Oral squamous cell carcinoma (OSCC) is a common head and neck malignancy. Approximately 50% to 60% of patients with OSCC are diagnosed at a locally advanced stage (clinical staging III-IVa). Even with comprehensive and sequential treatment primarily based on surgery, the 5-year overall survival rate remains below 50%, and patients often suffer from postoperative functional impairments such as difficulties with speaking and swallowing. Programmed death receptor-1 (PD-1) inhibitors are increasingly used in the neoadjuvant treatment of locally advanced OSCC and have shown encouraging efficacy. However, clinical practice still faces key challenges, including the definition of indications, optimization of combination regimens, and standards for efficacy evaluation. Based on the latest research advances worldwide and the clinical experience of the expert group, this expert consensus systematically evaluates the application of PD-1 inhibitors in the neoadjuvant treatment of locally advanced OSCC, covering combination strategies, treatment cycles and surgical timing, efficacy assessment, use of biomarkers, management of special populations and immune related adverse events, principles for immunotherapy rechallenge, and function preservation strategies. After multiple rounds of panel discussion and through anonymous voting using the Delphi method, the following consensus statements have been formulated: 1) Neoadjuvant therapy with PD-1 inhibitors can be used preoperatively in patients with locally advanced OSCC. The preferred regimen is a PD-1 inhibitor combined with platinum based chemotherapy, administered for 2-3 cycles. 2) During the efficacy evaluation of neoadjuvant therapy, radiographic assessment should follow the dual criteria of Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and immune RECIST (iRECIST). After surgery, systematic pathological evaluation of both the primary lesion and regional lymph nodes is required. For combination chemotherapy regimens, PD-L1 expression and combined positive score need not be used as mandatory inclusion or exclusion criteria. 3) For special populations such as the elderly (≥ 70 years), individuals with stable HIV viral load, and carriers of chronic HBV/HCV, PD-1 inhibitors may be used cautiously under the guidance of a multidisciplinary team (MDT), with close monitoring for adverse events. 4) For patients with a poor response to neoadjuvant therapy, continuation of the original treatment regimen is not recommended; the subsequent treatment plan should be adjusted promptly after MDT assessment. Organ transplant recipients and patients with active autoimmune diseases are not recommended to receive neoadjuvant PD-1 inhibitor therapy due to the high risk of immune related activation. Rechallenge is generally not advised for patients who have experienced high risk immune related adverse events such as immune mediated myocarditis, neurotoxicity, or pneumonitis. 5) For patients with a good pathological response, individualized de escalation surgery and function preservation strategies can be explored. This consensus aims to promote the standardized, safe, and precise application of neoadjuvant PD-1 inhibitor strategies in the management of locally advanced OSCC patients.

Background/Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a significant risk factor for gallstone formation, but mechanisms underlying MASH-related gallstone formation remain unclear. Golgi membrane protein 1 (GOLM1) participates in hepatic cholesterol metabolism and is upregulated in MASH. Here, we aimed to explore the role of GOLM1 in MASH-related gallstone formation. Methods: The UK Biobank cohort was used for etiological analysis. GOLM1 knockout (GOLM1-/-) and wild-type (WT) mice were fed with a high-fat diet (HFD). Livers were excised for histology and immunohistochemistry analysis. Gallbladders were collected to calculate incidence of cholesterol gallstones (CGSs). Biles were collected for biliary lipid analysis. HepG2 cells were used to explore underlying mechanisms. Human liver samples were used for clinical validation. Results: MASH patients had a greater risk of cholelithiasis. All HFD-fed mice developed MASH, and the incidence of gallstones was 16.7% and 75.0% in GOLM1-/- and WT mice, respectively. GOLM1-/- decreased biliary cholesterol concentration and output. In vivo and in vitro assays confirmed that GOLM1 facilitated cholesterol efflux through upregulating ATP binding cassette transporter subfamily G member 5 (ABCG5). Mechanistically, GOLM1 translocated into nucleus to promote osteopontin (OPN) transcription, thus stimulating ABCG5-mediated cholesterol efflux. Moreover, GOLM1 was upregulated by interleukin-1β (IL-1β) in a dose-dependent manner. Finally, we confirmed that IL-1β, GOLM1, OPN, and ABCG5 were enhanced in livers of MASH patients with CGSs. Conclusions In MASH livers, upregulation of GOLM1 by IL-1β increases ABCG5-mediated cholesterol efflux in an OPN-dependent manner, promoting CGS formation. GOLM1 has the potential to be a molecular hub interconnecting MASH and CGSs.

Background/Aims: The association between caffeine intake and constipation remains inconclusive. This study aims to investigate whether caffeine intake is associated with constipation. Methods: This cross-sectional study included 13 941 adults from the 2005-2010 National Health and Nutrition Examination Survey. The weighted logistic regression analyses were exerted to evaluate the association between caffeine intake and constipation. Besides, stratified analyses and interaction tests were conducted to determine the potential modifying factors. Results: After adjusting for confounders, increased caffeine intake by 100 mg was not associated with constipation, as defined by stool frequency (OR, 1.01; 95% CI, 0.94-1.10) or stool consistency (OR, 1.01; 95% CI, 0.98-1.05). Subgroup analyses showed that cholesterol intake modified the relationship between increased caffeine by 100 mg and stool frequency-defined constipation (P for interaction = 0.037). Each 100 mg increase in caffeine intake was associated with a 20% decreased risk of constipation defined by stool frequency in participants who consumed high cholesterol (OR, 0.80; 95% CI, 0.64-1.00), but no association in the other 2 cholesterol level groups. Furthermore, the association between caffeine intake and stool consistency-defined constipation was not found in different cholesterol groups. Conclusions Caffeine consumption is not associated with stool frequency or consistency-defined constipation. Nevertheless, increased caffeine intake may decrease the risk of constipation (defined by stool frequency) among participants in the high-cholesterol intake group.

Purpose: Diagnosing sarcopenia necessitates the measurement of skeletal muscle mass. However, guidelines lack a standardized imaging modality with thresholds validated among Asians. This systematic review compared ultrasonography, computed tomography (CT), magnetic resonance imaging (MRI), and bioelectrical impedance analysis (BIA)/body composition monitoring in the detection of sarcopenia within Asian populations. Methods: PubMed and Embase were systematically searched for studies analyzing ultrasonography, CT, MRI, and BIA in diagnosing sarcopenia among Asians. Study quality was assessed using the Newcastle-Ottawa scale. Results: Pooled findings from 21,598 patients across 25 studies were examined. In receiver operating characteristic analysis, ultrasound displayed a pooled mean area under the curve (AUC) of 0.767 (95% confidence interval [CI], 0.709–0.806), with mean sensitivity of 81.1% (95% CI, 0.744–0.846) and specificity of 73.1% (95% CI, 0.648–0.774), for detecting sarcopenia in Asian populations. CT exhibited an AUC of 0.720 (sensitivity, 54.0%; specificity, 92.0%). MRI demonstrated an AUC of 0.839 (sensitivity, 67.0%; specificity, 66.0%). BIA displayed an AUC of 0.905 (95% CI, 0.842–0.968), 80.7% sensitivity (95% CI, 0.129–0.679), and 82.4% specificity (95% CI, 0.191–0.633). Conclusion Various modalities aid in diagnosing sarcopenia, and selection should be individualized. Although only BIA and dual-energy x-ray absorptiometry are recommended by the Asian Working Group for Sarcopenia and the European Working Group on Sarcopenia in Older People, ultrasound imaging may hold diagnostic value for sarcopenia in the Asian population. In certain groups, diagnostic use of CT and MRI is warranted. Future research can standardize and validate modality-specific thresholds and protocols within Asian populations.

Objective To investigate the genetic diversity of sandfly populations in endemic areas of visceral leishmaniasis in China, so as to provide references insights into management of visceral leishmaniasis and the vector sandflies. MethodsSixteen sampling sites were selected from main endemic foci of visceral leishmaniasis in China from June to September 2024, including Shanxi Province, Shaanxi Province, Henan Province, Gansu Province, Sichuan Province, and Xinjiang Uygur Autonomous Region. Sandflies were captured using light traps and manual aspirators from sheep pens, chicken coops, cave dwellings, bovinesheds, and pig pens at each sampling site. A single sandfly sample was washed in phosphate-buffered saline (PBS), and genomic DNA was extracted from sandfly samples. Cytochrome oxidase subunit 1 (COI) gene was amplified using PCR assay with universal primers, and analyzed and retrieved with the nucleotide sequence analysis tool (BLAST) software, and the sequence of COI gene was aligned with the ClustalX 1.83 and MEGA 7.0 software. The base composition and variation site of the COI gene sequence were analyzed using the software MEGA 7.0, and the number of haplotypes, total number of segregating sites, haplotype diversity, nucleotide diversity, and average nucleotide differences were calculated in the COI gene sequence using the software DnaSP 5.10, followed by Tajima’s D test for neutrality. Haplotypes were screened using the software DnaSP 5.10, and the haplotype network map of sandfly samples was plotted using the software Network 5.0. MEGA 7.0 software was employed for gene sequence editing and alignment, and calculation of genetic distances among sandfly species sampled from different regions, and a phylogenetic tree was built with a neighbor-joining method. Results A total of 466 sandflies were captured from 16 sampling sites in China from June to September 2024, and 430 gene sequences were yielded following PCR amplification and sequencing of the COI gene, with 652 to 688 bp in the length of amplification fragments. The captured sandfly samples were characterized as Phlebotomus chinensis, Sergentomyia squamirostris, Se. koloshanensis, Ph. sichuanensis, and Ph. longiductus following the COI gene sequence alignment in BLAST. A total of 251 haplotypes were identified in the 430 gene sequences from sandfly samples (50.5%), and the average haplotype diversity, nucleotide diversity and average number of nucleotide difference were 0.885, 0.257 and 160.761, respectively. The Tajima’s D values were -0.92 for sandfly populations from Yangquan City, Shanxi Province and -1.73 for sandfly populations from Sanmenxia City, Henan Province, and were all more than 0 for sandfly populations from other sampling sites. Haplotype analysis identified 50 haplotypes, which were classified into two haplogroups. Heplogroup 1 included 29 haplotypes, which had a high homology, and heplogroup 2 included 21 haplotypes. The average genetic distance was 0.000 to 0.604 among sandfly samples from different sampling sites, and phylogenetic analysis revealed that the five sandfly species were clustered into distinct clades, all with 100% clade confidence. Conclusions There is a high genetic polymorphism in the COI gene from five sandfly populations in main endemic foci of visceral leishmaniasis in China, and COI gene may serve as a marker gene for analysis of the genetic structure of sandfly populations.

Background/Aims: The association between caffeine intake and constipation remains inconclusive. This study aims to investigate whether caffeine intake is associated with constipation. Methods: This cross-sectional study included 13 941 adults from the 2005-2010 National Health and Nutrition Examination Survey. The weighted logistic regression analyses were exerted to evaluate the association between caffeine intake and constipation. Besides, stratified analyses and interaction tests were conducted to determine the potential modifying factors. Results: After adjusting for confounders, increased caffeine intake by 100 mg was not associated with constipation, as defined by stool frequency (OR, 1.01; 95% CI, 0.94-1.10) or stool consistency (OR, 1.01; 95% CI, 0.98-1.05). Subgroup analyses showed that cholesterol intake modified the relationship between increased caffeine by 100 mg and stool frequency-defined constipation (P for interaction = 0.037). Each 100 mg increase in caffeine intake was associated with a 20% decreased risk of constipation defined by stool frequency in participants who consumed high cholesterol (OR, 0.80; 95% CI, 0.64-1.00), but no association in the other 2 cholesterol level groups. Furthermore, the association between caffeine intake and stool consistency-defined constipation was not found in different cholesterol groups. Conclusions Caffeine consumption is not associated with stool frequency or consistency-defined constipation. Nevertheless, increased caffeine intake may decrease the risk of constipation (defined by stool frequency) among participants in the high-cholesterol intake group.

Purpose: Diagnosing sarcopenia necessitates the measurement of skeletal muscle mass. However, guidelines lack a standardized imaging modality with thresholds validated among Asians. This systematic review compared ultrasonography, computed tomography (CT), magnetic resonance imaging (MRI), and bioelectrical impedance analysis (BIA)/body composition monitoring in the detection of sarcopenia within Asian populations. Methods: PubMed and Embase were systematically searched for studies analyzing ultrasonography, CT, MRI, and BIA in diagnosing sarcopenia among Asians. Study quality was assessed using the Newcastle-Ottawa scale. Results: Pooled findings from 21,598 patients across 25 studies were examined. In receiver operating characteristic analysis, ultrasound displayed a pooled mean area under the curve (AUC) of 0.767 (95% confidence interval [CI], 0.709–0.806), with mean sensitivity of 81.1% (95% CI, 0.744–0.846) and specificity of 73.1% (95% CI, 0.648–0.774), for detecting sarcopenia in Asian populations. CT exhibited an AUC of 0.720 (sensitivity, 54.0%; specificity, 92.0%). MRI demonstrated an AUC of 0.839 (sensitivity, 67.0%; specificity, 66.0%). BIA displayed an AUC of 0.905 (95% CI, 0.842–0.968), 80.7% sensitivity (95% CI, 0.129–0.679), and 82.4% specificity (95% CI, 0.191–0.633). Conclusion Various modalities aid in diagnosing sarcopenia, and selection should be individualized. Although only BIA and dual-energy x-ray absorptiometry are recommended by the Asian Working Group for Sarcopenia and the European Working Group on Sarcopenia in Older People, ultrasound imaging may hold diagnostic value for sarcopenia in the Asian population. In certain groups, diagnostic use of CT and MRI is warranted. Future research can standardize and validate modality-specific thresholds and protocols within Asian populations.

Background/Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a significant risk factor for gallstone formation, but mechanisms underlying MASH-related gallstone formation remain unclear. Golgi membrane protein 1 (GOLM1) participates in hepatic cholesterol metabolism and is upregulated in MASH. Here, we aimed to explore the role of GOLM1 in MASH-related gallstone formation. Methods: The UK Biobank cohort was used for etiological analysis. GOLM1 knockout (GOLM1-/-) and wild-type (WT) mice were fed with a high-fat diet (HFD). Livers were excised for histology and immunohistochemistry analysis. Gallbladders were collected to calculate incidence of cholesterol gallstones (CGSs). Biles were collected for biliary lipid analysis. HepG2 cells were used to explore underlying mechanisms. Human liver samples were used for clinical validation. Results: MASH patients had a greater risk of cholelithiasis. All HFD-fed mice developed MASH, and the incidence of gallstones was 16.7% and 75.0% in GOLM1-/- and WT mice, respectively. GOLM1-/- decreased biliary cholesterol concentration and output. In vivo and in vitro assays confirmed that GOLM1 facilitated cholesterol efflux through upregulating ATP binding cassette transporter subfamily G member 5 (ABCG5). Mechanistically, GOLM1 translocated into nucleus to promote osteopontin (OPN) transcription, thus stimulating ABCG5-mediated cholesterol efflux. Moreover, GOLM1 was upregulated by interleukin-1β (IL-1β) in a dose-dependent manner. Finally, we confirmed that IL-1β, GOLM1, OPN, and ABCG5 were enhanced in livers of MASH patients with CGSs. Conclusions In MASH livers, upregulation of GOLM1 by IL-1β increases ABCG5-mediated cholesterol efflux in an OPN-dependent manner, promoting CGS formation. GOLM1 has the potential to be a molecular hub interconnecting MASH and CGSs.