Based on the α7 nicotinic acetylcholine receptor(α7nAChR), this study examined how tetrahydropalmatine(THP) affected BV2 microglia exposed to lipopolysaccharide(LPS), aiming to clarify the possible mechanism underlying the anti-depression effect of THP from the perspectives of preventing inflammation and regulating polarization. First, after molecular docking and determination of the content of Corydalis saxicola Bunting total alkaloids, THP was initially identified as a possible anti-depression component. The BV2 microglia model of inflammation was established with LPS. BV2 microglia were allocated into a normal group, a model group, low-and high-dose(20 and 40 μmol·L~(-1), respectively) THP groups, and a THP(20 μmol·L~(-1))+α7nAChR-specific antagonist MLA(1 μmol·L~(-1)) group. The CCK-8 assay was used to screen the safe concentration of THP. A light microscope was used to examine the morphology of the cells. Western blot and immunofluorescence were used to determine the expression of α7nAChR. qRT-PCR was performed to determine the mRNA levels of inducible nitric oxide synthase(iNOS), cluster of differentiation 86(CD86), suppressor of cytokine signaling 3(SOCS3), arginase-1(Arg-1), cluster of differentiation 206(CD206), tumor necrosis factor(TNF)-α, interleukin(IL)-6, and IL-1β. Enzyme-linked immunosorbent assay(ELISA) was employed to measure the levels of TNF-α, IL-6, and IL-1β in the cell supernatant. The experimental results showed that THP at concentrations of 40 μmol·L~(-1) and below had no effect on BV2 microglia. THP improved the morphology of BV2 microglia, significantly up-regulated the protein level of α7nAChR, significantly down-regulated the mRNA levels of iNOS, CD86, SOCS3, TNF-α, IL-6, and IL-1β, significantly up-regulated the mRNA levels of Arg-1 and CD206, and dramatically lowered the levels of TNF-α, IL-6, and IL-1β in the cell supernatant. However, the antagonist MLA abolished the above-mentioned ameliorative effects of THP on LPS-treated BV2 microglia. As demonstrated by the aforementioned findings, THP protected LPS-treated BV2 microglia by regulating the M1/M2 polarization and preventing inflammation, which might be connected to the regulation of α7nAChR on BV2 microglia.
Berberine Alkaloids/chemistry* ; alpha7 Nicotinic Acetylcholine Receptor/chemistry* ; Microglia/metabolism* ; Mice ; Animals ; Cell Line ; Corydalis/chemistry* ; Humans ; Molecular Docking Simulation ; Inflammation/drug therapy* ; Nitric Oxide Synthase Type II/immunology* ; Tumor Necrosis Factor-alpha/immunology*

BACKGROUND: Hemorrhagic stroke (HS) is associated with significant disability and mortality. However, the relationship between meteorological factors and hemorrhagic stroke, as well as the potential moderating role of these factors, remains unclear. METHODS: Daily data on HS, air pollution, and meteorological conditions were collected from January 2015 to December 2021 in Ganzhou to analyze the relationship between meteorological factors and HS admissions. This analysis employed a time-stratified case-crossover design in conjunction with a distributional lag nonlinear model. Additionally, a bivariate response surface modelling was utilized to further investigate the interaction between meteorological factors and particulate matter. The study also stratified the analyses by gender and age. To investigate the potential impact of extreme weather conditions on HS, this study defined the 97.5th percentile as representing extremely high weather conditions, while the 2.5th percentile was classified as extremely low. RESULTS: In single-day lags, the risk of admissions for HS was significantly associated with extremely low temperature (lag 1-2 and lag 13-14), extremely low humidity (lag 1 and lag 9-12), and extremely high precipitation (lag 2-7). Females exhibited greater susceptibility to extremely low temperature than males within the single-day lag pattern in the subcomponent layer, with a maximum relative risk (RR) that was 7% higher. In the cumulative lag analysis, the risk of HS admissions was significantly associated with extremely high temperature (lag 0-8∼lag 0-14), extremely low humidity (lag 0-2∼lag 0-14), and extremely high precipitation (lag 0-4∼lag 0-14). Within the cumulative lag day structure of the subcomponent layer, both extremely low and extremely high temperature had a more pronounced effect on females and aged ≥65 years. The risk of HS admissions was positively associated with extremely high barometric pressure in the female subgroups (lag 0-1 and lag 0-2). The highest number of HS admissions occurred when high PM_2.5 concentrations coexisted with low precipitation. CONCLUSIONS Meteorological factors were significantly associated with the risk of hospital admissions for HS. Individuals who were female and aged ≥65 years were found to be more susceptible to these meteorological influences. Additionally, an interaction was observed between airborne particulate matter and meteorological factors. These findings contributed new evidence to the association between meteorological factors and HS.
China/epidemiology* ; Humans ; Female ; Male ; Aged ; Middle Aged ; Cross-Over Studies ; Hospitalization/statistics & numerical data* ; Adult ; Hemorrhagic Stroke/etiology* ; Meteorological Concepts ; Weather ; Particulate Matter/analysis* ; Air Pollution/adverse effects* ; Environmental Exposure/adverse effects* ; Aged, 80 and over ; Young Adult

Ovarian tumor (OT) is the most lethal form of gynecologic malignancy, with minimal improvements in patient outcomes over the past several decades. Metastasis is the leading cause of ovarian cancer-related deaths, yet the underlying mechanisms remain poorly understood. Psychological stress is known to activate the glucocorticoid receptor (NR3C1), a factor associated with poor prognosis in OT patients. However, the precise mechanisms linking NR3C1 signaling and metastasis have yet to be fully elucidated. In this study, we demonstrate that chronic restraint stress accelerates epithelial-mesenchymal transition (EMT) and metastasis in OT through an NR3C1-dependent mechanism involving nuclear protein 1 (NUPR1). Mechanistically, NR3C1 directly regulates the transcription of NUPR1, which in turn increases the expression of snail family transcriptional repressor 2 (SNAI2), a key driver of EMT. Clinically, elevated NR3C1 positively correlates with NUPR1 expression in OT patients, and both are positively associated with poorer prognosis. Overall, our study identified the NR3C1/NUPR1 axis as a critical regulatory pathway in psychological stress-induced OT metastasis, suggesting a potential therapeutic target for intervention in OT metastasis.

Enamel demineralization, the formation of white spot lesions, is a common issue in clinical orthodontic treatment. The appearance of white spot lesions not only affects the texture and health of dental hard tissues but also impacts the health and aesthetics of teeth after orthodontic treatment. The prevention, diagnosis, and treatment of white spot lesions that occur throughout the orthodontic treatment process involve multiple dental specialties. This expert consensus will focus on providing guiding opinions on the management and prevention of white spot lesions during orthodontic treatment, advocating for proactive prevention, early detection, timely treatment, scientific follow-up, and multidisciplinary management of white spot lesions throughout the orthodontic process, thereby maintaining the dental health of patients during orthodontic treatment.
Humans ; Consensus ; Dental Caries/etiology* ; Dental Enamel/pathology* ; Tooth Demineralization/etiology* ; Tooth Remineralization

OBJECTIVE: Psoriasis, a common chronic inflammatory skin condition with genetic underpinnings, is traditionally managed with cupping therapy. Although used historically, the precise mechanical effects and therapeutic mechanisms of cupping in psoriasis remain largely unexamined. This study aimed to evaluate cupping therapy's efficacy for psoriasis and investigate its role in modulating inflammatory responses and cellular metabolism. METHODS: Psoriasis was induced in mice using topical imiquimod (IMQ). The effects of cupping on psoriatic lesions were assessed using the Psoriasis Area and Severity Index score, histology, immunohistochemistry, and immunofluorescence staining. polymerase chain reaction sequencing (RNA-seq) and Western blotting were conducted to examine changes in mRNA expression and the AMP-activated protein kinase (AMPK) signaling pathway. RESULTS: Cupping therapy significantly reduced inflammation, epidermal thickness, and inflammatory cell infiltration in mice with IMQ-induced psoriasis. Immunohistochemistry and immunofluorescence showed lower expression of inflammatory markers and a shift in T-cell populations. RNA-seq and Western blotting indicated that cupping upregulated Piezo1 and activated the AMPK pathway, improving energy metabolism in psoriatic skin. CONCLUSION Cupping therapy reduces epidermal hyperproliferation and inflammation in psoriasis, rebalancing the local immune microenvironment. Mechanistically, cupping promotes calcium influx via Piezo1, activates AMPK signaling, and supports metabolic homeostasis, suggesting therapeutic potential for psoriasis. Please cite this article as: Xi RF, Liu X, Wang Y, Lu HZ, Yuan SJ, Guo DJ, Zhu JY, Li FL, Duan YJ. Mechanosensory activation of Piezo1 via cupping therapy: Harnessing neural networks to modulate AMPK pathway for metabolic restoration in a mouse model of psoriasis. J Integr Med. 2025; 23(6):721-732.
Animals ; Psoriasis/chemically induced* ; Mice ; AMP-Activated Protein Kinases/metabolism* ; Disease Models, Animal ; Cupping Therapy/methods* ; Signal Transduction ; Imiquimod ; Ion Channels/genetics* ; Male ; Mechanotransduction, Cellular

Objective:To investigate the safety and efficacy of the TRIANGLE operation after neoadjuvant chemotherapy in locally advanced pancreatic cancer(LAPC).Methods:This study is a retrospective case series analysis. Between January 2020 and December 2022, a total of 103 patients were diagnosed as LAPC who underwent neoadjuvant chemotherapy at the Pancreas Center, the First Affiliated Hospital of Nanjing Medical University. Among them, 26 patients (25.2%) underwent the TRIANGLE operation. There were 15 males and 11 females,with a age of (59±7) years (range: 49 to 74 years). The pre-treatment serum CA19-9( M(IQR)) was 248.8(391.6)U/ml (range: 0 to 1 428 U/ml),and the serum carcinoembryonic antigen was 4.1(3.8)μg/L(range: 1.4 to 13.4 μg/L). The neoadjuvant chemotherapy regimens included: mFOLFIRINOX regimen in 6 cases(23.1%), GnP regimen in 14 cases(53.8%), and mFOLFIRINOX+GnP regimen in 6 cases(23.1%). The follow-up duration extended until June 2023 or until the occurrence of the patient′s death or loss to follow-up. The Kaplan-Meier method was employed to estimate the 1-year and 3-year overall survival rates. Results:After neoadjuvant chemotherapy,CA19-9 levels decreased by 92.3(40.1)%(range:2.1% to 97.7%). Evaluation of the response to treatment revealed 13 cases(50.0%) of stable disease,11 cases(42.3%) of partial response,and 2 cases(7.7%) of complete response. The surgical operation consisted of 12 cases(46.2%) of pancreaticoduodenectomy,12 cases(46.2%) of distal pancreatectomy,and 2 cases(7.7%) of total pancreatectomy. Margin determination was based on the “standardised pathology protocol” and the “1 mm” principle. No R2 and R1(direct) resections were observed,while the R0 resection rate was 61.5%(16/26), and the R1(1 mm) resection rate was 38.5%(10/26).The R1(1 mm) resection rates for the anterior margin,posterior margin,transected margin,portal vein groove margin,and uncinate margin were 23.1%(6/26),19.2%(5/26),12.5%(3/24),2/14, and 1/12, respectively. The overall postoperative complication rate was 57.8%(15/26),with major complications including grade B/C pancreatic fistula 25.0%(6/24,excluding 2 cases of total pancreatectomy),delayed gastric emptying in 23.1%(6/26),wound complications 11.5%(3/26),postoperative hemorrhage 7.7%(2/26), chylous fistula 7.7%(2/26) and bile fistula 3.8%(1/26). No reoperation was performed during the perioperative period(<90 days). One patient died on the 32 nd day postoperatively due to a ruptured pseudoaneurysm. A total of 25 patients were followed up,with a follow-up time of 21(24)months(range: 8 to 42 months). During the follow-up period,8 cases(32.0%) died due to tumor recurrence and metastasis,while 17 patients(68.0%) remained alive,including 11 cases of disease-free survival,5 cases of distant metastasis,and 1 case of local recurrence. The overall survival rates at 1- and 3-year after the initiation of neoadjuvant chemotherapy were 95.8% and 58.9%, respectively. The overall survival rates at 1- and 3-year after surgery were 77.7% and 57.8%, respectively. Conclusion:Performing pancreatoduodenectomy according to the Heidelberg triangle protocol in LAPC patients after neoadjuvant chemotherapy might increase the R0 resection rate without increasing perioperative mortality or the incidence of major postoperative complications.

Objective:To investigate the safety and efficacy of the TRIANGLE operation after neoadjuvant chemotherapy in locally advanced pancreatic cancer(LAPC).Methods:This study is a retrospective case series analysis. Between January 2020 and December 2022, a total of 103 patients were diagnosed as LAPC who underwent neoadjuvant chemotherapy at the Pancreas Center, the First Affiliated Hospital of Nanjing Medical University. Among them, 26 patients (25.2%) underwent the TRIANGLE operation. There were 15 males and 11 females,with a age of (59±7) years (range: 49 to 74 years). The pre-treatment serum CA19-9( M(IQR)) was 248.8(391.6)U/ml (range: 0 to 1 428 U/ml),and the serum carcinoembryonic antigen was 4.1(3.8)μg/L(range: 1.4 to 13.4 μg/L). The neoadjuvant chemotherapy regimens included: mFOLFIRINOX regimen in 6 cases(23.1%), GnP regimen in 14 cases(53.8%), and mFOLFIRINOX+GnP regimen in 6 cases(23.1%). The follow-up duration extended until June 2023 or until the occurrence of the patient′s death or loss to follow-up. The Kaplan-Meier method was employed to estimate the 1-year and 3-year overall survival rates. Results:After neoadjuvant chemotherapy,CA19-9 levels decreased by 92.3(40.1)%(range:2.1% to 97.7%). Evaluation of the response to treatment revealed 13 cases(50.0%) of stable disease,11 cases(42.3%) of partial response,and 2 cases(7.7%) of complete response. The surgical operation consisted of 12 cases(46.2%) of pancreaticoduodenectomy,12 cases(46.2%) of distal pancreatectomy,and 2 cases(7.7%) of total pancreatectomy. Margin determination was based on the “standardised pathology protocol” and the “1 mm” principle. No R2 and R1(direct) resections were observed,while the R0 resection rate was 61.5%(16/26), and the R1(1 mm) resection rate was 38.5%(10/26).The R1(1 mm) resection rates for the anterior margin,posterior margin,transected margin,portal vein groove margin,and uncinate margin were 23.1%(6/26),19.2%(5/26),12.5%(3/24),2/14, and 1/12, respectively. The overall postoperative complication rate was 57.8%(15/26),with major complications including grade B/C pancreatic fistula 25.0%(6/24,excluding 2 cases of total pancreatectomy),delayed gastric emptying in 23.1%(6/26),wound complications 11.5%(3/26),postoperative hemorrhage 7.7%(2/26), chylous fistula 7.7%(2/26) and bile fistula 3.8%(1/26). No reoperation was performed during the perioperative period(<90 days). One patient died on the 32 nd day postoperatively due to a ruptured pseudoaneurysm. A total of 25 patients were followed up,with a follow-up time of 21(24)months(range: 8 to 42 months). During the follow-up period,8 cases(32.0%) died due to tumor recurrence and metastasis,while 17 patients(68.0%) remained alive,including 11 cases of disease-free survival,5 cases of distant metastasis,and 1 case of local recurrence. The overall survival rates at 1- and 3-year after the initiation of neoadjuvant chemotherapy were 95.8% and 58.9%, respectively. The overall survival rates at 1- and 3-year after surgery were 77.7% and 57.8%, respectively. Conclusion:Performing pancreatoduodenectomy according to the Heidelberg triangle protocol in LAPC patients after neoadjuvant chemotherapy might increase the R0 resection rate without increasing perioperative mortality or the incidence of major postoperative complications.

Aim To investigate the effect of benzyl iso-thiocyanate (BITC) on the proliferation of mouse U14 cervical cancer cells and to explore the mechanism of cytotoxicity based on transcriptomic data analysis. Methods The effect of BITC on U14 cell activity was detected by MTT, nuclear morphological changes were observed by Hochest 33258 and fluorescent inverted microscope, cell cycle and apoptosis were determined by flow cytometry, and the transcriptome database of U14 cells before and after BITC (20 μmol · L

Surgical operation is the main treatment of oral and maxillofacial tumors.Dysphagia is a common postoperative complication.Swal-lowing disorder can not only lead to mis-aspiration,malnutrition,aspiration pneumonia and other serious consequences,but also may cause psychological problems and social communication barriers,affecting the quality of life of the patients.At present,there is no systematic evalua-tion and rehabilitation management plan for the problem of swallowing disorder after oral and maxillofacial tumor surgery in China.Combining the characteristics of postoperative swallowing disorder in patients with oral and maxillofacial tumors,summarizing the clinical experience of ex-perts in the field of tumor and rehabilitation,reviewing and summarizing relevant literature at home and abroad,and through joint discussion and modification,a group of national experts reached this consensus including the core contents of the screening of swallowing disorders,the phased assessment of prognosis and complications,and the implementation plan of comprehensive management such as nutrition management,respiratory management,swallowing function recovery,psychology and nursing during rehabilitation treatment,in order to improve the evalua-tion and rehabilitation of swallowing disorder after oral and maxillofacial tumor surgery in clinic.

Cryoablation therapy with explicit anti-tumor mechanisms and histopathological manifestations has a long history.A large number of clinical practice has shown that cryoablation therapy is safe and effective,making it an ideal tumor treatment method in theory.Previously,its efficacy and clinical application were constrained by the limitations of refrigerants and refrigeration equipment.With the development of the new generation of cryoablation equipment represented by argon helium knives,significant progress has been made in refrigeration efficien-cy,ablation range,and precise temperature measurement,greatly promoting the progression of tumor cryoablation technology.This consensus systematically summarizes the mechanism of cryoablation technology,indications for oral mucosal melanoma(OMM)cryotherapy,clinical treatment process,adverse reactions and management,cryotherapy combination therapy,etc.,aiming to provide reference for carrying out the standardized cryoablation therapy of OMM.