Tumor-associated macrophages(TAM)are a current focus in the study of the tumor microenvironment.To achieve their functionally distinct roles,macrophages undergo phenotypic polarization resulting in two major subgroups:M1 macrophages with pro-inflammatory and anti-tumor effects,and M2 macrophages with anti-inflammatory and pro-tumor effects.Of these,M2 polarization,as the main manifestation of TAMs,has been associated with a poor prognosis in various cancers and has been shown to support malignancies.Gastric carcinoma has a low early-diagnosis rate,late disease stage,and poor prognosis,with biological behavioral characteristics of easy recurrence and metastasis.Drug resistance and toxic side effects currently limit the application and effectiveness of treatments,and there is thus an urgent need to explore new therapeutic drugs and targets.This review summarizes recent progress in studies of TAM in relation to the occurrence,development,and drug resistance of gastric carcinoma,providing new ideas for clinical treatment and prognosis prediction in patients with gastric carcinoma.

Objective To investigate the mechanism of effects of histone deacetylase 3(HDAC3)on re-nal fibrosis in mice with unilateral ureteral obstruction(UUO)by regulating CIC-5.Methods A UUO mouse model was constructed,and intervention was performed on the expression of HDAC3 and CIC-5 in mice.A UUO mouse model was constructed and the mice were divided into the following groups:sham-operated group(Sham group),UUO group(UUO model mice without any treatment),sh-NC group(UUO model mice injec-ted with sh-NC via tail vein),sh-HDAC3 group(UUO model mice injected with sh-HDAC3 via tail vein),HDAC3 overexpression group(UUO model mice injected with HDAC3 overexpression vector via tail vein),and HDAC3+CIC-5 overexpression group(UUO model mice injected with HDAC3 and CIC-5 overexpression vectors via tail vein),with 5 mice in each group.Intervention was performed on the expression of HDAC3 and CIC-5 in the mice.HE staining and Masson staining were used to detect the pathological changes of mouse kidney tissue.The expression of renal fibrosis markers(α-SMA,Collagen-Ⅰ,MMP2)in mouse kidney tissue was detected by RT-qPCR and Western blot.The levels of blood urea nitrogen(BUN)and creatinine(Cr)in the serum of mice were detected by an automatic biochemical analyzer.Results UUO mice showed obvious renal tissue damage and increased fibrosis.The mRNA and protein expression levels of CIC-5 in the renal tis-sue of the UUO group were lower than those in the Sham group,while the mRNA and protein expression lev-els of HDAC3 were higher(P<0.05).The BUN,Cr levels,and the mRNA and protein expression levels of α-SMA,Collagen-I,and MMP2 were higher in the UUO group than in the Sham group(P<0.05).The BUN,Cr levels,and the mRNA and protein expression levels of α-SMA,Collegan-Ⅰ,and MMP2 were lower in the sh-HDAC3 group than in the sh-NC group(P<0.05).The BUN,Cr levels,and the mRNA and protein ex-pression levels of α-SMA,Collegan-Ⅰ,and MMP2 were higher in the HDAC3 group than in the Sham group and UUO group(P<0.05).The BUN,Cr levels,and the mRNA and protein expression levels of α-SMA,Col-legan-Ⅰ,and MMP2 were lower in the HDAC3+CIC-5 group than in the HDAC3 group(P<0.05).Conclu-sion HDAC3 inhibits the expression of CIC-5 by regulating its acetylation,thereby promoting renal fibrosis in UUO mice.Inhibiting the expression of HDAC3 is expected to be an effective way to improve UUO renal fibrosis.

Objective To analyze the serum 25-hydroxy vitamin D[25(OH)D]levels and vitamin D nutri-tional status of 0-14 years old children in Hangzhou,and to provide scientific basis for the prevention of vita-min D deficiency.Methods A total of 26 225 healthy children aged 0 to 14 who were tested in Hangzhou Dian Medical Diagnosis Center from January 1,2021 to December 31,2023 were selected as the study objects.The 25(OH)D levels were detected by direct chemiluminescence method,and the 25(OH)D levels and vitamin D nutritional status of children with different genders,ages and seasons were analyzed and compared.Results The level of 25(OH)D in girls was slightly higher than that in boys,and the difference was statisti-cally significant(P＜0.05).With the increase of age,the level of 25(OH)D continued to decline,and the pro-portion of vitamin D deficiency and vitamin D insufficiency gradually increased.The level of 25(OH)D was the highest in children＜3 years old and the lowest in children 10-14 years old.There was statistical significance in the proportion of vitamin D nutritional status between boys and girls aged 10 to 14(P＜0.05).In the four seasons,children's 25(OH)D level is the highest in spring and the lowest in summer.The difference of 25(OH)D level and vitamin D nutritional status in different seasons was statistically significant(P＜0.05).The proportion of vitamin D deficiency and vitamin D insufficiency in winter was higher than that in other seasons,and the difference was statistically significant(P＜0.05).Conclusion The nutritional status of vitamin D in 0-14 year old children in Hangzhou is good,but the importance of vitamin D supplementation for children should not be ignored,and active publicity and education should be carried out to prevent vitamin D deficiency.

Objective:To predict pre-treatment clinical parameters that are associated with poor response and prognosis to ursodeoxycholic acid (UDCA) in patients with primary biliary cholangitis (PBC) and to use second-line treatment drugs in the early stages to delay the progression of the disease so that patients can benefit from early-stage treatment.Methods:Patients diagnosed with PBC at the Second Affiliated Hospital of Kunming Medical University from 2013 to 2022 were collected. Two hundred fifty-seven cases were screened in accordance with the inclusion and exclusion criteria. The response and prognosis conditions one year after treatment were followed up in outpatient and inpatient departments, as well as through telephone calls. Statistical analyses were performed using t-tests, Mann-Whitney U test, χ2 test, Fisher's exact test, and logistic regression analysis according to different data. Results:A total of 257 PBC cases were included, with 223 females (86.80%) and 34 males (13.20%). Univariate and multivariate binary logistic regression analyses showed that baseline high albumin levels [odds ratio ( OR): 0.882, 95% confidence interval ( CI): 0.805～0.967, P=0.008] were a protective factor for PBC patients' response to UDCA treatment after adjusting for different confounding factors, while baseline high alkaline phosphatase ( OR: 1.012, 95% CI: 1.008～1.016, P<0.001) and baseline high neutrophil/lymphocyte ratio (NLR) level ( OR: 1.462, 95% CI:1.079～1.981, P=0.014) were risk factors for a poor response to UDCA. Trend analysis showed that the baseline NLR quantile was positively correlated with the risk of poor response to UDCA ( OR: 5.512, 95% CI: 1.040～29.216, P=0.045) in patients with PBC. Cox proportional hazards regression analysis identified that age [hazard ratio ( HR): 1.050, 95% CI: 1.019～1.082] and NLR value ( HR:1.089, 95% CI:1.021～1.161) were independent influencing risk factors for all-cause mortality in PBC patients ( P<0.05). Conclusion:Baseline high albumin levels are protective factors against a poor biochemical response to UDCA, while baseline high alkaline phosphatase levels and high NLR are risk factors for a poor biochemical response to UDCA in patients with PBC. Additionally, baseline high NLR values are positively correlated with poor biochemical response to UDCA treatment.

Objective In this paper,CiteSpace(V6.3.R1)was used to sort out and summarize the experimental study on the mechanism and development trend of acupuncture intervention in Alzheimer's disease(AD),so as to provide basis and suggestions for subsequent research.Methods Relevant literatures on the mechanism of acupuncture intervention in AD were retrieved from CNKI database from March 1997 to March 2024.CiteSpace(V6.3.R1)software was used to visually display keywords,draw corresponding maps,and discuss the hot spots of acupuncture intervention mechanism in AD.Results After screening,a total of 397 articles were included in this study.The mechanism of acupuncture intervention in AD mainly focuses on the regulation of synaptic plasticity,regulation of neurotransmitter release,regulation of neuroinflammation,regulation of apoptosis,influence on mitochondrial autophagy,anti-oxidative stress and so on.Conclusion Acupuncture intervention in AD has developed rapidly,involving Notch1/Hes signaling pathway,Shh signaling pathway,NF-κB signaling pathway,PI3K/Akt signaling pathway and other signaling pathways.The research heat of TCM acupuncture intervention in AD continues to rise,and various research teams have harvested rich research results,diversified research hotspots,and in-depth exploration of acupuncture treatment of AD has rich clinical value.

Schizophrenia (SZ) stands as a severe psychiatric disorder. This study applied diffusion tensor imaging (DTI) data in conjunction with graph neural networks to distinguish SZ patients from normal controls (NCs) and showcases the superior performance of a graph neural network integrating combined fractional anisotropy and fiber number brain network features, achieving an accuracy of 73.79% in distinguishing SZ patients from NCs. Beyond mere discrimination, our study delved deeper into the advantages of utilizing white matter brain network features for identifying SZ patients through interpretable model analysis and gene expression analysis. These analyses uncovered intricate interrelationships between brain imaging markers and genetic biomarkers, providing novel insights into the neuropathological basis of SZ. In summary, our findings underscore the potential of graph neural networks applied to multimodal DTI data for enhancing SZ detection through an integrated analysis of neuroimaging and genetic features.
Humans ; Schizophrenia/pathology* ; Diffusion Tensor Imaging/methods* ; Male ; Female ; Adult ; Brain/metabolism* ; Young Adult ; Middle Aged ; White Matter/pathology* ; Gene Expression ; Nerve Net/diagnostic imaging* ; Graph Neural Networks

BACKGROUND: Preclinical studies have indicated that Angong Niuhuang Pills (ANP) reduce cerebral infarct and edema volumes. This study aimed to investigate whether ANP safely reduces cerebral infarct and edema volumes in patients with moderate to severe acute ischemic stroke. METHODS: This randomized, double-blind, placebo-controlled pilot trial included patients with acute ischemic stroke with National Institutes of Health Stroke Scale (NIHSS) scores ranging from 10 to 20 in 17 centers in China between April 2021 and July 2022. Patients were allocated within 36 h after onset via block randomization to receive ANP or placebo (3 g/day for 5 days). The primary outcomes were changes in cerebral infarct and edema volumes after 14 days of treatment. The primary safety outcome was severe adverse events (SAEs) for 90 days. RESULTS: There were 57 and 60 patients finally included in the ANP and placebo groups, respectively for modified intention-to-treat analysis. The median age was 66.0 years, and the median NIHSS score at baseline was 12.0. The changes in cerebral infarct volume at day 14 were 0.3 mL and 0.4 mL in the ANP and placebo groups, respectively (median difference: -7.1 mL; interquartile range [IQR]: -18.3 to 2.3 mL, P = 0.30). The changes in cerebral edema volume of the ANP and placebo groups on day 14 were 11.4 mL and 4.0 mL, respectively ( median difference: 3.0 mL, IQR: -1.3 to 9.9 mL, P = 0.15). The rates of SAE within 90 days were similar in the ANP (3/57, 5%) and placebo (7/60, 12%) groups ( P = 0.36). Changes in serum mercury and arsenic concentrations were comparable. In patients with large artery atherosclerosis, ANP reduced the cerebral infarct volume at 14 days (median difference: -12.3 mL; IQR: -27.7 to -0.3 mL, P = 0.03). CONCLUSIONS: ANP showed a similar safety profile to placebo and non-significant tendency to reduce cerebral infarct volume in patients with moderate-to-severe stroke. Further studies are warranted to assess the efficacy of ANP in reducing cerebral infarcts and improving clinical prognosis. TRAIL REGISTRATION Clinicaltrials.gov , No. NCT04475328.
Aged ; Female ; Humans ; Male ; Middle Aged ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Ischemic Stroke/drug therapy* ; Pilot Projects ; Stroke/drug therapy* ; Treatment Outcome

Objective To explore the efficacy of Yishen Yangyin Gujing Prescription[derived from Zuogui Wan(Bolus for Replenishing Kidney-Yin)]for the treatment of diabetic nephropathy in type 2 diabetes mellitus(T2DM)with qi and yin deficiency syndrome,and to observe its effects on inflammatory responses,pancreatic β-cell function and renal function.Methods A total of 162 T2DM patients with diabetic nephropathy of qi and yin deficiency syndrome who admitted to the Affiliated Hospital of Shaanxi University of Chinese Medicine from May 2020 to July 2023 were randomly divided into an observation group and a control group according to the random number table method,with 81 cases in each group.The control group was given conventional western medicine treatment for lowering blood pressure and renal protection,while the observation group was treated with Yishen Yangyin Gujing Prescription on the basis of treatment for the control group.The course of treatment for the two groups covered 12 weeks.Before and after the treatment,the changes in the outcomes of the two groups were observed,and the outcomes included the total scores of traditional Chinese medicine(TCM)syndrome,insulin sensitivity index,insulin secretion index,24-h urine total protein quantification(24hUTP),and serum levels of glycosylated hemoglobin(HbA1c),fasting insulin(FINS),fasting blood glucose(FBG),serum creatinine(SCr),blood urea nitrogen(BUN),transforming growth factor β1(TGF-β1),NLRP3 inflammasome,interleukin 6(IL-6),superoxide dismutase(SOD)and sphingosine-1-phosphate(S1P).After treatment,the clinical efficacy of the two groups of patients was compared.Results(1)After 12-week treatment,the total effective rate of the observation group was 93.83%(76/81),and that of the control group was 83.95%(68/81).The intergroup comparison showed that the efficacy of the observation group was significantly superior to that of the control group(χ2=9.163,P<0.05).(2)After treatment,the insulin sensitivity index and insulin secretion index in the two groups of patients were increased(P<0.05)and the total scores of TCM syndromes were decreased(P<0.05)when compared with those before treatment,and the increase of insulin sensitivity index and insulin secretion index as well as the decrease of the total scores of TCM syndrome in the observation group was significantly superior to that in the control group(P<0.05).(3)After treatment,the serum levels of HbA1c,FINS,FBG,SCr,BUN and 24hUTP in the two groups of patients were decreased when compared with those before treatment(P<0.05),and the decrease of the above indicators in the observation group was significantly superior to that in the control group(P<0.05).(4)After treatment,the serum TGF-β1,IL-6,and NLRP3 inflammasome levels in the two groups of patients were decreased(P<0.05)and the serum S1P and SOD levels were increased(P<0.05)when compared with those before treatment,and the decrease of serum TGF-β1,IL-6,and NLRP3 inflammasome levels as well as the increase of serum S1P and SOD levels in the observation group was significantly superior to that in the control group(P<0.05).Conclusion For T2DM patients with diabetic nephropathy of qi and yin deficiency syndrome,the combined use of western medicine and Yishen Yangyin Gujing Prescription treatment is helpful to alleviate inflammatory response,improve the function of pancreatic β-cells,regulate the blood glucose level,improve renal function,and enhance the clinical efficacy.

Objective This study aimed to develop an automated method for syndrome element differenti-ation in Traditional Chinese Medicine(TCM).Methods We first constructed and trained an Instruction-tuned Multi-Task TCM text embedding model(Instr-MT-TCM)using four distinct TCM task datasets,including domain knowledge,synonymous terminology,syndrome differentiation and treatment,and TCM case labels.Subsequently,five TCM diagnostics experts holding master's degrees or higher were organized to screen a real-world TCM case dataset and annotate symptoms and signs.The purpose was to evaluate the F1-score of the proposed method—the combination of Instr-MT-TCM and a Large Language Model(LLM)—by comparing its performance against the manual annotation result on the syndrome element differentiation task.Finally,to validate its feasibility in real-world clinical settings,the method was applied to 48 prostate cancer cases to calculate the syndrome element scores.Results The Instr-MT-TCM model showed rapid performance improvement in its early training phase,achieving a Recall@1(R@1)of 0.848.Experts curated a dataset of 1,793 real-world clinical cases,covering 34 common diseases and 66 syndrome patterns.In the syndrome element differentiation task,the collaborative framework of LLM and Instr-MT-TCM achieved a mean F1-score of 0.927,outperforming the 0.512 from manual annota-tion.The syndrome element analysis revealed that the predominant elements of disease nature were fire(heat)and yin deficiency,while the main elements of disease location were bladder and kidney.Conclusion This study proposes and validates a novel method for automated TCM syndrome element dif-ferentiation based on the synergy between LLM and our custom Instr-MT-TCM model.Achieving a high F1-score(0.927)on real-world data,the method demonstrates excellent accuracy and generalization ability.Its application in prostate cancer analysis highlights its significant clinical potential,offering effective technical support,and a new research direction for intelligent TCM syndrome element differentiation.