Decubitus ulcers (DUs) represent a substantial global public health challenge, significantly diminishing patient quality of life and increasing the incidence of infection and early mortality. Given the rapidly aging populations in major East Asian economies, including China, Japan, South Korea, and Taiwan (Province of China), a comparative analysis of the DU burden across these regions is lacking. Leveraging data from the Global Burden of Disease (GBD) 2021 study, this study quantified the epidemiological burden of DUs globally and specifically within China, Japan, South Korea, and Taiwan (Province of China) during the period 1990–2021. Analyses evaluated key metrics including incidence, mortality, and disability-adjusted life years (DALYs), presenting both absolute counts and age-standardized rates (ASRs). Temporal trends in these burden estimates were assessed using Joinpoint regression analysis to identify significant inflection points. Future burden projections were generated via autoregressive integrated moving average (ARIMA) modeling. Comprehensive stratification by sex, age group, geographical region, and temporal interval was performed throughout all analyses. Between 1990 and 2021, the global disease burden of DUs escalated markedly, with incident cases surging by 116.03

Gastric cancer (GC) remains a lethal malignancy with limited therapeutic targets, while recent studies revealed YAP could be a promising target for GC treatment. In our study, we identify oxytocin receptor (OXTR) as an important regulator of Hippo/YAP axis. Through bioinformatics analysis, RNA sequencing analysis, functional research, and molecular mechanism research, we found that OXTR could facilitate Hippo/YAP axis, while YAP were shown to bind the OXTR promoter, enhancing its expression and establishing an interesting positive feedback loop. These findings propose the significance of OXTR in GC progression and its potential as a therapeutic target for YAP-driven cancer.

Ménétrier’s disease is a rare, progressive disorder of unclear etiology, typically affecting middle-aged men and characterized by giant gastric mucosal folds, mainly in the fundus and body, with occasional antral involvement. Diagnosis is challenging due to its rarity and the need to differentiate from hypertrophic lymphocytic gastritis, Zollinger-Ellison syndrome, gastric cancer, and lymphoma. We report a young male with Menetrier’s disease presenting as generalized edema due to hypoproteinemia. After a challenging diagnostic process and ineffective medical management, the patient underwent robot-assisted total gastrectomy with Roux-en-Y esophagojejunostomy, which corrected the hypoproteinemia. He recovered uneventfully and was discharged on postoperative day 12. At 23 months post-surgery, he showed no hypoalbuminemia, edema, or related symptoms; body weight and serum albumin remained normal. Robot-assisted total gastrectomy is a surgical method for treating Meniere’s disease; however, its cost-effectiveness should be carefully considered, and in the long term, more high-quality studies may be required to validate its feasibility.

Declining estrogen in perimenopausal women reduces bone mineral density and increases bone fragility, elevating fall and fracture risk. This presents major challenges for patients and society, yet prior studies lack systematic analysis of this population. This study is the first to utilize mortality and disability-adjusted life years (DALYs) related to falls among perimenopausal women from the Global Burden of Disease (GBD) 2021 database, and to conduct a comprehensive and systematic analysis of the evolving burden of falls in perimenopausal women from 1990 to 2021, as well as to project trends through 2050. This study offers key guidance for optimizing healthcare resource allocation, enhancing patient management, and developing targeted prevention and intervention strategies. This study used GBD 2021 data to systematically analyze fall-related mortality, DALYs, age-standardized rates (ASRs), and estimated annual percentage change (EAPC) among perimenopausal women, examining their associations with the Socio-demographic Index (SDI) at global, regional, and national levels. Joinpoint regression, decomposition, health inequality, and frontier analyses quantified trends, identified factors, and assessed disparities. This study also explored fall risk factors and utilized the Bayesian Age-Period-Cohort (BAPC) model to project global trends in fall burden among perimenopausal women from 2022 to 2050. Between 1990 and 2021, global mortality attributable to falls among perimenopausal women surged by 116.99

Background Ubiquitous mitochondrial creatine kinase (uMtCK) transfers high-energy phosphates from mitochondrially generated ATP to creatine to generate phosphocreatine. uMtCK overexpression has been reported in several malignant tumors, however, the clinical significance and impact of uMtCK in gastric cancer (GC) has not been comprehensively studied. Methods We first examined uMtCK expression in GC by quantitative real-time PCR and western blot assays. Then the clinicopathological significance of aberrant uMtCK expression was determined by immunohistochemical staining in a GC tissue microarray. Kaplan–Meier analysis was used for survival analysis. The biological functions of uMtCK in GC cells were explored by wound-healing, transwell assays and glucose metabolism assays in vitro as well as a liver metastasis model by spleen injection in nude mice in vivo. Results We verified that the expression of uMtCK was substantially elevated in GC tissues, significantly associating with a poorer prognosis in GC patients, especially for those with advanced stage. In univariate and multivariate analyses, uMtCK expression emerged as an independent prognostic factor for both disease-free survival and overall survival. Functionally, we demonstrated that uMtCK promoted glycolysis in GC cells and facilitated their migration, invasion and liver metastasis in vitro and in vivo. Mechanistically, uMtCK enhanced GC progression in a HK2-dependent glycolysis via acting the JNK-MAPK/JUN signaling pathway. Conclusions uMtCK could serve as a novel independent prognostic biomarker as well as potential therapeutic target for GC patients, particularly for GC patients with an advanced UICC stage and tumor recurrence.

The dysregulation of Hippo signaling is a crucial factor driving the progression of gastric cancer, making the targeting of the Hippo pathway a promising therapeutic strategy. However, effective drugs targeting the Hippo/YAP axis remain unavailable. Thus, identifying potential therapeutic targets and mechanisms that inhibit the activity of the Hippo/YAP axis in gastric cancer is of paramount importance. The ubiquitination modification of the Hippo/YAP pathway plays a significant role in signaling transduction and cancer progression. In an effort to shed light on effective therapeutic targets, we conducted a screening using a deubiquitinase small interfering RNA library, leading to the identification of USP12 as an important deubiquitinase in the context of Hippo/YAP axis and the progression of gastric cancer. Our bioinformatic analysis further demonstrated a correlation between USP12 and poor survival, as well as a positive association with classical YAP target genes in gastric cancer samples. Notably, USP12 depletion was found to inhibit gastric cancer progression via the Hippo/YAP axis, whereas USP12 overexpression exhibited the opposite effect, promoting gastric cancer growth and enhancing YAP activity. Further studies through immuno-staining and immuno-precipitation assays indicated the nuclear localization of USP12 and its association with YAP to enhance YAP stability. Specifically, our findings revealed that USP12 could inhibit K48-linked poly-ubiquitination of YAP, predominantly at the K315 site. As a result, we have identified a novel regulatory mechanism involving USP12 and Hippo signaling in the progression of gastric cancer, with the potential for blockade of USP12 to materialize as a promising strategy for combating gastric cancer.

Abstract Background The Hippo pathway is crucial in organ size control and tumorigenesis. Dysregulation of the Hippo/YAP axis is commonly observed in gastric cancer, while effective therapeutic targets for the Hippo/YAP axis are lacking. Identification of reliable drug targets and the underlying mechanisms that could inhibit the activity of the Hippo/YAP axis and gastric cancer progression is urgently needed. Methods We used several gastric cancer cell lines and xenograft models and performed immunoblotting, qPCR, and in vivo studies to investigate the function of CXCR7 in gastric cancer progression. Results In our current study, we demonstrate that the membrane receptor CXCR7 (C-X-C chemokine receptor 7) is an important modulator of the Hippo/YAP axis. The activation of CXCR7 could stimulate gastric cancer cell progression through the Hippo/YAP axis in vitro and in vivo, while pharmaceutical inhibition of CXCR7 via ACT-1004–1239 could block tumorigenesis in gastric cancer. Molecular studies revealed that the activation of CXCR7 could dephosphorylate YAP and facilitate YAP nuclear accumulation and transcriptional activation in gastric cancer. CXCR7 functions via G-protein Gαq/11 and Rho GTPase to activate YAP activity. Interestingly, ChIP assays showed that YAP could bind to the promoter region of CXCR7 and facilitate its gene transcription, which indicates that CXCR7 is both the upstream signalling and downstream target of the Hippo/YAP axis in gastric cancer. Conclusion In general, we identified a novel positive feedback loop between CXCR7 and the Hippo/YAP axis, and blockade of CXCR7 could be a plausible strategy for gastric cancer.

Gastric cancer is one of the most lethal human malignancies in the world. Although great efforts are put in developing novel therapeutic targets, the effective targeting drugs are still limited. Recent studies reveal the abnormality of Hippo/YAP axis play critical role in the oncogenic process of gastric cancer. It is of great importance to demonstrate the regulation of Hippo signaling activity and YAP protein turnover in gastric cancer. Besides, the phosphorylation cascade on YAP function, which has been thoroughly investigated, the ubiquitination of YAP is also important in Hippo signaling status. Here, We utilized the DUB (Deubiquitinase) siRNA library to identify critical DUB for Hippo signaling. We discovered OTUB1 as a critical factor to facilitate gastric cancer cell stemness and progression, which deubiquitinated and stabilized YAP protein. The clinical data analysis implicated OTUB1 was higher expressed in gastric cancer, which correlated with YAP activity and poor survival. OUTB1 interacted with YAP protein via its OTU domain (Ovarian tumor domain) and deubiquitinated YAP at several lysine sites (K90, K280, K343, K494 and K497), which subsequently inhibited YAP degradation. Our study revealed a novel deubiquitinase of Hippo/YAP axis and one possible therapeutic target for YAP-driven gastric cancer.

Ovarian cancer is one of the most lethal gynecologic malignancies worldwide, with the 5-year survival is less than 50%. Although some clinical achievements have been achieved, the overall survival rate has remained unchanged over the past 20 years. Therefore, it is necessary and urgent to develop the potential modifiers and therapeutic approach to improve the overall survival rate in ovarian cancer patients. RBCK1 is an RING protein E3 ubiquitin ligase, which was revealed to involve in the progression of several cancers through its ubiquitination function. In this research, we report that RBCK1 expression is significantly elevated in human ovarian cancer and strongly associated with poor patients' prognosis. RBCK1 deficiency induces cell apoptosis and inhibits cell proliferation and migration in ovarian cancer cells. In terms of molecular mechanism, we report that RBCK1 interacts with PTEN and promotes PTEN degradation in K48-linked ubiquitination. Our study suggests a new and interesting regulatory mechanism that RBCK1 facilitates PTEN degradation, which could be a new potential therapeutic target for ovarian cancer treatment.

The ubiquitination process, which involves that binding of an ubiquitin protein to certain substrates, regulates several human biological processes and human cancers. Several studies report that the abnormal expression of quite a few E3 ubiquitin ligases could play critical role in carcinogenic process and cancer progression. In our current study, we identify UHRF1 (Ubiquitin Like with PHD And Ring Finger Domain 1) is an important regulator for breast cancer growth. UHRF1 depletion significantly decreases breast cancer growth in vitro and in vivo. Clinical data analysis reveals that UHRF1 is dramatically elevated in breast cancer, compared to normal breast tissue. UHRF1 correlates with poor survival in luminal type of breast cancer patients, but not in ER-negative groups. The molecular biological studies show that UHRF1 localizes in the nuclear and interact with ERα via its SRA domain, which subsequently inhibits K48-linked ubiquitination of ERα and enhances ERα stability. Our study provides a novel function of UHRF1 in regulation estrogen signaling in breast cancer and a promising target for breast cancer therapeutics.

BACKGROUND:The Hippo pathway functions as a tumor suppressor pathway in human cancers, while dysfunction of the Hippo pathway is frequently observed in malignancies. Although YAP/TAZ activity is tightly controlled by the phosphorylation cascade of the MST-LATS-YAP/TAZ axis, it is still unclear why the YAP/TAZ proteins are activated in human cancers despite Hippo pathway activation. Recent studies have suggested that in addition to phosphorylation, several other posttranslational modifications, including ubiquitination, also play critical roles in modulating TAZ function.METHODS:We used several gastric cancer cell lines and performed western blot analysis, real-time PCR, immunoprecipitation assays, and in vitro ubiquitination assays and established a xenograft mouse model.RESULTS:Here, by screening a DUB (deubiquitinase) siRNA library, we discovered that DUB1 functions as a critical modulator that facilitates gastric cancer stemness and progression by deubiquitinating and activating the TAZ protein. We also found that DUB1 expression was elevated in gastric cancer and that elevated DUB1 expression correlated with TAZ activation and poor survival. DUB1 associates with the TAZ protein and deubiquitinates TAZ at several lysine residues, which subsequently stabilizes TAZ and facilitates its function.CONCLUSIONS:Our study revealed a novel deubiquitinase in the Hippo/TAZ axis and identified one possible therapeutic target for Hippo-driven gastric cancer.

Introduction: Shunt placement is an effective therapy for hydrocephalus. Ventriculoperitoneal shunt draining excess cerebrospinal fluid connects the cerebral ventricles to the abdominal cavity. However, intestinal obstruction may ensue as an infrequent complication of the shunt.Case presentation: A 65 years old female patient presented with abdominal pain, abdominal bloating, and ceased passage of flatus and stool for six days. She had a history of undergoing a VP shunt procedure due to midbrain obstruction and supratentorial hydrocephalus. Conservative treatment at another local hospital couldn't relieve her symptoms. Laboratory investigations revealed elevated CRP and neutrophils. CT scan showed distended small bowel loops with aerated effusion. Thus, she was admitted to our hospital and underwent an emergent laparotomy following diagnostic modalities completion.Discussion: Adhesive intestinal obstruction secondary to ventriculoperitoneal shunt is a rare but fatal shunt complication. The possible mechanisms involved include rubbing movements between the greater omentum and the catheter, cerebrospinal fluid reaction with abdominal organs, immunological rejection of the catheter, and deposition of brain tumor cells with the resultant abdominal metastatic lesions. Laparoscopic and laparotomy are warranted in the surgical management of the disease.Conclusion: A high index of suspicion for adhesive intestinal obstruction is key to timely diagnosis and treatment.

Background The Hippo pathway functions as a tumor-suppressor pathway in human cancers, while the dys-function of Hippo pathway is frequently observed in malignancies. Although the YAP/TAZ activity is tightly controlled by the phosphorylation cascade of MST-LATS-YAP/TAZ axis, it is still unclear why YAP/TAZ protein is activated in human cancers, even Hippo pathway is still active. Besides phosphorylation, recent studies implicate that several post-translational modifications also play critical roles in modulating TAZ function, including ubiquitination. Methods We work on the ER alpha positive breast cancer cell lines and performed western blots, real-time PCR, immuno-precipitation assay, in vitro ubiquitin assay and xenograft mice studies Results Here, by a DUB (Deubiquitinases) siRNA screening library, we discovered DUB1 as a critical modulator to facilitate gastric cancer stemness and progression, which deubiquitinated and activated TAZ protein. We also identified DUB1 was elevated in gastric cancer, which correlated with TAZ activation and poor survival. DUB1 associated with TAZ protein and deubiquitinated TAZ at several lysine sites, which subsequently stabilized and facilitated TAZ function. Conclusions Our study revealed a novel deubiquitinase of Hippo/TAZ axis and one possible therapeutic target for Hippo-driven gastric cancer.

目的:通过腹腔镜结肠次全切除联合改良Duhamel手术治疗慢传输型便秘(STC),研究围手术期加速康复外科(ERAS)应用的安全性和有效性.方法:回顾性分析2014年1月-2018年1月期间27例重度慢传输型便秘,进行腹腔镜结肠次全切除联合改良Duhamel手术,随机分为两组:加速康复组(ERAS组)12例按加速康复外科理念进行围手术期治疗,对照组15例按传统理念行围手术期治疗.对两组结果进行比较并对分析.结果:ERAS组的离床时间、肠道功能恢复时间、自行排尿时间、进流食时间、术后营养状态较对照组均显著提前,术后住院时间缩短(P＜0.05).术后不良反应发生率ERAS组3例,对照组4例.结论:ERAS技术的应用能加速慢传输型便秘手术患者的术后康复.