Fluorescence molecular tomography based on an online maximum a posteriori estimation algorithm.

Fluorescence molecular tomography (FMT) is a non-invasive, radiation-free, and highly sensitive optical molecular imaging technique for early tumor detection. However, inadequate measurement information along with significant scattering of near-infrared light within the tissue leads to high ill-posedness in the inverse problem of FMT. To improve the quality and efficiency of FMT reconstruction, we build a reconstruction model based on log-sum regularization and introduce an online maximum a posteriori estimation (OPE) algorithm to solve the non-convex optimization problem. The OPE algorithm approximates a stationary point by evaluating the gradient of the objective function at each iteration, and its notable strength lies in the remarkable speed of convergence. The results of simulations and experiments demonstrate that the OPE algorithm ensures good reconstruction quality and exhibits outstanding performance in terms of reconstruction efficiency.

Injectable chitosan-polyvinylpyrrolidone composite thermosensitive hydrogels with sustained submucosal lifting for endoscopic submucosal dissection.

To develop a submucosal injection material with sustained submucosal lifting for endoscopic submucosal dissection (ESD), this study designed and prepared a novel composite thermosensitive hydrogel system with high pH chitosan-polyvinylpyrrolidone-ß-glycerophosphate (HpHCS-PVP-GP). HpHCS improved the injectability of the hydrogels and retained the rapid gelation ability at low concentrations. The modification of PVP significantly improved the stability of low-temperature hydrogel precursor solutions and the integrity of hydrogels formed at 37 °C through hydrogen bonds between PVP and HpHCS. A mathematical model was established using response surface methodology (RSM) to evaluate the synergistic effect of HpHCS, GP, and PVP concentrations on gelation time. This RSM model and submucosal lifting evaluation using in vitro pig esophageal models were used to determine the optimal formula of HpHCS-PVP-GP hydrogels. Although the higher PVP concentration (5 % (w/v)) prolonged gelation time, it improved hydrogel mechanical strength, resulting in better submucosal lifting performance. The experiments of Bama mini pigs showed that the heights of the cushions elevated by the HpHCS-5%PVP-GP hydrogel remained about 80 % 1 h after injection. Repeated injections were avoided, and the hydrogel had no cytotoxicity after electric cutting. Therefore, the HpHCS-PVP-GP thermosensitive hydrogel might be a promising submucosal injection material for ESD.

Non-invasive diagnosis of esophageal cancer by a simplified circulating cell-free DNA methylation assay targeting OTOP2 and KCNA3: a double-blinded, multicenter, prospective study.

BACKGROUND: Esophageal cancer (EC) is a highly lethal disease lacking early detection approaches. We previously identified that OTOP2 and KCNA3 were specifically hypermethylated in circulating cell-free DNA from patients with EC. We then developed a blood-based methylation assay targeting OTOP2 and KCNA3 (named "IEsohunter") for esophageal cancer noninvasive detection. This double-blinded, multicenter, prospective study aimed to comprehensively evaluate its clinical diagnostic performance. METHODS: Participants with EC, high-grade intraepithelial neoplasia (HGIN), other malignancies, benign gastrointestinal lesions, or no abnormalities were prospectively enrolled from 5 tertiary referral centers across China. Peripheral blood samples were collected, followed by plasma cell-free DNA methylation analysis using the IEsohunter test based on multiplex quantitative polymerase chain reaction adopting an algorithm-free interpretation strategy. The primary outcome was the diagnostic accuracy of IEsohunter test for EC. RESULTS: We prospectively enrolled 1116 participants, including 334 patients with EC, 71 with HGIN, and 711 controls. The areas under the receiver operating characteristic curves of the IEsohunter test for detecting EC and HGIN were 0.903 (95% CI 0.880-0.927) and 0.727 (95% CI 0.653-0.801), respectively. IEsohunter test showed sensitivities of 78.5% (95% CI 69.1-85.6), 87.3% (95% CI 79.4-92.4), 92.5% (95% CI 85.9-96.2), and 96.9% (95% CI 84.3-99.8) for stage I-IV EC, respectively, with an overall sensitivity of 87.4% (95% CI 83.4-90.6) and specificity of 93.3% (95% CI 91.2-94.9) for EC detection. The IEsohunter test status turned negative (100.0%, 47/47) after surgical resection of EC. CONCLUSIONS: The IEsohunter test showed high diagnostic accuracy for EC detection, indicating that it could potentially serve as a tool for noninvasive early detection and surveillance of EC.

TREM2 deficiency aggravates renal injury by promoting macrophage apoptosis and polarization via the JAK-STAT pathway in mice.

The triggering receptor expressed on myeloid cells 2 (TREM2) is an immune receptor that affects cellular phenotypes by modulating phagocytosis and metabolism, promoting cell survival, and counteracting inflammation. Its role in renal injury, in particular, unilateral ureteral obstruction (UUO) or ischemia-reperfusion injury (IRI)-induced renal injury remains unclear. In our study, WT and Trem2-/- mice were employed to evaluate the role of TREM2 in renal macrophage infiltration and tissue injury after UUO. Bone marrow-derived macrophages (BMDM) from both mouse genotypes were cultured and polarized for in vitro experiments. Next, the effects of TREM2 on renal injury and macrophage polarization in IRI mice were also explored. We found that TREM2 expression was upregulated in the obstructed kidneys. TREM2 deficiency exacerbated renal inflammation and fibrosis 3 and 7 days after UUO, in association with reduced macrophage infiltration. Trem2-/- BMDM exhibited increased apoptosis and poorer survival compared with WT BMDM. Meanwhile, TREM2 deficiency augmented M1 and M2 polarization after UUO. Consistent with the in vivo observations, TREM2 deficiency led to increased polarization of BMDM towards the M1 proinflammatory phenotype. Mechanistically, TREM2 deficiency promoted M1 and M2 polarization via the JAK-STAT pathway in the presence of TGF-ß1, thereby affecting cell survival by regulating mTOR signaling. Furthermore, cyclocreatine supplementation alleviated cell death caused by TREM2 deficiency. Additionally, we found that TREM2 deficiency promoted renal injury, fibrosis, and macrophage polarization in IRI mice. The current data suggest that TREM2 deficiency aggravates renal injury by promoting macrophage apoptosis and polarization via the JAK-STAT pathway. These findings have implications for the role of TREM2 in the regulation of renal injury that justify further evaluation.

Identification of microbial diversity in buried ivory soil at the Sanxingdui site in Guanghan City, China, using high-throughput sequencing.

Introduction: The Sanxingdui Site in Guanghan City, Sichuan Province, China, is one of the precious heritage sites of the ancient Chinese civilization. Archaeological work at Sanxingdui is of great significance in clarifying the origins and main contents of the ancient Shu culture and the Yangtze River civilization. Since the 1920s, archaeologists have conducted extensive excavations and research at the site, with particular attention given to the large number of ivory artifacts unearthed. However, the buried ivory is influenced by soil pH, temperature, humidity, and other physical and chemical factors, along with the potential impact of microbial activities that may lead to the corrosion and decomposition of ivory. By understanding the types and activities of microorganisms, appropriate measures can be taken to protect and preserve cultural relics. Methods: Multi-point sampling of soil samples around the ivory of the three sacrificial pits at the Sanxingdui site was carried out, and strict aseptic operation was carried out during the sampling process. Subsequently, the microbial community structure and diversity in the buried ivory soil of Sanxingdui site were identified and analyzed by Illumina high-throughput sequencing technology. Results: 16S rRNA and internal transcribed spacer sequence analysis revealed significant differences in the soil microbial community structure among different sacrificial pits. The dominant bacterial phyla were the Proteobacteria, GAL15, Actinobacteriota, Bacteroidota, and Methylomirabilota. The dominant fungal phyla were Ascomycota, Mortierellomhcota, and Basidiomycota. Most dominant bacterial and fungal communities play an indispensable role in the ivory corrosion mechanism, promoting the decay and decomposition process through various means such as decomposing organic matter and producing acidic substances. Discussion: It is particularly important to take a series of measures to control microbial activity to effectively protect ivory. Our preliminary study of the mechanism of action of microorganisms on ivory in a buried environment provides a scientific basis to prevent and protect against microbial degradation in ancient ivory unearthed in Sanxingdui. Following the research results, suitable antibacterial agents tailored to the preservation environment and microbial characteristics of ancient ivory can be prepared. Ensure that the selected antibacterial agents meet safety and effectiveness requirements to maximize protection against microbial degradation of ancient ivory.

Platelet Activation Pathways Controlling Reversible Integrin αIIbß3 Activation.

Background Agonist-induced platelet activation, with the integrin αIIbß3 conformational change, is required for fibrinogen binding. This is considered reversible under specific conditions, allowing a second phase of platelet aggregation. The signaling pathways that differentiate between a permanent or transient activation state of platelets are poorly elucidated. Objective To explore platelet signaling mechanisms induced by the collagen receptor glycoprotein VI (GPVI) or by protease-activated receptors (PAR) for thrombin that regulate time-dependent αIIbß3 activation. Methods Platelets were activated with collagen-related peptide (CRP, stimulating GPVI), thrombin receptor-activating peptides, or thrombin (stimulating PAR1 and/or 4). Integrin αIIbß3 activation and P-selectin expression was assessed by two-color flow cytometry. Signaling pathway inhibitors were applied before or after agonist addition. Reversibility of platelet spreading was studied by microscopy. Results Platelet pretreatment with pharmacological inhibitors decreased GPVI- and PAR-induced integrin αIIbß3 activation and P-selectin expression in the target order of protein kinase C (PKC) > glycogen synthase kinase 3 > ß-arrestin > phosphatidylinositol-3-kinase. Posttreatment revealed secondary αIIbß3 inactivation (not P-selectin expression), in the same order, but this reversibility was confined to CRP and PAR1 agonist. Combined inhibition of conventional and novel PKC isoforms was most effective for integrin closure. Pre- and posttreatment with ticagrelor, blocking the P2Y 12 adenosine diphosphate (ADP) receptor, enhanced αIIbß3 inactivation. Spreading assays showed that PKC or P2Y 12 inhibition provoked a partial conversion from filopodia to a more discoid platelet shape. Conclusion PKC and autocrine ADP signaling contribute to persistent integrin αIIbß3 activation in the order of PAR1/GPVI > PAR4 stimulation and hence to stabilized platelet aggregation. These findings are relevant for optimization of effective antiplatelet treatment.

Optical enhancement mode 2 improves the detection rate of gastric neoplastic lesion in high-risk populations: A multicenter randomized controlled clinical study.

OBJECTIVES: Detection of early neoplastic lesions is crucial for improving the survival rates of patients with gastric cancer. Optical enhancement mode 2 is a new image-enhanced endoscopic technique that offers bright images and can improve the visibility of neoplastic lesions. This study aimed to compare the detection of neoplastic lesions with optical enhancement mode 2 and white-light imaging (WLI) in a high-risk population. METHODS: In this prospective multicenter randomized controlled trial, patients were randomly assigned to optical enhancement mode 2 or WLI groups. Detection of suspicious neoplastic lesions during the examinations was recorded, and pathological diagnoses served as the gold standard. RESULTS: A total of 1211 and 1219 individuals were included in the optical enhancement mode 2 and WLI groups, respectively. The detection rate of neoplastic lesions was significantly higher in the optical enhancement mode 2 group (5.1% vs. 1.9%; risk ratio, 2.656 [95% confidence interval, 1.630-4.330]; p < 0.001). The detection rate of neoplastic lesions with an atrophic gastritis background was significantly higher in the optical enhancement mode 2 group (8.6% vs. 2.6%, p < 0.001). The optical enhancement mode 2 group also had a higher detection rate among endoscopists with different experiences. CONCLUSIONS: Optical enhancement mode 2 was more effective than WLI for detecting neoplastic lesions in the stomach, and can serve as a new method for screening early gastric cancer in clinical practice. CLINICAL REGISTRY: United States National Library of Medicine (https://www. CLINICALTRIALS: gov), ID: NCT040720521.

Endoscopic closure of large gastric defects with a novel through-the-scope closing device in a porcine model (with videos).

BACKGROUND AND AIM: After endoscopic full-thickness resection (EFTR), defects require a reliable and sustained closure. We present a novel, through-the-scope "bow-tie" (TTS-BT) closing device enabling direct defect closure without scope withdrawal. This preclinical study aimed to evaluate the feasibility and safety of this device for large defect closure after EFTR in a porcine model. METHODS: Exposed EFTR was performed for virtual lesions > 2 cm in the stomach of twelve pigs. Subsequently, TTS-BT closing devices were used for defect closure. Conventional metal clips were used to close any remaining defects. Gastroscopy was performed for 8 weeks to examine the wound sites and the pigs were subsequently sacrificed. After sacrificing the pigs, the wound healing was histologically verified by hematoxylin-eosin (HE) staining. The primary outcome was a successful closure rate, while the secondary outcomes were complete healing rate, closure time, and incidence of adverse events. RESULTS: The median long and short diameters of perforations were 4.0 (3.0-6.0) cm and 3.0 (2.0-4.0) cm, respectively. Defect closure using novel TTS-BT closure devices and conventional metal clips was successfully performed in all pigs. Complete healing was achieved in the defects of 12 pigs. The median closure time was 13 (9-38) minutes. No serious adverse events occurred during the 8-week follow-up. CONCLUSIONS: The novel TTS-BT closure device is feasible and safe for closing large gastric perforations and could be a promising tool for clinical practice.

Corneal densitometry in Chinese adults with healthy corneas: associations with sex, age, ocular metrics, and optical characteristics.

BACKGROUND: Standardized corneal densitometry (CD) values in large samples of healthy Chinese individuals are scarce. Therefore, we aimed to determine the standard CD values using a Scheimpflug camera in healthy corneas, investigate the correlations of sex, age, and ocular parameters with corneal density, and explore the impact of corneal density on the forward scattering and optical quality of the eye. METHODS: This retrospective observational study involved 990 healthy Chinese individuals, including 494 males and 496 females (mean age: 23.88 ± 6.90 years). The CD values at various depths and radial areas of 0-12 mm were measured using a Scheimpflug camera. Densitometric measurements were expressed in standardized grayscale units (GSU). The optical scatter index (OSI), modulation transfer function cutoff values (MTFcutoff), and Strehl's ratio (SR) were also determined using an optical quality analysis system. RESULTS: The average CD within a 12 mm diameter area was 16.26 ± 1.35 GSU. The highest and lowest optical densities at different depths were observed in the anterior (21.41 ± 2.16 GSU) and posterior (12.00 ± 1.01 GSU) layers, respectively (P < 0.001). Similarly, the maximum and minimum optical densities at different radial areas were observed in the 10-12 mm (14.09 ± 0.93 GSU) and 2-6 mm (25.93 ± 4.77 GSU) circles, respectively (P < 0.001). There was no significant difference in the average CD within a 12 mm diameter area between males and females (P > 0.05). However, upon adjusting for age, central corneal thickness (CCT), corneal curvature, white-to-white (WTW) corneal diameter, and axial length, females exhibited a greater average CD within the 12 mm diameter and in the 6-10 mm and 10-12 mm circles than males. Age-related changes in CD were evident, except in the 2-6 mm circle. CCT, corneal curvature, WTW corneal diameter, and partial depth correlated with CD in the radial area, and CD in different areas correlated with the OSI, MTFcutoff, and SR (P < 0.05). CONCLUSIONS: This study provides the normative CD measurement data of Chinese adults with healthy corneas, emphasizing the significance of sex, age, CCT, corneal curvature, and WTW corneal diameter in CD evaluation. Notably, elevated CD can lead to increased forward scattering within the eye, thereby affecting the optical quality.

Methods to increase the diagnostic efficiency of endoscopic ultrasound-guided fine-needle aspiration for solid pancreatic lesions: An updated review.

Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is a means to procure adequate specimens for histological and cytologic analysis. The ideal EUS-FNA should be safe, accurate, and have a high sample adequacy rate and low adverse events rate. In recent years, many guidelines and trials on EUS-FNA have been published. The purpose of this article is to provide an update on the influence of some of the main factors on the diagnostic efficiency of EUS-FNA as well as a rare but serious complication known as needle tract seeding.

Role of albumin-bilirubin score in non-malignant liver disease.

The albumin-bilirubin (ALBI) score, which was proposed to assess the prognosis of patients with hepatocellular carcinoma, has gradually been extended to other liver diseases in recent years, including primary biliary cholangitis, liver cirrhosis, hepatitis, liver transplantation, and liver injury. The ALBI score is often compared with classical scores such as the Child-Pugh and model for end-stage liver disease scores or other noninvasive prediction models. It is widely employed because of its immunity to subjective evaluation indicators and ease of obtaining detection indicators. An increasing number of studies have confirmed that it is highly accurate for assessing the prognosis of patients with chronic liver disease; additionally, it has demonstrated good predictive performance for outcomes beyond survival in patients with liver diseases, such as decompensation events. This article presents a review of the application of ALBI scores in various non-malignant liver diseases.

Diagnostic value of endoscopic ultrasound in pelvic masses with bowel involvement.

BACKGROUND: The diagnostic ability of endoscopic ultrasound (EUS) for intestinal infiltration by pelvic masses has aroused considerable interest in many oncological settings. This study aimed to evaluate the effectiveness of EUS in predicting colorectal invasion in patients with pelvic masses and compare its accuracy with that of other imaging methods, namely pelvic MRI and abdominal computed tomography (CT), in predicting intestinal involvement in patients with histologically confirmed colorectal invasion. METHODS: A hundred and eighty-four female patients with histologically confirmed benign or malignant pelvic masses were enrolled in a retrospective-prospective study. All patients underwent EUS, pelvic MRI, and one or more of abdominal CT, transvaginal sonography, and colonoscopy examinations before surgery. The surgical and pathological results were used as the gold standard to evaluate the diagnostic accuracy of EUS for colorectal invasion of pelvic masses. RESULTS: This study included 184 patients who underwent surgery, with the time between EUS and surgery ranging from 1 to 309 (mean, 13.2) days. The diagnostic sensitivity, specificity, positive predictive value, and negative predictive value of EUS for benign and malignant pelvic masses infiltrating the intestine were 83.3, 97.8, 99.1, and 66.2%, respectively. The overall diagnostic accuracy was 87.0%. CONCLUSIONS: EUS is a simple, noninvasive, reliable, and accurate technique for the preoperative diagnosis of pelvic masses infiltrating the intestine. The authors recommend the use of this technology by gynecologists, as well as its incorporation into the preoperative diagnostic process to determine the most suitable surgical method. This would help in avoiding unexpected situations and unnecessary resource wastage during surgery.

Exploration the interaction of cadmium and copper toxic effects in pakchoi (Brassica chinensis L) roots through combinatorial transcriptomic and weighted gene co-expression network analysis.

The interaction between cadmium(Cd) and copper(Cu) during combined pollution can lead to more complex toxic effects on humans and plants.However, there is still a lack of sufficient understanding regarding the types of interactions at the plant molecular level and the response strategies of plants to combined pollution. To assess this, we investigated the phenotypic and transcriptomic patterns of pakchoi (Brassica chinensis L) roots in response to individual and combined pollution of Cd and Cu. The results showed that compared to single addition, the translocation factor of heavy metals in roots significantly decreased (p < 0.05) under the combined addition, resulting in higher accumulation of Cd and Cu in the roots. Transcriptomic analysis of pakchoi roots revealed that compared to single pollution, there were 312 and 1926 differentially expressed genes (DEGs) specifically regulated in the Cd2Cu20 and Cd2Cu100 combined treatments, respectively. By comparing the expression of these DEGs among different treatments, we found that the combined pollution of Cd and Cu mainly affected the transcriptome of the roots in an antagonistic manner. Enrichment analysis indicated that pakchoi roots upregulated the expression of genes involved in glucosetransferase activity, phospholipid homeostasis, proton transport, and the biosynthesis of phenylpropanoids and flavonoids to resist Cd and Cu combined pollution. Using weighted gene co-expression network analysis (WGCNA), we identified hub genes related to the accumulation of Cd and Cu in the roots, which mainly belonged to the LBD, thaumatin-like protein, ERF, MYB, WRKY, and TCP transcription factor families. This may reflect a transcription factor-driven trade-off strategy between heavy metal accumulation and growth in pakchoi roots. Additionally, compared to single metal pollution, the expression of genes related to Nramp, cation/H+ antiporters, and some belonging to the ABC transporter family in the pakchoi roots was significantly upregulated under combined pollution. This could lead to increased accumulation of Cd and Cu in the roots. These findings provide new insights into the interactions and toxic mechanisms of multiple metal combined pollution at the molecular level in plants.

Gut microbiota and female health.

The gut microbiota is recognized as an endocrine organ with the capacity to influence distant organs and associated biological pathways. Recent advancements underscore the critical role of gut microbial homeostasis in female health; with dysbiosis potentially leading to diseases among women such as polycystic ovarian syndrome, endometriosis, breast cancer, cervical cancer, and ovarian cancer etc. Despite this, there has been limited discussion on the underlying mechanisms. This editorial explores the three potential mechanisms through which gut microbiota dysbiosis may impact the development of diseases among women, namely, the immune system, the gut microbiota-estrogen axis, and the metabolite pathway. We focused on approaches for treating diseases in women by addressing gut microbiota imbalances through probiotics, prebiotics supplementation, and fecal microbiota transplantation (FMT). Future studies should focus on determining the molecular mechanisms underlying associations between dysbiosis of gut microbiota and female diseases to realize precision medicine, with FMT emerging as a promising intervention.

Photothermal hydrogels for infection control and tissue regeneration.

In this review, we report investigating photothermal hydrogels, innovative biomedical materials designed for infection control and tissue regeneration. These hydrogels exhibit responsiveness to near-infrared (NIR) stimulation, altering their structure and properties, which is pivotal for medical applications. Photothermal hydrogels have emerged as a significant advancement in medical materials, harnessing photothermal agents (PTAs) to respond to NIR light. This responsiveness is crucial for controlling infections and promoting tissue healing. We discuss three construction methods for preparing photothermal hydrogels, emphasizing their design and synthesis, which incorporate PTAs to achieve the desired photothermal effects. The application of these hydrogels demonstrates enhanced infection control and tissue regeneration, supported by their unique photothermal properties. Although research progress in photothermal hydrogels is promising, challenges remain. We address these issues and explore future directions to enhance their therapeutic potential.

The Prognostic and Immune Significance of BZW2 in Pan-Cancer and its Relationship with Proliferation and Apoptosis of Cervical Cancer.

BACKGROUND: Basic leucine zipper and W2 domains 2 (BZW2), a member of the basic domain leucine zipper superfamily of transcription factors, has been implicated in the development and progression of various cancers. However, the precise biological role of BZW2 in pan-cancer datasets remains to be explored. This study aimed to assess the prognostic significance of BZW2 and its immune-related signatures in various tumors. METHODS: Our study investigated the expression, epigenetic modifications, and clinical prognostic relevance of BZW2 using multi-omics data in different cancer types. Additionally, the immunological characteristics, tumor stemness, drug sensitivity, and correlation of BZW2 with immunotherapy response were explored. Finally, in vitro experiments were conducted to assess the impact of BZW2 knockdown on Hela cells, a cell line derived from cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC). RESULTS: BZW2 exhibited elevated expression levels in various tumor tissues and significantly impacted the prognosis of different cancer types. BZW2 emerged as an independent prognostic factor in CESC. We found that copy number amplification and methylation levels of BZW2 were associated with its mRNA expression. Immunological analyses revealed that BZW2 shapes a non-inflamed immunosuppressive tumor microenvironment across multiple cancers. Furthermore, our cell experiments demonstrated that BZW2 knockdown reduced proliferation, migration, and apoptosis activities in CESC cells. CONCLUSIONS: BZW2 promotes cancer progression by shaping a non-inflamed immunosuppressive tumor microenvironment. Additionally, BZW2 was shown to significantly influence the proliferation, migration, and apoptosis of CESC cells.

[Research progress of CD93+ B lymphocyte subsets in inflammation and inflammation related diseases].

CD93 is expressed in progenitor B (pro-B) cells, precursor B (pre-B) cells and various immature B cells. It can interact with moesin, MMRN2 and other molecules to participate in cell migration, adhesion and phagocytosis, so it plays an important role in inflammation and angiogenesis. Detection of CD93+ B cell subsets has a crucial role in the diagnosis, treatment and prognosis monitoring of inflammation and inflammation-related diseases, such as Helicobacter pylori-related gastritis, sepsis, non-obese diabetes and periodontitis.

Muscle strength and non-alcoholic fatty liver disease/metabolic-associated fatty liver disease.

This editorial comments on an article published in a recent issue of World Journal of Gastroenterology, entitled "Association of low muscle strength with metabolic dysfunction-associated fatty liver disease: A nationwide study". We focused on the association between muscle strength and the incidence of non-alcoholic fatty liver disease (NAFLD) and metabolic-associated fatty liver disease (MAFLD), as well as the mechanisms underlying the correlation and related clinical applications. NAFLD, which is now redefined as MAFLD, is one of the most common chronic liver diseases globally with an increasing prevalence and is characterized by malnutrition, which may contribute to decreased muscle strength. Reduction of muscle strength reportedly has a pathogenesis similar to that of NAFLD/ MAFLD, including insulin resistance, inflammation, sedentary behavior, as well as insufficient vitamin D. Multiple studies have focused on the relationship between sarcopenia or muscle strength and NAFLD. However, studies investigating the relationship between muscle strength and MAFLD are limited. Owing to the shortage of specific medications for NAFLD/MAFLD treatment, early detection is essential. Furthermore, the relationship between muscle strength and NAFLD/MAFLD suggests that improvements in muscle strength may have an impact on disease prevention and may provide novel insights into treatments including dietary therapy, as well as tailored physical activity.

Can serum immunoglobulin G4 levels and age serve as reliable predictors of relapse in autoimmune pancreatitis?

We are writing in response to the paper published in the World Journal of Gastroenterology by Zhou et al. The authors identified higher serum immunoglobulin (Ig) G4 levels and age over 55 years as independent risk factors for disease relapse. Despite notable strengths, it is crucial to address potential biases. Firstly, the cohort study included 189 patients with autoimmune pancreatitis (AIP) type 1 (with higher IgG4 seropositivity and higher relapse) and 24 with type 2 (with lower IgG4 seropositivity and lower relapse). Consequently, most, if not all, AIP type 2 patients were assigned to the normal group, possibly inflating the association of higher serum IgG4 levels with relapse and potentially exaggerating the association of older age with relapse. Secondly, the authors did not provide sufficient details regarding AIP diagnosis, such as the ratio of definitive vs probable cases and the proportion of biopsies. In cases where histological evidence is unavailable or indeterminate, AIP type 2 may be misdiagnosed as definitive type 1, and type 1 may also be misdiagnosed as probable type 2, particularly in cases with normal or mildly elevated serum IgG4 levels. Lastly, in this retrospective study, approximately one-third of the consecutive patients initially collected were excluded for various reasons. Accordingly, the impact of non-random exclusion on relapse outcomes should be carefully considered. In conclusion, the paper by Zhou et al offers plausible, though not entirely compelling, evidence suggesting a predictive role of elevated serum IgG4 levels and advanced age in AIP relapse. The foundation for future investigations lies in ensuring a reliable diagnosis and accurate disease subtyping, heavily dependent on obtaining histological specimens. In this regard, endoscopic ultrasound-guided fine-needle biopsy emerges as a pivotal component of the diagnostic process, contributing to mitigating biases in future explorations of the disease.