Recurrence rates and risk factors in obscure gastrointestinal bleeding.

Obscure gastrointestinal bleeding (OGIB), defined in 2010, involves bleeding from the GI tract that remains unexplained after standard diagnostic procedures. OGIB, which accounts for about 5% of all GI bleeds, poses diagnostic and management challenges, particularly due to the anatomical features of the small intestine. Advances in capsule endoscopy (CE) and balloon-assisted endoscopy have improved the diagnostic and therapeutic landscape for small intestinal lesions. Objective: To determine the recurrence rate and identify risk factors for recurrence following diagnostic and therapeutic interventions using CE and balloon-assisted endoscopy in patients with OGIB. Methods: A retrospective cohort study at Gifu University Hospital analyzed CE procedures for patients with OGIB from 2008 to 2022. Patients underwent CE with subsequent treatments based on the findings. Statistical analyses, including Kaplan-Meier and Cox proportional hazards models, were used to estimate cumulative recurrence rates and identify recurrence risk factors. Results: Out of 417 patients, 65.2% had positive CE findings, leading to therapeutic interventions in 16.3% of cases. The cumulative recurrence rates at 12, 24, and 36 months were 4.3%, 9.0%, and 13.9%, respectively. Liver cirrhosis (hazard rate: 4.15, 95% confidence interval 1.88-9.18, p < 0.01) was identified as a significant risk factor for recurrence. Conclusions: A significant recurrence rate in OGIB patients, with liver cirrhosis being a major risk factor. Despite diagnostic and therapeutic advances, a comprehensive approach including careful follow-up and consideration of risk factors is essential for management.

Safety and efficacy of low-power pure-cut hot snare polypectomy for small nonpedunculated colorectal polyps compared with conventional resection methods: A propensity score matching analysis.

Objectives: Cold snare polypectomy (CSP) is widely performed for small colorectal polyps. However, small colorectal polyps sometimes include high-grade adenomas or carcinomas that require endoscopic resection with electrocautery. This study aimed to evaluate the efficacy and safety of a novel resection technique, hot snare polypectomy with low-power pure-cut current (LPPC-HSP) for small colorectal polyps, compared with CSP and conventional endoscopic mucosal resection (EMR). Methods: Records of patients who underwent CSP, EMR, or LPPC-HSP for nonpedunculated colorectal polyps less than 10 mm between April 2021 and March 2022 were retrospectively evaluated. We analyzed and compared the treatment outcomes of CSP and EMR with those of LPPC-HSP using propensity score matching. Results: After propensity score matching of 396 pairs, an analysis of CSP and LPPC-HSP indicated that LPPC-HSP had a significantly higher R0 resection rate (84% vs. 68%; p < 0.01). Delayed bleeding was observed in only two cases treated with CSP before matching. Perforation was not observed with either treatment. After propensity score matching of 176 pairs, an analysis of EMR and LPPC-HSP indicated that their en bloc and R0 resection rates were not significantly different (99.4% vs. 100%, p = 1.00; 79% vs. 81%, p = 0.79). Delayed bleeding and perforation were not observed with either treatment. Conclusions: The safety of LPPC-HSP was comparable to that of CSP. The treatment outcomes of LPPC-HSP were comparable to those of conventional EMR for small polyps. These results suggest that this technique is a safe and effective treatment for nonpedunculated polyps less than 10 mm.

Clinical usefulness and acceptability of small-bowel capsule endoscopy with panoramic imaging compared with axial imaging in Japanese patients.

Objectives: We aimed to evaluate the usefulness and acceptability of CapsoCam Plus (CapsoCam) in Japanese patients. Methods: This retrospective single-center study enrolled 930 patients with suspected small-bowel bleeding (SSBB) who underwent capsule endoscopy. Thirty-three patients using CapsoCam and PillCam SB3 (SB3) were matched using propensity score matching. The diagnostic yield and the acceptability of CapsoCam were evaluated. Results: There was no SSBB case where capsule endoscopy was performed within 48 h of bleeding. CapsoCam had a significantly higher observation rate of the entire small bowel (97% vs. 73%, p = 0.006) and Vater's papilla (82% vs. 15%, p < 0.001) than SB3. The reading time of CapsoCam was significantly longer than that of SB3 (30 vs. 25 min, p < 0.001), and CapsoCam's time from the capsule endoscopy swallowing to read completion was longer than that of SB3 (37 vs. 12 h, p < 0.001). The two groups showed no difference in the capsule endoscopy findings according to the P classification. Notably, 85% of the patients using CapsoCam reported examination distress as "not at all" or "almost not," and 94% reported swallowing difficulty as "very easy" or "easy." Conclusions: CapsoCam took time to read; however, it is a well-tolerated examination with a high observation rate of Vater's papilla and entire small-bowel mucosa. Detectability of bleeding sources was comparable in both modalities for cases of occult SSBB and overt SSBB more than 48 h after bleeding. CapsoCam is a useful modality for patients with SSBB.

Orchestrated metal-coordinated carrier-free celastrol hydrogel intensifies T cell activation and regulates response to immune checkpoint blockade for synergistic chemo-immunotherapy.

The challenges generated by insufficient T cell activation and infiltration have constrained the application of immunotherapy. Making matters worse, the complex tumor microenvironment (TME), resistance to apoptosis collectively poses obstacles for cancer treatment. The carrier-free small molecular self-assembly strategy is a current research hotspot to overcome these challenges. This strategy can transform multiple functional agents into sustain-released hydrogel without the addition of any excipients. Herein, a coordination and hydrogen bond mediated tricomponent hydrogel (Cel hydrogel) composed of glycyrrhizic acid (GA), copper ions (Cu2+) and celastrol (Cel) was initially constructed. The hydrogel can regulate TME by chemo-dynamic therapy (CDT), which increases reactive oxygen species (ROS) in conjunction with GA and Cel, synergistically expediting cellular apoptosis. What's more, copper induced cuproptosis also contributes to the anti-tumor effect. In terms of regulating immunity, ROS generated by Cel hydrogel can polarize tumor-associated macrophages (TAMs) into M1-TAMs, Cel can induce T cell proliferation as well as activate DC mediated antigen presentation, which subsequently induce T cell proliferation, elevate T cell infiltration and enhance the specific killing of tumor cells, along with the upregulation of PD-L1 expression. Upon co-administration with aPD-L1, this synergy mitigated both primary and metastasis tumors, showing promising clinical translational value.

PCP-bε is a novel positive regulator of pollen germination in Arabidopsis thaliana.

small cysteine-rich peptides play essential roles in different stages of the plant reproductive process. Pollen germination is a prerequisite for double fertilization and is directly related to seed formation and crop yield. However, the small cysteine-rich peptides that are involved in pollen germination remain to be identified. In this study, identification and phylogenetic analysis of PCP-Bε genes in sequenced Brassicaceae show that pollen coat protein B-class protein PCP-Bε gene is widespread in Arabidopsis and its high relatives, but lost in some Brassica species. Expression analyses display that AtPCP-Bε gene is expressed in Arabidopsis pollen. Arabidopsis PCP-Bε knockout mutants are generated by CRISPR/Cas9, Phenotypic analyses show that the absence of AtPCP-Bε obviously impairs in vitro pollen germination, but has no influence on pollen tube growth, which demonstrates that AtPCP-Bε is a novel positive regulator of pollen germination. It is speculated that AtPCP-Bε should interact with the receptor from pollen to perform its function. These findings are useful for further analysis on the molecular mechanism of pollen germination.

Enlarged perivascular space burden predicts declines in cognitive and functional performance.

INTRODUCTION: We evaluated the relationship between baseline enlarged perivascular space (ePVS) burden and later cognitive decline. METHODS: 83 community-dwelling, older adults (aged 56-86) completed three annual cognitive assessments that included the Clinical Dementia Rating (CDR®) Dementia Staging Instrument Sum of Boxes (CDR-SB) and composite measures of executive function and episodic memory. An MRI scan at baseline was used to count ePVS in the basal ganglia and centrum semiovale. Mixed effects models were run with ePVS as the predictor variable and cognitive measures as the dependent variable. Covariates included age, sex, education, cerebral small vessel disease (cSVD) risk factors, and cSVD neuroimaging biomarkers. RESULTS: At baseline, high basal ganglia ePVS counts were associated with lower executive function scores and episodic memory scores. Moreover, baseline basal ganglia ePVS predicted worse longitudinal CDR-SB scores over the study period. DISCUSSION: Basal ganglia ePVS burden is a promising biomarker for cSVD-related cognitive and functional decline.

Molecular-phylogenetic analyses of Babesia and Theileria species from small mammals and their ticks in northern China suggest new reservoirs of bovine and equine piroplasms.

Babesia and Theileria species (Apicomplexa: Piroplasmida) are tick-borne protozoan parasites that can cause mild to severe infection in humans, wildlife, livestock and companion animals. To date, reports on the molecular study of piroplasms from wild living small mammals and their ticks are still limited, especially in Asia. This study encompassed an extensive survey involving 907 liver samples and 145 ixodid ticks from 16 different species of small mammals (Rodentia, Lagomorpha, Eulipotyphla). These were collected in 13 cities and counties in northern China. DNA extracts from these samples were screened for the presence of piroplasm 18S rRNA gene. Samples that tested positive were further evaluated for other genetic markers of piroplasms, including the cox1 gene and the ITS1-5.8S rDNA-ITS2 region. Several piroplasm species were identified, including Babesia sp. tavsan2, Babesia occultans, Theileria sp. Xinjiang, Theileria equi, and Theileria sp. Kalecik. Among these, Theileria sp. Xinjiang was shown to be the most prevalent. Importantly, Babesia sp. tavsan2 was identified in the tick Rhipicephalus sanguineus from the Yarkand hare and Theileria sp. Kalecik in Hyalomma asiaticum from the long-eared hedgehog, in line with the detection of these pathogens in tissue samples of the relevant hosts. This study further disclosed the presence of DNA from B. occultans and T. equi, typically found in cattle and horses respectively, with an additional discovery in small mammals. Moreover, Theileria sp. Kalecik, which was first detected in small-sized mammals, and Babesia sp. tavsan2, were both reported for the first time in China.

Evaluation of plant commercial feed additives for equine cyathostomin control.

The increasing emergence of anthelmintic-resistant parasitic isolates prompts us to reassess the management of intestinal strongylosis in horses. Additionally, societal demand is shifting toward reducing the use of chemical treatments, aligning with environmentally-friendly practices and the exploration of natural alternatives. In this context, we provide an initial view of the antiparasitic activity and the effect on immune circulating blood cells of three commercialized plant-based feed additives in ponies. Three treatments, based either on mugwort (Artemisia vulgaris), echinacea (Echinacea purpurea) or curcumin (Curcuma longa) were administrated to 18 (six per treatment) Welsh female ponies naturally infected with cyathostomins to mimic their practical use in farming conditions. Another group of six untreated ponies was used as a control. Fecal egg count (FEC), the larval development percentage and the number of red blood cells, lymphocytes, monocytes, neutrophils, eosinophils and basophils were measured the first and the last day of each treatment, and compared with those characterizing the control group. None of the three treatments showed a significant effect on the studied parameters. Moreover, the efficacy of treatments, measured from the FEC reduction compared to the control group, was weak (≤ 38.6%). Therefore, these results do not support the practical use of these additives in equine farming, even if the determination of Cohen's d values associated with the three treatments revealed some incidences on FEC and blood immune cell counts, as well as on larval development for mugwort.

Cerebral small vessel disease markers and long-term prognosis in spontaneous intracerebral hemorrhage: the HAGAKURE-ICH study.

We investigated the effects of individual and cumulative cerebral small vessel disease (SVD) markers on long-term clinical outcomes in spontaneous intracerebral hemorrhage (sICH) patients. This prospective, single-center cohort study was conducted from 2012 to 2019. SVD markers, including lacunae, cerebral microbleeds, white matter hyperintensity (WMH), and perivascular spaces in the basal ganglia, were assessed to calculate a summary SVD score. Patients were categorized into severe (score ≥3) and non-severe (score 0-2) SVD burden groups. Functional prognosis was defined as recovery, no change, or decline based on modified Rankin Scale changes at 2 years after discharge, excluding death. Associations of SVD burden and individual SVD markers with outcomes were evaluated using Cox proportional hazards modeling for recurrent stroke and all-cause mortality, and using ordinal logistic regression for functional prognosis. Among 155 sICH patients who underwent MRI, 98 showed severe SVD burden. Recurrent stroke and all-cause mortality rates were 2.2 and 8.3 per 100 patient-years, respectively, over a median 2.1-year follow-up. In terms of functional prognosis, 57 patients (51.8%) recovered, 32 (29.1%) showed no change, and 21 (19.1%) declined. A significant association was apparent between severe SVD burden and poorer functional prognosis (odds ratio [OR] 2.48, 95% confidence interval [CI] 1.04-6.04; p = 0.042), particularly with moderate-to-severe WMH (OR 2.54, 95%CI 1.02-6.54; p = 0.048). The cumulative effects of SVD markers inhibited long-term functional recovery in sICH patients. Severe SVD burden, as well as moderate-to-severe WMH, can be indicators of long-term prognosis after sICH.

Extracellular vesicle miRNome during subclinical mastitis in dairy cows.

Bovine mastitis is one of the main inflammatory diseases that can affect the udder during lactation. Somatic cell counts and sometimes microbiological tests are routinely adopted during monitoring diagnostics in dairy herds. However, subclinical mastitis is challenging to identify, reducing the possibility of early treatments. The main aim of this study was to investigate the miRNome profile of extracellular vesicles isolated from milk as potential biomarkers of subclinical mastitis. Milk samples were collected from a total of 60 dairy cows during routine monitoring tests. Small RNA sequencing technology was applied to extracellular vesicles of milk samples collected from cows classified according to the somatic cell count to identify differences in the miRNome between mastitic and healthy cows. A total of 1997 miRNAs were differentially expressed between both groups. Among them, 68 miRNAs whose FDRs were < 0.05 were mostly downregulated, with only one upregulated miRNA (i.e., miR-361). Functional analysis revealed that miR-455-3p, miR-503-3p, miR-1301-3p and miR-361-5p are involved in the regulation of several biological processes related to mastitis, including immune system-related processes. This study suggests the involvement of extracellular vesicle-derived miRNAs in the regulation of mastitis. Moreover, these findings provide evidence that miRNAs from milk extracellular vesicles can be used to identify biomarkers of mastitis. However, further studies must be conducted to validate these miRNAs, especially for subclinical diagnosis.

Duodenal transcriptomics demonstrates signatures of tissue inflammation and immune cell infiltration in children with environmental enteric dysfunction across global centers.

BACKGROUND: Environmental enteric dysfunction (EED) is an inflammatory condition of the small intestine that is prevalent in children residing in low- and middle-income countries. EED is accompanied by profound histopathologic changes in the small bowel, loss of absorptive capacity, increased intestinal permeability, increased microbial translocation, and nutrient loss. OBJECTIVES: We sought to identify dysregulated genes and pathways that might underlie pediatric EED. METHODS: RNA-sequencing libraries were generated from endoscopically obtained duodenal tissue from undernourished children with EED from 3 prospective cohorts of children with EED. The EED transcriptome was defined in comparison to North American children without EED. Weighted gene coexpression network analysis (WGCNA) was tested for gene modules associated with EED and its histologic features. RESULTS: The 1784 upregulated genes in EED were highly enriched for immune and inflammatory processes, including IL-17 and JAK-STAT signaling, and cytokine-cytokine receptor interactions. The 1388 downregulated genes included genes corresponding to xenobiotic metabolism, detoxification, and antioxidant capacities. A gene coexpression module enriched for antimicrobial responses and chemokine activity was significantly associated with villous blunting, goblet cell depletion, and overall histologic severity of EED. CONCLUSIONS: The transcriptome signatures of EED include specific innate and adaptive immune responses that are consistently elevated across study centers, coupled with reduced detoxification and antioxidant capacities. These data may have implications for targeted interventions to improve EED outcomes.

Clinical factors associated with high PD-L1 expression in patients with early-stage non-small cell lung cancer.

BACKGROUND: Superior outcomes have been obtained for neoadjuvant treatment with immune checkpoint inhibitors (ICI) plus chemotherapy over neoadjuvant chemotherapy alone, especially in patients with high programmed cell death ligand 1 (PD-L1) expression. However, it is not always possible to obtain sufficient tumor specimens for biomarker testing before surgery. In this study, we explored clinical factors that can predict high PD-L1 expression. METHODS: We retrospectively enrolled 340 lung cancer patients who received pulmonary resection between 2014 and 2023 and who had PD-L1 expression data. Chi-squared tests and logistic regression analyses were used to identify clinical factors associated with high PD-L1 status. RESULTS: Univariable and multivariable analyses revealed that smoking, high maximum standardized uptake value (SUVmax) of 18F-fluorodeoxyglucose positron emission computed tomography (18F-FDG PET/CT), and high plasma fibrinogen are independent predictors of high PD-L1 expression. A predictive score for high PD-L1 expression (ranging from 0 to 3) was developed based on these parameters. Notably, only 5% of patients with a score of 0 exhibited high PD-L1 expression, whereas this proportion increased to 53% for patients with a score of 3. CONCLUSION: These results showed that plasma fibrinogen, smoking history, and SUVmax are predictors of high PD-L1 expression, providing a basis for identifying patients expected to benefit from neoadjuvant ICI treatment.

[Transverse small incision intrathecal "loop" minimally invasive suture for treatment of acute Achilles tendon rupture].

Objective: To evaluate the effectiveness and feasibility of a transverse small incision intrathecal "loop" minimally invasive suture for acute Achilles tendon rupture. Methods: The clinical data of 30 patients with acute Achilles tendon rupture treated with transverse small incision intrathecal "loop" minimally invasive suture between January 2022 and October 2023 was retrospectively analyzed. The patients were all male, aged from 29 to 51 years, with an average of 39.8 years. The cause of injury was acute sports injury, and the time from injury to operation was 1-14 days, with an average of 3.4 days. The operation time, incision length, intraoperative blood loss, intraoperative complications, wound healing, and hospital stay were recorded. Postoperative appearance and function of ankle were evaluated by American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score, Vancouver Scar Scale (VSS) score, and Arner-Lindholm score. Results: The operation time ranged from 30 to 90 minutes, with an average of 54.2 minutes; the incision length ranged from 1.3 to 3.5 cm, with an average of 2.2 cm; the intraoperative blood loss ranged from 5 to 70 mL, with an average of 22.3 mL; and the hospital stay ranged from 2 to 6 days, with an average of 3.7 days. All incisions healed by first intention, and there was no incision infection, poor healing, and deep venous thrombosis. All patients were followed up 5.3-22.0 months (mean, 14.7 months). During the follow-up, all the 30 patients had returned to exercise, and there was no complication such as Achilles tendon re-rupture, postoperative infection, and gastrocnemius muscle injury. At last follow-up, the AOFAS ankle-hindfoot score was 82-100, with an average of 95.1; the VSS score was 1-4, with an average of 2.1; according to the Arner-Lindholm score, 24 cases were rated as excellent and 6 cases as good. Conclusion: Transverse small incision intrathecal "loop" minimally invasive suture for the treatment of acute Achilles tendon rupture has the advantages of simple instrument, convenient operation, small trauma, quick recovery, and satisfactory effectiveness.

"Veterinary medicine is not finished when I have diagnosed an incurable disease, that's when it starts for me." A qualitative interview study with small animal veterinarians on hospice and palliative care.

In the wake of recent medical developments in small animal practice, curing animals of their illnesses and restoring their health can be realized better than ever before. However, the growing medical possibilities are also leading to an increase in demand for better care for patients suffering from terminal illnesses. Consequently, the field of animal hospice and palliative care has become increasingly available, enabling veterinarians to optimize the quality of life of patients, such as dogs and cats, who no longer have a prospect of full recovery. Using qualitative, semi-structured interviews with 20 small animal veterinarians involved in hospice and palliative care, we investigated the factors that motivate veterinarians to become involved in hospice and palliative care and explored the importance of relationships, communication, time and infrastructure in this area. Findings show that personal experiences with their own pets or during training or work life motivated veterinarians to provide this service. Although veterinarians highlighted the importance of empathetic-driven relationships, they were aware that keeping an emotional distance from the patient and caregiver is significant to provide successful care. Further, veterinarians emphasized their high investment of time that resulted primarily from the increased frequency and provided opportunities to communicate with caregivers. The overall conclusion is that having time for patients and the patients' caregivers is one of the most important aspects of work in this field. However, as it will be also shown, veterinarians must consider aspects of self-care management by reflecting on their own time and energy resources while caring for animals and their caregivers.

Disney Rash in Las Vegas: Benign Lower Extremity Purpura Following Prolonged Walking.

This case follows an adult middle-aged female patient who developed a purpuric rash, soreness, and swelling on her legs after walking for several days in Las Vegas. With no prior petechial rash history or presence of systemic symptoms, exercise-induced purpura (EIP) was suspected due to her protracted walking in warm weather. She recovered fully with supportive treatment. EIP, also known as exercise-induced vasculitis (EIV), is often poorly recognized, misdiagnosed, and inappropriately treated. There is a need for increased awareness and clinical diagnosis of EIV based on thorough history and physical examination.

Mechanisms of resistance to KRASG12C inhibitors in KRASG12C-mutated non-small cell lung cancer.

The KRAS protein, a product of the KRAS gene (V-ki-ras2 Kirsten rat sarcoma viral oncogene homolog), functions as a small GTPase that alternates between an active GTP-bound state (KRAS(ON)) and an inactive GDP-bound state (KRAS(OFF)). The KRASG12C mutation results in the accumulation of KRASG12C(OFF), promoting cell cycle survival and proliferation primarily through the canonical MAPK and PI3K pathways. The KRASG12C mutation is found in 13% of lung adenocarcinomas. Previously considered undruggable, sotorasib and adagrasib are the first available OFF-state KRASG12C inhibitors, but treatment resistance is frequent. In this review, after briefly summarizing the KRAS pathway and the mechanism of action of OFF-state KRASG12C inhibitors, we discuss primary and acquired resistance mechanisms. Acquired resistance is the most frequent, with "on-target" mechanisms such as a new KRAS mutation preventing inhibitor binding; and "off-target" mechanisms leading to bypass of KRAS through gain-of-function mutations in other oncogenes such as NRAS, BRAF, and RET; or loss-of-function mutations in tumor suppressor genes such as PTEN. Other "off-target" mechanisms described include epithelial-to-mesenchymal transition and histological transformation. Multiple co-existing mechanisms can be found in patients, but few cases have been published. We highlight the lack of data on non-genomic resistance and the need for comprehensive clinical studies exploring histological, genomic, and non-genomic changes at resistance. This knowledge could help foster new treatment initiatives in this challenging context.

Claudin 1, 4, 6 and 18 isoform 2 as targets for the treatment of cancer (Review).

The 24 claudin (CLDN) genes in the human genome encode 26 representative CLDN family proteins. CLDNs are tetraspan­transmembrane proteins at tight junctions. Because several CLDN isoforms, such as CLDN6 and CLDN18.2, are specifically upregulated in human cancer, CLDN­targeting monoclonal antibodies (mAbs), antibody­drug conjugates (ADCs), bispecific antibodies (bsAbs) and chimeric antigen receptor (CAR) T cells have been developed. In the present review, CLDN1­, 4­, 6­ and 18.2­targeting investigational drugs in clinical trials are discussed. CLDN18.2­directed therapy for patients with gastric and other types of cancer is the most advanced area in this field. The mouse/human chimeric anti­CLDN18.2 mAb zolbetuximab has a single­agent objective response rate (ORR) of 9%, and increases progression­free and overall survival in combination with chemotherapy. The human/humanized anti­CLDN18.2 mAb osemitamab, and ADCs AZD0901, IBI343 and LM­302, with single­agent ORRs of 28­60%, have been tested in phase III clinical trials. In addition, bsAbs, CAR T cells and their derivatives targeting CLDN4, 6 or 18.2 are in phase I and/or II clinical trials. AZD0901, IBI343, zolbetuximab and the anti­CLDN1 mAb ALE.C04 have been granted fast track designation or priority review designation by the US Food and Drug Administration.

[Retracted] Long non­coding RNA SNHG3 promotes the development of non­small cell lung cancer via the miR­1343­3p/NFIX pathway.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that certain of the Transwell cell migration and invasion assay data shown in Fig. 3B were strikingly similar to data appearing in different form in a pair of other articles written by different authors at different research institutes, one of which had already been published elsewhere prior to the submission of this paper to International Journal of Molecular Medicine, and one of which was under consideration for publication at around the same time. In view of the fact that the abovementioned data had already apparently been published previously, the Editor of International Journal of Molecular Medicine has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a satisfactory reply. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Molecular Medicine 48: 147, 2021; DOI: 10.3892/ijmm.2021.4980].

The combination of a PTP1B inhibitor, TNFR2 blocker, and PD­1 antibody suppresses the progression of non­small cell lung cancer tumors by enhancing immunocompetence.

Lung cancer is increasingly recognized as a leading cause of cancer­related mortality. Immunotherapy has emerged as a promising therapeutic approach for lung cancer, particularly non­small cell lung cancer (NSCLC). Nonetheless, the response rate to programmed cell death 1 (PD­1) inhibitors remains less than optimal. It has been suggested that protein tyrosine phosphatase 1B (PTP1B) plays a crucial role in the development and progression of cancer by facilitating T cell expansion and cytotoxicity. Our previous research demonstrated that the combination of tumor necrosis factor receptor 2 (TNFR2) with immune activity treatments synergistically suppresses tumor growth. This insight led to exploring the efficacy of a combined treatment strategy involving PD­1 inhibitors, PTP1B inhibitors and TNFR2 antibodies (triple therapy) in NSCLC. In this context, the therapeutic effectiveness of these combination immunotherapies was validated in mouse models with NSCLC by analyzing the expansion and function of immune cells, thereby assessing their impact on tumor growth. The results indicated that inhibiting PTP1B decreases the expression of PD­L1 and TNFR2 on LLC cells, along with an increase in the proportion of CD4+T and CD8+T cells. Compared with other treatment groups, the triple therapy significantly reduced tumor volume in mice with NSCLC and extended their survival. Moreover, this combination therapy altered the distribution of myeloid­derived suppressor cells, dendritic cells, B cells and M1 macrophages, while increasing the proportion of CD8+T cells and reducing the proportion of Treg cells in the spleens, lymph nodes, and tumors of NSCLC models. The triple therapy also resulted in a decrease in PD­L1, PTP1B and TNFR2 expression within NSCLC tumor tissues in mice. Overall, the triple therapy effectively suppressed tumor growth and improved outcomes in mice with NSCLC by modulating immune cell distribution and reducing levels of target immune proteins.

Roles of small GTPases in cardiac hypertrophy (Review).

Cardiac hypertrophy results from the heart reacting and adapting to various pathological stimuli and its persistent development is a major contributing factor to heart failure. However, the molecular mechanisms of cardiac hypertrophy remain unclear. Small GTPases in the Ras, Rho, Rab, Arf and Ran subfamilies exhibit GTPase activity and play crucial roles in regulating various cellular responses. Previous studies have shown that Ras, Rho and Rab are closely linked to cardiac hypertrophy and that their overexpression can induce cardiac hypertrophy. Here, we review the functions of small GTPases in cardiac hypertrophy and provide additional insights and references for the prevention and treatment of cardiac hypertrophy.