Xerostomia (dry mouth) is frequently experienced by patients treated with radiotherapy for head and neck cancers or with Sjögren's syndrome, with no permanent cure existing for this debilitating condition. To this end, in vitro platforms are needed to test therapies directed at salivary (fluid-secreting) cells. However, since these are highly differentiated secretory cells, the maintenance of their differentiated state while expanding in numbers is challenging. In this study, the efficiency of three reversible thermo-ionically crosslinked gels: (1) alginate-gelatin (AG), (2) collagen-containing AG (AGC), and (3) hyaluronic acid-containing AG (AGHA), to recapitulate a native-like environment for human salivary gland (SG) cell expansion and 3D spheroid formation was compared. Although all gels were of mechanical properties comparable to human SG tissue (~11 kPa) and promoted the formation of 3D spheroids, AGHA gels produced larger (>100 cells/spheroid), viable (>93%), proliferative, and well-organized 3D SG spheroids while spatially and temporally maintaining the high expression of key SG proteins (aquaporin-5, NKCC1, ZO-1, α-amylase) for 14 days in culture. Moreover, the spheroids responded to agonist-induced stimulation by increasing α-amylase secretory granules. Here, we propose alternative low-cost, reproducible, and reversible AG-based 3D hydrogels that allow the facile and rapid retrieval of intact, highly viable 3D-SG spheroids.
Humans ; Hydrogels/chemistry* ; Acinar Cells/cytology* ; Spheroids, Cellular/cytology* ; Salivary Glands/cytology* ; Gelatin/chemistry* ; Collagen/chemistry* ; Alginates/chemistry* ; Cell Culture Techniques/methods* ; Hyaluronic Acid/chemistry* ; Cell Proliferation ; Cell Survival ; Cells, Cultured

Background: According to the World Health Organization (WHO), 6.7 million people die annually due to air pollution caused by solid fuel use, with the majority of deaths resulting from respiratory diseases and cardiovascular conditions. In Mongolia, air pollution ranks as the fourth leading risk factor contributing to mortality, following hypertension, diabetes, and other major health risks. Although there have been numerous studies on outdoor air pollution in Mongolia, research linking indoor air pollution at the household level with the health status of residents remains limited. Aim: To compare indoor PM2.5 concentrations in households of Ulaanbaatar and Darkhan and examine their association with hypertension during the winter season. Materials and Methods: The study was conducted during November and December 2023, and January 2024, involving 240 households in Ulaanbaatar and Darkhan. Indoor PM2.5 concentrations were measured using Purple Air real-time sensors continuously for 24 hours over approximately one month. After measuring indoor air pollution, individuals aged 18–60 years living in the selected households were recruited based on specific inclusion criteria. Blood pressure was measured three times and the average value was recorded. Information on respiratory illnesses was collected through structured questionnaires. Statistical analysis was performed using STATA version 19.0. Results: A total of 241 households participated in the study, with 116 from Ulaanbaatar and 125 from Darkhan. Of the participants, 46.5% were male and 53.5% were female. In terms of housing type, 96 households (39.8%) lived in gers, 97 (40.2%) lived in stove-heated houses, and 48 (19.9%) lived in apartments. Among all participants, 66.0% (n=159) had hypertension and 34.0% (n=79) had normal blood pressure. Among participants aged over 40, 69.9–88.5% had hypertension, which is statistically significantly higher compared to younger individuals (p=0.0001). By body mass index, 75.3% (n=72) of overweight individuals and 78.4% (n=58) of obese participants had hypertension, showing a statistically significant difference compared to participants with normal weight (p=0.0001). The 24-hour average concentration of indoor PM2.5 was measured using the Purple Air device, and the levels in gers and stove-heated houses exceeded the limit set by the MNS 4585:2025 standard (37.5 µg/m³) Conclusion This study identified a relationship between environmental factors, such as air pollution and housing type, and the prevalence of hypertension. The indoor PM2.5 concentration in gers and stove-heated houses was above the standard limit, indicating a negative impact on the health of those residents. Furthermore, the high prevalence of hypertension among participants over the age of 40 and those who are overweight suggests a possible link to lifestyle and environmental conditions.

Background: Particulate matter with an aerodynamic diameter of 2.5 micrometers or smaller (PM2.5) penetrates deep into the alveoli through the respiratory tract and is characterized by its ability to induce oxidative stress, systemic inflammation, and vascular inflammation. Mongolia ranks among the countries with the highest levels of air pollution. In Ulaanbaatar, where more than half of the country’s population resides, wintertime PM2.5 concentrations often exceed 200 μg/m³, which is about eight times higher than the World Health Organization (WHO) guideline value. A study involving 1,200 adults in Ulaanbaatar showed that quality of life deteriorated sharply during periods of high air pollution, with effects more pronounced among individuals who already had impaired respiratory function. Aim: To examine the relationship between indoor household PM2.5 concentrations and lung function indicators among adults in Ulaanbaatar and Darkhan. Materials and Methods: This analytical cross-sectional study recruited adult participants from Ulaanbaatar and Darkhan through targeted sampling. Household air quality was measured using PurpleAir sensors, which were installed in participants’ homes for one month. After exposure measurement, lung function was assessed via spirometry. Statistical analyses were conducted using SPSS version 25.0. Results: A total of 236 participants were included: 114 (48.3%) from Ulaanbaatar and 122 (51.7%) from Darkhan. The sample consisted of 111 men (47.0%) and 125 women (53.0%). The mean indoor PM2.5 concentration was 66.24 μg/m³ (SD 44.87 μg/m³), ranging from a minimum of 7.79 μg/m³ to a maximum of 264.55 μg/m³. Stratification by housing type showed the highest PM2.5 levels in gers (82.34 μg/m³), followed by detached houses (67.34 μg/m³), while apartments had the lowest concentrations (32.24 μg/m³). Correlation analysis revealed statistically significant negative associations between PM2.5 levels and measures of expiratory function, including the FEV1/FVC ratio, peak expiratory flow (PEF), and mid-expiratory flow (FEF25–75). Reduced forced vital capacity (FVC) was observed in 9.4% of participants, reduced forced expiratory volume in one second (FEV1) in 15.3%, and a decreased FEV1/FVC ratio in 3.8%. Conclusion Indoor household PM2.5 concentrations were highest in gers, and expiratory flow-related lung function parameters showed significant negative associations with particulate exposure. This suggests that indoor PM2.5 primarily affects airflow limitation rather than overall lung volumes in this population.

Purinergic P2Y Receptor Antagonists ; Consensus ; Cardiovascular System ; Cardiology ; Asia

Objective: To investigate the safety and efficacy of laparoscopic surgery in locally advanced gastric cancer patients with neoadjuvant SOX chemotherapy combined with PD-1 inhibitor immunotherapy. Methods: Between November 2020 and April 2021, patients with locally advanced gastric cancer who were admitted to the Union Hospital of Tongji Medical College of Huazhong University of Science and Technology were prospectively enrolled in this study. Inclusion criteria were: (1) patients who signed the informed consent form voluntarily before participating in the study; (2) age ranging from 18 to 75 years; (3) patients staged preoperatively as cT3-4N+M0 by the TNM staging system; (4) Eastern Collaborative Oncology Group score of 0-1; (5) estimated survival of more than 6 months, with the possibility of performing R0 resection for curative purposes; (6) sufficient organ and bone marrow function within 7 days before enrollment; and (7) complete gastric D2 radical surgery. Exclusion criteria were: (1) history of anti-PD-1 or PD-L1 antibody therapy and chemotherapy; (2) treatment with corticosteroids or other immunosuppre- ssants within 14 days before enrollment; (3) active period of autoimmune disease or interstitial pneumonia; (4) history of other malignant tumors; (5) surgery performed within 28 days before enrollment; and (6) allergy to the drug ingredients of the study. Follow-up was conducted by outpatient and telephone methods. During preoperative SOX chemotherapy combined with PD-1 inhibitor immunotherapy, follow-up was conducted every 3 weeks to understand the occurrence of adverse reactions of the patients; follow-up was conducted once after 1 month of surgical treatment to understand the adverse reactions and survival of patients. Observation indicators were: (1) condition of enrolled patients; (2) reassessment after preoperative therapy and operation received (3) postoperative conditions and pathological results. Evaluation criteria were: (1) tumor staged according to the 8th edition of the American Joint Committee on Cancer (AJCC) TNM staging system; (2) tumor regression grading (TRG) of pathological results were evaluated with reference to AJCC standards; (3) treatment-related adverse reactions were evaluated according to version 5.0 of the Common Terminology Criteria for Adverse Events; (4) tumor response was evaluated by CT before and after treatment with RECIST V1.1 criteria; and (5) Clavien-Dindo complication grading system was used for postoperative complications assessment. Results: A total of 30 eligible patients were included. There were 25 males and 5 females with a median age of 60.5 (35-74) years. The primary tumor was located in the gastroesophageal junction in 12 cases, in the upper stomach in 8, in the middle stomach in 7, and in the lower stomach in 3. The preoperative clinical stage of 30 cases was III. Twenty-one patients experienced adverse reactions during neoadjuvant chemotherapy combined with immunotherapy, including four cases of CTCAE grade 3-4 adverse reactions resulting in bone marrow suppression and thoracic aortic thrombosis. All cases of adverse reactions were alleviated or disappeared after active symptomatic treatment. Among the 30 patients who underwent surgery, the time from chemotherapy combined with immunotherapy to surgery was 28 (23-49) days. All 30 patients underwent laparoscopic radical gastrectomy, of which 20 patients underwent laparoscopic-assisted radical gastric cancer resection; 10 patients underwent total gastrectomy for gastric cancer, combined with splenectomy in 1 case and cholecystectomy in 1 case. The surgery time was (239.9±67.0) min, intraoperative blood loss was 84 (10-400) ml, and the length of the incision was 7 (3-12) cm. The degree of adenocarcinoma was poorly differentiated in 18 cases, moderately differentiated in 12 cases, nerve invasion in 11 cases, and vascular invasion in 6 cases. The number lymph nodes that underwent dissection was 30 (17-58). The first of gas passage, the first postoperative defecation time, the postoperative liquid diet time, and the postoperative hospitalization time of 30 patients was 3 (2-6) d, 3 (2-13) d, 5 (3-12) d, and 10 (7-27) d, respectively. Postoperative complications occurred in 23 of 30 patients, including 7 cases of complications of Clavien-Dindo grade IIIa or above. Six patients improved after treatment and were discharged from hospital, while 1 patient died 27 days after surgery due to granulocyte deficiency, anemia, bilateral lung infection, and respiratory distress syndrome. The remaining 29 patients had no surgery-related morbidity or mortality within 30 days of discharge. Postoperative pathological examination showed TRG grades 0, 1, 2, and 3 in 8, 9, 4, and 9 cases, respectively, and the number of postoperative pathological TNM stages 0, I, II, and III was 8, 7, 8, and 7 cases, respectively. The pCR rate was 25.0% (8/32). Conclusion: Laparoscopic surgery after neoadjuvant SOX chemotherapy combined with PD-1 inhibitor immunotherapy for locally advanced gastric cancer is safe and feasible, with satisfactory short-term efficacy. Early detection and timely treatment of related complications are important.
Male ; Female ; Humans ; Middle Aged ; Aged ; Adolescent ; Young Adult ; Adult ; Stomach Neoplasms/pathology* ; Neoadjuvant Therapy ; Immune Checkpoint Inhibitors ; Gastrectomy/methods* ; Esophagogastric Junction/pathology* ; Laparoscopy ; Immunotherapy ; Postoperative Complications ; Retrospective Studies ; Treatment Outcome

Pain is often debilitating, and current treatments are neither universally efficacious nor without risks. Transient receptor potential (TRP) ion channels offer alternative targets for pain relief, but little is known about the regulation or identities of endogenous TRP ligands that affect inflammation and pain. Here, transcriptomic and targeted lipidomic analysis of damaged tissue from the mouse spinal nerve ligation (SNL)-induced chronic pain model revealed a time-dependent increase in Cyp1b1 mRNA and a concurrent accumulation of 8,9-epoxyeicosatrienoic acid (EET) and 19,20-EpDPA post injury. Production of 8,9-EET and 19,20-EpDPA by human/mouse CYP1B1 was confirmed in vitro, and 8,9-EET and 19,20-EpDPA selectively and dose-dependently sensitized and activated TRPA1 in overexpressing HEK-293 cells and Trpa1-expressing/AITC-responsive cultured mouse peptidergic dorsal root ganglia (DRG) neurons. TRPA1 activation by 8,9-EET and 19,20-EpDPA was attenuated by the antagonist A967079, and mouse TRPA1 was more responsive to 8,9-EET and 19,20-EpDPA than human TRPA1. This latter effect mapped to residues Y933, G939, and S921 of TRPA1. Intra-plantar injection of 19,20-EpDPA induced acute mechanical, but not thermal hypersensitivity in mice, which was also blocked by A967079. Similarly, Cyp1b1-knockout mice displayed a reduced chronic pain phenotype following SNL injury. These data suggest that manipulation of the CYP1B1-oxylipin-TRPA1 axis might have therapeutic benefit.

Humans ; Thyroid Cancer, Papillary ; Neck/pathology* ; Lymph Nodes/pathology* ; Thyroid Neoplasms/pathology* ; Lymphoma, T-Cell/pathology*

Objective: To investigate the expression differences of LLGL2 between prostatic ductal adenocarcinoma (PDA) and prostatic acinar adenocarcinoma, and its potential clinical significance. Methods: Eighteen patients diagnosed of PDA or prostatic acinar adenocarcinoma with PDA component by histopathology during January 2015 and December 2019 in the Beijing Hospital, China were retrospectively studied. The transcriptome analysis was conducted using the tissue of PDA and prostatic acinar adenocarcinoma. Differentially expressed genes and the differences in expression profiles were identified. Further, differentially expressed proteins were verified by immunohistochemistry. Results: The tissue from 8 of the 18 patients were used for transcriptome analysis, the results of which were compared with data from public databases. 129 differentially expressed genes were identified. 45 of them were upregulated while 84 were downregulated. The results of gene enrichment analysis and gene oncology (GO) analysis revealed that the differentially expressed genes were mostly enriched in the hypertrophic cardiomyopathy and interleukin-17 related pathways. GPAT2, LLGL2, MAMDC4, PCSK9 and SMIM6 were differentially expressed between PDA and prostatic acinar adenocarcinoma. Moreover, LLGL2 was more likely expressed in the cytoplasm (P=0.04) than the nucleus (P<0.01) in PDA, compared with prostatic acinar adenocarcinoma. Conclusions: The gene expression profiling indicates that PDA are very similar to prostatic acinar adenocarcinoma. Among the differentially expressed proteins screened and verified in this study, the expression of GPAT2, LLGL2, MAMDC4 and PCSK9 is increased in PDA, while that of SMIM6 is reduced in PDA. The expression of LLGL2 shows significantly different patterns between PDA and prostatic acinar carcinoma, and thus may help differentiate PDA from prostatic acinar adenocarcinoma in clinical practice.
Male ; Humans ; Carcinoma, Acinar Cell/pathology* ; Proprotein Convertase 9 ; Prostate/pathology* ; Retrospective Studies ; Prostatic Neoplasms/metabolism*

Humans ; Ulcer/pathology* ; Herpesvirus 4, Human ; Epstein-Barr Virus Infections ; Skin Diseases