[摘 要] 目的：探讨核仁小RNA（snoRNA）71A通过TLR3/PD-L1通路对食管鳞状细胞癌（ESCC）细胞增殖、迁移及侵袭能力的影响。方法：qPCR检测52例ESCC患者的配对肿瘤组织、癌旁组织，以及人ESCC细胞中SNORA71A的表达情况。将反义寡核苷酸（SNORA71A-ASO-29、SNORA71A-ASO-102和NC-ASO）或小干扰RNA（siTLR3、siTLR3-NC）分别转染至人ESCC TE-1细胞，分别记为SNORA71A-ASO1组、SNORA71A-ASO2组、NC-ASO组及siTLR3组、siNC组。另外将过表达质粒pcDNA3.1-SNORA71A和pcDNA3.1空载体质粒分别转染至TE-1细胞，分别记为SNORA71A组和Vector组。细胞功能学实验（MTS实验、划痕愈合实验，以及Transwell侵袭实验）评估各组细胞在敲低或过表达SNORA71A后增殖、迁移和侵袭能力的变化。高通量转录组测序筛选SNORA71A下游作用靶基因，基因本体论（GO）和京都基因与基因组百科全书（KEGG）功能富集分析预测SNORA71A下游作用靶基因可能参与的生物学过程和信号通路。qPCR检测测序筛选出的下游作用靶基因TLR3在ESCC组织以及细胞中的表达。同时，qPCR和WB检测TE-1细胞在敲低或过表达TLR3后PD-L1 mRNA和蛋白质表达变化。细胞功能学实验检测TLR3敲低对SNORA71A所促进的TE-1细胞恶性生物行为（增殖、迁移、侵袭）的影响。结果：在52例ESCC患者的肿瘤组织以及ESCC细胞中SNORA71A表达均呈高水平（P < 0.01或P < 0.05）。敲低SNORA71A抑制TE-1细胞增殖、迁移和侵袭（P < 0.01或P < 0.05），过表达SNORA71A则促进TE-1细胞增殖、迁移和侵袭（P < 0.01或P < 0.05）。高通量转录组测序筛选到TLR3为SNORA71A下游作用靶基因。TLR3在ESCC组织以及TE-1细胞中呈低表达（P < 0.01或P < 0.05）。TLR3正向调控PD-L1 mRNA和蛋白质表达（P < 0.01或P < 0.05）。细胞功能学实验中，TLR3可以部分削弱SNORA71A对PD-L1表达的调控（P < 0.01）。结论：SNORA71A通过调控TLR3/PD-L1通路调节TE-1细胞增殖、迁移和侵袭。

Background/Aims: Chronic constipation is prevalent yet under-diagnosed across Asia, compromising quality of life and burdening healthcare systems. Cultural stigma, varied diets, and limited access to standardized diagnostic tools delay timely care. Methods: The Bali Chronic Constipation Roundtable in November 2024, brought together experts from 11 Asian countries. The group reviewed epidemiological data, analyzed multinational questionnaire on clinical practice pattern, and conducted structured discussions to identify key barriers and propose region-specific recommendations. Results: Chronic constipation prevalence varies across Asia, ranging from 1.8% in India to 16.6% in Japan, with women and the elderly disproportionately affected. Under-reporting persists owing to cultural taboos and widespread self treatment with laxatives and traditional medications. Although the Rome IV criteria remains the global standard, they may not fully reflect Asian symptom profiles, and diagnosis is limited by scarce motility laboratories. First line therapies such as dietary-fiber optimization and osmotic laxatives are widely available, but newer pharmacotherapies (prucalopride, linaclotide, lubiprostone, and elobixibat) remain costly and unevenly accessible. Biofeedback for dyssynergic defecation is underutilized due to limited availability. Experts recommend expanded regional research on to refine diagnostic criteria, coupled with enhanced physician education and public awareness. They advocate accessibility to second-line and novel therapies that incorporate culturally attuned regional guidelines, and improved access to gastrointestinal motility testing. Conclusions The Bali Chronic Constipation Roundtable highlighted Asia’s need for region specific diagnostics and management. Addressing diagnostic and treatment gaps will improve outcomes, while ongoing researcher clinician policy collaboration must standardize guidelines, advance research, and ensure equitable care across Asia.

Background/Aims: Ineffective esophageal motility (IEM) is common in patients with gastroesophageal reflux disease (GERD) and can be associated with poor esophageal contraction reserve on multiple rapid swallows. Alterations in the esophageal microbiome have been reported in GERD, but the relationship to presence or absence of contraction reserve in IEM patients has not been evaluated. We aim to investigate whether contraction reserve influences esophageal microbiome alterations in patients with GERD and IEM. Methods: We prospectively enrolled GERD patients with normal endoscopy and evaluated esophageal motility and contraction reserve with multiple rapid swallows during high-resolution manometry. The esophageal mucosa was biopsied for DNA extraction and 16S ribosomal RNA gene V3-V4 (Illumina)/full-length (Pacbio) amplicon sequencing analysis. Results: Among the 56 recruited patients, 20 had normal motility (NM), 19 had IEM with contraction reserve (IEM-R), and 17 had IEM without contraction reserve (IEM-NR). Esophageal microbiome analysis showed a significant decrease in microbial richness in patients with IEM-NR when compared to NM. The beta diversity revealed different microbiome profiles between patients with NM or IEM-R and IEM-NR (P = 0.037). Several esophageal bacterial taxa were characteristic in patients with IEM-NR, including reduced Prevotella spp.and Veillonella dispar, and enriched Fusobacterium nucleatum. In a microbiome-based random forest model for predicting IEM-NR, an area under the receiver operating characteristic curve of 0.81 was yielded. Conclusions In symptomatic GERD patients with normal endoscopic findings, the esophageal microbiome differs based on contraction reserve among IEM. Absent contraction reserve appears to alter the physiology and microbiota of the esophagus.

[摘 要] 目的：构建负载二氧化锰（MnO2）纳米颗粒的可得然（Cur）复合水凝胶MnO2@Cur（简称MGel），研究其对黑色素瘤B16-F10细胞的杀伤效果。方法：采用热诱导法制备Cur水凝胶（Gel），物理负载MnO2构建MGel，表征其宏观和微观形貌，检测其机械性能、降解性能以及光热转换性能等理化性能，并研究其联合PTT对小鼠皮肤黑色素瘤B16-F10细胞的光热杀伤效果。结果：MGel具有优异的机械和可降解性能，抗拉伸强度达（127.97±3.60）kPa、抗压缩强度达（151.44±5.23）kPa，28 d降解率约58.17%。MGel负载MnO2纳米片（粒径约180 nm）获得优异的光热转换性能，负载1.0 mg/mL MnO2的MGel在1.0 W/cm2的808 nm NIR光照4 min后到达最高温度50 ℃。细胞毒性实验和Calcein-AM/PI荧光双染色实验表明，MGel联合PTT有效杀伤B16-F10黑色素瘤细胞，NIR光照使得MGel组细胞存活率降低至（4.68±0.66）%（P<0.000 1）。结论：MGel复合水凝胶具备优异的机械性能、可降解性能以及光热转换性能，其联合PTT能有效杀伤肿瘤细胞，可能成为一种有效治疗黑色素瘤的新手段。

Objective: To obtain experience and generate suggestions for reducing average hospital stays, optimizing perioperative management of patients with gastric cancer and improving utilization of medical resources by analyzing the factors influencing super-long hospital stays in patients undergoing radical gastrectomy in the age of enhanced recovery after surgery (ERAS). Methods: This was a case-control study. Inclusion criteria: (1) pathologically diagnosed gastric adenocarcinoma; (2) radical surgery for gastric cancer; and (3) complete clinicopathologic data. Exclusion criteria: (1) history of upper abdominal surgery; (2) presence of distant metastasis of gastric cancer or other ongoing neoplastic diseases; (3) concurrent chemoradiotherapy; and (4) preoperative gastric cancer-related complications such as obstruction or perforation. The study cohort comprised 285 eligible patients with hospital stays of ≥30 days (super-long hospital stay group). Using propensity score matching in a 1:1 ratio, age, sex, medical insurance, pTNM stage, and extent of surgical resection as matching factors, 285 patients with hospital stays of < 30 days during the same period were selected as the control group (non-long hospital stay group). The primary endpoint was relationship between pre-, intra-, and post-operative characteristics and super-long hospital stays. Clavien-Dindo grade was used to classify complications. Results: Univariate analysis showed that number of comorbidities, number of preoperative consultations, preoperative consultation, inter-departmental transference, operation time, open surgery, blood loss, intensive care unit time, presence of surgical or non-surgical complications, Clavien-Dindo grade of postoperative complications, and reoperation were associated with super-long hospital stays (all P<0.05). Inter-departmental transference (OR=4.876, 95% CI: 1.500-16.731, P<0.001), preoperative consultation time ≥ 3 d (OR=1.758, 95%CI: 1.036-2.733, P=0.034), postoperative surgery-related complications (OR = 6.618, 95%CI: 2.141-20.459, P=0.01), and higher grade of complications (Clavien-Dindo Grade I: OR = 7.176, 95%CI: 1.785-28.884, P<0.001; Clavien-Dindo Grade II: OR = 18.984, 95%CI: 6.286-57.312, P<0.001; Clavien-Dindo Grade III-IV: OR=7.546, 95%CI:1.495-37.952, P=0.014) were independent risk factors for super-long hospital stays. Conclusion: Optimizing preoperative management, enhancing perioperative management, and surgical quality control can reduce the risk of prolonging average hospital stay.
Humans ; Case-Control Studies ; Retrospective Studies ; Length of Stay ; Stomach Neoplasms/pathology* ; Enhanced Recovery After Surgery ; Gastrectomy/adverse effects* ; Postoperative Complications/etiology*

Purpose: Neoadjuvant therapy modality can increase the operability rate and mitigate pathological risks in locally advanced cervical cancer, but treatment response varies widely. It remains unclear whether genetic alterations correlate with the response to neoadjuvant therapy and disease-free survival (DFS) in locally advanced cervical cancer. Materials and Methods: A total of 62 locally advanced cervical cancer (stage IB-IIA) patients who received neoadjuvant chemoradiation plus radical hysterectomy were retrospectively analyzed. Patients’ tumor biopsy samples were comprehensively profiled using targeted next generation sequencing. Pathologic response to neoadjuvant treatment and DFS were evaluated against the association with genomic traits. Results: Genetic alterations of PIK3CA were most frequent (37%), comparable to that of Caucasian populations from The Cancer Genome Atlas. The mutation frequency of genes including TERT, POLD1, NOS2, and FGFR3 was significantly higher in Chinese patients whereas RPTOR, EGFR, and TP53 were underrepresented in comparison to Caucasians. Germline mutations were identified in 21% (13/62) of the cohort and more than half (57%) had mutations in DNA damage repair genes, including BRCA1/2, TP53 and PALB2. Importantly, high tumor mutation burden, TP53 polymorphism (rs1042522), and KEAP1 mutations were found to be associated with poor pathologic response to neoadjuvant chemoradiation treatment. KEAP1 mutations, PIK3CA-SOX2 co-amplification, TERC copy number gain, and TYMS polymorphism correlated with an increased risk of disease relapse. Conclusion We report the genomic profile of locally advanced cervical cancer patients and the distinction between Asian and Caucasian cohorts. Our findings highlight genomic traits associated with unfavorable neoadjuvant chemoradiation response and a higher risk of early disease recurrence.

Background/Aims: Straight leg raise (SLR) can be utilized to evaluate the integrity of the esophagogastric junction during high-resolution manometry (HRM). We aim to assess the value of transient hiatal separation during SLR in symptomatic reflux patients. Methods: Consecutive reflux patients undergoing esophageal HRM and pH monitoring were included. Transient hiatal separation was defined by a ≥ 1 cm separation between the lower esophageal sphincter and crural diaphragm during SLR. We compared esophageal motor patterns and reflux monitoring parameters between patients with normal, transiently abnormal and consistently abnormal esophagogastric junction morphology during SLR. Results: Of 85 (56.3% female, mean age: 46.7 ± 12.3 years) completed SLR, esophagogastric junction morphology was normal in 31 (36.5%), transient hiatal separation in 19 (22.3%), and consistently hiatal hernia in 35 (41.2%). The values of total acid exposure time (P= 0.016), longest acid reflux episodes (P = 0.024), and DeMeester scores (P = 0.016) were higher in hiatal hernia compared to patients with non-transient hiatal separation, but there were no differences between those with and without transient hiatal separation. Within ineffective esophageal motility, the presence of transient hiatal separation during SLR significantly associated with a higher total acid exposure time (P = 0.014), higher DeMeester scores (P = 0.019), higher total acid reflux events (P = 0.037), and higher longest acid reflux episodes (P = 0.006). Conclusion Our work suggests that SLR may have value as a provocative test during HRM, and future outcome studies are warranted to elucidate the clinical relevance of motor abnormalities depicted from SLR.

OBJECTIVE To establish the fingerprints of dried Houttuynia cordata and its decoction pieces ，conduct chemometrics analysis and determine the contents of 5 flavonoids such as neochlorogenic acid. METHODS High performance liquid chromatography （HPLC）method was adopted. Using quercitrin as reference ，HPLC fingerprints of 10 batches of dried H. cordata and its decoction pieces were drawn. The similarity evaluation was conducted by Similarity Evaluation System of TCM Chromatographic Fingerprint （2012 edition），the common peaks were also confirmed. SIMCA-P 14.1 software was applied for principal component analysis （PCA）and partial least square-discriminant analysis （PLS-DA），and the variable importance in projection（VIP）value more than 1 was considered as a standard to screen the differential components affecting the quality of these two products ；meanwhile，the contents of 5 components such as neochlorogenic acid in both products were determined by the same HPLC method. RESULTS There were 20 common peaks in 10 batches of dried H. cordata and 10 batches of its decoction pieces with the similarity values more than 0.960. A total of 5 common peaks were identified ，which were neochlorogenic acid （peak 1）， chlorogenic acid （peak 3），cryptochlorogenic acid （peak 4），rutin（peak 7）and quercitrin （peak 11）. The results of PCA and PLS-DA showed that dried H. cordata could be distinguished from its decoction pieces obviously ；the common peaks with VIP value greater than 1 were as follows ：peak 7（rutin），peak 20，peak 5，peak 13，peak 2，peak 18，peak 3（chlorogenic acid ）， peak 14，peak 17 and peak 19. The linear range of neochlorogenic acid ，chlorogenic acid ，cryptochlorogenic acid ，rutin and quercitrin were 3.77-60.29 μg/mL（r＝0.999 7），1.40-22.42 μg/mL（r＝0.999 5），3.76-60.22 μg/mL（r＝0.999 9），2.19-35.06 μg/mL （r＝0.999 9）and 25.49-407.88 μg/mL（r＝0.999 7），respectively. RSDs of precision ，stability（24 h）and reproducibility E-mail：20190394@njucm.edu.cn tests were all lower than 3％. The average recoveries of the above components in these two products were 98.72％-101.12％ and 98.86％ -100.63％ with RSDs less than 3％（n＝9）. In dried H. cordata ，the average contents of 5 components were 0.87，0.33，0.59，0.61 and 6.17 mg/g，while the average contents were 0.42，0.11，0.26，0.23 and 3.16 mg/g in its decoction pieces ，respectively. CONCLUSIONS HPLC fingerprint and the method of content determination are stable and feasible ，which could be used for the quality control of dried H. cordata and its decoction pieces. Besides ，rutin and other components may be the differential components which could affect the quality of these two products ；the average contents of the 5 flavonoids such as neochlorogenic acid in dried H. cordata all decrease after processing.

Arsenic/toxicity* ; Bangladesh ; Female ; Humans ; Infant, Newborn ; Pregnancy ; Premature Birth/chemically induced* ; Rural Population ; Zinc