Global incidence and mortality trends of gastric cancer and predicted mortality of gastric cancer by 2035.

OBJECTIVE: To study the historical global incidence and mortality trends of gastric cancer and predicted mortality of gastric cancer by 2035. METHODS: Incidence data were retrieved from the Cancer Incidence in Five Continents (CI5) volumes I-XI, and mortality data were obtained from the latest update of the World Health Organization (WHO) mortality database. We used join-point regression analysis to examine historical incidence and mortality trends and used the package NORDPRED in R to predict the number of deaths and mortality rates by 2035 by country and sex. RESULTS: More than 1,089,000 new cases of gastric cancer and 769,000 related deaths were reported in 2020. The average annual percent change (AAPC) in the incidence of gastric cancer from 2003 to 2012 among the male population, South Korea, Japan, Malta, Canada, Cyprus, and Switzerland showed an increasing trend (P > 0.05); among the female population, Canada [AAPC, 1.2; (95%Cl, 0.5-2), P < 0.05] showed an increasing trend; and South Korea, Ecuador, Thailand, and Cyprus showed an increasing trend (P > 0.05). AAPC in the mortality of gastric cancer from 2006 to 2015 among the male population, Thailand [3.5 (95%cl, 1.6-5.4), P < 0.05] showed an increasing trend; Malta Island, New Zealand, Turkey, Switzerland, and Cyprus had an increasing trend (P > 0.05); among the male population aged 20-44, Thailand [AAPC, 3.4; (95%cl, 1.3-5.4), P < 0.05] showed an increasing trend; Norway, New Zealand, The Netherlands, Slovakia, France, Colombia, Lithuania, and the USA showed an increasing trend (P > 0.05). It is predicted that the mortality rate in Slovenia and France's female population will show an increasing trend by 2035. It is predicted that the absolute number of deaths in the Israeli male population and in Chile, France, and Canada female population will increase by 2035. CONCLUSION: In the past decade, the incidence and mortality of gastric cancer have shown a decreasing trend; however, there are still some countries showing an increasing trend, especially among populations younger than 45 years. Although mortality in most countries is predicted to decline by 2035, the absolute number of deaths due to gastric cancer may further increase due to population growth.

Laparoscopic Spleen-Preserving Hilar Lymphadenectomy for Advanced Proximal Gastric Cancer Without Greater Curvature Invasion: Five-Year Outcomes From the Fuges-02 Randomized Clinical Trial.

Importance: Splenic hilar lymphadenectomy has been recommended for locally advanced proximal gastric cancer (APGC) involving the greater curvature. However, it is unclear whether laparoscopic spleen-preserving splenic hilar lymphadenectomy (LSPSHL) is associated with a long-term survival benefit for APGC without greater curvature invasion. Objective: To present the 5-year follow-up data from a randomized clinical trial that compared laparoscopic total gastrectomy (D2 group) with D2 plus LSPSHL (D2 + No. 10 group) among patients with resectable APGC. Design, Setting, and Participants: This is a post hoc secondary analysis of a randomized clinical trial that enrolled 536 patients with potentially resectable APGC (cT2-4a, N0 or N+, and M0) without greater curvature invasion from January 5, 2015, to October 10, 2018. All patients were tracked for at least 5 years. The final follow-up was on October 30, 2023. Interventions: Patients were randomly assigned in a 1:1 ratio to the D2 + No. 10 or D2 groups. Main Outcomes and Measures: The 5-year disease-free survival (DFS) and overall survival (OS) rates were measured. Recurrence patterns and causes of death were compared. Results: A total of 526 patients (392 men [74.5%]; mean [SD] age, 60.6 [9.6] years) were included in the modified intent-to-treat analysis, with 263 patients in each group. The 5-year DFS rate was 63.9% (95% CI, 58.1%-69.7%) for the D2 + No. 10 group and 55.1% (95% CI, 49.1%-61.1%) for the D2 group (log-rank P = .04). A statistically significant difference was observed in the 5-year OS between the D2 + No. 10 group and the D2 group (66.2% [95% CI, 60.4%-71.9%] vs 57.4% [95% CI, 51.4%-63.4%]; log-rank P = .03). The No. 10 lymph node exhibited a therapeutic value index (TVI) of 6.5, surpassing that of Nos. 8a (TVI, 3.0), 11 (TVI, 5.8), and 12a (TVI, 0.8). A total of 86 patients in the D2 + No. 10 group (cumulative incidence, 32.7%) and 111 patients in the D2 group (cumulative incidence, 42.2%) experienced recurrence (hazard ratio, 0.72; 95% CI, 0.54-0.95; P = .02). The multivariable competing risk regression model demonstrated that D2 + No. 10 remained an independent protective factor for a lower 5-year cumulative recurrence rate after surgery (hazard ratio, 0.75; 95% CI, 0.56-1.00; P = .05). There was a significant difference in the 5-year cumulative recurrence rate at the No. 10 lymph node area between the 2 groups (D2 + No. 10 group vs D2 group: 0% vs 2.3% [n = 6]; P = .01). Conclusions: This post hoc secondary analysis of a randomized clinical trial found that laparoscopic total gastrectomy with LSPSHL can improve the prognosis and reduce recurrence for APGC without greater curvature invasion. Future multicenter studies are warranted to validate these findings. Trial Registration: ClinicalTrials.gov Identifier: NCT02333721.

Comparative chemical profiling of leaf essential oils from Cinnamomum kanehirae and related species using steam distillation and solvent extraction: Implications for plant-based classification.

Cinnamomum kanehirae Hayata, belonging to Lauraceae family, is an indigenous and endangered species of considerable economic importance in Taiwan. It plays a crucial role as the host for the economically valuable saprotrophic fungus, Taiwanofungus camphorates. However, accurate species identification poses a challenge due to the similarity in morphological features and frequent natural hybridization with closely related species. Acquiring high-quality and pure leaf oils becomes imperative for precise species identification and producing superior goods. In this study, our objective was to establish methodologies for analyzing the chemical composition of leaf essential oils and subsequently apply this knowledge to differentiate among three Cinnamomum species. Gas chromatography-mass spectrometry (GC/MS) was employed to scrutinize the chemical makeup of leaf essential oils from three closely related species: C. kanehirae, C. micranthum, and C. camphora. We utilized Steam Distillation (SD) and steam distillation-solvent extraction (SDSE) methods, with the SDSE-Hexane approach chosen for optimization, enhancing extraction efficiency and ensuring essential oil purity. Through the SDSE-Hexane method, we identified seventy-four compounds distributed across three major classes: monoterpenes hydrocarbons (0.0-7.0 %), oxygenated monoterpenes (3.8-90.9 %), sesquiterpenes hydrocarbons (0.0-28.3 %), and oxygenated sesquiterpenes (1.6-88.1 %). Our findings indicated the presence of more than one chemotype in both C. kanehirae and C. camphora, whereas no specific chemotype could be discerned in C. micranthum. Furthermore, clustering based on chemotypes allowed for the differentiation of samples from the three species. Notably, we demonstrated that the chemical compositions of grafted C. kanehirae remained largely unaffected by the rootstock. Conversely, natural hybrids between C. kanehirae and C. camphora exhibited profiles more closely aligned with C. kanehirae. The optimized extraction method and the chemotype-based classification system established in this study present valuable tools for essential oil preparation, species identification, and further exploration into the genetic variation of Cinnamomum.

Robotic versus laparoscopic distal gastrectomy for resectable gastric cancer: a randomized phase 2 trial.

Robotic surgery may be an alternative to laparoscopic surgery for gastric cancer (GC). However, randomized controlled trials (RCTs) reporting the differences in survival between these two approaches are currently lacking. From September 2017 to January 2020, 300 patients with cT1-4a and N0/+ were enrolled and randomized to either the robotic (RDG) or laparoscopic distal gastrectomy (LDG) group (NCT03313700). The primary endpoint was 3-year disease-free survival (DFS); secondary endpoints reported here are the 3-year overall survival (OS) and recurrence patterns. The remaining secondary outcomes include intraoperative outcomes, postoperative recovery, quality of lymphadenectomy, and cost differences, which have previously been reported. There were 283 patients in the modified intention-to-treat analysis (RDG group: n = 141; LDG group: n = 142). The trial has met pre-specified endpoints. The 3-year DFS rates were 85.8% and 73.2% in the RDG and LDG groups, respectively (p = 0.011). Multivariable Cox regression model including age, tumor size, sex, ECOG PS, lymphovascular invasion, histology, pT stage, and pN stage showed that RDG was associated with better 3-year DFS (HR: 0.541; 95% CI: 0.314-0.932). The RDG also improved the 3-year cumulative recurrence rate (RDG vs. LDG: 12.1% vs. 21.1%; HR: 0.546, 95% CI: 0.302-0.990). Compared to LDG, RDG demonstrated non-inferiority in 3-year DFS rate.

Illuminating the Genetic Basis of Congenital Heart Disease in Patients with Kabuki Syndrome.

Congenital heart defects (CHDs) affect a substantial proportion of patients with Kabuki syndrome. However, the prevalence and type of CHD and the genotype-phenotype correlations in Asian populations are not fully elucidated. This study performed a retrospective analysis of 23 Taiwanese patients with molecularly confirmed Kabuki syndrome. Twenty-two patients presented with pathogenic variants in the KMT2D gene. Comprehensive clinical assessments were performed. A literature review was conducted to summarize the spectrum of CHDs in patients with Kabuki syndrome. In total, 16 (73.9%) of 22 patients with pathogenic KMT2D variants had CHDs. The most common types of CHD were atrial septal defects (37.5%), ventricular septal defects (18.8%), coarctation of the aorta (18.8%), bicuspid aortic valve (12.5%), persistent left superior vena cava (12.5%), mitral valve prolapse (12.5%), mitral regurgitation (12.5%), and patent ductus arteriosus (12.5%). Other cardiac abnormalities were less common. Further, there were no clear genotype-phenotype correlations found. A literature review revealed similar patterns of CHDs, with a predominance of left-sided obstructive lesions and septal defects. In conclusion, the most common types of CHDs in Taiwanese patients with Kabuki syndrome who presented with KMT2D mutations are left-sided obstructive lesions and septal defects.

Syndromic ciliopathy: a taiwanese single-center study.

BACKGROUND: Syndromic ciliopathies are a group of congenital disorders characterized by broad clinical and genetic overlap, including obesity, visual problems, skeletal anomalies, mental retardation, and renal diseases. The hallmark of the pathophysiology among these disorders is defective ciliary functions or formation. Many different genes have been implicated in the pathogenesis of these diseases, but some patients still remain unclear about their genotypes. METHODS: The aim of this study was to identify the genetic causes in patients with syndromic ciliopathy. Patients suspected of or meeting clinical diagnostic criteria for any type of syndromic ciliopathy were recruited at a single diagnostic medical center in Southern Taiwan. Whole exome sequencing (WES) was employed to identify their genotypes and elucidate the mutation spectrum in Taiwanese patients with syndromic ciliopathy. Clinical information was collected at the time of patient enrollment. RESULTS: A total of 14 cases were molecularly diagnosed with syndromic ciliopathy. Among these cases, 10 had Bardet-Biedl syndrome (BBS), comprising eight BBS2 patients and two BBS7 patients. Additionally, two cases were diagnosed with Alström syndrome, one with Oral-facial-digital syndrome type 14, and another with Joubert syndrome type 10. A total of 4 novel variants were identified. A recurrent splice site mutation, BBS2: c.534 + 1G > T, was present in all eight BBS2 patients, suggesting a founder effect. One BBS2 patient with homozygous c.534 + 1G > T mutations carried a third ciliopathic allele, TTC21B: c.264_267dupTAGA, a nonsense mutation resulting in a premature stop codon and protein truncation. CONCLUSIONS: Whole exome sequencing (WES) assists in identifying molecular pathogenic variants in ciliopathic patients, as well as the genetic hotspot mutations in specific populations. It should be considered as the first-line genetic testing for heterogeneous disorders characterized by the involvement of multiple genes and diverse clinical manifestations.

Robot-assisted versus laparoscopic-assisted gastrectomy among malnourished patients with gastric cancer based on textbook outcome.

BACKGROUND: Textbook outcome (TO) has been widely employed as a comprehensive indicator to assess the short-term prognosis of patients with cancer. Preoperative malnutrition is a potential risk factor for adverse surgical outcomes in patients with gastric cancer (GC). This study aimed to compare the TO between robotic-assisted gastrectomy (RAG) and laparoscopic-assisted gastrectomy (LAG) in malnourished patients with GC. METHODS: According to the diagnostic consensus of malnutrition proposed by Global Leadership Initiative on Malnutrition (GLIM) and Nutrition Risk Index (NRI), 895 malnourished patients with GC who underwent RAG (n = 115) or LAG (n = 780) at a tertiary referral hospital between January 2016 and May 2021 were included in the propensity score matching (PSM, 1:2) analysis. RESULTS: After PSM, no significant differences in clinicopathological characteristics were observed between the RAG (n = 97) and LAG (n = 194) groups. The RAG group had significantly higher operative time and lymph nodes harvested, as well as significantly lower blood loss and hospital stay time compared to the LAG group. More patients in the RAG achieved TO. Logistic regression analysis revealed that RAG was an independent protective factor for achieving TO. There were more adjuvant chemotherapy (AC) cycles in the RAG group than in the LAG group. After one year of surgery, a higher percentage of patients (36.7% vs. 22.8%; P < 0.05) in the RAG group recovered from malnutrition compared to the LAG group. CONCLUSIONS: For malnourished patients with GC, RAG performed by experienced surgeons can achieved a higher rate of TO than those of LAG, which directly contributed to better AC compliance and a faster restoration of nutritional status.

Oncological outcomes of sequential laparoscopic gastrectomy after treatment with camrelizumab combined with nab-paclitaxel plus S-1 for gastric cancer with serosal invasion.

Objective: To explore the oncological outcomes of sequential laparoscopic gastrectomy after treatment with camrelizumab in combination with nab-paclitaxel plus S-1 for the treatment of gastric cancer with serosal invasion. Methods: This study is a retrospective cohort study and retrospectively analyzed the clinicopathological data of 128 patients with serosal invasion gastric cancer (cT4NxM0) who received nab-paclitaxel + S-1(SAP) or camrelizumab + nab-paclitaxel + S-1 (C-SAP) regimen and underwent laparoscopy assisted gastrectomy in Fujian Union Hospital from March 2019 to December 2020. The patients were divided into SAP group and C-SAP group. The 2-years overall survival rate, 2-year recurrence free survival rate recurrence rate and initial recurrence time were compared between the two groups. Results: A total of 128 patients were included, including 90 cases in SAP group and 38 cases in C-SAP group. There were no significant differences in age, gender, gastrectomy method, surgical approach, R0 resection, nerve invasion, vascular invasion, total number of harvested lymph nodes, number of positive lymph nodes and major pathologic response (MPR) rate between the two groups (P>0.05). However, the proportion of ypT0, ypN0 and pCR rate in C-SAP group were significantly higher than those in SAP group (P<0.05). The 2-year OS of C-SAP group (80.7%) was higher than that of SAP group (67.8%), and the difference was not statistically significant (P = 0.112); At 2 years after operation, the recurrence rate of C-SAP group (44.3%) was lower than that of SAP group (55.8%) (P = 0.097); Further analysis showed that the average time to recurrence in the C-SAP group was 18.9 months, which was longer than that in SAP group 13.1 months (P = 0.004); The 2-year recurrence free survival rate in C-SAP group was higher than that in SAP group (P=0.076); There was no significant difference in the overall survival time after recurrence between the two groups (P= 0.097). Conclusion: Camrelizumab combined with neoadjuvant chemotherapy can improve the proportion of ypT0, ypN0 and pCR in patients, while prolonging the initial recurrence time of patients in the C-SAP group, but did not increase the immunotherapy/chemotherapy related side effects and postoperative complications.

Clinical Characteristics of Pediatric Clavicular Lesions: A Retrospective Analysis of 20 Cases.

Background This research aims to study the diagnostic patterns, anatomical locations, and age-related trends in pediatric clavicular lesions, filling a gap in pediatric-specific data for these conditions. Methodology A retrospective study of 20 pediatric patients (aged ≤14 years) with clavicular lesions was conducted based on inclusion and exclusion criteria emphasizing confirmed diagnosis and treatment specifics. The diagnostic process relied on open biopsy, followed by excision or curettage and histopathological examination. Results The study primarily involved patients with an average age of 7.1 ± 3.8 years. Eosinophilic granuloma was the most common diagnosis (30% of cases), particularly in the age group of 0-3 years. Clavicular lesions predominantly manifested as either a palpable lump or localized swelling with pain. The medial of the clavicle was the most frequent lesion location. No malignant tumors were found, and the functional outcomes post-treatment were satisfactory. Conclusions Pediatric clavicular lesions exhibit distinct diagnostic and anatomical characteristics compared to adults. Eosinophilic granuloma is significantly prevalent in early childhood, necessitating age-specific diagnostic and therapeutic approaches. The study advocates for multidisciplinary collaboration in the treatment and improved understanding of these lesions, which are vital for pediatric orthopedic oncology.

Long-term oncological outcomes of 3D versus 2D laparoscopic gastrectomy for gastric cancer: a randomized clinical trial.

BACKGROUND: Laparoscopy-assisted gastrectomy (LG) is rapidly gaining popularity owing to its minimal invasiveness. Previous studies have found that compared with two-dimensional (2D)-LG, three-dimensional (3D)-LG showed better short-term outcomes. However, the long-term oncological outcomes in patients with locally resectable gastric cancer (GC) remain controversial. METHODS: In this noninferiority, open-label, randomized clinical trial, a total of 438 eligible GC participants were randomly assigned in a 1:1 ratio to either 3D-LG or 2D-LG from January 2015 to April 2016. The primary endpoint was operating time, while the secondary endpoints included 5-year overall survival (OS), disease-free survival (DFS), and recurrence pattern. RESULTS: Data from 401 participants were included in the per-protocol analysis, with 204 patients in the 3D group and 197 patients in the 2D group. The 5-year OS and DFS rates were comparable between the 3D and 2D groups (5-year OS: 70.6% vs. 71.1%, Log-rank P = 0.743; 5-year DFS: 68.1% vs. 69.0%, log-rank P = 0.712). No significant differences were observed between the 3D and 2D groups in the 5-year recurrence rate (28.9% vs. 28.9%, P = 0.958) or recurrence time (mean time, 22.6 vs. 20.5 months, P = 0.412). Further stratified analysis based on the type of gastrectomy, postoperative pathological staging, and preoperative BMI showed that the 5-year OS, DFS, and recurrence rates of the 3D group in each subgroup were similar to those of the 2D group (all P > 0.05). CONCLUSIONS: For patients with locally resectable GC, 3D-LG performed by experienced surgeons in high-volume professional institutions can achieve long-term oncological outcomes comparable to those of 2D-LG. REGISTRATION NUMBER: NCT02327481 ( http://clinicaltrials.gov ).

Clinical application of super-low-positioned intestinal decompression tube in the treatment of intestinal obstruction: a pilot study.

OBJECTIVE: This study aimed to evaluate the clinical application and efficacy of a super-low-positioned intestinal decompression tube in the treatment of intestinal obstruction. METHODS: A total of 130 patients with postoperative small bowel obstruction were included in this study. The patients were divided into a super-low-positioned intestinal decompression group and a conventional intestinal decompression group. The clinical data, treatment outcomes, and complications were compared between the two groups. RESULTS: The technical success rate of placing the super-low-positioned intestinal decompression tube was 100%, with no intraoperative complications. The patients in the super-low-positioned intestinal decompression group had a significantly shorter hospital stay (8.3 ± 5.2 vs 17.7 ± 13.3, P < 0.001) and a higher non-operative treatment success rate (83.6% vs 57.9%, P = 0.001) compared to the conventional intestinal decompression group. Multivariate logistic regression analysis showed that the placement of a super-low-positioned intestinal decompression tube was an independent protective factor for treatment outcomes (P = 0.001). The hospital stay was significantly shorter in the super-low-positioned intestinal decompression group compared to the conventional group in both successful non-operative treatment patients (6.9 ± 3.0 vs 11.2 ± 7.5, P < 0.001) and failed non-operative treatment patients (16.2 ± 7.4 vs 26.6 ± 14.4, P < 0.001). The super-low-positioned intestinal decompression tube effectively relieved the "Self-strangulation" phenomenon in patients with intestinal obstruction. CONCLUSION: The super-low-positioned intestinal decompression tube is a safe and effective method for the treatment of intestinal obstruction, with better treatment outcomes and shorter hospital stays compared to conventional intestinal decompression. Further prospective studies are needed to validate these findings.

Crosstalk between GABAA receptors in astrocytes and neurons triggered by general anesthetic drugs.

General anesthetic drugs cause cognitive deficits that persist after the drugs have been eliminated. Astrocytes may contribute to such cognition-impairing effects through the release of one or more paracrine factors that increase a tonic inhibitory conductance generated by extrasynaptic γ-aminobutyric acid type A (GABAA) receptors in hippocampal neurons. The mechanisms underlying this astrocyte-to-neuron crosstalk remain unknown. Interestingly, astrocytes express anesthetic-sensitive GABAA receptors. Here, we tested the hypothesis that anesthetic drugs activate astrocytic GABAA receptors to initiate crosstalk leading to a persistent increase in extrasynaptic GABAA receptor function in neurons. We also investigated the signaling pathways in neurons and aimed to identify the paracrine factors released from astrocytes. Astrocytes and neurons from mice were grown in primary cell cultures and studied using in vitro electrophysiological and biochemical assays. We discovered that the commonly used anesthetics etomidate (injectable) and sevoflurane (inhaled) stimulated astrocytic GABAA receptors, which in turn promoted the release paracrine factors, that increased the tonic current in neurons via a p38 MAPK-dependent signaling pathway. The increase in tonic current was mimicked by exogenous IL-1ß and abolished by blocking IL-1 receptors; however, unexpectedly, IL-1ß and other cytokines were not detected in astrocyte-conditioned media. In summary, we have identified a novel form of crosstalk between GABAA receptors in astrocytes and neurons that engages a p38 MAPK-dependent pathway. Brief commentary BACKGROUND: Many older patients experience cognitive deficits after surgery. Anesthetic drugs may be a contributing factor as they cause a sustained increase in the function of "memory blocking" extrasynaptic GABAA receptors in neurons. Interestingly, astrocytes are required for this increase; however, the mechanisms underlying the astrocyte-to-neuron crosstalk remain unknown. TRANSLATIONAL SIGNIFICANCE: We discovered that commonly used general anesthetic drugs stimulate GABAA receptors in astrocytes, which in turn release paracrine factors that trigger a persistent increase in extrasynaptic GABAA receptor function in neurons via p38 MAPK. This novel form of crosstalk may contribute to persistent cognitive deficits after general anesthesia and surgery.

Spectrum of PHEX Mutations and FGF23 Profiles in a Taiwanese Cohort With X-Linked Hypophosphatemia Including 102 Patients.

BACKGROUND/AIM: X-linked hypophosphatemia (XLH), the most common form of hereditary rickets, results from loss-of-function mutations in the phosphate-regulating PHEX gene. Elevated fibroblast growth factor 23 (FGF23) contributes to hypophosphatemia in XLH. This study aimed to characterize PHEX variants and serum FGF23 profiles in Taiwanese patients with XLH. PATIENTS AND METHODS: We retrospectively reviewed the records of 102 patients clinically suspected of having hypophosphatemic rickets from 2006 to 2022. Serum intact Fibroblast growth factor-23 (iFGF23) levels were measured on clinic visit days. PHEX mutations were identified using Sanger sequencing, and negative cases were analyzed using whole-exome sequencing. RESULTS: The majority (92.1%) of patients exhibited elevated FGF23 compared with normal individuals. Among 102 patients, 44 distinct PHEX mutations were identified. Several mutations recurred in multiple unrelated Taiwanese families. We discovered a high frequency of novel PHEX mutations and identified variants associated with extreme FGF23 elevation and tumorigenesis. CONCLUSION: Our findings revealed the PHEX genotypic variants and FGF23 levels in Taiwanese patients with XLH. These results are crucial given the recent approval of burosumab, a monoclonal FGF23 antibody, for XLH therapy. This study provides key insights into the clinical management of XLH in Taiwan.

Primary biliary cholangitis with features of autoimmune hepatitis in a 19-year-old adolescent with 14q24.1q24.2 deletion: a case report.

Introduction: Primary biliary cholangitis (PBC) is a rare and chronic autoimmune liver disease characterized by the progressive destruction of small intrahepatic bile ducts that may eventually lead to cirrhosis. PBC with features of autoimmune hepatitis (AIH) has rarely been reported in pediatric patients with genetic defects. We present the case of an adolescent with chromosome 14q24.1q24.2 deletion who was given the diagnosis of stage IV PBC with features of AIH. Case presentation: A 19-year-old male adolescent with multiple congenital abnormalities and an intellectual disability presented with abnormal liver enzymes levels and pruritus for more than 5 years. Laboratory examinations revealed elevated levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and gamma-glutamyl transpeptidase. After the exclusion of viral hepatitis, alpha-1 antitrypsin deficiency, Wilson's disease, and other genetic cholestatic liver diseases by laboratory tests and whole exome sequencing, a liver biopsy was performed and stage IV PBC was diagnosed. Notably, features of AIH were also noted in the histopathological report, indicating the presence of PBC with AIH features. The patient responded well to a combination therapy of ursodeoxycholic acid and steroids. Array comparative genomic hybridization analysis performed to study the congenital abnormalities revealed a 3.89 Mb 14q24.1q24.2 deletion. Conclusion: PBC with AIH features has rarely been reported in an adolescent with a chromosomal abnormality. The present case can increase awareness for early-onset PBC and its possible correlation with chromosomal defects.

CDK5 promotes apoptosis and attenuates chemoresistance in gastric cancer via E2F1 signaling.

BACKGROUND: Chemoresistance is a major clinical challenge that leads to tumor metastasis and poor clinical outcome. The mechanisms underlying gastric cancer resistance to chemotherapy are still unclear. METHODS: We conducted bioinformatics analyses of publicly available patient datasets to establish an apoptotic phenotype and determine the key pathways and clinical significance. In vitro cell models, in vivo mouse models, and numerous molecular assays, including western blotting, qRT-PCR, immunohistochemical staining, and coimmunoprecipitation assays were used to clarify the role of factors related to apoptosis in gastric cancer in this study. Differences between datasets were analyzed using the Student's t-test and two-way ANOVA; survival rates were estimated based on Kaplan-Meier analysis; and univariate and multivariate Cox proportional hazards models were used to evaluate prognostic factors. RESULTS: Bulk transcriptomic analysis of gastric cancer samples established an apoptotic phenotype. Proapoptotic tumors were enriched for DNA repair and immune inflammatory signaling and associated with improved prognosis and chemotherapeutic benefits. Functionally, cyclin-dependent kinase 5 (CDK5) promoted apoptosis of gastric cancer cells and sensitized cells and mice to oxaliplatin. Mechanistically, we demonstrate that CDK5 stabilizes DP1 through direct binding to DP1 and subsequent activation of E2F1 signaling. Clinicopathological analysis indicated that CDK5 depletion correlated with poor prognosis and chemoresistance in human gastric tumors. CONCLUSION: Our findings reveal that CDK5 promotes cell apoptosis by stabilizing DP1 and activating E2F1 signaling, suggesting its potential role in the prognosis and therapeutic decisions for patients with gastric cancer.

Single and coupled cavity mode sensing schemes using a diagnostic field.

Precise optical mode matching is of critical importance in experiments using squeezed-vacuum states. Automatic spatial-mode matching schemes have the potential to reduce losses and improve loss stability. However, in quantum-enhanced coupled-cavity experiments, such as gravitational-wave detectors, one must also ensure that the sub-cavities are also mode matched. We propose what we believe to be a new mode sensing scheme, which works for simple and coupled cavities. The scheme requires no moving parts, nor tuning of Gouy phases. Instead a diagnostic field tuned to the HG20/LG10 mode frequency is used. The error signals are derived to be proportional to the difference in waist position, and difference in Rayleigh ranges, between the sub-cavity eigenmodes. The two error signals are separable by 90 degrees of demodulation phase. We demonstrate reasonable error signals for a simplified Einstein Telescope optical design. This work will facilitate routine use of extremely high levels of squeezing in current and future gravitational-wave detectors.

Structural properties and biological activities of soluble dietary fibers rich in pectic-polysaccharides from different buckwheat green leaves.

Buckwheat green leaves are commonly consumed as functional tea materials due to their various beneficial effects. Although buckwheat green leaves have abundant soluble dietary fibers (SDFs), the information about their structural properties and functional properties remains unknown, largely hindering their applications as functional/health products. Hence, to enhance the usage and application of SDFs from buckwheat green leaves as value-added health products, the structures and biological activities of SDFs derived from different buckwheat green leaves were investigated and compared. Results revealed that SDFs derived from Tartary buckwheat green leaves (TBSDF) and common buckwheat green leaves (CBSDF) were rich in complex pectic-polysaccharides, mainly composing of homogalacturonan (HG) and rhamnogalacturonan I (RG I) pectic domains. Besides, TBSDF had higher proportion of RG I pectic domains than that of CBSDF. Furthermore, the existence of a high content of complex pectic-polysaccharides in TBSDF and CBSDF could contribute to their various biological activities, such as antioxidant, antiglycation, fat/bile acid binding, anticancer, and prebiotic effects. These results can provide some new insights into further development of buckwheat green leaves and related SDFs as value-added health products.

Limosilactobacillus reuteri DSM 17938 as a probiotic in preterm infants: An updated systematic review with meta-analysis and trial sequential analysis.

BACKGROUND: Our previous strain-specific systematic review (SR) showed that Lactobacillus reuteri (LR) DSM 17938 reduces necrotizing enterocolitis (NEC), late-onset sepsis (LOS), and time to full feeds (TFF) in preterm infants. Considering progress in the field over the past 6 years, we aimed to update our SR. METHODS: SR of randomized controlled trials (RCTs) and non-RCTs was conducted. MEDLINE, Embase, Emcare, Cochrane CENTRAL, and gray literature were searched in June 2023. Primary outcomes were TFF, NEC stage ≥II, LOS, and all-cause mortality. Meta-analysis was performed using random-effects model. Certainty of evidence (CoE) was summarized using Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) guidelines. Trial sequential analysis (TSA) was applied for outcome of NEC in RCTs. RESULTS: Twelve RCTs (n = 2284) and four non-RCTs (n = 1616) were included. Six RCTs and three non-RCTs were new. Meta-analysis of RCTs showed LR significantly reduced TFF (mean difference, -2.70 [95% CI, -4.90 to -1.31] days; P = 0.0001), NEC stage ≥II (risk ratio [RR], 0.57 [95% CI, 0.37-0.87]; P = 0.009; eight RCTs), and LOS (RR, 0.72 [95% CI, 0.54-0.97]; P = 0.03); but not mortality (RR, 0.76 [95% CI, 0.54-1.06]; P = 0.10). TSA showed diversity-adjusted required information size (DARIS) as 3624 for NEC. Overall CoE was "very low." Meta-analysis of non-RCTs showed LR reduced NEC (odds ratio, 0.34 [95% CI, 0.15-0.77]; P = 0.01) but not LOS. LR had no adverse effects. CONCLUSIONS: Very low CoE suggests that LR DSM 17938 may reduce NEC and LOS and shorten TFF in preterm infants. Additional RCTs are required to confirm our findings.

Case report: Pediatric floating elbow fracture with monteggia-equivalent lesion, ipsilateral humeral shaft fracture, and radial nerve injury: a unique case and favorable treatment outcomes.

This case report presents a rare and intricate pediatric floating elbow fracture involving a Monteggia-equivalent fracture, ipsilateral humeral shaft fracture, and radial nerve injury. The unique mechanism of injury highlights the importance of increased awareness and parental education for accident prevention. Elastic intramedullary nailing was employed for both humeral shaft and forearm fractures, leading to favorable outcomes. Despite the severity of the fractures and radial nerve injury, the prognosis was positive, with nerve function restoration and satisfactory functional recovery. However, the development of avascular necrosis of the radial head remains a challenge, emphasizing the need for further research to better understand and manage these uncommon and complex injuries.

Both epilepsy and anti-seizure medications affect bone metabolism in children with self-limited epilepsy with centrotemporal spikes.

OBJECTIVE: Bone metabolism can be influenced by a range of factors. We selected children with self-limited epilepsy with centrotemporal spikes (SeLECTS) and lifestyles similar to those of healthy children to control for the confounding factors that may influence bone metabolism. We aimed to identify the specific effects of epilepsy and/or anti-seizure medications (ASMs) on bone metabolism. METHODS: Patients with SeLECTS were divided into an untreated group and a monotherapy group, and the third group was a healthy control group. We determined the levels of various biochemical markers of bone metabolism, including procollagen type I nitrogenous propeptide (PINP), alkaline phosphatase (ALP), osteocalcin (OC), collagen type I cross-linked C-telopeptide (CTX), calcium, magnesium, phosphorus, parathyroid hormone (PTH), and vitamin D3 (VD3 ). RESULTS: A total of 1487 patients (from 19 centers) were diagnosed with SeLECTS; 1032 were analyzed, including 117 patients who did not receive any ASMs (untreated group), 643 patients who received only one ASM (monotherapy group), and 272 children in the healthy control group. Except for VD3 , other bone metabolism of the three groups were different (p < .001). Bone metabolism was significantly lower in the untreated group than the healthy control group (p < .05). There were significant differences between the monotherapy and healthy control group in the level of many markers. However, when comparing the monotherapy and untreated groups, the results were different; oxcarbazepine, levetiracetam, and topiramate had no significant effect on bone metabolism. Phosphorus and magnesium were significantly lower in the valproic acid group than the untreated group (adjusted p < .05, Cliff's delta .282-.768). CTX was significantly higher in the lamotrigine group than in the untreated group (adjusted p = .012, Cliff's delta = .316). SIGNIFICANCE: Epilepsy can affect many aspects of bone metabolism. After controlling epilepsy and other confounders that affect bone metabolism, we found that the effects of ASMs on bone metabolism differed. Oxcarbazepine, levetiracetam, and topiramate did not affect bone metabolism, and lamotrigine corrected some of the abnormal markers of bone metabolism in patients with epilepsy.