It is believed that patients with cirrhotic ascites exhibit a pathological mechanism characterized by the decline of healthy qi and the accumulation of pathogenic factors. Clinically， treatment should be based on the theory of tonification and purging， with a staged approach distinguishing between the active phase and the remission phase. The balance between tonification and purging should be adjusted according to the progression of pathogenic and healthy actors. In the acute phase， purging should take precedence over tonification， using purging as a means of tonification to facilitate the flow of water and qi through the triple energizer. The severity of water retention， dampness， blood stasis， and heat should be carefully assessed to ensure thorough elimination of pathogenic factors while avoiding harm to healthy qi. Medication adjustments should be made once the pathogenic factors are significantly weakened. In the remission phase， an integrated approach combining both tonification and purging should be adopted， incorporating purging within tonification to clear residual pathogens and prevent recurrence. Concurrently， proactive treatment of the underlying disease is essential to achieve complete recovery and prevent the recurrence of ascites.

Intestinal fibrosis is a significant clinical challenge in inflammatory bowel diseases, but no effective anti-fibrotic therapy is currently available. Glucagon receptor (GCGR) and glucagon-like peptide 1 receptor (GLP1R) are both peptide hormone receptors involved in energy metabolism of epithelial cells. However, their role in intestinal fibrosis and the underlying mechanisms remain largely unexplored. Herein GCGR and GLP1R were found to be reduced in the stenotic ileum of patients with Crohn's disease as well as in the fibrotic colon of mice with chronic colitis. The downregulation of GCGR and GLP1R led to the accumulation of the metabolic byproduct lactate, resulting in histone H3K9 lactylation and exacerbated intestinal fibrosis through epithelial-to-mesenchymal transition (EMT). Dual activating GCGR and GLP1R by peptide 1907B reduced the H3K9 lactylation in epithelial cells and ameliorated intestinal fibrosis in vivo. We uncovered the role of GCGR/GLP1R in regulating EMT involved in intestinal fibrosis via histone lactylation. Simultaneously activating GCGR/GLP1R with the novel dual agonist peptide 1907B holds promise as a treatment strategy for alleviating intestinal fibrosis.

Lacking therapeutic targets highlights the crucial roles of chemotherapy and radiotherapy in the clinical management of triple-negative breast cancer (TNBC). To relieve the side effects of the chemoradiotherapy combination regimen, we design and develop a self-assembled micelle nanosystem consisting of perfluorocarbon chain-modified cisplatin prodrug. By incorporating perfluorodecalin, this nanosystem can effectively carry ozone and promote irradiation-derived reactive oxygen species (ROS) production. By leveraging the perfluorocarbon sidechain, the nanosystem exhibits efficient internalization by TNBC cells and effectively escapes from lysosomal entrapment. Under X-ray irradiation, ozone-generated ROS disrupts the intracellular redox balance, thereby facilitating the release of cisplatin in a reduction-responsive manner mediated by reduced glutathione. Moreover, oxygen derived from ozone decomposition enhances the efficacy of radiotherapy by alleviating tumor hypoxia. Notably, the combination of irradiation with ozone-loaded cisplatin prodrug nano system synergistically prompts antitumor efficacy and reduces cellular/systemic toxicity in vitro and in vivo. Furthermore, the combo regimen remodels the tumor microenvironment into an immune-favored state by triggering immunogenic cell death and relieving hypoxia, which provides a promising foundation for a combination regimen of immunotherapy. In conclusion, our nanosystem presents a novel strategy for integrating chemotherapy and radiotherapy to optimize the efficacy and safety of TNBC clinical treatment.

Poly(ADP-ribosyl)ation (PARylation) is a specific form of post-translational modification (PTM) predominantly triggered by the activation of poly-ADP-ribose polymerase 1 (PARP1). However, the role and mechanism of PARylation in the advancement of acute kidney injury (AKI) remain undetermined. Here, we demonstrated the significant upregulation of PARP1 and its associated PARylation in murine models of AKI, consistent with renal biopsy findings in patients with AKI. This elevation in PARP1 expression might be attributed to trimethylation of histone H3 lysine 4 (H3K4me3). Furthermore, a reduction in PARylation levels mitigated renal dysfunction in the AKI mouse models. Mechanistically, liquid chromatography-mass spectrometry indicated that PARylation mainly occurred in receptor for activated C kinase 1 (RACK1), thereby facilitating its subsequent phosphorylation. Moreover, the phosphorylation of RACK1 enhanced its dimerization and accelerated the ubiquitination-mediated hypoxia inducible factor-1α (HIF-1α) degradation, thereby exacerbating kidney injury. Additionally, we identified a PARP1 proteolysis-targeting chimera (PROTAC), A19, as a PARP1 degrader that demonstrated superior protective effects against renal injury compared with PJ34, a previously identified PARP1 inhibitor. Collectively, both genetic and drug-based inhibition of PARylation mitigated kidney injury, indicating that the PARylated RACK1/HIF-1α axis could be a promising therapeutic target for AKI treatment.

Objectives:To evaluate the safety and feasibility of simultaneous bilateral adrenal vein sampling(AVS)via the basilic vein approach. Methods:21 consecutive patients with primary aldosteronism(PA)who underwent simultaneous bilateral AVS via the basilic vein in Fuwai Hospital between July 2023 and November 2023 were enrolled in this study.The puncture site,catheter used in AVS,operation time,fluoroscopy time,contrast agent dosages,success rate of bilateral sampling,adverse events,and complications were recorded and analyzed.Successful sampling was determined by a selectivity index(cortisol in the adrenal vein/cortisol in inferior vena cava)greater than or equal to 2. Results:The average age of 21 patients was(49.3±7.7)years,with 13 male patients.The first 5F sheath was successfully inserted into the right basilic vein in all patients,the second 5F sheath insertion failed in two patients and switched to the ipsilateral cephalic vein approach.The 5F MPA1 catheter was inserted into the right adrenal vein and the 5F TIG catheter into the left adrenal vein in all patients.Operation time was 17.50(12.00,22.00)min,fluoroscopy time was 5.90(4.75,10.55)min,and contrast agent dosage was 25.00(25.00,35.00)ml.Bilateral AVS was successful in all patients.Two patients experienced adverse events,one case was catheter entanglement,which resulted in 5F TIG catheter slipped from adrenal vein,and another case was vascular spasm.No complications were recorded. Conclusions:Simultaneous bilateral AVS via basilic vein approach is safe and feasible in most PA patients,further researches with larger patient cohort are needed to validate the results from this study.

Objectives:To investigate long-term clinical outcomes of renal denervation(RDN)for the treatment of resistant hypertension. Methods:This study retrospectively enrolled 58 patients with resistant hypertension who received RDN treatment via femoral artery approach at Fuwai Hospital between February 2012 and November 2019.Follow up was performed at 1,3,6 months,1 year,and annually after RDN,and the last follow-up was June 2023.The baseline data and postoperative follow-up data including office blood pressure,24-hour mean blood pressure and heart rate,types and load of antihypertensive drugs,renal function,and major adverse events(including renal artery stenosis,acute myocardial infarction,stroke,cardiovascular death,and all-cause death)were obtained and analyzed.The impact of RDN on 10-year cardiovascular and cerebrovascular events was evaluated using the Framingham risk assessment model and the Chinese model. Results:A total of 58 patients were enrolled,with 1 patient(1.72%)died from lung cancer.Forty-one patients(70.69%)were visited in the last follow-up and the average follow-up time was(10.21±1.75)years.Compared with baseline,the office systolic/diastolic blood pressure was decreased by(12.59±21.65)/(9.87±14.27)mmHg(P<0.01,1 mmHg=0.133 kPa),24-hour mean systolic/diastolic blood pressure reduced by(11.28±15.33)/(7.94±12.29)mmHg(P<0.01),24-hour mean heart rate reduced by(2.45±9.46)bpm(P>0.05),the types of antihypertensive drugs decreased by 1.17±2.25(P<0.01),the drug load reduced by 1.45±2.37(P<0.001),and the estimated glomerular filtration rate decreased by(6.83±18.37)ml/(min·1.73 m2)(P<0.05)at the last follow-up.The impact of RDN on 10-year cardiovascular events and stroke risk was as follows:Framingham risk assessment showed an absolute risk decrease of 14.25%and 2.12%,respectively,and decreased by 5.72%and 17.46%using the Chinese cardiovascular and cerebrovascular risk assessment. Conclusions:This study showed that RDN could significantly reduce blood pressure levels in patients with resistant hypertension in the long-term follow up,and was expected to further reduce cardiovascular and cerebrovascular risks.

In recent years,aldosterone synthase inhibitor(ASI)has attracted widespread attention as a treatment option for hypertension.Drugs such as osilodrostat,baxdrostat,lorundrostat,and dexfadrostat have been developed and the therapeutic effects have been evaluated in a series of clinical studies.This article intends to elaborate current clinical research results,problems,and controversies of ASI for the treatment of hypertension,and explore the feasibility of using ASI for the treatment of primary aldosteronism.

This article inherited and summarized the application of Professor Tang Xudong's"New Eight Principles in the Syndrome Differentiation and Treatment of Spleen and Stomach Diseases"(abbreviated as"New Eight Principles")in the field of chronic liver disease.It believed that chronic liver disease should be distinguished from the four aspects of"zangfu organs-qi and blood-deficiency and excess-cold and heat".The differentiation of zangfu organs is mainly focused on regulating the liver and spleen,while also taking into account other organs;the differentiation of qi and blood emphasizes the knowing of its excess and deficiency,and the administrative levels of the disease;the differentiation of deficiency and excess is based on the principle of qi-deficency and blood-stasis,and strengthens body resistance and eliminating evil;for the differentiation of cold and heat,liver-gallbladder dampness-heat syndrome is the most common,but do not forget the liver cold syndrome.On this basis,Tongjiang theory is used as the treatment legislation,making it easier to be mastered,and guiding the prescription and medication of chronic liver disease throughout the entire stage,which can achieve good efficacy.

Objective:To systematically appraise and summarize existing evidence on enteral nutrition in patients receiving radiotherapy for head and neck cancer.Methods:Based on the 6S Pyramid of Evidence-based Resources, a systematic search was conducted to identify guidelines, expert consensuses, and evidence summaries related to enteral nutrition for radiotherapy patients with head and neck cancer published from January 2018 to September 2023. The search covered relevant websites of guidelines, websites of academic societies, and databases (in Chinese and English). Literature screening, quality assessment, and data extraction were performed independently by the researchers.Results:A total of 19 studies were included, consisting of 10 guidelines, 7 expert consensuses, and 2 evidence summaries. Four aspects and 67 items of best evidence on organizational management, nutritional screening and assessment, enteral nutritional intervention programs, and monitoring and follow-up were summarized.Conclusion:This study summarized the best evidence for enteral nutrition in patients receiving radiotherapy for head and neck cancer, which can inform the standardized nutritional management and promote the translation of evidence-based knowledge into practice.

Objective To compare pregnancy outcomes among pregnant women undergoing cervical polypectomy during different gestational periods.Methods A total of 125 pregnant women were diagnosed with cervical polyps and underwent surgical removal.These participants were divided into the natural pregnancy group(n=71)and the in vitro fertilization and embryo transfer group(IVF-ET group,n=54).Retrospective analysis was conducted on various clinical parameters including age,gestational times,delivery times,abortion times,history of adverse preg-nancy outcomes,history of endometrial polyps,pre-polyp removal vaginal bleeding episodes,gestational age at the time of polyp removal procedure,number of polyps detected during surgery,postoperative pathology results as well as pregnancy outcomes.Results Vaginal bleeding was the most common symptom of pregnancy combined with cer-vical polyps,accounting for 111 cases(88.8％)(62 cases in the natural pregnancy group(87.32％)and 49 ca-ses in the IVF-ET group(90.74％)).Some patients had increased vaginal discharge or were found during a gyne-cological exam,accounting for 11.2％of the patients.All patients underwent cervical polypectomy during pregnan-cy,except for 9 cases of continued pregnancy(4 cases in the natural pregnancy group and 5 cases in the IVF-ET group),of which 13 had miscarriage,10 had preterm birth(6 in the natural pregnancy group and 4 in the IVF group)and 93(54 cases in natural pregnancy group,39 cases in IVF group)(74.4％)delivered at full term.Postoperative pathology was mostly inflammatory polyps(105 cases,84％),deciduous polyps(20 cases,8％)(10 cases in the natural pregnancy group and 10 cases in the IVF-ET group,14.09％and 18.52％,respective-ly).The incidence of preoperative vaginal bleeding,decidual polyp,postoperative abortion,and postoperative pre-term birth in the IVF-ET group exhibited higher rates compared to those observed in the natural pregnancy group;however,these differences did not reach statistical significance.Conclusion The cervical polypectomy procedure was performed during pregnancy for both the natural conception group and the IVF-ET group,with no significant disparity observed in pregnancy outcomes between these two cohorts.