Objective:To explore the association between spicy food intake and the risk for cardio/cerebrovascular diseases.Methods:Data were collected from the China Kadoorie Biobank project conducted in Pengzhou, Sichuan Province. Using the Cox proportional hazards regression model, we analyzed the associations of the frequency of spicy food intake, spicy level, types of spicy food, and the age when regular intake of spicy food began (intake in 1 day/week), with the risk for cardio/cerebrovascular disease. Furthermore, the associations with the risks for ischemic heart disease (IHD) and cerebrovascular diseases, as well as the risk of ischemic stroke (IS) and hemorrhagic stroke (HS) were analyzed.Results:A total of 54 859 study participants were included in the study, in whom 49 320 had spicy food intake (89.90%). In these participants, 37 680 (68.69%) had spicy food intake in 6-7 days/week, 5 036 (9.18%) had spicy food intake in 1-5 days/week, and 6 604 (12.03%) had spicy food intake once a week; 5 539 (10.10%) had never/almost never had spicy food intake. After adjusting for multiple confounding factors, compared with those who never/almost never had spicy food intake, intake of spicy food was associated with reduced risks for IHD (intake in 6-7 days/week: HR=0.86, 95% CI: 0.78-0.95), cerebrovascular diseases (intake in 6-7 days/week: HR=0.88, 95% CI: 0.81-0.96), and IS (intak in 6-7 days/week: HR=0.85, 95% CI: 0.76-0.95). With the increase of spicy food intake frequency, the risk for cardio/cerebrovascular disease decreased (intake in 1-5 days/week: HR=0.91, 95% CI: 0.85-0.98; intake in 6-7 days/week: HR=0.89, 95% CI: 0.84-0.94) (trend test P<0.001). However, no statistical association was found between spicy food intake and the risk for HS. In terms of spicy level, after adjusting for multiple confounding factors, compared with those who never/almost never had spicy food intake, intake of spicy food was associated with reduced risk for cardio/cerebrovascular disease (moderate: HR=0.86, 95% CI: 0.82-0.90) and cerebrovascular disease (moderate: HR=0.90, 95% CI: 0.84-0.97). With the increase of spicy level, the risk for IHD decreased (moderate: HR=0.86, 95% CI: 0.79-0.93; strong: HR=0.84, 95% CI: 0.74-0.95) (trend test P<0.001). After adjusting for multiple confounding factors, compared with those who never/almost never had spicy food intake, intake of any type of spicy food was associated with reduced risk for cardio/cerebrovascular disease, IHD, and cerebrovascular disease. Regulat intake of spicy food from age 0-10 years was associated with reduced risk for cardio/cerebrovascular disease, IHD, and cerebrovascular disease. Regular intake of spicy food from age 11-20 years reduced the risk for cardio/cerebrovascular disease and IHD. There was no significant association between the regular intake of spicy food from age 21-79 years and the risks for cardio/cerebrovascular disease, IHD and cerebrovascular disease. Conclusion:The intake of spicy food could reduced the risk for cardio/cerebrovascular diseases, IHD, cerebrovascular diseases and IS in residents aged 30-79 years in Sichuan.

Objective:To explore the association between spicy food intake and the risk for cardio/cerebrovascular diseases.Methods:Data were collected from the China Kadoorie Biobank project conducted in Pengzhou, Sichuan Province. Using the Cox proportional hazards regression model, we analyzed the associations of the frequency of spicy food intake, spicy level, types of spicy food, and the age when regular intake of spicy food began (intake in 1 day/week), with the risk for cardio/cerebrovascular disease. Furthermore, the associations with the risks for ischemic heart disease (IHD) and cerebrovascular diseases, as well as the risk of ischemic stroke (IS) and hemorrhagic stroke (HS) were analyzed.Results:A total of 54 859 study participants were included in the study, in whom 49 320 had spicy food intake (89.90%). In these participants, 37 680 (68.69%) had spicy food intake in 6-7 days/week, 5 036 (9.18%) had spicy food intake in 1-5 days/week, and 6 604 (12.03%) had spicy food intake once a week; 5 539 (10.10%) had never/almost never had spicy food intake. After adjusting for multiple confounding factors, compared with those who never/almost never had spicy food intake, intake of spicy food was associated with reduced risks for IHD (intake in 6-7 days/week: HR=0.86, 95% CI: 0.78-0.95), cerebrovascular diseases (intake in 6-7 days/week: HR=0.88, 95% CI: 0.81-0.96), and IS (intak in 6-7 days/week: HR=0.85, 95% CI: 0.76-0.95). With the increase of spicy food intake frequency, the risk for cardio/cerebrovascular disease decreased (intake in 1-5 days/week: HR=0.91, 95% CI: 0.85-0.98; intake in 6-7 days/week: HR=0.89, 95% CI: 0.84-0.94) (trend test P<0.001). However, no statistical association was found between spicy food intake and the risk for HS. In terms of spicy level, after adjusting for multiple confounding factors, compared with those who never/almost never had spicy food intake, intake of spicy food was associated with reduced risk for cardio/cerebrovascular disease (moderate: HR=0.86, 95% CI: 0.82-0.90) and cerebrovascular disease (moderate: HR=0.90, 95% CI: 0.84-0.97). With the increase of spicy level, the risk for IHD decreased (moderate: HR=0.86, 95% CI: 0.79-0.93; strong: HR=0.84, 95% CI: 0.74-0.95) (trend test P<0.001). After adjusting for multiple confounding factors, compared with those who never/almost never had spicy food intake, intake of any type of spicy food was associated with reduced risk for cardio/cerebrovascular disease, IHD, and cerebrovascular disease. Regulat intake of spicy food from age 0-10 years was associated with reduced risk for cardio/cerebrovascular disease, IHD, and cerebrovascular disease. Regular intake of spicy food from age 11-20 years reduced the risk for cardio/cerebrovascular disease and IHD. There was no significant association between the regular intake of spicy food from age 21-79 years and the risks for cardio/cerebrovascular disease, IHD and cerebrovascular disease. Conclusion:The intake of spicy food could reduced the risk for cardio/cerebrovascular diseases, IHD, cerebrovascular diseases and IS in residents aged 30-79 years in Sichuan.

ObjectiveTo explore the effect of different drying conditions on the appearance and intrinsic quality indicators of Pinelliae Rhizoma for screening suitable drying conditions， so as to provide reference for its standardized production and quality evaluation. MethodsDifferent dried samples of Pinelliae Rhizoma were prepared by lime-assisted sweating method and intermittent drying method. Visual analysis was employed to measure the color brightness values（L^*） of the surface， cross-section and powder of the samples， texture analyzer was used to determine the hardness of the samples under different drying conditions. The total starch content was calculated by measuring the contents of amylose and amylopectin in the samples with ultraviolet-visible spectroscopy. High performance liquid chromatography（HPLC） was used to determine the contents of seven nucleoside components（uracil， hypoxanthine， uridine， inosine， guanosine， β-thymidine and adenosine） in the samples. Pearson correlation analysis was conducted to explore the correlation between the external characteristics and intrinsic indicators of the different dried samples. Principal component analysis（PCA） was used to comprehensively rank the data of various indicators， and partial least squares-discriminant analysis（PLS-DA） was used to screen differential components with variable importance in the projection（VIP） value>1. Furthermore， the difference between the optimal drying condition for Pinelliae Rhizoma and the traditional sun-drying method was explored by independent samples t-test. ResultsWith the increase of temperature， the color of the intermittently dried samples gradually deepened， while their hardness gradually decreased. Concurrently， the contents of extract， total starch， uridine and adenosine exhibited an upward trend， whereas the contents of uracil， hypoxanthine and inosine displayed a downward trajectory. Compared with the intermittent drying group， the content of extract in the samples subjected to lime-assisted sweating increased. With the increase of lime dose， the hardness and the total content of nucleoside components in the samples showed a downward trend， while the total starch content showed an upward trend. Correlation analysis showed that the comprehensive score of L^* was negatively correlated with the contents of uracil， hypoxanthine and inosine， and positively correlated with the contents of uridine， guanosine and adenosine. Hardness was negatively correlated with adenosine content， and positively correlated with the contents of inosine， uracil and hypoxanthine. Through comprehensive consideration and comprehensive score of principal components， the method of 5% lime-mixed sweating for 6 days emerged as the top-ranking approach. Except for the extract， the results of independent samples t-test showed that there was no significant difference between the 5% lime-mixed sweating for 6 days and the traditional sun-drying in terms of other content indicators. ConclusionThe whiteness and firmness of Pinelliae Rhizoma exhibit significant correlations with its chemical composition， while uridine， uracil， guanosine， adenosine and inosine are the key constituents responsible for the quality difference of Pinelliae Rhizoma under different drying conditions. The lime-assisted sweating method optimized in this study can be proposed as a viable alternative to the traditional sun-drying method. This method not only ensures the quality of the medicinal material but also effectively reduces the drying time and prevents mold contamination， which provides a valuable reference for the standardization of drying conditions and the establishment of quality evaluation criteria for Pinelliae Rhizoma.

Idiopathic pulmonary fibrosis (IPF) is a progressive disease lacking effective therapy. Metformin, an antidiabetic medication, has shown promising therapeutic properties in preclinical fibrosis models; however, its precise cellular targets and associated mechanisms in fibrosis resolution remain incompletely defined. Most research on metformin's effects has focused on mesenchymal and inflammatory responses with limited attention to epithelial cells. In this study, we utilized Sftpc lineage-traced and Fgfr2b conditional knockout mice, along with BMP2/PPARγ and AMPK inhibitors, to explore metformin's impact on alveolar epithelial cells in a bleomycin-induced pulmonary fibrosis model and cell culture. We found that metformin increased the proliferation and differentiation of alveolar type 2 (AT2) cells, particularly the recently identified injury-activated alveolar progenitors (IAAPs)-a subpopulation characterized by low SFTPC expression but enriched for PD-L1. Single-cell RNA sequencing revealed a reduction in apoptosis among mature AT2 cells. Interestingly, metformin's therapeutic effects were not significantly affected by BMP2 or PPARγ inhibition, which blocked the lipogenic differentiation of myofibroblasts. However, Fgfr2b deletion in Sftpc lineage cells significantly impaired metformin's ability to promote fibrosis resolution, a process linked to AMPK signaling. In conclusion, metformin alleviates fibrosis by directly activating AT2 cells, especially the IAAPs, through a mechanism that involves AMPK and FGFR2b signaling, but is largely independent of BMP2/PPARγ pathways.

Objective·To establish a research framework for serotonylation of proteins and to provide a methodological basis for the identification of serotonylated proteins.Methods·The Cancer Genome Atlas(TCGA)and Genotype-Tissue Expression(GTEx)databases were used to analyze the expression of the transglutaminase 2(TGM2)gene,which encodes the key enzyme for serotonylation,and the solute carrier family 6(SLC6A4)gene,which encodes the serotonin transporter(SERT),in normal and pan-cancer tissues.5-Propargyltryptamide(5-PT),a serotonin derivative,was synthesized stepwise from serotonin hydrochloride,and its structure was characterized by the Fourier transform infrared spectroscopy(FT-IR),proton nuclear magnetic resonance(1H-NMR),carbon nuclear magnetic resonance(13C-NMR),and time-of-flight mass spectrometry(TOF-MS).The intracellular uptake of 5-PT in the human pancreatic cancer cell line AsPC-1 and mouse immune cells,including CD4+T cells,CD8+T cells,and bone marrow-derived macrophages(BMDMs),was detected by using flow cytometry.Click chemistry,co-immunoprecipitation,and mass spectrometry analysis techniques were employed to identify serotonylated proteins,and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis was performed.Results·Bioinformatics analysis indicated that TGM2 and SLC6A4 were widely expressed in various normal tissues and across pan-cancer tissues.The flow cytometry results showed that the synthesized 5-PT can be taken up into the human pancreatic cancer cell line AsPC-1 and mouse immune cells,including CD4+T cells,CD8+T cells,and BMDMs,via the SERT.Mass spectrometry analysis data showed that a significant amount of serotonylated proteins were enriched in various cells treated with 5-PT.KEGG enrichment analysis revealed that these proteins were involved in important pathways related to glycolysis and amino acid synthesis.Conclusion·By using the synthesized 5-PT,multiple serotonylated proteins are enriched in various cell types.A research system for identifying serotonylated proteins has been successfully established,providing a relatively simple and efficient method for studying protein serotonylation.

Objective·To establish a research framework for serotonylation of proteins and to provide a methodological basis for the identification of serotonylated proteins.Methods·The Cancer Genome Atlas(TCGA)and Genotype-Tissue Expression(GTEx)databases were used to analyze the expression of the transglutaminase 2(TGM2)gene,which encodes the key enzyme for serotonylation,and the solute carrier family 6(SLC6A4)gene,which encodes the serotonin transporter(SERT),in normal and pan-cancer tissues.5-Propargyltryptamide(5-PT),a serotonin derivative,was synthesized stepwise from serotonin hydrochloride,and its structure was characterized by the Fourier transform infrared spectroscopy(FT-IR),proton nuclear magnetic resonance(1H-NMR),carbon nuclear magnetic resonance(13C-NMR),and time-of-flight mass spectrometry(TOF-MS).The intracellular uptake of 5-PT in the human pancreatic cancer cell line AsPC-1 and mouse immune cells,including CD4+T cells,CD8+T cells,and bone marrow-derived macrophages(BMDMs),was detected by using flow cytometry.Click chemistry,co-immunoprecipitation,and mass spectrometry analysis techniques were employed to identify serotonylated proteins,and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis was performed.Results·Bioinformatics analysis indicated that TGM2 and SLC6A4 were widely expressed in various normal tissues and across pan-cancer tissues.The flow cytometry results showed that the synthesized 5-PT can be taken up into the human pancreatic cancer cell line AsPC-1 and mouse immune cells,including CD4+T cells,CD8+T cells,and BMDMs,via the SERT.Mass spectrometry analysis data showed that a significant amount of serotonylated proteins were enriched in various cells treated with 5-PT.KEGG enrichment analysis revealed that these proteins were involved in important pathways related to glycolysis and amino acid synthesis.Conclusion·By using the synthesized 5-PT,multiple serotonylated proteins are enriched in various cell types.A research system for identifying serotonylated proteins has been successfully established,providing a relatively simple and efficient method for studying protein serotonylation.

Background: and Purpose CGG repeat expansion in the 5' untranslated region (5'UTR) of the Notch 2 N-terminal-like C gene (NOTCH2NLC) has been associated with neuronal intranuclear inclusion disease (NIID) and oculopharyngodistal myopathy type 3 (OPDM3). Few OPDM3 patients have been reported. This report describes two OPDM3 patients with novel imaging findings who presented the typical features of NIID, and reviews all OPDM3 cases available in the literature. Methods: The available clinical, imaging, and pathological information was reviewed and investigated. CGG repeat expansion in the 5'UTR of NOTCH2NLC was tested using the repeatprimed polymerase chain reaction (PCR), followed by the fluorescence amplicon-length PCR to determine the number of CGG repeats. Results: Our two OPDM3 patients and most patients reported in the literature developed the typical clinical characteristics of NIID, including leukoencephalopathy, peripheral neuropathy, cognitive deterioration, pigmentary retinopathy, ataxia, tremor, acute encephalitis-like episodes, pigmentary retinopathy, miosis, and sensorineural hearing loss. In addition to typical imaging findings of NIID, our two patients exhibited diffusion weighted imaging (DWI) hyperintensities in the middle cerebellar peduncles, which have not been described previously. Muscle biopsies revealed rimmed vacuoles and p62-positive intranuclear inclusions in the myofibers in both patients. The skin biopsy performed in one patient detected typical eosinophilic intranuclear inclusions. Genetic analysis identified CGG repeat expansion in NOTCH2NLC as the causative mutation in the two patients. Conclusions Our two patients with OPDM3 had clinical characteristics of NIID and exhibited DWI abnormality in the cerebellum. Our results indicate that OPDM3 is within the spectrum of NIID and that DWI hyperintensities in the cerebellum are helpful for diagnosing NIID or OPDM3.

Background: and Purpose CGG repeat expansion in the 5' untranslated region (5'UTR) of the Notch 2 N-terminal-like C gene (NOTCH2NLC) has been associated with neuronal intranuclear inclusion disease (NIID) and oculopharyngodistal myopathy type 3 (OPDM3). Few OPDM3 patients have been reported. This report describes two OPDM3 patients with novel imaging findings who presented the typical features of NIID, and reviews all OPDM3 cases available in the literature. Methods: The available clinical, imaging, and pathological information was reviewed and investigated. CGG repeat expansion in the 5'UTR of NOTCH2NLC was tested using the repeatprimed polymerase chain reaction (PCR), followed by the fluorescence amplicon-length PCR to determine the number of CGG repeats. Results: Our two OPDM3 patients and most patients reported in the literature developed the typical clinical characteristics of NIID, including leukoencephalopathy, peripheral neuropathy, cognitive deterioration, pigmentary retinopathy, ataxia, tremor, acute encephalitis-like episodes, pigmentary retinopathy, miosis, and sensorineural hearing loss. In addition to typical imaging findings of NIID, our two patients exhibited diffusion weighted imaging (DWI) hyperintensities in the middle cerebellar peduncles, which have not been described previously. Muscle biopsies revealed rimmed vacuoles and p62-positive intranuclear inclusions in the myofibers in both patients. The skin biopsy performed in one patient detected typical eosinophilic intranuclear inclusions. Genetic analysis identified CGG repeat expansion in NOTCH2NLC as the causative mutation in the two patients. Conclusions Our two patients with OPDM3 had clinical characteristics of NIID and exhibited DWI abnormality in the cerebellum. Our results indicate that OPDM3 is within the spectrum of NIID and that DWI hyperintensities in the cerebellum are helpful for diagnosing NIID or OPDM3.

Background: and Purpose CGG repeat expansion in the 5' untranslated region (5'UTR) of the Notch 2 N-terminal-like C gene (NOTCH2NLC) has been associated with neuronal intranuclear inclusion disease (NIID) and oculopharyngodistal myopathy type 3 (OPDM3). Few OPDM3 patients have been reported. This report describes two OPDM3 patients with novel imaging findings who presented the typical features of NIID, and reviews all OPDM3 cases available in the literature. Methods: The available clinical, imaging, and pathological information was reviewed and investigated. CGG repeat expansion in the 5'UTR of NOTCH2NLC was tested using the repeatprimed polymerase chain reaction (PCR), followed by the fluorescence amplicon-length PCR to determine the number of CGG repeats. Results: Our two OPDM3 patients and most patients reported in the literature developed the typical clinical characteristics of NIID, including leukoencephalopathy, peripheral neuropathy, cognitive deterioration, pigmentary retinopathy, ataxia, tremor, acute encephalitis-like episodes, pigmentary retinopathy, miosis, and sensorineural hearing loss. In addition to typical imaging findings of NIID, our two patients exhibited diffusion weighted imaging (DWI) hyperintensities in the middle cerebellar peduncles, which have not been described previously. Muscle biopsies revealed rimmed vacuoles and p62-positive intranuclear inclusions in the myofibers in both patients. The skin biopsy performed in one patient detected typical eosinophilic intranuclear inclusions. Genetic analysis identified CGG repeat expansion in NOTCH2NLC as the causative mutation in the two patients. Conclusions Our two patients with OPDM3 had clinical characteristics of NIID and exhibited DWI abnormality in the cerebellum. Our results indicate that OPDM3 is within the spectrum of NIID and that DWI hyperintensities in the cerebellum are helpful for diagnosing NIID or OPDM3.

Objective:To describe the clinical features of a patient of anti-neurofascin 186 (NF186) antibody associated acute immune sensory polyradiculopathy (AISP), and enhance understanding of AISP/chronic immune sensory polyradiculopathy (CISP).Methods:The clinical characteristics, diagnosis and treatment of a domestic AISP patient with NF186 antibody positive admitted to the First Hospital of Shanxi Medical University in December 2021 were summarized, and the previously reported cases of AISP/CISP were systematically reviewed.Results:The patient was a 62-year-old male with acute onset. The clinical manifestations included severe sensory ataxia, increased protein in cerebrospinal fluid, no response to stimulation of the central segment of somatosensory evoked potentials (SEP), normal sensory and motor nerve conduction, and positive serum anti-NF186 antibody (1∶32). After glucocorticoid treatment, the clinical symptoms and SEP were significantly improved. The drug was stopped for 2 months, and there was no recurrence. There were 23 cases of AISP and CISP with complete data reported in the literature (including this patient). The age of onset was (54.7±17.7) years, and the ratio of male to female was 1.88. Three patients with acute onset were classified as AISP. A total of 95.7% (22/23) of patients showed sensory ataxia without limb weakness, 95.0% (19/20) of patients showed prolonged cortical potential latency or even no response, and 95.5% (21/22) of patients showed increased cerebrospinal fluid protein in varying degrees, and nerve root thickening or abnormal enhancement was not common. All 10 patients receiving immunotherapy responded to corticosteroids or intravenous immune globulin. Only 6 AISP/CISP articles reported screening for anti-ganglioside antibodies or Ranvier′s node-paranodal region-related antibodies, and no positive NF186 antibodies were reported. All the 3 patients with AISP had some characteristics of CISP/chronic inflammatory demyelinating polyradiculoneuropathy, and there was no significant difference between AISP and CISP patients in clinical features except the mode of onset.Conclusions:NF186 antibody could cause AISP, which presents as acute onset sensory ataxia. AISP is responsive to glucocorticoid therapy. Except for the mode of onset, AISP and CISP are difficult to distinguish from clinical, electrophysiological, pathological aspects and pathogenic antibodies, so they may be two different manifestations of the same disease.