ObjectiveTo optimize the processing technology of honey bran-fried Rosae Laevigatae Fructus（h-RLF）， formulate relevant quality standards， and explore its improving effect and mechanism on mice with ulcerative colitis（UC） induced by dextran sodium sulfate（DSS）. MethodsTaking the content of polysaccharides and water-soluble extract as the indexes， L₉（3⁴） orthogonal test was used to optimize parameters of the amount of honey bran， frying time and frying temperature. The quality of 15 batches of h-RLF decoction pieces was evaluated according to the optimized process， and the inspection limit standard was preliminarily drawn up. Eighty SPF male Kunming mice were randomly divided into 8 groups， including the blank group， model group， mesalazine group（0.13 g·kg^-1）， RLF group（3.77 g·kg^-1）， bran-fried RLF group（3.77 g·kg^-1）， h-RLF low， medium and high dose groups（1.89， 3.77， 7.54 g·kg^-1）， with 10 mice in each group. The mice in the blank group were free to drink pure water， and the other groups were free to drink 3% DSS solution for 7 days to prepare UC mouse model. Each treatment group was given corresponding drugs by intragastric administration， and the blank and model groups were given equal volume of normal saline. The body weight of mice was recorded daily and the disease activity index（DAI） was calculated. After the administration， the colon tissues of mice were collected to observe the pathological changes by hematoxylin-eosin（HE） staining. The levels of tumor necrosis factor（TNF）-α， interleukin（IL）-1β， IL-6 and IL-10 in the colon of mice were detected by enzyme-linked immunosorbent assay（ELISA）. Western blot was used to detect the expression levels of phosphorylation nuclear transcription factor-κB p65（p-NF-κB p65）， Toll-like receptor 4（TLR4）， p-p38 mitogen-activated protein kinase（p-p38 MAPK）， p-extracellular signal-regulated kinase（p-ERK） and p-c-Jun N-terminal kinase（p-JNK） proteins in colon tissues. ResultsThe optimum processing technology of h-RLF was 20 g honey bran per 100 g RLF， and stir-frying at 200 ℃ for 8 min. The limit standard under the examination of h-RLF was preliminarily formulated as follows：the polysaccharide content should not be less than 25% based on anhydrous glucose（C₆H₁₂O₆）， the content of water-soluble extract should not be less than 38%， the moisture content should not be more than 12.0%， the total ash content should not be more than 5.0%， and the acid-insoluble ash content should not be more than 1.0%. The cluster heat map analysis showed that the quality of RLF from Huanggang， Hubei province was better. Animal experiments showed that compared with the blank group， the DAI score of the model group was significantly increased， the levels of TNF-α， IL-1β and IL-6 in the colon tissue were significantly increased， the IL-10 level was significantly decreased， the colonic mucosa was seriously damaged， accompanied by a large number of inflammatory cell infiltration， tissue congestion and a significant reduction in glands， and the expression levels of p-NF-κB p65， TLR4， p-p38 MAPK， p-ERK and p-JNK proteins were significantly increased（P<0.01）. Compared with the model group， each administration group could alleviate the symptoms of colonic ulcer， the structure of colonic crypt was basically intact， and the glands were arranged in an orderly manner. Among them， the high-dose group of h-RLF had a better effect， which could significantly reduce the DAI score and the levels of TNF-α， IL-1β and IL-6 in colon tissue（P<0.01）， and significantly increase the level of IL-10（P<0.01）， alleviate the colonic mucosal injury， and effectively inhibit the expression levels of p-NF-κB p65， TLR4， p-p38 MAPK， p-ERK and p-JNK proteins（P<0.01）. ConclusionThe key parameters of the processing technology of h-RLF are determined， and the optimized technology is stable and feasible. The established quality standard is simple and reliable， and can be used for the quality control. h-RLF can effectively alleviate DSS-induced UC， and its mechanism may be related to inhibiting the activation of NF-κB/TLR4/MAPK pathway.

INTRODUCTION: Lecanemab has shown promise in treating early Alzheimer's disease (AD), but its safety and efficacy in Chinese populations remain unexplored. This study aimed to evaluate the safety and 6-month clinical outcomes of lecanemab in Chinese patients with mild cognitive impairment (MCI) or mild AD. METHODS: In this single-arm, real-world study, participants with MCI due to AD or mild AD received biweekly intravenous lecanemab (10 mg/kg). The study was conducted at Hainan Branch, Ruijin Hospital Shanghai Jiao Tong University School of Medicine. Patient enrollment and baseline assessments commenced in November 2023. Safety assessments included monitoring for amyloid-related imaging abnormalities (ARIA) and other adverse events. Clinical and biomarker changes from baseline to 6 months were evaluated using cognitive scales (mini-mental state examination [MMSE], montreal cognitive assessment [MoCA], clinical dementia rating-sum of boxes [CDR-SB]), plasma biomarker analysis, and advanced neuroimaging. RESULTS: A total of 64 patients were enrolled in this ongoing real-world study. Safety analysis revealed predominantly mild adverse events, with infusion-related reactions (20.3%, 13/64) being the most common. Of these, 69.2% (9/13) occurred during the initial infusion and 84.6% (11/13) did not recur. ARIA-H (microhemorrhages/superficial siderosis) and ARIA-E (edema/effusion) were observed in 9.4% (6/64) and 3.1% (2/64) of participants, respectively, with only two symptomatic cases (one ARIA-E presenting with headache and one ARIA-H with visual disturbances). After 6 months of treatment, cognitive scores remained stable compared to baseline (MMSE: 22.33 ± 5.58 vs . 21.27 ± 4.30, P = 0.733; MoCA: 16.38 ± 6.67 vs . 15.90 ± 4.78, P = 0.785; CDR-SB: 2.30 ± 1.65 vs . 3.16 ± 1.72, P = 0.357), while significantly increasing plasma amyloid-β 42 (Aβ42) (+21.42%) and Aβ40 (+23.53%) levels compared to baseline. CONCLUSIONS: Lecanemab demonstrated a favorable safety profile in Chinese patients with early AD. Cognitive stability and biomarker changes over 6 months suggest potential efficacy, though high dropout rates and absence of a control group warrant cautious interpretation. These findings provide preliminary real-world evidence for lecanemab's use in China, supporting further investigation in larger controlled studies. REGISTRATION ClinicalTrials.gov , NCT07034222.
Humans ; Alzheimer Disease/drug therapy* ; Male ; Female ; Aged ; Middle Aged ; Cognitive Dysfunction/drug therapy* ; Aged, 80 and over ; Amyloid beta-Peptides/metabolism* ; Biomarkers ; East Asian People

Invasive fungal infections (IFIs) have become prominent global health threats, escalating the burden on public health systems. The increasing occurrence of invasive fungal infections is due primarily to the extensive application of chemotherapy, immunosuppressive therapies, and broad-spectrum antifungal agents. At present, therapeutic practices utilize multiple categories of antifungal agents, such as azoles, polyenes, echinocandins, and pyrimidine analogs. Nevertheless, the clinical effectiveness of these treatments is progressively weakened by the emergence of drug resistance, thereby substantially restricting their therapeutic utility. Consequently, there is an imperative need to expedite the discovery of novel antifungal agents. This review seeks to present an exhaustive synthesis of novel antifungal drugs and candidate agents that are either under current clinical investigation or anticipated to progress into clinical evaluation. These emerging compounds exhibit unique benefits concerning their modes of action, antimicrobial spectra, and pharmacokinetic characteristics, potentially leading to improved therapeutic outcomes relative to conventional antifungal regimens. It is anticipated that these novel therapeutic agents will furnish innovative treatment modalities and enhance clinical outcomes in managing invasive fungal infections.

Dysregulation of p53 and phosphoinositide (PIPn) signaling are both key drivers of oncogenesis and metastasis. Our recent findings reveal a previously unrecognized interaction between these pathways, converging in the nucleus to form a PIPn-p53 signalosome that modulates nuclear AKT activation and downstream signaling, thereby influencing cancer cell survival and motility. This review examines recent insights into nuclear PIPn signaling in the context of established roles for p53 in cell dynamics and migration while also deliberating current research on how nuclear PIPns interact with p53 to form signalosomes that affect cell motility. We emphasize the critical role of PIPns in stabilizing p53 and activating de novo nuclear AKT signaling, which subsequently modulates key motility-related pathways. Understanding the unique operation and function of the PIPn-p53 signalosome in nuclear phosphatidylinositol 3-kinase (PI3K)-AKT activation offers novel therapeutic strategies for controlling cancer metastasis by targeting pertinent interactions and events.
Humans ; Tumor Suppressor Protein p53/metabolism* ; Signal Transduction ; Cell Movement ; Cell Nucleus/metabolism* ; Phosphatidylinositols/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Animals ; Neoplasms/pathology* ; Phosphatidylinositol 3-Kinases/metabolism*

Multiple myeloma is a malignant proliferative disease of plasma cells,and some patients may develop systemic amyloidosis.Cardiac amyloidosis is a common cause of death in these patients.Secondary adrenal insufficiency is caused by dysfunction of the hypothalamus and/or the pituitary gland,and multiple myeloma cases combined with secondary adrenal cortical dysfunction have been rarely reported in China.The patient,55-year-old,male,was admitted to the Emergency Department of Shenzhen Luohu People's Hospital on June 5,2018 due to"repeated chest tightness and fatigue for 7 months,and fainting for 1 hour".Later,he was transferred to Department of Hematology and was diagnosed as having multiple myeloma(λ light chain type)with systemic amyloidosis through bone marrow puncture and other examinations.The first course regimen of chemotherapy was bortezomib,cyclophosphamide,and dexamethasone.After the course,the patient was infected with a mixture of bacteria and fungi in the lung and had improvement after treatment.Then the regimen was adjusted to bortezomib and dexamethasone from the second course.After the fourth course,the patient achieved complete remission of multiple myeloma.After the fifth course,the patient experienced severe pulmonary-mixed infection again,which was improved after treatment.Thereafter,the patient presented with refractory hypotension,and decreased levels of cortisol and adrenocorticotropic hormone(ACTH),which was diagnosed as secondary adrenal cortical dysfunction.Hydrocortisone replacement therapy was administered.After 9 courses of chemotherapy,the patient received maintenance treatment with ixazomib.Multiple myeloma was evaluated as a stringent complete response.Cardiac amyloidosis was evaluated as a very good partial response,and secondary adrenal cortical dysfunction was treated with hydrocortisone maintenance therapy and with the cortisol level in the normal range.

Chronic kidney disease（CKD）has a significant impact on global public health and is one of the important factors leading to the rise of incidence rate and mortality of non communicable diseases.Intestinal microecology is involved in many pathophysiological activities，such as immunity and nutrient absorption.With proposal of the concept of intestine-kidney axis in 2002，researchers found that the decline of glomerular filtration rate led to accumulation of uremic toxins in intestine，destroyed the intestinal mucosal barrier，led to the translocation of toxins，activated the systemic oxidative stress response，further promoted the progress of CKD.This article reviewed the function of gut microbiota，intestine-gut kidney axis，and the application of microbial preparations in CKD.

In order to standardize the clinical diagnosis and treatment of upper airway cough syndrome (UACS) for children in China, Dongzhimen Hospital of Beijing University of Chinese Medicine and Affiliated Hospital of Liaoning University of Traditional Chinese Medicine initiated the development of this Traditional Chinese Medicine Diagnosis and Treatment Guidelines for Children with Upper Airway cough Syndrome based on evidence-based medical evidence. This guideline will process registration, write a plan, and develop relevant processes and writing norms, develop and publish official documents. This plan mainly introduces the scope of the guidelines, the purpose and significance, the composition of the guidelines working group, the management of conflicts of interest, the collection, selection and determination of clinical problems, the retrieval, screening and rating of evidence, and the consensus of recommendations. Registration information: This study has been registered in the international practice guidelines registry platform with the registration code of PREPARE-2023CN087.

Objective:To investigate the association between the Doppler variables of the ophthalmic artery with the severity of preeclampsia(PE).Methods:Systematic literature was searched between January 1995 and March 2023 in PubMed,Web of Science,Embase,and the Cochrane Library.Studies comparing ophthalmic artery Doppler variables,including peak systolic velocity(PSV),end-diastolic velocity(EDV),resistive index(Rl),pulsa-tility index(PI),and peak ratio(PR,the ratio of the flow velocity of the second peak to that of the initial peak)in patients with PE,severe preeclampsia(sPE),and healthy pregnant women were included.The random-effects model was adopted as the method of pooled analysis,and the I2value was used to assess heterogeneity.The pooled standardized mean difference(SMD)with 95％confidence interval(CI)was used to estimate the associa-tion between ophthalmic artery Doppler variables and PE patient's characteristics.Results:Eight retrospective studies were eventually included in this Meta-analysis.Our pooled results suggested that compared with PE ca-ses,sPE patients had lower PI levels(SMD-0.56,95％CI-0.92～-0.20,P=0.000),higher EDV levels(SMD 0.47,95％CI 0.12～0.83,P=0.028)and higher PR levels(SMD0.96,95％CI 0.13～1.78,P=0.023).Howev-er,there was no significant difference between PE and sPE patients about the PSV and RI(P=0.361,P=0.626).Conclusions:This review demonstrates that ophthalmic artery Doppler variables(PI,EDV and PR)could be useful for predicting PE and PE development(especially in identifying sPE),which in turn may help the practitioner in the management of these complicated cases and in taking early necessary precautions.

Fermentum Rubrum（FR） is a kind of traditional Chinese medicine with dual-use functions of medicine and food， which has been used for more than 1 000 years. By referring to the ancient herbal classics and modern laws and regulations， the author sorted out the origin of FR， sorted out the development of processing， and analyzed the problems existing in the quality standard， aiming to provide a basis for further research and development of FR. There are many theories about the origin of FR. After summarizing and sorting out the relevant literature， three viewpoints are mainly drawn， including Han dynasty origin theory， Wei and Jin origin theory and Tang dynasty origin theory. After synthesizing the views of various schools， it is believed that the origin of FR should be no later than the Eastern Han dynasty. FR is made from rice by fermentation， which has the effect of strengthening the spleen， eliminating food， promoting blood circulation and removing stasis after fermentation. Although the natural fermentation in ancient times has been able to pay attention to the influence of temperature， humidity and strain on the quality of FR， due to the low level of science and technology， there are still problems such as complicated and cumbersome process， large workload and high labor cost. To the pure fermentation in modern times， the fermentation processing method of FR has been evolved， gradually improved and perfected. However， due to the lack of standardized research， there is no unified standard for the fermentation process of FR in various regions， and the quality standard lags behind seriously， which leads to the unstable product quality on the market. Among the 15 specifications for the preparation of FR， only 6 have been published in the past 5 years， and most of them have not been revised in a timely manner， and some of them have not been included in the updated version. Based on this， it is recommended to carry out a systematic study on processing technology of FR， and the best process is selected to accelerate the revision and improvement of its standardization， so as to improve the quality of FR sold in the market and promote its stable and sustainable development.

Objective:To explore the differences of gene expression profiles of precursors of exhausted T cells (Tpex) and terminal exhausted T cells (Tex) in the peripheral blood of patients with active pulmonary tuberculosis (ATB).Methods:Twenty-five cases of ATB, 13 cases of latent tuberculosis infection (LTBI) and 10 health controls were enrolled from January 2021 to October 2022 in the Fifth People′s Hospital of Wuxi. The proportions of Tpex and Tex in the peripheral blood mononuclear cells (PBMCs) of the three groups were detected by flowcytometry. PBMCs of ATB were separated into Tpex and Tex by fluorescence-activated cell sorting. RNA-sequencing was performed and up-regulated and down-regulated genes were screended. Differently expressed genes were analyzed by gene set enrichment analysis of gene ontology (GO) to find regulatory pathways affecting cell metabolism and function. Wilcoxon matched-pairs signed rank test, Kruskal-Wallis test and Dunn multiple comparsion test were used for statistical analysis.Results:The proportion of Tpex in ATB group was 2.86%(1.74%), which was lower than 7.93%(6.16%) of Tex, and the difference was statistically significant ( Z=-3.91, P<0.001). The proportions of Tpex and Tex in LTBI group were 9.47%(6.26%) and 7.43%(5.48%), respectively, and the difference was not statistically significant ( Z=-0.93, P=0.345). The proportions of Tpex and Tex in healthy control group were 8.42%(2.69%) and 6.49%(5.14%), respectively, with no statistical significance ( Z=-1.36, P=0.170). There was statistical difference of the proportion of Tpex among the three groups ( H=21.93, P<0.001), and the proportion of Tpex in ATB group was lower than those in LTBI and heathy control groups, and the differences were both statistically significant ( Z=4.16, P<0.001 and Z=3.34, P=0.003, respectively), while the proportions of Tex in these three groups were not statistically different ( H=2.17, P=0.338). Compared with Tex, the gene expressions of memory markers, such as B-cell lymphoma 2 of Tpex were up-regulated, and the gene expressions of exhausted markers, such as lymphocyte activation gene 3 were down-regulated. In terms of cellular metabolism, the gene expressions of mitochondrial protein complex, mitochondrial matrix and oxidative phosphorylation of Tpex were up-regulated, and the gene expressions of glycolysis were down-regulated. The gene expressions of pyruvate metabolism in Tex were up-regulated, and the gene expressions of CD4 + T lymphocyte activation and differentiation and glycolytic process in Tpex were down-regulated. Conclusions:Tpex in ATB express more characteristics of memory cells and less features of exhausted markers compared with Tex, and the function of mitochondria of Tpex preserves well.