden, organ function, frailty index, cognitive status, and social support, the model establishes an operational mechanism characterized by "single entry, precise stratification, and targeted selection". Accordingly, patients can be scientifically triaged into distinct intervention tiers, such as active surveillance, minimally invasive surgery, drug therapy, radiotherapy, and best supportive care, thereby achieving real-time alignment between treatment intensity and patient fitness. This article elaborates on the construction logic and key operational procedures of this novel decision-making framework, aiming to guide clinical practice beyond the limitations of a tumor-centric perspective toward a holistic, dynamic, whole-course management strategy. This transition seeks to ensure optimal quality of life and clinical net benefit for elderly patients alongside survival prolongation.

Background and aims The mechanism of cholestatic liver injury (CLI) is unclear, and effective therapies are lacking. While peroxisome proliferator-activated receptor alpha (PPARα) agonists show potential hepatoprotective effect and pyroptosis is implicated in hepatocellular damage, how PPARα activation mitigates lithocholic acid (LCA)-induced pyroptosis remains unknown. Methods The hepatoprotective effect of PPARα agonists was evaluated in a mouse model of intrahepatic cholestasis induced by LCA. Liver injury was assessed via serum biochemistry, hematoxylin and eosin and TUNEL staining, and electron microscopy. Pyroptosis pathways were analyzed using real-time quantitative polymerase chain reaction, Western blot, and co-immunoprecipitation. Results Combined morphological, histopathological, and biochemical analyses confirmed that PPARα activation protects against CLI. Compared with LCA treatment alone, PPARα activation significantly attenuated the elevation of serum lactate dehydrogenase (LDH), the increased TUNEL-positive cells, and the formation of hepatocyte membrane pores. Mechanistically, PPARα activation suppressed both NOD-like receptor protein 3 (NLRP3) inflammasome-mediated pyroptosis and apoptosis protease-activating factor-1 (APAF-1)/CASPASE-3/GSDME-mediated pyroptosis. Furthermore, PPARα agonist pretreatment inhibited activation of the nuclear factor-kappa B (NF-κB) and forkhead box O1 (FOXO1) signaling pathways. Conclusions PPARα protects against LCA-induced CLI by inhibiting both NLRP3 inflammasome-mediated pyroptosis associated with NF-κB and APAF-1/CASPASE-3/GSDME-mediated pyroptosis associated with the FOXO1 signaling pathway.

The accumulation of uremic toxins such as urea nitrogen, blood creatinine, and uric acid of patients with renal failure in vivo would lead to aggravated kidney damage. In this study, coated aldehyde oxy-starch (CAO) was used as an adsorbent to investigate its in vitro adsorption performance on renal failure indexes for urea, indoxyl sulfate (INS), monomethylamine (MMA), dimethylamine (DMA), uric acid (UA), and creatinine (Cr). The effects of variables such as pH, temperature, concentration, dosage, and time on the adsorption capacity of CAO were systematically investigated, employing analytical techniques of high-performance liquid chromatography (HPLC) and gas chromatography (GC). The results revealed that CAO exhibited a strong adsorption capacity for urea, INS, and MMA, alongside a moderate adsorption capacity for DMA, UA, and Cr. The adsorption kinetics and thermodynamic studies indicated that the adsorption of urea and UA by CAO were fitted in pseudo-first-order kinetics, and the adsorption isotherm aligned with the Freundlich adsorption model. The enthalpy change ΔH of urea in adsorption was in the range of 40 to 60 kJ·mol^-1, which demonstrated the presence of strong adsorption force due to the interactions of coordinating groups. The ΔH of UA was greater than 80 kJ·mol^-1, indicating the generation of chemical bonds during the adsorption. Both of them, Gibbs free energy ΔG was less than 0, within the range of -20 to 0 kJ·mol^-1, suggested that the adsorption of urea and UA by CAO occurred spontaneously as physical adsorption process. The adsorption entropy ΔS of urea and UA was > 0, which indicated an increase in entropy throughout the adsorption. The infrared spectroscopygram showed the formation of a chemical bond, specifically the imine bond, following the adsorption of urea by CAO, thereby indicating a chemical reaction during the adsorption. This study elucidates the adsorption mechanism of CAO on various indexes of renal failure, providing a scientific basis for its clinical usage.

Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.

Objective:To explore the feasibility, safety, and short-term efficacy of a total pelvic floor resection procedure as a component of combined resection of pelvic organs for locally advanced or locally recurrent rectal cancer.Methods:This was a descriptive case series. Relevant clinical data of patients with locally advanced or locally recurrent rectal cancer without extrapelvic metastasis or with only oligometastasis who had undergone combined pelvic organ resection with resection of the entire pelvic floor in the Department of Anorectal Surgery of the Second Affiliated Hospital of Naval Medical University from 1 January 2023 to 30 June 2024 were collected from a Chinese database of combined pelvic organ resection for rectal cancer. The study cohort comprised 143 patients, 74 of whom were male (51.7%) and 69 were female (48.3%); their ages averaged 54 (range: 31–75) years; 57 of the patients (39.9%) had locally advanced rectal cancer and 86 (60.1%) locally recurrent rectal cancer. In our institution, the pelvic floor is categorized into two anatomical layers: the levator ani/presacral anterior tissue, and the bone/ligament/pelvic floor soft tissue. The entire pelvic floor was resected en bloc after making incisions on both sides of the pelvic floor, followed by presacral sacral dissection, and abdominoperineal dissection of the anterior side of the pelvic floor. The main factors studied were related to the following: (1) surgical conditions, comprising the scope of surgical resection, operation time, intraoperative blood loss, tissue reconstruction; (2) postoperative recovery, comprising time to recovery of intestinal function, time to removal of drainage tubes, and time to healing of the empty pelvic cavity; and (3) postoperative complications, classified according to the international Clavien-Dindo classification. Results:Combined pelvic organ resection with entire pelvic floor resection was successfully completed in all patients. The operation time was 480 (390 to 1,020) minutes, intraoperative blood loss 800 (50 to 3,500) mL, and volume of blood transfused intraoperatively 1, 000 (400 to 7, 400). R0 resection was achieved in 116 cases (81.1%) and R1 resection in 27 (18.9%). The first layer of the pelvic floor wall (levator ani/sacral anterior tissue) was resected in 79 cases (55.2%) and the second layer of the pelvic floor wall (bone/ligament/pelvic floor soft tissue) in 64 (44.8%). The procedure was completed in the lithotomy position in 114 cases (79.7%) were and in the lithotomy + prone jackknife position in 29 (20.3%). The pelvic floor was reconstructed with mesh in 140 cases (97.7%) and with mesh plus pedicled omental flaps in 92 cases (64.3%). The urinary tract was reconstructed in 92 cases (64.3%). The time to recovery of intestinal function was 3.6 (2.0 to 7.0) days, to removal of drainage tubes 29.4 (24.0 to 54.0) days, and to healing of the empty pelvic cavity 36.2 (27.0 to 56.0) days. Twenty-three patients (16.1%) had Grade I - II complications and 36 (25.2%) Grade IIIa - IV complications. The median duration of follow-up was 15.5 (0.5 to 30.0) months. Six of the patients (4.2%) died, including two (1.4%) who died within 30 days after surgery.Conclusions:Pelvic floor en bloc resection has a high R0 resection rate and is a safe and feasible procedure for pelvic organ resection surgeries in patients with locally advanced or locally recurrent rectal cancer.

Objective:To investigate the value of pelvic floor reconstruction with gluteus maximus myocutaneous flap in second-stage surgery for patients with failed perineal wound healing after pelvic exenteration (PE).Methods:This was a descriptive case series study. The clinical data of 24 patients with locally advanced (LARC) or recurrent (LRRC) rectal cancer who underwent PE and had long-term nonunion of postoperative perineal wounds were collected from the department of colorectal surgery of the Second Affiliated Hospital of Navy Medical University (Shanghai Changzheng Hospital) from January 2022 to January 2023. The specific operation methods of pelvic reconstruction by gluteus maximus myocutaneous flap are as follows: the necrotic tissue of the perineal wound was debrided and rinsed repeatedly, the gluteus maximus muscle was cut and separated from the gluteus superior and inferior arteries, the middle muscle pedicle was retained, part of the skin and muscle were separated from the medial margin, part of the epidermis was removed, the muscle and subcutaneous tissue at the medial margin of the flap were fixed to the medial edge of the wound, negative pressure suction tubes were placed above and below the wound cavity and in the muscle space on the right side, and the subcutaneous muscle and fat layer were sutured. The skin was sutured intersegmentally, and a negative pressure suction device was placed on the wound surface. After surgery, the patient should remain prone, and the drainage tube should be placed for at least 7 days. The drainage tube can be removed after 24-hour drainage is less than 30 ml. Perineal wound healing and complications related to gluteal major myocutaneous flap were observed.Result:The median reconstruction time of 24 patients was 180 (150 ~ 230) minutes, and the median intraoperative blood loss was 100 (30 ~ 200) ml. 91.7% (22/24) patients had successful healing of perineal wound within 30 d after operation. After a follow-up of 6 months, no complete or partial flap necrosis occurred. The incidence of complications related to gluteus maximus myocutaneous flap was 8.3% (2/24). One patient had flap infection and sinus tract, and one patient had flap sinus tract. All patients healed after debridement under local anesthesia.Conclusion:For LARC/LRRC patients with poor perineal wound healing after PE, pelvic floor reconstruction with gluteus maximus myocutaneous flap in second-stage operation is safe and feasible, and could successfully close the perineal wound, and has a low incidence of postoperative flap-related complications.

Objective To explore the expression of miR-1247-5p in gastric cancer and its effect on migration and invasion of gastric cancer cells.Methods The differentially expressed miRNAs in adjacent non-cancerous tissue versus gastric cancer tissue of TCGA database were analyzed.The prognostic value of miR-1247-5p in malignant tumor was analyzed by receiver operating characteristic(ROC)curve.RT-qPCR assay was used to detect expression levels of miR-1247-5p of gastric cancer tissue and adjacent non-cancerous tissue collected in 10 cases from our hospital.Protein-Protein Interaction(PPI)analysis was used to identify downstream target genes of miR-1247-5p.Dual-luciferase reporter assay was used to observe the binding of miR-1247 to Smad2.Transwell assay was used to investigate the effect of miR-1247-5p overexpression on migration and invasion abilities of gastric cancer cells.RT-qPCR and Western blot experiments were used to examine the impact of miR-1247-5p on expression levels of Smad2 and epithelial-mesenchymal transition(EMT)marker molecules.Results The expression levels of miR-1247-5p were lower in gastric cancer tissue collected from both TCGA database and our hospital than those in adjacent normal tissue.ROC curve analysis indicated that the expression level of miR-1247-5p was an independent prognostic indicator for most tumor types.Overexpression of miR-1247-5p significantly inhibited the migration and invasion abilities of gastric cancer cells.Bioinformatics analysis suggested that the downstream target genes of miR-1247-5p were involved in EMT and other pathways closely related to tumor metastasis.PPI analysis revealed that Smad2 was a Hub gene in the EMT signaling pathway.Dual-luciferase reporter assay demonstrated the existence of binding sites between miR-1247-5p and Smad2.RT-qPCR and Western blot experiments confirmed that miR-1247-5p can inhibit the expression of Smad2 and the process of EMT.Conclusion miR-1247-5p is lowly expressed in gastric cancer tissue,and overexpression of miR-1247-5p can inhibit EMT signaling pathway and reduce the invasive metastatic potential of gastric cancer cells.

Aim To investigate the mechanism of ultra-fine garlic powder(UGP)in ameliorating dyslipidemia and aortic inflammation and fibrosis in atherosclerotic(AS)mice.Methods A 10-week ApoE-/-mouse AS model was constructed,cardiac index was meas-ured,and aortic histopathological changes were ob-served by oil red O staining.Serum inflammatory factor levels were detected by ELISA,and the expression of JNK,NF-κB,ERK and their phosphorylated proteins were detected by Western blot.Results Cardiac in-dex and other indicators as well as aortic lesions were worsened in the AS group,as compared with the normal control group.Compared with the AS group,the UGP treatment group and the traditional garlic grinding pow-der(TGP)treatment group significantly decreased total cholesterol(TC),triglyceride(TG),low-density lipo-protein cholesterol(LDL-C),atherosclerosis index(AI1,AI2),and coronary cardiac index and restored high-density lipoprotein cholesterol(HDL-C)levels,and the area of aortic lesions,inflammation and fibrosis were significantly improved,and at the same time,sig-nificantly inhibited the expression of TNF-α,IL-1β,and IL-6,as well as the expression of p-JNK,p-NF-κB and p-ERK proteins.The therapeutic effect of the UGP group was superior to that of the TGP group.Conclu-sion UGP can significantly inhibit the formation of aortic endothelial AS plaques,reduce the levels of in-flammation and fibrosis,and regulate blood lipids in a-orta of AS mice.