ObjectiveTo observe the effects of modified Shaofu Zhuyutang on key proteins of the epidermal growth factor receptor （EGFR）/phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway in SD rats with endometriosis. MethodsAfter successful establishment of an endometriosis model in 60 female SD rats of SPF grade via the auto-transplantation method， the rats were randomly divided into a model group， modified Shaofu Zhuyutang high-， medium-， and low-dose groups， and a gestrinone group， with another 12 rats serving as a blank group. The blank and model groups were administered 10 mL·kg^-1 normal saline， while the high-， medium-， and low-dose groups received 30， 15， and 7.5 g·kg^-1 modified Shaofu Zhuyutang， respectively. The gestrinone group was administered 0.25 mg·kg^-1 gestrinone suspension. After four weeks of treatment， uterine contractions were induced with 2 U of oxytocin， and the writhing response of rats was observed. After 24 h， the rats were euthanized， and the weight and volume of ectopic endometrial tissue were recorded. Hematoxylin-eosin （HE） staining was used to observe pathological changes in endometrial tissues， while the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling （TUNEL） assay was used to evaluate the apoptosis rate of endometrial tissues. Immunofluorescence was used to detect the relative expression areas of the B-cell lymphoma-2 gene-associated promoter （Bad） and B-cell lymphoma-2 （Bcl-2） proteins in endometrial tissues. Serum levels of interleukin-1β （IL-1β）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， epidermal growth factor （EGF）， and EGFR were measured by enzyme-linked immunosorbent assay （ELISA）. The relative protein expression levels of EGFR， PI3K， phosphorylated PI3K （p-PI3K）， Akt， and phosphorylated Akt （p-Akt） in endometrial tissues were analyzed by Western blot. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression levels of EGFR， PI3K， and Akt. ResultsCompared with the blank group， the model group showed endometrial thickening， glandular and mesenchymal hyperplasia， a significant decrease in the relative expression area of Bad in ectopic endometrial tissues， a significant increase in the relative expression area of Bcl-2， and a significant reduction in the apoptosis rate as indicated by TUNEL staining. Serum levels of IL-1β， IL-6， TNF-α， EGF， and EGFR were significantly elevated （P<0.01）. The relative protein expression levels of EGFR， PI3K， p-PI3K， Akt， and p-Akt， as well as the mRNA expression levels of EGFR， PI3K， and Akt， were also significantly increased （P<0.01）. Compared with the model group， the high- and medium-dose groups of modified Shaofu Zhuyutang and the gestrinone group exhibited reduced glandular and mesenchymal hyperplasia to varying degrees， with dilated glandular lumens. The number of writhing responses was significantly reduced， the latency to writhing response was significantly prolonged， and the weight and volume of ectopic endometrial tissue were significantly decreased. The relative expression area of Bad in ectopic endometrial tissue was significantly increased， the relative expression area of Bcl-2 was significantly decreased， and the apoptosis rate was significantly elevated as shown by TUNEL staining. Serum levels of IL-1β， IL-6， TNF-α， EGF， and EGFR were significantly reduced， and the relative protein expression levels of EGFR， PI3K， p-PI3K， Akt， and p-Akt， as well as the mRNA expression levels of EGFR， PI3K， and Akt， were significantly decreased （P<0.05，P<0.01）. ConclusionModified Shaofu Zhuyutang may exert therapeutic effects on endometriosis by interfering with key proteins of the EGFR/PI3K/Akt signaling pathway and inducing apoptosis in ectopic endometrial tissue.

Gastric cancer is a high-incidence malignancy that poses a serious threat to public health in China, ranking among the top three cancers in both incidence and mortality. The majority of patients are diagnosed at an advanced stage, resulting in limited treatment options and poor prognosis. To address key challenges in gastric cancer diagnosis and treatment, a research team led by Professor Jiafu Ji at Peking University Cancer Hospital has focused on the project "Development and Dissemination of Precision Medicine Approaches in Gastric Cancer Management". Through a series of high-quality multicenter clinical studies, the team established a set of new international standards in perioperative treatment, individua-lized drug selection, intelligent noninvasive diagnostics, and novel immunotherapy strategies. These advances have significantly improved treatment efficacy and reduced surgical trauma, achieving key technological breakthroughs in diagnosis, therapy, and mechanistic understanding, and systematically enhancing outcomes for gastric cancer patients. The project ' s findings had a broad international impact, including hosting China ' s first International Gastric Cancer Congress. Through nationwide dissemination, they have promoted the development of precision diagnosis and treatment of gastric cancer as a discipline, and led the formulation of the National Health Commission's guidelines for gastric cancer diagnosis and treatment. In recognition of its achievements, the project was awarded the First Prize of the 2024 Chinese Medical Science and Technology Award.
Stomach Neoplasms/genetics* ; Humans ; Precision Medicine/methods* ; China ; Immunotherapy/methods*

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.

Cardiac fibrosis is characterized by an elevated amount of extracellular matrix (ECM) within the heart. However, the persistence of cardiac fibrosis ultimately diminishes contractility and precipitates cardiac dysfunction. Circular RNAs (circRNAs) are emerging as important regulators of cardiac fibrosis. Here, we elucidate the functional role of a specific circular RNA CELF1 in cardiac fibrosis and delineate a novel feedback loop mechanism. Functionally, circ-CELF1 was involved in enhancing fibrosis-related markers' expression and promoting the proliferation of cardiac fibroblasts (CFs), thereby exacerbating cardiac fibrosis. Mechanistically, circ-CELF1 reduced the ubiquitination-degradation rate of BRPF3, leading to an elevation of BRPF3 protein levels. Additionally, BRPF3 acted as a modular scaffold for the recruitment of histone acetyltransferase KAT7 to facilitate the induction of H3K14 acetylation within the promoters of the Celf1 gene. Thus, the transcription of Celf1 was dramatically activated, thereby inhibiting the subsequent response of their downstream target gene Smad7 expression to promote cardiac fibrosis. Moreover, Celf1 further promoted Celf1 pre-mRNA transcription and back-splicing, thereby establishing a feedback loop for circ-CELF1 production. Consequently, a novel feedback loop involving CELF1/circ-CELF1/BRPF3/KAT7 was established, suggesting that circ-CELF1 may serve as a potential novel therapeutic target for cardiac fibrosis.

ObjectiveTo evaluate the clinical efficacy of modified Banxia Xiexintang combined with vedolizumab （VDZ） in the treatment of active moderate to severe Crohn's disease （CD） with the syndrome of cold and heat in complexity and the effect of the therapy on intestinal flora. MethodEighty patients were randomized based on the random number table method into a control group （40 cases） and an observation group （40 cases）. The control group was treated with VDZ， and the observation group was treated with modified Banxia Xiexintang （1 bag per day） combined with VDZ. The treatment in both groups lasted for 14 weeks and the follow-up lasted until the 52th weeks. The CD activity index （CDAI）， CD simplified endoscopic score （SES-CD）， inflammatory bowel disease questionnaire （IBDQ） score， and syndrome score of cold and heat in complexity were assessed before treatment， after treatment， and at the end of follow-up. The levels of hemoglobin （HGB）， hematocrit （HCT）， albumin （ALB）， C-reactive protein （CRP）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， interleukin-17 （IL-17）， and fecal calprotectin （FC） were measured before and after treatment. Intestinal flora was examined before and after treatment. The safety of the therapy was evaluated. ResultCompared with those before treatment， the scores of CDAI， SES-CD， and the syndrome of cold and heat in complexity decreased （P<0.05） and the IBDQ score increased after treatment （P<0.05）. Compared with those before treatment， the scores of CDAI， SES-CD， and the syndrome of cold and heat in complexity increased （P<0.05） and the IBDQ score decreased （P<0.05） at the end of follow-up. After treatment and at the end of follow-up， the observation group had lower scores of CDAI， SES-CD， and syndrome of cold and heat （P<0.05） and higher IBDQ score （P<0.05） than the control group. Moreover， the observation group had higher clinical remission rate（χ²=4.381，3.962） and response rate（χ²=5.541，4.306） and lower non-response rate（χ²=6.646，4.306） than the control group at the two time points （P<0.05）. The endoscopic remission rate（χ²=4.072，3.985） and response rate（χ²=4.528，5.161） in the observation group were higher than those in the control group （P<0.05）. After treatment， the HGB， HCT， and ALB levels in both groups elevated， and the observation group had higher levels than the control group （P<0.05）. The treatment in both groups lowered the levels of CRP， IL-6， TNF-α， IL-17， and FC （P<0.05）， and the observation group had lower levels of CRP， IL-6， TNF-α， IL-17， and FC than the control group after treatment （P<0.05）. The relative abundance of Bifidobacterium， Lactobacillus， and Prevotella increased （P<0.05）， while that of Proteus， Klebsiella， and Enterococcus decreased （P<0.05） in the two groups after treatment. Moreover， the changes in the relative abundance of these bacteria in the observation group were more obvious than those in the control group （P<0.05）. No adverse reactions related to the modified Modified Banxia Xiexintang were observed during the study period. ConclusionModified Banxia Xiexintang combined with VDZ can play a synergistic role and has good short-term and long-term efficacy. This therapy can improve the nutritional status， regulate intestinal flora， and reduce inflammatory injury in the treatment of moderate to severe active CD patients with the syndrome of cold and heat in complexity without causing severe adverse reactions.

Objective Based on ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF/MS),the potential biomarkers and metabolic mechanisms of adult calcium oxalate urolithiasis were identified to guide the diagnosis and treatment of calcium oxalate lithiasis.Methods Blood samples of 36 patients diagnosed with bilateral upper urinary tract calcium oxalate stones and 36 healthy controls admitted to our hospital during Oct.2017 and Jul.2018 were collected.Metabolic fingerprints were analyzed with UPLC-Q-TOF/MS.The multivariate data were analyzed with principal component analysis(PCA)and orthogonal partial least squares discriminant analysis(OPLS-DA).Potential biological markers were identified by comparing human metabolome datasets.Finally,the metabolic pathways of the identified compounds were analyzed and the metabolic network map was constructed.Results PCA and OPLS-DA showed significant differences in blood metabolites between patients and healthy controls,and identified 29 blood-related metabolites,including linoleic acid,citric acid,uric acid and so on.The most relevant blood metabolic pathways were bile acid synthesis pathway,fatty acid biosynthesis pathway,glycerophospholipid metabolism pathway,sphingolipid metabolism pathway and purine metabolism pathway.Conclusion Blood metabolomics analysis based on the UPLC-Q-TOF/MS platform identified 29 potential blood biomarkers of adult calcium oxalate urolithiasis,and purine and lipid metabolism may be related to the genesis of calcium oxalate stones.

Objective:To evaluate the optimization effect of transcutaneous electrical acupoint stimulation (TEAS) combined with moderate sedation with propofol (TEAS-propofol balanced anesthesia) for gastrointestinal endoscopy.Methods:This was a single-blind randomized controlled trial. American Society of Anesthesiologists Physical Status classification Ⅰ-Ⅲ patients, aged 18-64 yr, undergoing elective gastrointestinal endoscopy at the Endoscopic Diagnosis and Treatment Center of the Affiliated Hospital of Qingdao University from May to August 2022, were divided into 2 groups using the block random allocation method: conventional anesthesia group (group C) and TEAS-propofol balanced anesthesia group (group TPB). Patients received moderate sedation with propofol plus routine anesthesia with fentanyl 50 μg in group C. In TPB group, TEAS was performed at bilateral Neiguan, Hegu and Zusanli acupoints before surgery until the end of surgery, and patients received propofol for moderate sedation (Modified Observer′s Assessment of Alertness/Sedation scale score was 3). The efficacy and safety of anesthesia and parameters related to outcomes were observed and recorded.Results:In this study, 66 patients were recruited, with 33 in each group, the failure rate of anesthesia in both groups was 3%, and no reflux or aspiration was found. Compared with group C, no significant changes were found in the patients′ satisfaction on the same day, intraoperative pain response score, incidence of intraoperative adverse reactions (tachycardia, hypertension, bucking and body movement), awake time, consumption of propofol, rate of intraoperative awareness and rate of patients hoping to receive the same anesthesia method again postoperatively ( P>0.05), the patients′ satisfaction was significantly increased on the next day ( P<0.05), the incidence of intraoperative respiratory depression, physician satisfaction, and degree of postoperative dizziness and nausea were significantly reduced ( P<0.05), and the discharge time and time to the complete recovery of normal behavior function was significantly shortened in group TPB ( P<0.05). Conclusions:The combination of TEAS at bilateral Neiguan, Hegu and Zusanli acupoints with moderate sedation using propofol for gastrointestinal endoscopy is not only safe and effective, but also beneficial to the postoperative outcome of patients, and the effect is better than that of conventional anesthesia with propofol and fentanyl.

Recent advances in tumor immunology have made immunotherapy a new direction for neoadjuvant treatment of gastric cancer. Multiple clinical trials have confirmed that combining immunotherapy with chemotherapy and targeted therapy in the neoadjuvant treatment of gastric cancer can effectively improve treatment response and prolong patient survival time. This article aims to comment on the application of immunotherapy in the neoadjuvant treatment of gastric cancer, exploring its mechanisms, integration strategies with traditional treatments, safety, and personalized precision therapy in the hope of providing new insights and directions for the field of gastric cancer treatment.

Objective:To evaluate the safety and effectiveness of incision and drainage with Holmium laser under flexible ureteroscope in the treatment of parapelvic cysts.Methods:The clinical data of 21 patients with parapelvic cysts in Beijing Friendship Hospital, Capital Medical University from January 2018 to December 2022 were retrospectively analyzed, including 10 males and 11 females. The average age was (62.86±5.38) years, and median age was 63.0 years, aged from 36-72 years. The maximum diameter of the cyst was 33-71 mm, with an average of (53.46±9.68) mm. There were 15 cases with homolateral hydronephrosis and 6 cases with homolateral renal calculus. The patients included in the study were treated with incision and drainage with Holmium laser under flexible ureteroscope. The double J ureteral catheter was removed and the urinary system ultrasound was repeated one month after surgery. CT on bilateral kidney was repeated every 6 months until 12 months after surgery. Subsequently, ultrasound on bilateral kidney was reviewed regularly every year. Prognostic indexes sunch as operation time, postoperative hospital stay, postoperative time of getting out of bed, intraoperative blood loss, recurrence and shrinkage of renal cysts were recorded.Results:Of the 21 patients who underwent incision and drainage with Holmium laser under flexible ureteroscope, 9 cases (42.9%) underwent the one-stage operation and 12 cases (57.1%) underwent the two-stage operation. The mean operative time was (41.57±10.86) min, the mean postoperative hospitalization time was (2.90±1.06) d, the mean time of getting out of bed was (0.53±0.30) d, and the mean intraoperative blood loss was (6.52±2.15) mL. No significant recurrence of cysts was observed in all patients after 6-60 months of follow-up, and the cysts disappeared completely or shrank significantly.Conclusion:Incision and drainage with Holmium laser under flexible ureteroscope is safe and reliable in patients with parapelvic cysts, with short operation time, minor blood loss, rapid postoperative recovery and low recurrence rate, which is one of the ideal treatment options for parapelvic cysts.