ObjectiveTo observe the clinical efficacy of Sanren Runchang formula in treating constipation-predominant irritable bowel syndrome （IBS-C） by regulating the brain-gut axis and the effects of the formula on serum levels of 5-hydroxytryptamine （5-HT）， vasoactive intestinal peptide （VIP）， and substance P （SP）. MethodsA randomized controlled design was adopted， and 72 IBS-C patients meeting Rome Ⅳ criteria were randomized into observation and control groups （36 cases）.The observation group received Sanren Runchang formula granules twice daily， and the control group received lactulose oral solution daily for 4 weeks. IBS Symptom Severity Scale （IBS-SSS）， IBS Quality of Life Scale （IBS-QOL）， and Bristol Stool Form Scale （BSFS） were used to assess clinical symptoms， and bowel movement frequency was recorded. The Self-Rating Anxiety Scale （SAS） and Self-Rating Depression Scale （SDS） were employed to evaluate psychological status. ELISA was employed to measure the serum levels of 5-HT， VIP， and SP. ResultsThe total response rate in the observation group was 91.67% （33/36）， which was higher than that （77.78%， 28/36） in the control group （χ²=4.50， P<0.05）. After treatment， both groups showed increased defecation frequency and BSFS scores， decreased IBS-SSS total score， abdominal pain and bloating scores， IBS-QOL health anxiety， anxiety， food avoidance， and behavioral disorders scores， SAS and SDS scores， serum 5-HT and VIP levels， and increased SP levels （P<0.05， P<0.01）. Moreover， the observation group showed more significant changes in the indicators above than the control group （P<0.05， P<0.01）. The SP level showed no significant difference between the two groups. During the 4-week follow-up， the recurrence rate was 5.88% in the observation group and 31.25% in the control group. No adverse events occurred in observation group， and 2 cases of mild diarrhea occurred in the control group. ConclusionSanren Runchang formula demonstrated definitive efficacy in alleviating gastrointestinal symptoms and improving the psychological status and quality of life in IBS-C patients， with a low recurrence rate. The formula can regulate serum levels of neurotransmitters such as 5-HT and VIP， suggesting its potential regulatory effect on the brain-gut axis through modulating neurotransmitters and neuropeptides. However， its complete mechanism of action requires further investigation through detection of additional brain-gut axis-related biomarkers.

Alzheimer's disease (AD), a prototypical neurodegenerative disorder, encompasses multifaceted pathological processes. As pivotal cellular structures within the central nervous system, ion channels play critical roles in regulating neuronal excitability, synaptic transmission, and neurotransmitter release. Extensive research has revealed significant alterations in the expression and function of ion channels in AD, implicating an important role of ion channels in the pathogenesis of abnormal Aβ deposition, neuroinflammation, oxidative stress, and disruptions in calcium homeostasis and neural network functionality. This review systematically summarizes the crucial roles and underlying mechanisms of ion channels in the onset and progression of AD, highlighting how these channel abnormalities contribute to AD pathophysiology. We also discuss the therapeutic potential of ion channel modulation in AD treatment, emphasizing the importance of addressing multifactorial nature and heterogeneity of AD. The development of multi-target drugs and precision therapies is proposed as a future direction of scientific research.
Alzheimer Disease/therapy* ; Humans ; Ion Channels/physiology* ; Oxidative Stress ; Animals ; Amyloid beta-Peptides/metabolism* ; Synaptic Transmission ; Calcium/metabolism*

This study aims to systematically characterize the targeted effects of Quanduzhong Capsules on cartilage lesions in knee osteoarthritis by integrating spatial transcriptomics data mining and animal experiments validation, thereby elucidating the related molecular mechanisms. A knee osteoarthritis model was established using Sprague-Dawley(SD) rats, via a modified Hulth method. Hematoxylin and eosin(HE) staining was employed to detect knee osteoarthritis-associated pathological changes in knee cartilage. Candidate targets of Quanduzhong Capsules were collected from the HIT 2.0 database, followed by bioinformatics analysis of spatial transcriptomics datasets(GSE254844) from cartilage tissues in clinical knee osteoarthritis patients to identify spatially specific disease genes. Furthermore, a "formula candidate targets-spatially specific genes in cartilage lesions" interaction network was constructed to explore the effects and major mechanisms of Quanduzhong Capsules in distinct cartilage regions. Experimental validation was conducted through immunohistochemistry using animal-derived biospecimens. The results indicated that Quanduzhong Capsules effectively inhibited the degenerative changes in the cartilage of affected joints in rats, which was associated with the regulation of Quanduzhong Capsules on the thioredoxin-interacting protein(TXNIP)-NOD-like receptor family pyrin domain containing 3(NLRP3)-bone morphogenetic protein receptor type 2(BMPR2)-fibronectin 1(FN1)-matrix metallopeptidase 2(MMP2) signal axis in the articular cartilage surface and superficial zones, subsequently inhibiting cartilage matrix degradation leading to oxidative stress and inflammatory diffusion. In summary, this study clarifies the spatially specific targeted effects and protective mechanisms of Quanduzhong Capsules within pathological cartilage regions in knee osteoarthritis, providing theoretical and experimental support for the clinical application of this drug in the targeted therapy on the inflamed cartilage.
Animals ; Osteoarthritis, Knee/metabolism* ; Drugs, Chinese Herbal/administration & dosage* ; Rats, Sprague-Dawley ; Rats ; Male ; Humans ; Capsules ; Female ; Disease Models, Animal

To elucidate the mechanism by which steaming affects the quality of Curcuma kwangsiensis root tubers, methods such as LSCM, RVA, dual-wavelength spectrophotometry, LF-NMR, and LC-MS were employed to qualitatively and quantitatively detect changes in starch gelatinization characteristics, water distribution, and material composition of C. kwangsiensis root tubers under different steaming durations. Based on multivariate statistical analysis, the correlation between differences in gelatinization parameters, water distribution, and terpenoid material composition was investigated. The results indicate that steaming affects both starch gelatinization and water distribution in C. kwangsiensis. During the steaming process, transformations occur between amylose and amylopectin, as well as between semi-bound water and free water. After 60 min of steaming, starch gelatinization and water distribution reached an equilibrium state. The content of amylopectin, the amylose-to-amylopectin ratio, and parameters such as gelatinization temperature, viscosity, breakdown value, and setback value were significantly correlated(P≤0.05). Additionally, the amylose-to-amylopectin ratio was significantly correlated with total free water and total water content(P≤0.05). Steaming induced differences in the material composition of C. kwangsiensis root tubers. Clustering of primary metabolites in the OPLS-DA model was distinct, while secondary metabolites were classified into 9 clusters using the K-means clustering algorithm. Differential terpenoid metabolites such as(-)-α-curcumene were significantly correlated with zerumbone, retinal, and all-trans-retinoic acid(P<0.05). Curcumenol was significantly correlated with isoalantolactone and ursolic acid(P<0.05), while all-trans-retinoic acid was significantly correlated with both zerumbone and retinal(P<0.05). Alpha-tocotrienol exhibited a significant correlation with retinal and all-trans-retinoic acid(P<0.05). Amylose was extremely significantly correlated with(-)-α-curcumene, curcumenol, zerumbone, retinal, all-trans-retinoic acid, and α-tocotrienol(P<0.05). Amylopectin was significantly correlated with zerumbone(P<0.05) and extremely significantly correlated with(-)-α-curcumene, curcumenol, zerumbone, retinal, all-trans-retinoic acid, and 9-cis-retinoic acid(P<0.01). The results provide scientific evidence for elucidating the mechanism of quality formation of steamed C. kwangsiensis root tubers as a medicinal material.
Curcuma/chemistry* ; Starch/chemistry* ; Multivariate Analysis ; Water/chemistry* ; Terpenes/analysis* ; Plant Roots/chemistry* ; Plant Tubers/chemistry* ; Drugs, Chinese Herbal/chemistry*

Hepatocellular carcinoma (HCC) expresses abundant glycolytic enzymes and displays comprehensive glucose metabolism reprogramming. Aldolase A (ALDOA) plays a prominent role in glycolysis; however, little is known about its role in HCC development. In the present study, we aim to explore how ALDOA is involved in HCC proliferation. HCC proliferation was markedly suppressed both in vitro and in vivo following ALDOA knockout, which is consistent with ALDOA overexpression encouraging HCC proliferation. Mechanistically, ALDOA knockout partially limits the glycolytic flux in HCC cells. Meanwhile, ALDOA translocated to nuclei and directly interacted with c-Jun to facilitate its Thr93 phosphorylation by P21-activated protein kinase; ALDOA knockout markedly diminished c-Jun Thr93 phosphorylation and then dampened c-Jun transcription function. A crucial site Y364 mutation in ALDOA disrupted its interaction with c-Jun, and Y364S ALDOA expression failed to rescue cell proliferation in ALDOA deletion cells. In HCC patients, the expression level of ALDOA was correlated with the phosphorylation level of c-Jun (Thr93) and poor prognosis. Remarkably, hepatic ALDOA was significantly upregulated in the promotion and progression stages of diethylnitrosamine-induced HCC models, and the knockdown of A ldoa strikingly decreased HCC development in vivo. Our study demonstrated that ALDOA is a vital driver for HCC development by activating c-Jun-mediated oncogene transcription, opening additional avenues for anti-cancer therapies.

Objective To investigate the efficacy of Bushen Tiaojing Decoction,a prescription derived from Daying Decoction which recorded in Jing Yue Quan Shu(The Complete Works of ZHANG Jing-Yue)and with herbs added,combined with human recombinant interferon-α-2b for the treatment of endometriosis(EMs)and to observe its effects on humoral immunity,serum carbohydrate antigen 125(CA125)and anti-endometrial antibody(EMAb)levels of EMs patients.Methods A total of 86 cases of EMs patients with kidney deficiency and blood stasis syndrome were randomly divided into observation group and control group,with 43 cases in each group.The control group was treated with human recombinant interferon-α-2b alone,and the observation group was treated with Bushen Tiaojing Decoction combined with human recombinant interferon-α-2b.The course of treatment covered one month.The changes of humoral immune factors of immunoglobulin A(IgA),complement 3(C3)and complement 4(C4),endometrial ectopic mass diameter,and the levels of pathology-relevant factors of CA1 25 and EMAb in the two groups before and after treatment were observed.Moreover,the clinical efficacy and safety of the two groups were evaluated.Results(1)After one month of treatment,the total effective rate of the observation group was 97.67％(42/43),and that of the control group was 81.40％(35/43).The intergroup comparison(tested by chi-square test)showed that the efficacy of the observation group was significantly superior to that of the control group(P＜0.05).(2)After treatment,the serum IgA level of the two groups was significantly higher than that before treatment(P＜0.05),and the serum C3 and C4 levels were significantly lower than those before treatment(P＜0.05).The increase of serum IgA level and the decrease of serum C3 and C4 levels in the observation group were significantly superior to those in the control group(P＜0.01).(3)After treatment,the serum CA125 and EMAb levels and the diameter of endometrial ectopic mass in the two groups were significantly lower than those before treatment(P＜0.05),and the decrease of serum CA125 and EMAb levels and the diameter of endometriosis mass in the observation group was significantly superior to that in the control group(P＜0.01).(4)The total incidence of adverse reactions in the observation group was 6.98％(3/43)and that in the control group was 11.63％(5/43),and the difference between the two groups was not significant(P＞0.05).Conclusion Bushen Tiaojing Decoction combined with human recombinant interferon-α-2b has a significant clinical effect for the treatment of EMs patients with kidney deficiency and blood stasis syndrome.The combined therapy is effective on improving the levels of humoral immune factors,serum CA125 and EMAb,and reducing endometrial ectopic mass,with high safety.

With the improvement of China's socioeconomic status,the issue of aging has become increasingly prominent,making cerebral infarction a common disease among the elderly.In recent years,research on cerebral infarction has gradually deepened,shifting focus from merely protecting and repairing neurons to emphasizing the complex interplay between inflammatory response and autophagy in the brain vascular unit,covering various aspects such as the blood-brain barrier,astrocytes,microglia,and autophagy.This shift in research direction has provided us with a profound understanding of the mechanisms underlying cerebral infarction,offering strong support for innovative future treatment strategies.In this review,we delved into the importance of the interplay between inflammatory response and autophagy in the pathogenesis of cerebral infarction,emphasized the intricate interactions among these biological components,which might lay the groundwork for more effective managements and treatments of cerebral infarction.By comprehensively reviewing existing literatures,we proposed future research directions,aiming to provide more scientific and systematic guidance for the clinical management and treatment of cerebral infarction.

Objective To investigate the differences of characteristic of bone marrow plasma cells in patients of different plasma cell dyscrasias according to International Myeloma Working Group(IMWG)criteria.Methods We analyzed the serological and bone marrow flow cytometry results of patients with plasma cell dyscrasias diagnosed and treated in Department of Hematology,Zhongshan Hospital(Xiamen Branch),Fudan University from Jun 12,2019 to Sep 5,2023 retrospectively.Results A total of 102 patients,63 males and 39 females,aged 22 to 85 years,were included,including 46 patients with monoclonal gammaglobulinemia of unknown significance,39 patients with multiple myeloma,5 patients with smoldering multiple myeloma and 12 patients with light-chain amyloidosis.All patients had M proteinemia,including 58 patients with IgG type and 44 patients with non-IgG type.Plasma cells were detected in the bone marrow of all patients.Clonal plasma cells were detected in the bone marrow of 79 patients.Normal plasma cells were detected in the bone marrow of 63 patients.Both clonal and normal plasma cells were detected in the bone marrow of 40 patients.Clonal plasma cells from bone marrow of 52 patients expressed CD56 and 12 patients expressed CD117.There were no significant differences in gender,age among different disease groups.There were statistical differences in M protein type,the concentration of M protein,serum involved/uninvolved free light chain ratio,the proportion of plasma cells in bone marrow nucleated cells,the proportion of clonal plasma cells in bone marrow nucleated cells,the proportion of clonal plasma cells in all bone marrow plasma cells,and the proportion of normal plasma cells in all bone marrow plasma cells among different disease groups(P<0.05).There was statistical difference in the expression of CD56 in clonal plasma cells among different disease groups(P=0.009),but no statistical difference in the expression of CD117.Conclusion The proportion of clonal plasma cells to all nucleated cells,the proportion of clonal plasma cells to all plasma cells,and the proportion of CD56 expression in abnormal plasma cells in the bone marrow of patients with light amyloidosis were similar to those of monoclonal gammopathy of undetermined significance,but significantly different from those of patients with multiple myeloma.

Objective:To investigate the clinical characteristics and management status of children with Turner syndrome (TS) in China.Methods:As a cross-sectional study, 1 089 TS patients were included in the database of the National Collaborative Alliance for the Diagnosis and Treatment of Turner Syndrome from August 2019 to November 2023. Clinical characteristics (growth development, sexual development, organ anomalies, etc.), karyotypes, auxiliary examinations, and treatments were collected and analyzed.Results:Among the 1 089 TS cases, 809 were recorded karyotypes. The karyotype distribution was as follows: 45, X in 317 cases (39.2%), X chromosome structural variants (including partial deletions of p or q arm, ring chromosome, and marker chromosome) in 89 cases (11.0%), 45, X/46, XX mosaicism in 158 cases (19.5%), mosaicism with X chromosome structural variants in 209 cases (25.8%), and presence of Y chromosome material in 36 cases (4.4%). Among the 824 TS cases, the age of diagnosis was 9.7(6.4, 12.2) years, with a height standard deviation score (HtSDS) of -3.1±1.2. Five hundred and fifty three cases underwent growth hormone (GH) stimulation test, and 352 cases (63.7%) had GH peak values <10 μg/L and 75.9% (577/760) had low IGF1 levels, with IGF1 SDS ≤-2 accounting for 38.2% (290 cases). Among 471 cases aged ≥8 years, 132 cases (28.0%) showed spontaneous sexual development (mean bone age (11.0±1.7) years), 10 cases had spontaneous menarche (mean bone age (12.0±2.2) years), and 2 cases had regular menstrual cycles. Common physical features included cubitus valgus (311 cases (28.5%)), neck webbing (188 cases (17.2%)), low posterior hairline (185 cases (17.0%)), shield chest (153 cases (14.0%)), high arched palate (127 cases (11.6%)), short fourth metacarpal (43 cases (3.9%)), and spinal abnormalities (38 cases (3.5%)). Congenital cardiovascular and urogenital anomalies occurred in 91 cases (19.4%) and 66 cases (12.0%)respectively. Abdominal ultrasound in 33 cases (7.2%) indicated fatty liver, hepatomegaly, intrahepatic bile duct stones, and splenomegaly. Among 23 cases undergoing oral glucose tolerance test (OGTT) test, 2 were diagnosed with diabetes mellitus and 4 with impaired glucose tolerance. Following diagnosis, 669 cases (80.7%) received rhGH treatment at a chronological age of (9±4) years and bone age of (8.3±3.2) years. Additionally, 112 cases (19.4%) received sex hormone replacement therapy starting at the age of (14±4) years and bone age of (12.6±1.2) years.Conclusions:The karyotypes of 45, X and mosaicism were most common in Chinese children with TS. The clinical manifestations were mainly short stature and gonadal dysplasia. However, a few TS children could be in the normal range of height, and some cases among those aged of ≥8 years old had spontaneous sexual development. Some exhibited physical features, congenital cardiovascular and urogenital anomalies, and dysfunction of the hypothalamic-pituitary-IGF1 axis. Moreover, a few of them developed impaired glucose tolerance and diabetes mellitus. Following diagnosis, most of the patients received rhGH treatment, and a few of them received sex hormone replacement therapy.