OBJECTIVE To investigate the effects and mechanism of asperuloside （Asp） on the pyroptosis of intestinal epithelial cells in rats with ulcerative colitis （UC）. METHODS The male SD rats were randomly divided into Control group， model group （UC group）， ASP low-dose and high-dose groups [Asp-L， Asp-H groups， Asp 35， 70 mg/（kg·d）]， ASP high-dose group+AMPK inhibitor Compound C group [Asp-H+Compound C group， Asp 70 mg/（kg·d）+Compound C 0.2 mg/（kg·d）]， with 12 rats in each group. Except for Control group， the other groups were injected with 50% ethanol （0.25 mL）+5% 2，4， 6- trinitrobenzene sulfonic acid solution （2 mL/kg） into the intestinal cavity to construct UC model. After modeling， the rats in each drug group were given corresponding drug solution by gavage or （and） tail vein injection， once a day， for 14 consecutive days. After the last administration， the weight of rats in each group was measured， and the length of their colons was measured； disease activity index （DAI） score and colonic mucosal damage index （CMDI） score were performed， and the serum levels of inflammatory factors （interleukin-18， -1β， -6） were detected. The pathological changes of the colon tissue were observed. The expressions of pyroptosis-related proteins [caspase-1， gasdermin D （GSDMD）] in colon tissue， and pathway-related proteins such as adenosine monophosphate-activated protein kinase （AMPK）， thioredoxin-interacting protein （TXNIP）， NOD-like receptor protein 3 （NLRP3） and apoptosis-associated speck-like protein containing a CARD （ASC） were all detected. RESULTS Compared with Control group， the colon tissue structure of rats in UC group was damaged， with obvious infiltration of inflammatory cells and edema. Their body weight， colon length and phosphorylation level of AMPK protein were significantly reduced or shortened； DAI and CMDI scores， serum levels of inflammatory factors， and the protein expressions of caspase-1， GSDMD， TXNIP， NLRP3 and ASC in colon tissue were increased or upregulated significantly （P＜0.05）. Compared with UC group， the pathological damage of colon tissue in rats was relieved in Asp-L and Asp-H groups， and all quantitative indicators were significantly improved （P＜0.05）； the improvement effect of Asp-H group was more significant （P＜0.05）. Compound C could significantly reverse the improvement effect of high-dose of Asp on the above indicators in UC rats （P＜0.05）. CONCLUSIONS Asp can improve inflammatory damage in colon tissue and inhibit pyroptosis of intestinal epithelial cells in UC rats， which is associated with the activation of AMPK and inhibition of TXNIP/NLRP3 signaling pathway.

OBJECTIVE To investigate the effects and mechanism of asperuloside （Asp） on the pyroptosis of intestinal epithelial cells in rats with ulcerative colitis （UC）. METHODS The male SD rats were randomly divided into Control group， model group （UC group）， ASP low-dose and high-dose groups [Asp-L， Asp-H groups， Asp 35， 70 mg/（kg·d）]， ASP high-dose group+AMPK inhibitor Compound C group [Asp-H+Compound C group， Asp 70 mg/（kg·d）+Compound C 0.2 mg/（kg·d）]， with 12 rats in each group. Except for Control group， the other groups were injected with 50% ethanol （0.25 mL）+5% 2，4， 6- trinitrobenzene sulfonic acid solution （2 mL/kg） into the intestinal cavity to construct UC model. After modeling， the rats in each drug group were given corresponding drug solution by gavage or （and） tail vein injection， once a day， for 14 consecutive days. After the last administration， the weight of rats in each group was measured， and the length of their colons was measured； disease activity index （DAI） score and colonic mucosal damage index （CMDI） score were performed， and the serum levels of inflammatory factors （interleukin-18， -1β， -6） were detected. The pathological changes of the colon tissue were observed. The expressions of pyroptosis-related proteins [caspase-1， gasdermin D （GSDMD）] in colon tissue， and pathway-related proteins such as adenosine monophosphate-activated protein kinase （AMPK）， thioredoxin-interacting protein （TXNIP）， NOD-like receptor protein 3 （NLRP3） and apoptosis-associated speck-like protein containing a CARD （ASC） were all detected. RESULTS Compared with Control group， the colon tissue structure of rats in UC group was damaged， with obvious infiltration of inflammatory cells and edema. Their body weight， colon length and phosphorylation level of AMPK protein were significantly reduced or shortened； DAI and CMDI scores， serum levels of inflammatory factors， and the protein expressions of caspase-1， GSDMD， TXNIP， NLRP3 and ASC in colon tissue were increased or upregulated significantly （P＜0.05）. Compared with UC group， the pathological damage of colon tissue in rats was relieved in Asp-L and Asp-H groups， and all quantitative indicators were significantly improved （P＜0.05）； the improvement effect of Asp-H group was more significant （P＜0.05）. Compound C could significantly reverse the improvement effect of high-dose of Asp on the above indicators in UC rats （P＜0.05）. CONCLUSIONS Asp can improve inflammatory damage in colon tissue and inhibit pyroptosis of intestinal epithelial cells in UC rats， which is associated with the activation of AMPK and inhibition of TXNIP/NLRP3 signaling pathway.

With the widespread use of antibiotics, drug-resistant bacterial infections have become a significant threat to human health. Finding new antibacterial strategies that can effectively control drug-resistant bacterial infections has become an urgent task. Unlike small molecule drugs that target bacterial proteins, antisense oligonucleotide (ASO) can target genes related to bacterial resistance, pathogenesis, growth, reproduction and biofilm formation. By regulating the expression of these genes, ASO can inhibit or kill bacteria, providing a novel approach for the development of antibacterial drugs. To overcome the challenge of delivering antisense oligonucleotide into bacterial cells, various drug delivery systems have been applied in this field, including cell-penetrating peptides, lipid nanoparticles and inorganic nanoparticles, which have injected new momentum into the development of antisense oligonucleotide in the antibacterial realm. This review summarizes the current development of small nucleic acid drugs, the antibacterial mechanisms, targets, sequences and delivery vectors of antisense oligonucleotide, providing a reference for the research and development of antisense oligonucleotide in the treatment of bacterial infections.

Merkel cell polyomavirus (MCV) was named thus because it is the causative agent of Merkel cell carcinoma (MCC), with 80% of MCC cases being MCV-positive. MCV has been classified as a 2A carcinogen. It promotes carcinogenesis by integrating T antigens into the cell genome. The anti-MCV seroprevalence in the general population is as high as 90%. Usually, MCV is latent after infection in immunocompetent patients, and the incidence of MCC in immunosuppressive or defective patients, such as those with organ transplants, chronic lymphocytic leukemia, and HIV infection, is remarkably high. Patients with HIV/AIDS are a typical population with acquired immunodeficiency. At present, the research on patients with HIV/AIDS and MCV infection, activation, and pathogenesis is limited. In this paper, the progress of previous research is reviewed and the relationship between HIV infection and MCV activation is systematically investigated to provide a reference for the prevention and treatment of MCC in key populations, such as patients with HIV/AIDS.

Objectives: To elucidate the potential mechanisms of electroacupuncture (EA) in restoring detrusor-bladder neck dyssynergia (DBND) following suprasacral spinal cord injury (SSCI). Methods: A total of 52 specific pathogen-free (SPF) grade famale Sprague-Dawley (SD) rats (10 – 12 weeks, 250 – 280 g) were randomly assigned to either a sham group (n = 12) or a spinal cord injury model group (n = 40). In the model group, DBND was induced through Hassan Shaker spinal cord transection at T10 level, with 24 rats meeting inclusion criteria and subsequently randomized into DBND group (n = 12) and EA intervention group (DBND + EA group, n = 12). After spinal shock recovery (day 19 after modeling), DBND + EA group received EA treatment at Ciliao (BL32), Zhongji (RN3), and Sanyinjiao (SP6) acupoints for 20 min per session at 10/50 Hz frequencies, once daily for 10 d. Sham and DBND groups received anesthesia only without EA intervention. On day 29 post-modeling, all rats underwent urodynamic assessments, followed by hematoxylin and eosin (HE) staining, tandem mass tag (TMT) proteomics, and Western blot (WB) analysis of detrusor and bladder neck tissues. Differentially expressed proteins (DEPs) were defined as proteins with P < 0.05, unique peptides ≥ 2, and fold change > 1.2 or < 0.83. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was performed using KOBAS 3.0 (P < 0.01), and protein-protein interaction (PPI) networks were analyzed using Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) 11.5 and Cytoscape 3.9.1. Results: Compared with sham group, DBND group showed significantly elevated leak point pressure (LPP) and maximum cystometric capacity (MCC) (both P < 0.01). EA treatment significantly reduced both LPP and MCC compared with DBND group (P < 0.01 and P < 0.05, respectively). HE staining revealed that EA reduced detrusor fibrosis and improved bladder neck inflammation. TMT proteomics identified 30 overlapping DEPs in detrusor and 59 overlapping DEPs in bladder neck when comparing DBND + EA/DBND groups with sham group. In detrusor tissue, KEGG analysis revealed 10 significantly enriched pathways (P < 0.01), including mitogen-activated protein kinase (MAPK) signaling pathway. PPI analysis showed 22 of 30 DEPs were interconnected. In bladder neck tissue, 14 pathways were significantly enriched (P < 0.01), including relaxin signaling pathway, with 51 of 59 DEPs showing interconnections. Both TMT and WB validations demonstrated that compared with sham controls, DBND rats exhibited upregulated collagen type IV alpha 2 chain (Col4a2) and downregulated guanine nucleotide-binding protein G(z) subunit alpha (Gnaz) in detrusor tissue, while EA treatment normalized both proteins (both P < 0.05). In bladder neck tissue, DBND rats showed decreased expression of smoothelin (Smtn) and calcium-activated potassium channel subunit beta-1 (Kcnmb1) compared with sham controls (both P < 0.01), which were both upregulated following EA treatment (P < 0.01 and P < 0.05, respectively). Conclusion EA restores detrusor-bladder neck coordination in DBND through dual-target mechanisms. In detrusor tissue, EA modulates contraction via extracellular matrix remodeling, cyclic adenosine monophosphate (cAMP) signaling pathway regulation, and enhanced adenosine triphosphate (ATP) biosynthesis mediated by neurotransmitters. In bladder neck tissue, EA promotes relaxation by maintaining contractile phenotypes, reducing fibrosis, suppressing smooth muscle excitation, and regulating presynaptic neurotransmitter release. These findings provide mechanistic insights into EA's therapeutic role in managing DBND.

Platelets have long been recognized as key players in hemostasis and thrombosis; however, there is growing evidence that they are also involved in cancer. Preclinical and clinical studies have shown that platelets can promote tumorigenesis and metastasis through various crosstalks between platelets and cancer cells. Platelets play an active role in all stages of tumorigenesis, including tumor growth, tumor cell extravasation, and metastasis. In addition, thrombocytosis in cancer patients is associated with poor patient survival. Platelets are also well-placed to coordinate local and distant tumor-host interactions due to the a- bundance of microparticles and exosomes. Therefore, antitumor drugs targeting platelets have great development and application prospects. The following will review the research progress of anti-tumor drugs targeting platelets.

ObjectiveTo construct and validate a clinical prediction model for diabetic kidney disease （DKD） based on optical coherence tomography angiography （OCTA）. MethodsThis study enrolled 567 diabetes patients. The random forest algorithm as well as logistic regression analysis were applied to construct the prediction model. The model discrimination and clinical usefulness were evaluated by receiver operating characteristic curve （ROC） and decision curve analysis （DCA）， respectively. ResultsThe clinical prediction model for DKD based on OCTA was constructed with area under the curve （AUC） of 0.878 and Brier score of 0.11. ConclusionsThrough multidimensional verification， the clinical prediction nomogram model based on OCTA allowed for early warning and advanced intervention of DKD.

Objective:To compare the outcomes of robot-assisted laparoscopic partial nephrectomy (RAPN) and laparoscopic partial nephrectomy (LPN) in the treatment of tumors in isolated kidney, and analyze the factors influencing postoperative renal function and long-term survival in patients.Methods:A retrospective analysis was conducted on clinical data of 67 patients with tumors in isolated kidney who underwent surgery at the Chinese PLA General Hospital from November 2010 to January 2022. There were 48 males and 19 females, with an average age of (58.6±10.1) years old. The patients were divided into RAPN group (43 cases) and LPN group (24 cases) based on the surgical approach. The RAPN group had a higher R.E.N.A.L. score than the LPN group [(8.7±1.5) vs. (7.9±1.7), P=0.042]. There were no statistically significant differences between the two groups in terms of age [(57.4±10.2) years old vs. (60.9±9.8) years old, P=0.185], body mass index (BMI) [(25.7±3.5) kg/m 2 vs. (25.1±3.6) kg/m 2, P=0.518], and preoperative serum creatinine [(102.9±31.6) μmol/L vs. (102.3±22.4) μmol/L, P=0.930]. Twelve cases underwent hypothermic treatment during surgery, with 9 cases(20.9%) in the RAPN group and 3 cases(12.5%) in the LPN group( P=0.596). Surgical time, intraoperative warm ischemia time, intraoperative blood loss, postoperative fasting time, perioperative complication rate, postoperative serum creatinine, and other indicators were compared between the two groups. Multiple linear regression analysis was used to identify factors affecting postoperative serum creatinine. Kaplan-Meier curves were employed to analyze patient prognosis, and log-rank tests were performed to compare the differences between the two groups. Multiple Cox regression analysis was used to identify factors influencing patient prognosis. Results:All surgeries were completed successfully with negative pathological margins. There were no statistically significant differences between the RAPN and LPN groups in terms of surgical time [(136.6±47.6) min vs. (125.3±34.4) min, P=0.311], intraoperative ischemia time [23.0 (16.0, 30.0) min vs. 19.0 (13.5, 27.5) min, P =0.260], intraoperative blood loss [50.0 (50.0, 100.0) ml vs. 50.0 (22.5, 100.0) ml, P=0.247], postoperative hospital stay [(6.6±3.5) days vs. (7.7±4.2) days, P=0.244], time to drain removal [4(3, 5) days vs. 5(3, 6) days, P =0.175], postoperative fasting time [(2.1±0.7) days vs. (2.2±1.0) days, P=0.729], perioperative complication rate [18.6% (8/43) vs. 16.7% (4/24), P=1.000], postoperative serum creatinine [145.2 (128.3, 191.3) μmol/L vs. 157.8 (136.2, 196.3) μmol/L, P =0.229], and pathological staging [T 1a/T 1b/T 2a/T 3a/T 4 stage: 32/7/1/3/0 case vs. 17/5/0/1/1 case, P=0.804]. Kaplan-Meier survival curves showed that the total survival rates at 1, 3, and 5 years after surgery were 94.7%, 84.9%, and 84.9% for the RAPN group, and 100.0%, 95.5%, and 95.5% for the LPN group, with no statistically significant difference in the log-rank test ( P=0.116). Excluding 10 patients with preoperative tumor metastasis (7 in the RAPN group and 3 in the LPN group), the progression-free survival rates at 1, 3, and 5 years after surgery were 84.8%, 81.1%, and 81.1% for the RAPN group, and 100.0%, 95.0%, and 90.0% for the LPN group, with no statistically significant difference in the log-rank test ( P =0.142). Multiple linear regression analysis showed that the use of hypothermic treatment during surgery significantly reduced postoperative serum creatinine ( B=-72.191, P=0.048). Multiple Cox regression analysis revealed that BMI ( HR=0.743, P=0.044), pathological T stage ( HR=4.235, P=0.018), and preoperative metastasis ( HR=18.829, P=0.035) were independent factors affecting patient overall survival time. A smaller BMI, higher pathological stage, and preoperative metastasis were associated with poorer prognosis. Conclusions:Despite the higher R. E.N.A.L. score and greater surgical difficulty in the RAPN group, RAPN achieved similar perioperative and prognostic results as the LPN, indicating RAPN advantages in treating tumors in isolated kidney. Appropriate intraoperative hypothermic treatment can better protect postoperative renal function. BMI, pathological T stage, and preoperative metastasis are independent factors affecting overall survival time.

AIM To establish a quantitative analysis of multi-components by single-marker(QAMS)method for the simultaneous content determination of gastrodin,parishin E,syringin,parishin B,parishin C,ferulic acid,parishin A,buddleoside,harpagoside and cinnamic acid in Tianma Toufengling Capsules.METHODS The analysis was performed on a 30℃thermostatic GL Science InertsilTM ODS-3 column(150 mm×4.6 mm,5 μm),with the mobile phase comprising of acetonitrile-0.1%phosphoric acid flowing at 1.0 mL/min in a gradient elution manner,and the detection wavelengths were set at 220,280 nm.Syringin was used as an internal standard to calculate the relative correction factors of the other nine constituents,after which the content determination was made.RESULTS Ten constituents showed good linear relationships within their own ranges(r≥0.999 7),whose average recoveries were 98.53%-102.22%with the RSDs of 1.26%-2.68%.The result obtained by QAMS approximated those obtained by external standard method.CONCLUSION This accurate and specific method can be used for the quality control of Tianma Toufengling Capsules.

Diabetic retinopathy(DR), the most common ocular complication of diabetes, is one of the major causes of vision impairment and even blindness among the working population as well as middle-aged and elderly individuals. In the diabetic microvascular system, hyperglycemia damages retinal endothelial cells, enhances vascular permeability and disrupts the blood-retinal barrier through different mechanisms, all of which result in endothelial dysfunction. Retinal vascular dysfunction caused by multifactors, such as peroxisome proliferator-activated receptor-y disruption, oxidative stress, inflammation, increased advanced glycation end products and their receptors, and microRNA dysregulation can cause vascular endothelial damage, accelerate retinal endothelial dysfunction, lead to the progression of DR. Therefore, the available date and the contributors in the pathophysiology of DR are reviewed with a special emphasis on the retinal endothelial dysfunction, for a better understanding of the molecular cellular mechanism in the development of DR, to analyze the challenges in the treatment of DR and to provide new ideas and strategies for the clinical management and treatment of DR.