Hematochezia due to rectal invasion by an internal iliac artery aneurysm: A case report.

BACKGROUND: This case report presents the rare occurrence of hematochezia due to an internal iliac artery aneurysm leading to an arterioenteric fistula, expanding the differential diagnosis for gastrointestinal bleeding. It emphasizes the importance of considering vascular origins in cases of atypical hematochezia, particularly in the absence of common gastrointestinal causes, and highlights the role of imaging and multidisciplinary management in diagnosing and treating such unusual presentations. CASE SUMMARY: A 75-year-old man with a history of hypertension presented with 12 d of hematochezia, experiencing bloody stools 7-8 times per day. Initial computed tomography (CT) scans revealed an aneurysmal rupture near the right internal iliac artery with suspected hematoma development. Hemoglobin levels progressively decreased to 7 g/dL. Emergency arterial angiography and iliac artery-covered stent placement were performed, followed by balloon angioplasty. Despite initial stabilization, minor rectal bleeding and abdominal pain persisted, leading to further diagnostic colonoscopy. This identified a neoplasm and potential perforation at the proximal rectum. An exploratory laparotomy confirmed the presence of a hematoma and an aneurysm invading the rectal wall, necessitating partial rectal resection, intestinal anastomosis, and ileostomy. Postoperative recovery was successful, with no further bleeding incidents and normal follow-up CT and colonoscopy results after six months. CONCLUSION: In cases of unusual gastrointestinal bleeding, it is necessary to consider vascular causes for effective diagnosis and intervention.

Effectiveness of fecal DNA syndecan-2 methylation testing for detection of colorectal cancer in a high-risk Chinese population.

BACKGROUND: Colorectal cancer (CRC) is among the most prevalent and life-threatening malignancies worldwide. Syndecan-2 methylation (mSDC2) testing has emerged as a widely used biomarker for early detection of CRC in stool and serum samples. Cancer (CRC) is among the most prevalent and life-threatening malignancies worldwide. mSDC2 testing has emerged as a widely used biomarker for early detection of CRC in stool and serum samples. AIM: To validate the effectiveness of fecal DNA mSDC2 testing in the detection of CRC among a high-risk Chinese population to provide evidence-based data for the development of diagnostic and/or screening guidelines for CRC in China. METHODS: A high-risk Chinese cohort consisting of 1130 individuals aged 40-79 years was selected for evaluation via fecal mSDC2 testing. Sensitivity and specificity for CRC, advanced adenoma (AA) and advanced colorectal neoplasia (ACN) were determined. High-risk factors for the incidence of colorectal lesions were determined and a logistic regression model was constructed to reflect the efficacy of the test. RESULTS: A total of 1035 high-risk individuals were included in this study according to established criteria. Among them, 16 suffered from CRC (1.55%), 65 from AA (6.28%) and 189 from non-AAs (18.26%); 150 patients were diagnosed with polyps (14.49%). Diagnoses were established based upon colonoscopic and pathological examinations. Sensitivities of the mSDC2 test for CRC and AA were 87.50% and 40.00%, respectively; specificities were 95.61% for other groups. Positive predictive values of the mSDC2 test for CRC, AA and ACN were 16.09%, 29.89% and 45.98%, respectively; the negative predictive value for CRC was 99.79%. After adjusting for other high-risk covariates, mSDC2 test positivity was found to be a significant risk factor for the occurrence of ACN (P < 0.001). CONCLUSION: Our findings confirmed that offering fecal mSDC2 testing and colonoscopy in combination for CRC screening is effective for earlier detection of malignant colorectal lesions in a high-risk Chinese population.

6-O-angeloylplenolin inhibits osteoclastogenesis in vitro via suppressing c-Src/NF-κB/NFATc1 pathways and ameliorates bone resorption in collagen-induced arthritis mouse model.

One of the effective therapeutic strategies to treat rheumatoid arthritis (RA)-related bone resorption is to target excessive activation of osteoclasts. We discovered that 6-O-angeloylplenolin (6-OAP), a pseudoguaianolide from Euphorbia thymifolia Linn widely used for the treatment of RA in traditional Chinese medicine, could inhibit RANKL-induced osteoclastogenesis and bone resorption in both RAW264.7 cells and BMMs from 1 µM and protect a collagen-induced arthritis (CIA) mouse model from bone destruction in vivo. The severity of arthritis and bone erosion observed in paw joints and the femurs of the CIA model were attenuated by 6-OAP administered at both dosages (1 or 5 mg/kg, i.g.). BMD, Tb.N and BV/TV were also improved by 6-OAP treatment. Histological analysis and TRAP staining of femurs further confirmed the protective effects of 6-OAP on bone erosion, which is mainly due to reduced osteoclasts. Molecular docking indicated that c-Src might be a target of 6-OAP and that phosphorylation of c-Src was suppressed by 6-OAP treatment. CETSA and SPR assay further confirmed the potential interaction between 6-OAP and c-Src. Three signaling molecules downstream of c-Src that are vital to the differentiation and function of osteoclasts, NF-κB, c-Fos and NFATc1, were also suppressed by 6-OAP in vitro. In summary, the results demonstrated that the function of c-Src was disrupted by 6-OAP, which led to the suppression of downstream signaling vital to osteoclast differentiation and function. In conclusion, 6-OAP has the potential to be further developed for the treatment of RA-related bone erosion.

[Fuyu Decoction ameliorates myocardial fibrosis in rat model of heart failure by regulating Nrf2/GPX4-mediated ferroptosis].

This study aims to investigate the effect and mechanism of Fuyu Decoction(FYD) in the treatment of myocardial fibrosis in the rat model of heart failure(HF). Sixty Wistar rats were randomized into a modeling group(n=50) and a sham group(n=10). A post-myocardial infarction HF model was established by ligating the left anterior descending coronary artery in rats. The successfully modeled rats were assigned into model, low-dose(2.5 g·kg~(-1)) FYD(FYD-L), high-dose(5.0 g·kg~(-1)) FYD(FYD-H), and FYD+Nrf2 inhibitor(ML385, 30 mg·kg~(-1)) groups(n=10). FYD was administrated by gavage and ML385 by intraperitoneal injection. The rats in the sham and model groups were administrated with equal amounts of normal saline by gavage. After 8 weeks of intervention, the cardiac function indicators were measured, and the myocardial tissue morphology and collagen deposition were observed. The positive expression of collagens Ⅰ and Ⅲ, apoptosis, and oxidative stress were examined, and the levels of Fe~(2+) and reactive oxygen species(ROS) were determined. The protein levels of nuclear factor erythroid 2-related factor 2(Nrf2), solute carrier family 7 member 11(SLC7A11), glutathione peroxidase 4(GPX4), and acyl-coenzyme A synthase long chain family member 4(ACSL4) in the myocardial tissue were determined. Compared with sham group, the model group showed decreased left ventricular ejection fraction(LVEF) and left ventricular fractional shortening(LVFS), increased left ventricular end internal dimension in systole(LVIDs), left ventricular internal diameter in diastole(LVIDd), and myocardial collagen deposition, positive expression of collagens Ⅰ and Ⅲ, elevated apoptosis rate and malondialdehyde(MDA), Fe~(2+), and ROS levels, lowered superoxide dismutase(SOD) and glutathione peroxidase(GSH) levels, down-regulated protein levels of Nrf2, SLC7A11, and GPX4, and up-regulated protein level of ACSL4. Compared with the model group, the above indicators were restored by FYD. Moreover, ML385 reversed the protective effect of FYD on myocardial fibrosis in HF rats. In conclusion, FYD can inhibit ferroptosis by activating the Nrf2/GPX4 pathway, thereby ameliorating myocardial fibrosis in HF rats.

Effects of testosterone dose on depression-like behavior among castrated adult male rats.

Previous research has shown a decrease in serum testosterone levels in male patients with depression. In recent years, the results of testosterone replacement therapy (TRT) to improve depression have been mixed. Using the classic CUMS model, we induced depressive-like behaviors in rats and observed a decrease in their serum testosterone levels along with an increase in androgen receptor expression in the hippocampus. We then performed castration and sham surgery on male rats and found that testosterone deprivation led to the manifestation of depressive-like behavior that could be ameliorated by TRT. Through a repeated measures experiment consisting of five blocks over a period of 25 days, we discovered that the reduction in depressive-like behavior in testosterone-deprived rats began 22 days after drug administration (0.5 and 0.25 mg/rat). Furthermore, rats in 0.5mgT group showed the most significant improvements. Subsequently, this dose was used in CUMS rats and reduced the occurrence of depressive-like behaviors. Our study has demonstrated the complex interplay between depression and testosterone, as well as the intricate dose-response relationship between TRT and reduction in depression. Our research supports the use of TRT to alleviate depression, but dosage and duration of treatment are critical factors in determining efficacy.

Gradient inflammation in the pancreatic stump after pancreaticoduodenectomy: Two case reports and review of literature.

BACKGROUND: Postoperative pancreatic fistula (POPF) contributes significantly to morbidity and mortality after pancreaticoduodenectomy (PD). However, the underlying mechanisms remain unclear. This study explored this pathology in the pancreatic stumps and elucidated the mechanisms of POPF following PD. CASE SUMMARY: Pathological analysis and 16S rRNA gene sequencing were performed on specimens obtained from two patients who underwent complete pancreatectomy for grade C POPF after PD. Gradient inflammation is present in the pancreatic stump. The apoptosis was lower than that in the normal pancreas. Moreover, neutrophil-dominated inflammatory cells are concentrated in the ductal system. Notably, neutrophils migrated through the ductal wall in acinar duct metaplasia-formed ducts. Additionally, evidence indicates that gut microbes migrate from the digestive tract. Gradient inflammation occurs in pancreatic stumps after PD. CONCLUSION: The mechanisms underlying POPF include high biochemical activity in the pancreas, mechanical injury, and digestive reflux. To prevent POPF and address pancreatic inflammation and reflux, breaking the link with anastomotic dehiscence is practical.

Pedigree Analysis of Nonclassical Cholesteryl Ester Storage Disease with Dominant Inheritance in a LIPA I378T Heterozygous Carrier.

BACKGROUND: Cholesterol ester storage disorder (CESD; OMIM: 278,000) was formerly assumed to be an autosomal recessive allelic genetic condition connected to diminished lysosomal acid lipase (LAL) activity due to LIPA gene abnormalities. CESD is characterized by abnormal liver function and lipid metabolism, and in severe cases, liver failure can occur leading to death. In this study, one Chinese nonclassical CESD pedigree with dominant inheritance was phenotyped and analyzed for the corresponding gene alterations. METHODS: Seven males and eight females from nonclassical CESD pedigree were recruited. Clinical features and LAL activities were documented. Whole genome Next-generation sequencing (NGS) was used to screen candidate genes and mutations, Sanger sequencing confirmed predicted mutations, and qPCR detected LIPA mRNA expression. RESULTS: Eight individuals of the pedigree were speculatively thought to have CESD. LAL activity was discovered to be lowered in four living members of the pedigree, but undetectable in the other four deceased members who died of probable hepatic failure. Three of the four living relatives had abnormal lipid metabolism and all four had liver dysfunctions. By liver biopsy, the proband exhibited diffuse vesicular fatty changes in noticeably enlarged hepatocytes and Kupffer cell hyperplasia. Surprisingly, only a newly discovered heterozygous mutation, c.1133T>C (p. Ile378Thr) on LIPA, was found by gene sequencing in the proband. All living family members who carried the p.I378T variant displayed reduced LAL activity. CONCLUSIONS: Phenotypic analyses indicate that this may be an autosomal dominant nonclassical CESD pedigree with a LIPA gene mutation.

[Effect of Shikonin on Autophagy and Apoptosis of Human Promyelocytic Leukemia Cells].

OBJECTIVE: To explore the effect of shikonin on autophagy and apoptosis of human promyelocytic leukemia cells and its possible mechanism. METHODS: Human promyelocytic leukemia cells NB4 in the logarithmic growth phase were divided into control group (untreated NB4 cells), shikonin group (0.3 µmol/L shikonin treatment), 740Y-P group (15 µmol/L PI3K/Akt/mTOR pathway activator 740Y-P treatment), shikonin+740Y-P group (0.3 µmol/L shikonin and 15 µmol/L 740Y-P co-treatment), after 24 hours of treatment, the cells were used for subsequent experiments. CCK-8 method was used to detect cell viability, monodansylcadaverine (MDC) staining to detect the aggregation of autophagic vesicles, flow cytometry to detect cell apoptosis, and Western blot to detect the expression of Beclin1, LC3, p62, Bax, cleaved caspase-3, Bcl-2 and PI3K/Akt/mTOR pathway related proteins. RESULTS: Compared with the control group, the purple punctate fluorescence intensity, apoptosis rate, Beclin1, LC3-Ⅱ/LC3-Ⅰ, cleaved caspase-3, and Bax protein expression in NB4 cells were increased in the shikonin group, while OD450 value (24, 48 h) and the expressions of Bcl-2 and p62 proteins were decreased (all P < 0.05). Compared with the control group, the purple punctate fluorescence intensity, apoptosis rate, Beclin1, LC3-Ⅱ/LC3-Ⅰ, cleaved caspase-3, and Bax protein expression in NB4 cells were decreased, while OD450 value (24, 48 h) and the expressions of Bcl-2 and p62 proteins were increased in the 740Y-P group (all P < 0.05). Compared with the shikonin group, the purple punctate fluorescence intensity, apoptosis rate, Beclin1, LC3-Ⅱ/LC3-Ⅰ, cleaved caspase-3, and Bax protein expression in NB4 cells were decreased, while OD450 value (24, 48 h) and the expressions of Bcl-2 and p62 proteins were increased in the shikonin+740Y-P group (all P < 0.05). Compared with the control group, the expression of PI3K/Akt/mTOR pathway related proteins p-PI3K, p-Akt, and p-mTOR in NB4 cells were significantly decreased in the shikonin group, while those in the 740Y-P group were increased (all P < 0.05). Compared with the shikonin group, the expressions of p-PI3K, p-Akt, and p-mTOR proteins in NB4 cells were significantly increased in the shikonin+740Y-P group (all P < 0.05). CONCLUSION: Shikonin may promote autophagy and apoptosis of NB4 cells by inhibiting PI3K/Akt/mTOR pathway.

The effectiveness and safety of centralized early rehabilitation care for critically ill children with severe acquired brain injury: A retrospective cohort and implementation study.

BACKGROUND: Most children with neurocritical illness are at risk of physical, neurocognitive, and psychosocial sequelae and need centralized early rehabilitation care. OBJECTIVE: To identify the effectiveness and safety of centralized early rehabilitation care for children with severe acquired brain injury. METHODS: This is a mixed methods study-an implementation study and single-center retrospective cohort study with historical control. All children with severe acquired brain injury hospitalized in a specialized rehabilitation center in a comprehensive tertiary pediatric hospital between September 2016 and August 2020 were included. Patients treated in the centralized early rehabilitation unit were compared to historical controls dispersed in the normal inpatient rehabilitation ward. The effectiveness outcomes were measured by the Pediatric Cerebral Performance Category (PCPC) scale and the incidence of newly onset comorbidities. The safety outcomes were indicated by the mortality rate and the incidence of unexpected referrals. RESULTS: One hundred seventy-five patients were included. The delta PCPC scores of the first 4 weeks of inpatient rehabilitation in the intervention group were significantly lower than the control group (Z = -2.395, p = 0.017). The PCPC scores at 1 year in the intervention group were significantly reduced as compared to the control group (Z = -3.337, p = 0.001). The incidence of newly onset pneumonia/bronchitis was also decreased in the intervention group (χ2 = 4.517, p = 0.034). No death of patients was recorded, and there was no significant difference in unexpected referral rate between the two groups (χ2 = 0.374, p = 0.541). CONCLUSIONS: The centralized pediatrics early rehabilitation unit is effective and safe for children with severe acquired brain injury. Further multicenter prospective implementation studies on effectiveness, safety, and economic evaluation are needed.

Efficacy of the combination of BRII-196/BRII-198 in the treatment of COVID-19 vaccine breakthrough infections.

BACKGROUND: BRII-196 and BRII-198 are two recombinant human immunoglobulin (Ig) G1 monoclonal antibodies (mAbs) that non-competitively target distinct epitope regions within the receptor-binding domain (RBD) of the coronavirus spike glycoproteins. These antibodies are derived directly from human B cells of individuals who recovered from COVID-19. OBJECTIVE: To analyze the efficacy of BRII-196/BRII-198 in the treatment of coronavirus disease 2019 (COVID-19) vaccine breakthrough infections. METHODS: COVID-19 patients at high risk of progressing to severe and critical illness, with an initial SARS-CoV-2 immunoglobulin (Ig) G antibody level < 1.0 S/CO (detected within 24-48 hours post COVID-19 diagnosis), were treated with BRII-196/BRII-198 within three days of symptom onset. Treatment continued until the antibody level exceeded 1.0 S/CO. Patients whose absolute lymphocyte count (ALC) at first detection (within 24-48 h post-diagnosis) was < 0.8 × 109/L received thymalfasin therapy within three days of symptom onset, continuing until the ALC level surpassed 0.8 × 109/L. We determined the correlation of SARS-CoV-2 IgG antibody level and ALC with the condition of COVID-19 patients. Additionally, we analyzed the effects of BRII-196/BRII-198 on SARS-CoV-2 nucleic acid (NA) negative conversion, lymphocyte count recovery, and the change in SARS-CoV-2 IgG antibody level from the first positive NA test for SARS-CoV-2 to negative conversion in COVID-19 patients. RESULTS: A total of 61 cases of breakthrough infections were observed, classified as 10 mild cases, 31 ordinary cases, and 20 severe cases. Among these, 20%, 48.4% and 75% of the patients with mild, ordinary, and severe COVID-19, respectively, had initial SARS-CoV-2 IgG antibody level < 1.0 S/CO. Additionally, 0%, 35% and 70% had initial ALC < 0.8 × 109/L, respectively. Fifteen ordinary and 15 severe COVID-19 patients were treated with BRII-196/BRII-198. In severely infected patients, BRII-196/BRII-198 treatment showed statistically significant differences in NA negative conversion time and changes in SARS-CoV-2 IgG antibody levels (P < 0.05). However, in patients classified with ordinary severity, BRII-196/BRII-198 treatment did not lead to notable differences in NA negative conversion time or changes in SARS-CoV-2 IgG antibody level (P > 0.05). BRII-196/BRII-198 therapy was not associated with lymphocyte count recovery time in patients with either ordinary and/or severe COVID-19 (P > 0.05). CONCLUSIONS: The initial levels of SARS-CoV-2 IgG antibody and lymphocytes in fully vaccinated patients with breakthrough infections are inversely correlated with the severity of the disease. Early treatment with BRII-196/BRII-198 can shorten NA negative conversion time in severe COVID-19 patients and increase in vivo neutralizing antibody levels post-conversion, providing lasting protection. However, BRII-196/BRII-198 does not influence lymphocyte count recovery in patients with either ordinary and/or severe COVID-19.

Precise Determination of Selenium Forms and Contents in Selenium-Enriched Rapeseed Seedlings and Flowering Stalks by HPLC-ICP-MS.

Rapeseed (Brassica napus L.) has the ability of selenium (Se) enrichment. Identification of selenides in Se-rich rapeseed products will promote the development and utilization of high value. By optimizing the Se species extraction process (protease type, extraction reagent, enzyme sample ratio, extraction time, etc.) and chromatographic column, an efficient, stable, and accurate method was established for the identification of Se species and content in rapeseed seedlings and flowering stalks, which were cultured by inorganic Se hydroponics. Five Se compounds, including selenocystine (SeCys2), methylselenocysteine (MeSeCys), selenomethionine (SeMet), selenite (SeIV), and selenate (SeVI) were qualitatively and quantitatively identified. Organoselenium was absolutely dominant in both seedlings and flowering stalks among the detected rapeseed varieties, with 64.18-90.20% and 94.38-98.47%, respectively. Further, MeSeCys, a highly active selenide, predominated in rapeseed flowering stalks with a proportion of 56.36-72.93% and a content of 1707.3-5030.3 µg/kg. This study provides a new source of MeSeCys supplementation for human Se fortification.

Downregulation of GPX8 in hepatocellular carcinoma: impact on tumor stemness and migration.

PURPOSE: GPX8, which is found in the endoplasmic reticulum lumen, is a member of the Glutathione Peroxidases (GPXs) family. Its role in hepatocellular carcinoma (HCC) is unknown. METHODS: Immunohistochemical staining was used to detect the protein levels of GPX8 in HCC tissue microarrays. A short hairpin RNA lentivirus was used to knock down GPX8, and the main signaling pathways were investigated using transcriptome sequencing and a phosphorylated kinase array. The sphere formation assays, cloning-formation assays and cell migration assays were used to evaluate the stemness and migration ability of HCC cells. Identifying the GPX8-interacting proteins was accomplished through immunoprecipitation and protein mass spectrometry. RESULTS: The GPX8 protein levels were downregulated in HCC patients. Low expression of GPX8 protein was related to early recurrence and poor prognosis in HCC patients. GPX8 knockdown could enhance the stemness and migration ability of HCC cells. Consistently, Based on transcriptome analysis, multiple signaling pathways that include the PI3K-AKT and signaling pathways that regulate the pluripotency of stem cells, were activated after GPX8 knockdown. The downregulation of GPX8 could increase the expression of the tumor stemness markers KLF4, OCT4, and CD133. The in vivo downregulation of GPX8 could also promote the subcutaneous tumor-forming and migration ability of HCC cells. MK-2206, which is a small-molecule inhibitor of AKT, could reverse the tumor-promoting effects both in vivo and in vitro. We discovered that GPX8 and the 71-kDa heat shock cognate protein (Hsc70) have a direct interaction. The phosphorylation of AKT encouraged the translocation of Hsc70 into the nucleus and the expression of the PI3K p110 subunit, thereby increasing the downregulation of GPX8. CONCLUSION: The findings from this study demonstrate the anticancer activity of GPX8 in HCC by inactivating the Hsc70/AKT pathway. The results suggest a possible therapeutic target for HCC.

Retrospective cohort study investigating association between precancerous gastric lesions and colorectal neoplasm risk.

Background: Colorectal cancer (CRC) is considered the most prevalent synchronous malignancy in patients with gastric cancer. This large retrospective study aims to clarify correlations between gastric histopathology stages and risks of specific colorectal neoplasms, to optimize screening and reduce preventable CRC. Methods: Clinical data of 36,708 patients undergoing gastroscopy and colonoscopy from 2005-2022 were retrospectively analyzed. Correlations between gastric and colorectal histopathology were assessed by multivariate analysis. Outcomes of interest included non-adenomatous polyps (NAP), conventional adenomas (CAs), serrated polyps (SPs), and CRC. Statistical analysis used R version 4.0.4. Results: Older age (≥50 years) and Helicobacter pylori infection (HPI) were associated with increased risks of conventional adenomas (CAs), serrated polyps (SPs), non-adenomatous polyps (NAP), and colorectal cancer (CRC). Moderate to severe intestinal metaplasia specifically increased risks of NAP and CAs by 1.17-fold (95% CI 1.05-1.3) and 1.19-fold (95% CI 1.09-1.31), respectively. For CRC risk, low-grade intraepithelial neoplasia increased risk by 1.41-fold (95% CI 1.08-1.84), while high-grade intraepithelial neoplasia (OR 3.76, 95% CI 2.25-6.29) and gastric cancer (OR 4.81, 95% CI 3.25-7.09) showed strong associations. More advanced gastric pathology was correlated with progressively higher risks of CRC. Conclusion: Precancerous gastric conditions are associated with increased colorectal neoplasm risk. Our findings can inform screening guidelines to target high-risk subgroups, advancing colorectal cancer prevention and reducing disease burden.

Melt-quenched glass formation of a family of metal-carboxylate frameworks.

Metal-organic framework (MOF) glasses are an emerging class of glasses which complement traditional inorganic, organic and metallic counterparts due to their hybrid nature. Although a few zeolitic imidazolate frameworks have been made into glasses, how to melt and quench the largest subclass of MOFs, metal carboxylate frameworks, into glasses remains challenging. Here, we develop a strategy by grafting the zwitterions on the carboxylate ligands and incorporating organic acids in the framework channels to enable the glass formation. The charge delocalization of zwitterion-acid subsystem and the densely filled channels facilitate the coordination bonding mismatch and thus reduce the melting temperature. Following melt-quenching realizes the glass formation of a family of carboxylate MOFs (UiO-67, UiO-68 and DUT-5), which are usually believed to be un-meltable. Our work opens up an avenue for melt-quenching porous molecular solids into glasses.

Evaluating the efficacy and safety of oral triple sequential combination therapy for treating patients with pulmonary arterial hypertension: A multicenter retrospective study.

This study aimed to evaluate the effectiveness and safety of an oral sequential triple combination therapy with selexipag after dual combination therapy with endothelin receptor antagonist (ERA) and phosphodiesterase-5 inhibitor (PDE5I)/riociguat in pulmonary arterial hypertension (PAH) patients. A total of 192 PAH patients from 10 centers had received oral sequential selexipag therapy after being on dual-combination therapy with ERA and PDE5i/riociguat for a minimum of 3 months. Clinical data were collected at baseline and after 6 months of treatment. The study analyzed the event-free survival at 6 months and all-cause death over 2 years. At baseline, the distribution of patients among the risk groups was as follows: 22 in the low-risk group, 35 in the intermediate-low-risk group, 91 in the intermediate-high-risk group, and 44 in the high-risk group. After 6 months of treatment, the oral sequential triple combination therapy resulted in reduced NT-proBNP levels (media from 1604 to 678 pg/mL), a decline in the percentage of WHO-FC III/IV (from 79.2% to 60.4%), an increased in the 6MWD (from 325 ± 147 to 378 ± 143 m) and a rise in the percentage of patients with three low-risk criteria (from 5.7% to 13.5%). Among the low-risk group, there was an improvement in the right heart remodeling, marked by a decrease in right atrium area and eccentricity index. The intermediate-low-risk group exhibited significant enhancements in WHO-FC and tricuspid annular plane systolic excursion. For those in the intermediate-high and high-risk groups, there were marked improvements in activity tolerance, as reflected by WHO-FC and 6MWD. The event-free survival rate at 6 months stood at 88%. Over the long-term follow-up, the survival rates at 1 and 2 years were 86.5% and 86.0%, respectively. In conclusion, the oral sequential triple combination therapy enhanced both exercise capacity and cardiac remodeling across PAH patients of different risk stratifications.

Advanced biomass-based Janus materials: Classification, preparation and application: A review.

In contrast to conventional particles characterized by isotropic surfaces, Janus particles possess anisotropic surfaces, resulting in unique physicochemical properties and functional attributes. In recent times, there has been a surge in interest regarding the synthesis of Janus particles using biological macromolecules. Various synthesis techniques have been developed for the fabrication of Janus materials derived from biomass. These methods include electrospinning, freeze-drying, secondary casting film formation, self-assembly technology, and other approaches. In the realm of Janus composite materials, those derived from biomass have found extensive applications in diverse domains including oil-water separation, sensors, photocatalysis, and medical materials. This article provides a systematic introduction to the classification of Janus materials, with a specific focus on various types of biomass-based Janus materials (mainly cellulose-based Janus materials, lignin-based Janus materials and protein-based Janus materials) and the methods used for their preparation. This work will not only deepen the understanding of biomass-based Janus materials, but also contribute to the development of new methods for designing biomass-based Janus structures to optimize biomass utilization.

A peptide selectively recognizes Gram-negative bacteria and forms a bacterial extracellular trap (BET) through interfacial self-assembly.

An innate immune system intricately leverages unique mechanisms to inhibit colonization of external invasive Bacteria, for example human defensin-6, through responsive encapsulation of bacteria. Infection and accompanying antibiotic resistance stemming from Gram-negative bacteria aggregation represent an emerging public health crisis, which calls for research into novel anti-bacterial therapeutics. Herein, inspired by naturally found host-defense peptides, we design a defensin-like peptide ligand, bacteria extracellular trap (BET) peptide, with modular design composed of targeting, assembly, and hydrophobic motifs with an aggregation-induced emission feature. The ligand specifically recognizes Gram-negative bacteria via targeting cell wall conserved lipopolysaccharides (LPS) and transforms from nanoparticles to nanofibrous networks in situ to trap bacteria and induce aggregation. Importantly, treatment of the BET peptide was found to have an antibacterial effect on the Pseudomonas aeruginosa strain, which is comparable to neomycin. Animal studies further demonstrate its ability to trigger aggregation of bacteria in vivo. This biomimetic self-assembling BET peptide provides a novel approach to fight against pathogenic Gram-negative bacteria.

Adult type I Gaucher disease with splenectomy caused by a compound heterozygous GBA1 mutation in a Chinese patient: a case report.

Gaucher disease (GD) is an autosomal recessive ailment resulting from glucocerebrosidase deficiency caused by a mutation in the GBA1 gene, leading to multi-organ problems in the liver, spleen, and bone marrow. In China, GD is extremely uncommon and has a lower incidence rate than worldwide. In this study, we report the case of an adult male with an enlarged spleen for 13 years who presented with abdominal distension, severe loss of appetite and weight, reduction of the three-line due to hypersplenism, frequent nosebleeds, and bloody stools. Regrettably, the unexpected discovery of splenic pathology suggestive of splenic Gaucher disease was only made after a splenectomy due to a lack of knowledge about rare disorders. Our patient's delayed diagnosis may have been due to the department where he was originally treated, but it highlights the need for multidisciplinary consultation in splenomegaly of unknown etiology. We then investigated the patient's clinical phenotypes and gene mutation features using genetically phenotypical analysis. The analysis of the GBA1 gene sequence indicated that the patient carried a compound heterozygous mutation consisting of two potentially disease-causing mutations: c.907C > A (p. Leu303Ile) and c.1448 T > C (p. Leu483Pro). While previous research has linked the p. Leu483Pro mutation site to neurologic GD phenotypes (GD2 and GD3), the patients in this investigation were identified as having non-neuronopathic GD1. The other mutation, p. Leu303Ile, is a new GD-related mutation not indexed in PubMed that enriches the GBA1 gene mutation spectrum. Biosignature analysis has shown that both mutations alter the protein's three-dimensional structure, which may be a pathogenic mechanism for GD1 in this patient.