This paper summarizes Professor LU Fang's clinical experience in treating systemic lupus erythematosus （SLE） based on the differentiation and treatment of heat-toxin and blood-stasis in the collaterals. SLE is generally characterized by deficiency in origin with excess in manifestation. The core pathogenesis is heat-toxin obstructing the collaterals. During the acute active stage， the predominant pattern is blazing heat-toxin causing blood stasis， while in the chronic remitting stage， the main pattern is toxic stasis blocking the collaterals with qi and yin deficiency. Clinical treatment follows the basic principle that treat with salty-cold herbs， when heat invades internally and that assist with acrid-dispersing herbs when stasis obstructs the collaterals. The self-formulated Yimian Decoction （抑免汤） serves as the base formula and is applied in stages. During the acute active stage， it is often combined with herbs for clearing heat and detoxifying， cooling blood and resolving stasis， and unblocking the collaterals. In the chronic remitting stage， it is often combined with herbs for activating blood circulation and unblocking the collaterals， as well as tonifying qi and nourishing yin.

This paper summarizes professor LI Guolie's clinical experience in treating orthostatic hypotension （OH） based on the theory of "raising the clear and directing the turbid downward". It is considered that the core pathogenesis of OH lies in the body's transition from a supine to an upright position， during which dysfunction of the middle jiao （焦） transformation and transportation， along with impaired pivot function， hinders the ascending of clear yang and the descending of turbid yin. Treatment should follow the general principle of "ascending the clear and directing the turbid downward"， placing emphasis on distinguishing the primary and secondary aspects. For cases where the clear yang fails to ascend， the self-formulated Li's Shengqing Jiangzhuo Decoction （李氏升清降浊汤）is used to supplement qi， raise the clear， and strengthen the middle jiao. For cases where the turbid yin fails to descend， the self-formulated Wuxiang Qingzhuo Beverage（五香清浊饮）with modifications is applied to resolve phlegm， eliminate stasis， harmonize the middle， and descend the turbid.

This paper summarizes professor LI Guolie's clinical experience in treating orthostatic hypotension （OH） based on the theory of "raising the clear and directing the turbid downward". It is considered that the core pathogenesis of OH lies in the body's transition from a supine to an upright position， during which dysfunction of the middle jiao （焦） transformation and transportation， along with impaired pivot function， hinders the ascending of clear yang and the descending of turbid yin. Treatment should follow the general principle of "ascending the clear and directing the turbid downward"， placing emphasis on distinguishing the primary and secondary aspects. For cases where the clear yang fails to ascend， the self-formulated Li's Shengqing Jiangzhuo Decoction （李氏升清降浊汤）is used to supplement qi， raise the clear， and strengthen the middle jiao. For cases where the turbid yin fails to descend， the self-formulated Wuxiang Qingzhuo Beverage（五香清浊饮）with modifications is applied to resolve phlegm， eliminate stasis， harmonize the middle， and descend the turbid.

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.

Idiopathic pulmonary fibrosis (IPF), a chronic interstitial lung disease, is characterized by aberrant wound healing, excessive scarring and the formation of myofibroblastic foci. Although the role of alternative splicing (AS) in the pathogenesis of organ fibrosis has garnered increasing attention, its specific contribution to pulmonary fibrosis remains incompletely understood. In this study, we identified an up-regulation of serine/arginine-rich splicing factor 7 (SRSF7) in lung fibroblasts derived from IPF patients and a bleomycin (BLM)-induced mouse model, and further characterized its functional role in both human fetal lung fibroblasts and mice. We demonstrated that enhanced expression of Srsf7 in mice spontaneously induced alveolar collagen accumulation. Mechanistically, we investigated alternative splicing events and revealed that SRSF7 modulates the alternative splicing of pyruvate kinase (PKM), leading to metabolic dysregulation and fibroblast activation. In vivo studies showed that fibroblast-specific knockout of Srsf7 in conditional knockout mice conferred resistance to bleomycin-induced pulmonary fibrosis. Importantly, through drug screening, we identified lomitapide as a novel modulator of SRSF7, which effectively mitigated experimental pulmonary fibrosis. Collectively, our findings elucidate a molecular pathway by which SRSF7 drives fibroblast metabolic dysregulation and propose a potential therapeutic strategy for pulmonary fibrosis.

Congenital lower urinary tract obstruction (CLUTO) is a spectrum of fetal malformations caused by anatomical abnormalities of the urethra, characterized by high rates of perinatal complications and mortality. The 2024 joint guideline from the European Association of Urology (EAU) and the European Society for Paediatric Urology (ESPU) introduced systematic revisions to the comprehensive management of CLUTO. Key updates encompass advancements in prenatal and postnatal screening and precise diagnosis, refined fetal prognosis assessment, clearer indications and modality selection for prenatal intervention, optimization of postnatal treatment strategies, and the establishment of a lifelong follow-up framework within an integrated care pathway. This article elucidates these key updates by comparing the 2024 EAU/ESPU guideline with the 2022 European Rare Kidney Disease Reference Network (ERKNet) consensus. It also discusses ongoing controversies and future research directions. The aim is to provide clinicians with the latest evidence-based insights to inform practice, ultimately improving outcomes and quality of life for children with CLUTO.
Humans ; Urology ; Female ; Urethral Obstruction/therapy* ; Pregnancy ; Child ; Europe ; Prenatal Diagnosis ; Infant, Newborn ; Urethra/abnormalities*

Helicobacter pylori is a bacterium that can cause chronic gastritis, peptic ulcers, and other gastrointestinal diseases. The World Health Organization has classified H. pylori as a group Ⅰ carcinogen. Antibiotics are the primary clinical approach for eradicating H. pylori. However, incomplete eradication of H. pylori by antibiotics can lead to persistent infection, which is a major risk factor for the high incidence of gastric cancer. The widespread use of antibiotics has led to the emergence of multidrug resistance in H. pylori, contributing to treatment failures of chronic gastric diseases and increasing the risk of spreading resistant strains. Multidrug-resistant H. pylori has become a serious challenge in the diagnosis and treatment of gastrointestinal diseases. This paper reviews the global trends in the development of multidrug resistance in H. pylori, the underlying mechanisms, the challenges it poses to clinical diagnosis, and its impact on drug development, drawing on relevant literature and the research findings from our group. It proposes using cgt expression as a novel method for determining viable bacteria, identifying intracellularization as a new form of resistance in H. pylori, and exploring the potential of O-glycans as a therapeutic approach against H. pylori to address multidrug resistance. It provides new insights into understanding the mechanisms of H. pylori multidrug resistance and its prevention strategies, offering promising directions for future clinical treatments and antimicrobial drug development.
Helicobacter pylori/genetics* ; Humans ; Drug Resistance, Multiple, Bacterial ; Helicobacter Infections/microbiology* ; Anti-Bacterial Agents/therapeutic use* ; Gastrointestinal Diseases/drug therapy*

[Objective] To conduct serological identification and molecular mechanism study on a ambiguous ABO blood group. [Methods] Standard serological techniques were used for the forward and reverse typing of ABO blood type. ABO gene coding and regulatory regions were analyzed by PCR after DNA extraction. Monoclonal sequencing was used to detect the haplotypes of the DNA sequence, and bioinformatics analysis was applied to predict the possible translation outcomes of the mutated DNA sequence. [Results] The sample’s red blood cells showed mixed field agglutination with anti-A, and the serum agglutinated with B cells, exhibiting serological characteristics of subtype A. Direct sequencing and monoclonal sequencing analysis of the ABO gene confirmed one allele as O02, the other had a c.27delC mutation compared with A102, which could cause the translation sequence to terminate prematurely at the 19th amino acids. Analysis and prediction suggested that the mutation might affect the function of the transferase through mechanisms such as shifting the initiation codon, altering the reading frame and affecting the splice sites. [Conclusion] This case is a rare A subtype caused by the c.27delC variation, and the impact on the glycosyltransferase may involve multiple mechanisms, which require further research and exploration.

Objective:To explore differences in the radiation-induced intestinal injury in mice exposed to ultra-high dose rate (FLASH) and conventional-dose-rate (CONV) pulsed X-ray irradiation in order to provide evidence for the application of ultra-high dose rate pulsed X-rays in gastrointestinal radiotherapy.Methods:Using the random number table method, 32 C57BL/6J mice were randomly divided into four groups: a sham irradiation group (SHAM), two conventional dose rate groups (CONV0.067 and CONV0.1), and an ultra-high dose rate group (F215), with each group containing eight mice. All groups, except SHAM, received a single 12 Gy abdominal X-ray irradiation at dose rates of 0.067, 0.1, and 215 Gy/s, respectively. At 3 d post-irradiation, histopathological (hematoxylin-eosin staining, HE staining), immunohistochemical, and Western blot analysis were performed to assess the histopathological markers and oxidative stress indicators of intestinal tissues, as well as relevant proteins involved in signaling pathways.Results:At 3 d post-irradiation, mice in all irradiation groups suffered from varying degrees of intestinal tissue degeneration and necrosis, epithelial cell shedding, villus shortening, and crypt loss ( t = 5.75, 8.79, 5.71, P < 0.05). Regarding oxidative stress, at 3 d post-irradiation, mice in the CONV0.067 and CONV0.1 groups showed significantly lower levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-PX), glutathione (GSH), and total antioxidant capacity (T-AOC) compared to those in the F215 group ( t = 7.06-10.64, P < 0.01). In contrast, their malondialdehyde (MDA) levels were significantly elevated ( t = 11.06, 8.31, P < 0.01), with no statistical significance observed between them and mice in the F215 group ( P > 0.05). Immunohistochemical and Western blot analyses indicated that at 3 d post-irradiation, mice in the three irradiation groups exhibited an upward trend in the Nrf2 and HO-1 protein levels and a downward trend in the Keap1 protein level compared to those in the SHAM group. Notably, statistical significance was observed between the F215 group and the two conventional dose rate groups ( t = 4.89-20.95, P < 0.05). These result were consistent with the prior changes in antioxidant markers. Conclusions:Ultra-high-dose-rate X-ray irradiation reduces acute RIII by alleviating oxidative stress and modulating the expression of the Keap1-Nrf2-HO-1 signaling pathway.