OBJECTIVE: This study aimed to reexplore minimum iodine excretion and to build a dietary iodine recommendation for Chinese adults using the obligatory iodine loss hypothesis. METHODS: Data from 171 Chinese adults (19-21 years old) were collected and analyzed based on three balance studies in Shenzhen, Yinchuan, and Changzhi. The single exponential equation was accordingly used to simulate the trajectory of 24 h urinary iodine excretion as the low iodine experimental diets offered (iodine intake: 11-26 μg/day) and to further deduce the dietary reference intakes (DRIs) for iodine, including estimated average requirement (EAR) and recommended nutrient intake (RNI). RESULTS: The minimum iodine excretion was estimated as 57, 58, and 51 μg/day in three balance studies, respectively. Moreover, it was further suggested as 57, 58, and 51 μg/day for iodine EAR, and 80, 81, and 71 μg/day for iodine RNI or expressed as 1.42, 1.41, and 1.20 μg/(day·kg) of body weight. CONCLUSION The iodine DRIs for Chinese adults were established based on the obligatory iodine loss hypothesis, which provides scientific support for the amendment of nutrient requirements.
Humans ; Iodine/administration & dosage* ; Male ; Female ; China ; Young Adult ; Diet ; Adult ; Nutritional Requirements ; East Asian People

Alzheimer's disease(AD)is a neurodegenerative disease with highly heterogeneous pathological and clinical manifesta-tions,and it is the most common cause of dementia.This heterogeneity poses challenges for diagnosis,treatment,and evaluating novel pharmacological efficacy.This review summarizes the latest progress in the major clinical subtypes of AD based on clinical manifesta-tions,genetic,and pathological features.Early-onset and late-onset AD clinical subtypes may share the same symptoms but differ in etiology,age of onset,mode of presentation,disease progression,and associated comorbidities.Typical and atypical AD differ signifi-cantly in clinical manifestations,pathological features,and diagnostic criteria.Research on AD subtypes based on imaging and omics data has also made considerable progress.This review also outlines the molecular pathological heterogeneity of AD.A deep understand-ing of these heterogeneities is crucial for diagnosis,the formulation of pharmacological treatment strategies,and clinical management.

Objective:To analyze the epidemiological and clinical features of infectious diseases of the central nervous system (CNS).Methods:A cross-sectional study and analysis were conducted to summarize the epidemiological and clinical characteristics of 9 918 patients with CNS infectious diseases, who were diagnosed and treated at 29 hospitals across China from January 1, 2001 to December 31, 2020. Data collected included demographic data, clinical manifestations, health economic indicators, and prognostic outcomes.Results:Among the 9 918 collected cases of CNS infectious diseases, 5 559 were male (56.0%) and 4 359 were female (44.0%), with an onset age of 38 (25, 53) years. Education level: slightly more junior high school education (2 651 cases, 26.7%), and less elementary school education and below (2 181 cases, 22.0%) were found. Occupational distribution: farmers were found predominant (3 215 cases, 32.4%), followed by workers (1 826 cases, 18.4%) and students (1 633 cases, 16.5%). Clinical manifestations: headache (6 074 cases, 61.2%), fever (5 869 cases, 59.2%) and positive meningeal irritation signs (2 273 cases, 22.9%) were the 3 most common clinical manifestations, followed by nausea and (or) vomiting (2 095 cases, 21.1%), impaired consciousness (2 077 cases, 20.9%), psychiatric symptom (1 866 cases, 18.8%) and epilepsy (1 627 cases, 16.4%), etc., and cranial nerve involvement was found in 669 cases (6.7%). Major pathogens included viruses in 6 814 cases (68.7%), Mycobacterium tuberculosis in 1 677 cases (16.9%), common bacteria in 864 cases (8.7%), fungi in 254 cases (2.6%), spirochetes of syphilis in 183 cases (1.8%), parasites in 121 cases (1.2%), and rickettsiae in 5 cases (0.1%). Urban-rural distribution: slightly more cases were found in the countryside (5 418 cases, 54.6%) than in the towns (4 500 cases, 45.4%). Distribution of onset by season: 2 412 cases (24.3%) fell ill in spring, 2 835 cases (28.6%) in summer, 2 187 cases (22.1%) in fall, and 2 484 cases (25.0%) in winter. Health economics: the duration of hospitalization was 15 (8, 27) days, and the cost of hospitalization was 1.53 (0.91, 3.02)×10 000 yuan. Prognosis: 9 531 cases (96.1%) were cured or improved, and 92 cases (0.9%) died. Conclusions:The pathogens responsible for CNS infectious diseases are predominantly viruses. Although the incidence is slightly higher during the summer months, the overall seasonal pattern is not particularly pronounced. These infections are more commonly observed in young and middle-aged males and present with a diverse range of clinical manifestations, contributing to a significant disease burden.

Objective:To analyze the epidemiological and clinical features of infectious diseases of the central nervous system (CNS).Methods:A cross-sectional study and analysis were conducted to summarize the epidemiological and clinical characteristics of 9 918 patients with CNS infectious diseases, who were diagnosed and treated at 29 hospitals across China from January 1, 2001 to December 31, 2020. Data collected included demographic data, clinical manifestations, health economic indicators, and prognostic outcomes.Results:Among the 9 918 collected cases of CNS infectious diseases, 5 559 were male (56.0%) and 4 359 were female (44.0%), with an onset age of 38 (25, 53) years. Education level: slightly more junior high school education (2 651 cases, 26.7%), and less elementary school education and below (2 181 cases, 22.0%) were found. Occupational distribution: farmers were found predominant (3 215 cases, 32.4%), followed by workers (1 826 cases, 18.4%) and students (1 633 cases, 16.5%). Clinical manifestations: headache (6 074 cases, 61.2%), fever (5 869 cases, 59.2%) and positive meningeal irritation signs (2 273 cases, 22.9%) were the 3 most common clinical manifestations, followed by nausea and (or) vomiting (2 095 cases, 21.1%), impaired consciousness (2 077 cases, 20.9%), psychiatric symptom (1 866 cases, 18.8%) and epilepsy (1 627 cases, 16.4%), etc., and cranial nerve involvement was found in 669 cases (6.7%). Major pathogens included viruses in 6 814 cases (68.7%), Mycobacterium tuberculosis in 1 677 cases (16.9%), common bacteria in 864 cases (8.7%), fungi in 254 cases (2.6%), spirochetes of syphilis in 183 cases (1.8%), parasites in 121 cases (1.2%), and rickettsiae in 5 cases (0.1%). Urban-rural distribution: slightly more cases were found in the countryside (5 418 cases, 54.6%) than in the towns (4 500 cases, 45.4%). Distribution of onset by season: 2 412 cases (24.3%) fell ill in spring, 2 835 cases (28.6%) in summer, 2 187 cases (22.1%) in fall, and 2 484 cases (25.0%) in winter. Health economics: the duration of hospitalization was 15 (8, 27) days, and the cost of hospitalization was 1.53 (0.91, 3.02)×10 000 yuan. Prognosis: 9 531 cases (96.1%) were cured or improved, and 92 cases (0.9%) died. Conclusions:The pathogens responsible for CNS infectious diseases are predominantly viruses. Although the incidence is slightly higher during the summer months, the overall seasonal pattern is not particularly pronounced. These infections are more commonly observed in young and middle-aged males and present with a diverse range of clinical manifestations, contributing to a significant disease burden.

Objective To study on the effects and mechanisms of ganoderma lucidum polysaccharides(GLP)on enteritis induced by enterotoxigenic Escherichia coli(ETEC)in mice.Methods Twenty-four 6-to 8-weeks-old male SPF Kunming mice were selected.A mouse enteritis model was induced by intraperitoneal injection of ETEC bacterial suspension.Mice were divided into normal group,ETEC infection group,ETEC infection+high-dose GLP group,and ETEC infection+ow-dose GLP group using a random number table method,six mice in each group.Pathological changes in mice small intestine tissue were observed through HE staining.The expression of C-reactive protein(CRP),tumor necrosis factor-(TNF)-α,and interleukin(IL)-6 proteins in mice small intestine tissues were detected by Western blot method,and expression levels of Toll-like receptor 4(TLR4),nuclear factor-KB(NF-κB)p65,and myeloid differentiation factor 88(MyD88)mRNA in mice small intestine tissues were detected by RT-qPCR technique to explore the regulatory effect of GLP on ETEC-induced mice intestinal inflammation through TLR4/NF-κB signaling pathway.Results Compared with control group,mice infected with ETEC showed lethargy,reduced appetite,damaged intestinal villi,significant inflammatory infiltration in tissues,and an increasing trend in disease activity index(DAI)scores(P＜0.05).The relative expression levels of TLR4,NF-κB p65,and MyD88 mRNA,as well as protein expression levels of CRP,TNF-α,and IL-6 in small intestine tissues of mice,were significantly increased(P＜0.01).Compared with ETEC-infected group,mice in different dosage groups showed improvements in mental status and appetite.The relative expression levels of TLR4,NF-κB p65,and MyD88 mRNA in small intestine tissues of mice were significantly decreased in all dosage groups(P＜0.01).In ETEC infection+high-dose group,protein expression levels of CRP,TNF-α,and IL-6 in small intestine tissues of mice were significantly decreased(P＜0.01),while the decrease in ETEC infection+low-dose group was not significant(P＞0.05).Compared with ETEC infection+low-dose group,ETEC infection+high-dose group showed significant decreases in relative expression levels of TLR4 and MyD88 mRNA,as well as in protein expression level of IL-6 in small intestine tissues of mice(P＜0.01 or P＜0.05).Conclusion GLP can effectively relieve intestinal inflammation induced by ETEC,and may exert its anti-inflammatory effect through regulating TLR4/NF-κB signaling pathway,which may be proportional to its concentration.

Objective To study on the effects and mechanisms of ganoderma lucidum polysaccharides(GLP)on enteritis induced by enterotoxigenic Escherichia coli(ETEC)in mice.Methods Twenty-four 6-to 8-weeks-old male SPF Kunming mice were selected.A mouse enteritis model was induced by intraperitoneal injection of ETEC bacterial suspension.Mice were divided into normal group,ETEC infection group,ETEC infection+high-dose GLP group,and ETEC infection+ow-dose GLP group using a random number table method,six mice in each group.Pathological changes in mice small intestine tissue were observed through HE staining.The expression of C-reactive protein(CRP),tumor necrosis factor-(TNF)-α,and interleukin(IL)-6 proteins in mice small intestine tissues were detected by Western blot method,and expression levels of Toll-like receptor 4(TLR4),nuclear factor-KB(NF-κB)p65,and myeloid differentiation factor 88(MyD88)mRNA in mice small intestine tissues were detected by RT-qPCR technique to explore the regulatory effect of GLP on ETEC-induced mice intestinal inflammation through TLR4/NF-κB signaling pathway.Results Compared with control group,mice infected with ETEC showed lethargy,reduced appetite,damaged intestinal villi,significant inflammatory infiltration in tissues,and an increasing trend in disease activity index(DAI)scores(P＜0.05).The relative expression levels of TLR4,NF-κB p65,and MyD88 mRNA,as well as protein expression levels of CRP,TNF-α,and IL-6 in small intestine tissues of mice,were significantly increased(P＜0.01).Compared with ETEC-infected group,mice in different dosage groups showed improvements in mental status and appetite.The relative expression levels of TLR4,NF-κB p65,and MyD88 mRNA in small intestine tissues of mice were significantly decreased in all dosage groups(P＜0.01).In ETEC infection+high-dose group,protein expression levels of CRP,TNF-α,and IL-6 in small intestine tissues of mice were significantly decreased(P＜0.01),while the decrease in ETEC infection+low-dose group was not significant(P＞0.05).Compared with ETEC infection+low-dose group,ETEC infection+high-dose group showed significant decreases in relative expression levels of TLR4 and MyD88 mRNA,as well as in protein expression level of IL-6 in small intestine tissues of mice(P＜0.01 or P＜0.05).Conclusion GLP can effectively relieve intestinal inflammation induced by ETEC,and may exert its anti-inflammatory effect through regulating TLR4/NF-κB signaling pathway,which may be proportional to its concentration.

The rol genes on pRiA4 plasmid of Agrobacterium rhizogenes are potent genes that promote secondary metabolism. Molecular breeding of Atropa belladonna can be conducted by introducing rol genes to increase tropane alkaloids (TAs) content in A. belladonna. In this study, the rolB gene was overexpressed in A. belladonna plants to study the effect of rolB gene on the biosynthesis of TAs. The phenotype, TAs content and expression levels of key enzyme genes in the pathway of TAs biosynthesis of transgenic A. belladonna were analyzed. The results showed that transgenic A. belladonna had developed root system, enlarged leaves, increased leaf fresh weight, deepened leaf color, enlarged flowers, changed flower shape, reduced pistil height and decreased pollen vitality. The content of TAs in the stems of transgenic A. belladonna was significantly higher than that of the control, and the contents of scopolamine, anisodamine, hyoscyamine can reach 2.11-2.91, 1.23-2.37 and 4.88-5.20 times of the control, respectively. Compared with the control group, the expressions of key enzymes putrescine N-methyltransferase (PMT), type III polyketide synthase (PYKS), tropinone reductase I (TRI), aromatic amino acid aminotransferase 4 (ArAT4), UDP-glycosyltransferase 1 (UGT1) and hyoscyamine 6-β-hydroxylase (H6H) in the TAs biosynthesis pathway were up-regulated, and the expression of tropinone reductase II (TRII) as a metabolic shunting gene was down-regulated. The results indicated that rolB gene enhanced TAs synthesis ability in roots and accumulation in stems of A. belladonna by enhancing metabolic flow of TAs synthesis pathway and weakening the metabolic shunt of competing pathway. This study laid a foundation for molecular breeding of A. belladonna with high-yield TAs content using rolB gene.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

Serum and glucocorticoid-regulated kinase 1 (SGK1) plays an important role in the physiological processes of hormone release, neuronal excitation and cell proliferation. SGK1 also participates in the pathophysiological processes of inflammation and apoptosis in the central nervous system (CNS). Increasing evidence demonstrates that SGK1 may serve as a target of the intervention of neurodegenerative diseases. In this article, we summarize the recent progress on the role and molecular mechanisms of SGK1 in the regulation of the function of the CNS. We also discuss the potential of newly discovered SGK1 inhibitors in the treatment of CNS diseases.
Humans ; Cell Proliferation ; Central Nervous System Diseases/drug therapy* ; Inflammation ; Protein Serine-Threonine Kinases/physiology*

ObjectiveTo review the ancient and modern literature of Huanglian Ejiaotang and learn about the historical evolution and clinical application， thereby providing a theoretical basis for the modern application of the classical prescription. MethodLiterature in the Chinese Medical Classics Database was retrieved with "Huanglian Ejiaotang" as the keyword. In China National Knowledge Infrastructure （CNKI） and PubMed， "Huanglian Ejiaotang" in Chinese and English was used as the keyword to retrieve literature. The items and modern clinical application studies related to the prescription， medicine， dosage， syndrome， and treatment of Huanglian Ejiaotang were selected and recorded. The inclusion and exclusion criteria were used to screen out literature. The information about the dynasty， book title， function， and indication was integrated to understand the history， evolution， and clinical application of Huanglian Ejiaotang. ResultFinally， 89 ancient books were included with 111 items. Huanglian Ejiaotang was initially recorded in ZHANG Zhongjing's Treatise on Cold Damage and Miscellaneous Diseases in the Han dynasty. It was composed of five herbs， namely Coptidis Rhizoma， Scutellariae Radix， Paeoniae Radix Alba， Asini Corii Colla， and egg yolk. With the change of historical dynasties， the composition， origin basis， dosage， and preparation method of Huanglian Ejiaotang all changed， but the changes in the processing were not obvious， which was basically consistent with Treatise on Cold Damage and Miscellaneous Diseases. In addition， 48 studies were included to analyze the clinical application of Huanglian Ejiaotang， which was mainly used for insomnia， anxiety， depression， diabetes， and so on. ConclusionAccording to the ancient and modern literature， the origin basis， dosage， processing， decoction， administration， and other content of Huanglian Ejiaotang are consistent with Treatise on Cold Damage and Miscellaneous Diseases. The present clinical application has expanded the usage scale of the ancient record， which promotes the innovation and development of the classic prescription and provides references for later research， development， and accurate application.