To address the constrains imposed by insufficient hydrogen peroxide (H2O2) and high glutathione (GSH) expression in tumor cells on the efficacy of chemodynamic therapy (CDT), zeolitic imidazolate framework-8 (ZIF-8) loaded with disulfiram (DSF) and 3-amino-1,2,4-triazole (3-AT) was synthesized via a one-pot approach. Subsequently, hyaluronic acid (HA)-modified cupric peroxide (CuO2) was in-situ grown on its surface through biomineralization to construct a multifunctional copper-based nanozyme ADZCH (3-AT/DSF@ZIF-8@CuO2-HA). This nanoplatform disrupts the intratumoral H2O2 homeostasis, depletes GSH, and synchronously delivers DSF and Cu2+ via cascade catalysis, thereby enhancing CDT and sensitizing tumors to DSF-based chemotherapy. The results of physicochemical characterization indicated that ADZCH presented a uniform core-shell structure with favorable dispersibility. Its particle size and Zeta potential were 196.5 nm and −19.5 mV, respectively. It possessed a microporous structure with a specific surface area of 81.8600 m2/g, and demonstrated efficient loading capacity for DSF and 3-AT, achieving drug loading efficiencies of 5.91% and 45.07%, respectively. Moreover, ADZCH can continuously and slowly release drugs in an acidic environment and maintain good stability under diverse physiological conditions. In vitro functional assays verified that ADZCH catalytically generated H2O2 and hydroxyl radicals while concurrently depleting GSH in a concentration- and incubation time-dependent manner. Cellular uptake experiments showed that HA modification significantly improved the uptake of nanoparticles by 4T1 cells. Cytotoxicity tests showed that 80 μg/mL ADZCH had a significant cytotoxic effect on 4T1 cells but no significant toxicity on L929 cells. DCFH-DA probe detection indicated that ADZCH could significantly induce intracellular reactive oxygen species (ROS) generation, thereby enhancing CDT efficacy. Live/dead staining experiments showed that ADZCH efficiently induced apoptosis, with the proportion of dead cells reaching 94.74%, demonstrating its promising potential for anti-tumor applications.This study provides new research ideas and experimental basis for overcoming the tumor microenvironment barrier and enhancing the anti-tumor effect of CDT combined with chemotherapy.

Abstract Obesity in children and adolescents is closely associated with cardiometabolic risk factors. Body mass index (BMI) is currently a widely used indicator for assessing obesity. However, it has limitations, such as reduced validity during growth and development and the inability to distinguish between fat and muscle mass. In recent years, the tri-ponderal mass index (TMI) has gained attention because of its relative stability during adolescence and its ability to more specifically reflect body fat levels. The review systematically summarizes recent research progress on the use of TMI in predicting body fat levels and cardiometabolic risk factors in children and adolescents, indicating that TMI performs well in assessing body fat during adolescence and is superior or non-inferior to BMI in predicting cardiometabolic risk. However, the predictive ability of TMI is influenced by age, sex, and population differences, and unified diagnostic cutoffs have not yet been established. Future prospective cohort studies are needed to further validate the predictive value of TMI and establish population specific reference cutoffs.

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 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.

Hepatocellular carcinoma(HCC),as the most common type of liver cancer,poses a significant threat to global public health due to its high incidence and mortality rates.This paper delves into the etiology,pathogenesis,and syndrome differentiation of liver cancer from the perspective of"dispersing qi and fortifying the body resistance",based on the clinical experience of renowned traditional Chinese medicine(TCM)practitioner,Prof.Changquan Ling.Prof.Ling believes that the development of liver cancer is closely related to the disruption of liver qi flow,the accumulation of blood stasis over time,and the generation of toxin from long-term stagnation,accompanied by pathological changes such as imbalance of yin and yang,deficiency of the body's vital qi and accumulation of pathogenic factors,and internal blazing of cancer toxins.In terms of treatment,he emphasizes the principles of dispersing qi and fortifying the body resistance,addressing both the root cause and symptoms.This is achieved by regulating the functions of viscera,improving the stagnation of qi flow,and supplemented by methods such as clearing heat and detoxifying,and softening and dispersing hard masses,aiming to break the vicious cycle of qi stagnation,deficiency of vital qi,and pathogenic factor generation,thereby promoting the recovery from the disease.Through detailed analysis of clinical cases,this paper demonstrates Prof.Ling's unique insights and significant efficacy in treating liver cancer through"dispersing qi"to"fortify the body resistance",ultimately achieving"tumor suppression".This provides new references and perspectives for the clinical diagnosis and treatment of liver cancer in TCM.

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.

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 To investigate the predictive value of dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI)radiomics combined with Magee equation 3(ME3)for pathological response following neoadjuvant chemotherapy(NAC)in patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative(HR+/HER2-)breast cancer.Methods A ret-rospective analysis was performed on 325 breast cancer patients diagnosed with HR+/HER2-in two hospitals.Patients from the first hospital were randomly divided into training and internal validation sets at a ratio of 7∶3.Patients from the second hospital served as external validation set.The volume of interest(VOI)of breast cancer was delineated on DCE-MRI images.Then the rele-vant radiomics features were extracted and selected,and the Radiomics score(Radscore)was calculated.The statistically significant clinical and pathological features and Radscore were incorporated into a multivariate analysis.The combined radiomics-clinical model and nomogram were established,and the prediction performance was evaluated by using the receiver operating characteristic(ROC)curve,calibration curve,and decision curve analysis(DCA).Results In the training set,seven radiomics features were selected to construct the radiomics model.ME3 score emerged as the independent factor for pathological complete response(pCR)(P＜0.001).By integrating ME3 score and Radscore,a combined radiomics-clinical model was developed.This model demonstrated robust predictive accuracy,with area under the curve(AUC)of 0.88[95％confidence interval(CI)0.80-0.95],0.90(95％CI 0.82-0.98),and 0.82(95％CI 0.70-0.93)in the training,internal validation,and external validation sets,respectively.The nomogram construc-ted from the combined model exhibited excellent discrimination and calibration,with P-values of 0.455,0.312 and 0.062 in the train-ing,internal validation,and external validation sets.Conclusion DCE-MRI radiomics combined with ME3 can be used to predict the pathological response of NAC in HR+/HER2-breast cancer.

Objective:To explore the factors that tend to lead to a low normal fertilization rate in spindle transfer of mouse oocytes and its strategies.Methods:Oocytes in metaphase Ⅱ (MⅡ) of C57BL/6 and ICR strains mouse were obtained for observations of mitochondrial replacement operations. Spindle karyoplasts of three different sizes (large, medium, small) were isolated by micromanipulation, and their morphology was observed under bright field and polarized light at 0 min, 10 min, 20 min and 30 min after suction. For small spindle karyoplasts, 2% paraformaldehyde fixation was performed after 10 min, 20 min and 30 min respectively, and the morphology of spindle and chromosomes was observed after immunofluorescence staining. Intracytoplasmic sperm injection (ICSI) was performed on oocytes, followed by small spindle karyoplasts isolation, and then fusion was conducted after 30 min (traditional method), 10 min (modified method 1) and 0 min (modified method 2) respectively. ICSI-oocytes without spindle transfer were used as control group, and 14-16 h later, the fertilization of reconstructed oocytes was observed and statistically analyzed.Results:1) When spindle karyoplast was just retrieved (0 min), the karyoplast membrane was smooth and complete, and the spindle showed a normal spindle shape. After 10 min, 20 min and 30 min of suction, the karyoplast membrane was twisted or elongated with an irregular morphology, and the spindle was also twisted, stretched or scattered with a weaker brightness. And the smaller spindle karyoplast, the more serious the deformation was. 2) When the spindle was just taken out (0 min), immunofluorescence staining showed that the spindle was in a standard spindle shape, and the chromosomes were regularly and neatly arranged on the equatorial plate. With the prolongation of placement time, spindles were elongated and tapered or dumbbell-shaped, and chromosomes were scattered and irregularly arranged. 3) For the traditional method of spindle transfer, the normal fertilization rate of C57BL/6 mouse reconstructed oocytes was 63.16% (24/38), which was statistically different from that of control group ( P=0.002). The normal fertilization rate [68.00% (34/50)] in the modified method 1 group was significantly lower than that in control group [90.00% (36/40), P=0.019], but there was no statistical difference with the traditional method ( P=0.260). However, the normal fertilization rate [82.50% (33/40)] in the modified method 2 group was similar to control group ( P=0.422), and was significantly higher than that of the traditional method group ( P=0.010). Conclusion:The longer the spindle karyoplast of mouse oocytes is stayed after retrieval, the more serious the morphological changes, the more unstable the spindles and chromosomes, and the lower normal fertilization rate. Immediate fusion of spindle karyoplast after isolation is the best time for mitochondrial replacement micromanipulation.

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.