ObjectiveTo observe the clinical efficacy of Gandou Fumu Granules （GDFMG） combined with sodium dimercaptosulphonate （DMPS） on liver fibrosis in Wilson disease （WD） patients with the syndrome of phlegm and blood stasis， evaluate its effect on cuproptosis-related indicators， and explore the possible mechanisms of cuproptosis in WD-related liver fibrosis. MethodsSixty WD patients diagnosed with the syndrome of phlegm and blood stasis between January 2023 and December 2023 were randomly divided into a control group and an observation group， with 30 patients in each group. The control group received the copper chelator DMPS for the first 6 days， followed by calcium gluconate injection for the next 2 days， completing an 8-day treatment cycle. The observation group received GDFMG in addition to the treatment regimen of the control group， with both groups treated for 21 cycles. A Beckman fully automated biochemical analyzer was used to detect levels of type Ⅳ collagen （CⅣ）， hyaluronic acid （HA）， laminin （LN）， N-terminal propeptide of type Ⅲ procollagen （PⅢ-NP）， and serum copper （SCu） before and after treatment in both groups. Enzyme-linked immunosorbent assay （ELISA） was used to measure levels of ferredoxin 1 （FDX1）， lipoic acid synthetase （LIAS）， and dihydrolipoamide S-acetyltransferase （DLAT）. Atomic absorption spectroscopy measured 24-hour urine copper levels before treatment and after the 7， 14， and 21 treatment cycles in both groups. An Fibro Touch （FT） non-invasive liver fibrosis diagnostic device was used to measure liver stiffness （LSM） in both groups before and after treatment. Traditional Chinese medicine syndrome score （TCMSS） was evaluated at the same intervals. Clinical efficacy， adverse events， and safety indicators were also compared. ResultsAfter treatment， levels of CⅣ， HA， LN， and PⅢNP significantly decreased in both groups compared to pre-treatment levels （P<0.01）. The observation group showed a more pronounced reduction compared to the control group （P<0.05）. There were no statistically significant differences in SCu levels in both groups before and after treatment. After treatment， levels of FDX1，LIAS and DLAT significantly increased in both groups（P<0.01）. The observation group showed more notable improvements in these indicators than the control group （P<0.05）. After the 7， 14， 21 treatment cycles， 24-hour urine copper levels significantly increased in both groups compared to pre-treatment levels （P<0.01）. The observation group had a greater increase in 24-hour urine copper levels than the control group after treatment （P<0.05，P<0.01）， and although 24-hour urine copper levels increased after 7 cycles， a gradual decline was observed in subsequent cycles. After treatment， LSM levels significantly decreased in both groups compared to pre-treatment levels （P<0.01）， with the observation group showing a greater reduction than the control group （P<0.05）. Clinical efficacy was significantly better in the observation group than the control group （P<0.05）. No significant differences in the incidence of adverse events or safety indicators were observed between the two groups after treatment. ConclusionGDFMG combined with DMPS can reduce LSM in WD patients with liver fibrosis and the syndrome of phlegm and blood stasis， inhibit cuproptosis， and improve clinical efficacy.

ObjectiveTo observe the clinical effectiveness and safety of Xiaozhong Zhitong Mixture （消肿止痛合剂） combined with antibiotic bone cement in the treatment of diabetic foot ulcer （DFU） with damp-heat obstructing syndrome. MethodsA total of 72 DFU patients with damp-heat obstructing syndrome were randomly assigned to treatment group （36 cases） and the control group （36 cases）. Both groups received standard treatment and topical antibiotic bone cement for ulcer wounds， while the treatment group received oral Xiaozhong Zhitong Mixture （50 ml per time， three times daily） in additionally. Both groups underwent daily wound dressing changes for 21 consecutive days. Ulcer healing rate， serum levels of tumor necrosis factor-alpha （TNF-α）， interleukin-1 beta （IL-1β）， malondialdehyde （MDA）， superoxide dismutase （SOD）， C-reactive protein （CRP）， and white blood cell （WBC） count were observed before and after treatment， and visual analog scale （VAS） scores for wound pain， traditional Chinese medicine （TCM） syndrome scores， and the DFU Healing Scale （DMIST scale） were also compared. Liver and kidney function were evaluated before and after treatment， and adverse events such as allergic reactions， worsening ulcer pain were recorded. ResultsTotally 35 patients in the treatment group and 33 in the control group were included in the final analysis. The ulcer healing rate in the treatment group was （87.93±9.34）%， significantly higher than （81.82±12.02）% in the control group （P = 0.035）. Compared to pre-treatment levels， both groups showed significant reductions in serum CRP， WBC， MDA， IL-1β， and TNF-α levels， with an increase in SOD level （P＜0.05）. TCM syndrome scores， VAS， and DMIST scores also significantly decreased in both groups （P＜0.05）， with greater improvements in the treatment group （P＜0.05）. No significant adverse reactions were observed in either group during treatment. ConclusionXiaozhong Zhitong Mixture combined with antibiotic bone cement has significant advantages in promoting DFU healing， reducing inflammatory response， and alleviating oxidative stress in DFU patients with damp-heat obstructing syndrome， with good safety for DFU patients with damp-heat obstructing syndrome.

Objective To explore the feasibility of automatic segmentation of clinical target volume(CTV)and organs at risk(OARs)for cervical cancer using AccuLearning(AL)based on geometric and dosimetric indices.Methods Seventy-five CT localization images with manual contouring data of postoperative cervical cancer were enrolled in this study.Sixty cases were randomly selected to trained to generate automatic segmentation model by AL,and the CTV and OARs of the remaining 15 cases were automatically contoured.Radiotherapy plans on the automatic segmentation contours were imported on the CT images of manual contours.The efficiency,Dice similarity coefficient(DSC),Hausdorff distance(HD)and dosimetric parameters were compared between the two methods.Results The time of automatic segmentation was significantly shorter than that of the manual contour(P<0.05).The DSC of all structures were≥0.87.The HD of bowel bag and rectum were about 10 mm,and that of the rest of OARs were less than 5 mm.CTV(D98,V90% ,V95% ,Dmean,HI),bowel bag(V50)and bladder(V50)had significant differences in dosimetric comparison(P<0.05).Conclusion The automatic segmentation model based on AL can improve the efficiency of radiotherapy.Automatic segmentation of OARs has the potential of clinical application,while that of CTV still needs to be further modified.

Objective To explore the effects of simethicone on gastrointestinal hormones,intestinal floras and inflammatory process mediated by NOD-like receptor protein 3(NLRP3)inflammasome in patients with irritable bowel syndrome(IBS).Methods A total of 120 patients with IBS admitted to the hospital were prospectively enrolled as the research objects between January 1,2021 and December 31,2022,and they were randomly divided into control group(60 cases)and treatment group(60 cases).The control group was treated with compound eosinophil-Lactobacillus,while treatment group was additionally treated with simethicone.The curative effect after treatment,scores of gastrointestinal symptom rating scale(GSRS),levels of somatostatin(SS),vasoactive intestinal peptide(VIP),NLRP3 inflammasome,interleukin-8(IL-8)and interleukin-1β(IL-1β),counts of intestinal floras before and after treatment,and safety during treatment were compared between the two groups.Results After treatment,total response rate of treatment group was higher than that of control group(91.67% vs.76.67% ,P<0.05).After treatment,GSRS scores in both groups were decreased,which were lower in treatment group than control group(P<0.05).After treatment,levels of SS and VIP in both groups were decreased,which were lower in treatment group than control group(P<0.05).After treatment,counts of eosinophil-Lactobacillus and Bifidobacteria were increased in both groups,the difference was statistically significant(P<0.05),but there was no significant difference in counts of intestinal floras between the two groups(P>0.05).After treatment,levels of NLRP3 inflammasome,IL-8 and IL-1β were decreased in both groups,the difference was statistically significant(P<0.05),but there was no significant difference between the two groups(P>0.05).During treatment,there was no significant difference in side effects between the two groups(P>0.05).Conclusion Simethicone can significantly improve response rate of treatment,improve gastrointestinal symptoms and gastrointestinal hormones in IBS patients,which has no significant effects on intestinal floras and inflammatory process mediated by NLRP3 inflammasome,with good safety.

Objective To explore the correlation between intestinal dose and acute radiation enteritis(ARE)in patients with cervical cancer received concurrent chemoradiotherapy,and optimize the dose limit of intestinal tissue.Methods 158 cervical cancer patients received concurrent chemoradiotherapy from 2014 to 2019 were selected in this study.According to CTCAE 5.0,patients with ARE≥grade 2 were classified as ARE≥grade 2 group,otherwise classified as ARE0.7,P<0.05).Conclusions For patients with cervical cancer received concurrent chemoradiotherapy,the dose of bowelbag V5 and V40 should be considered to rationally optimize the dose of bowelbag in the radiotherapy plan,so as to reduce the incidence of ARE≥grade 2.

Polyunsaturated fatty acids (PUFAs) have diverse health-promoting effects, such as potentially protecting in immune, nervous, and cardiovascular systems by targeting a variety of sites, including most ion channels. Voltage-gated potassium channels of the K_V7 family and large-conductance Ca²⁺- and voltage-activated K⁺ (BK_Ca) channels are expressed in many tissues, therefore, their physiological importance is evident from the various disorders linked to dysfunctional K_V7 channels and BK_Ca channels. Thus, it is extremely important to learn how potassium channels are regulated by PUFAs. The aim of this review is to provide an overview of the effects of PUFAs on K_V7 channels and BK_Ca channels functions, as well as the mechanisms underlying these effects. In summarizing reported effects of PUFAs on K_V7 and BK_Ca channels mediated currents, we generally conclude that PUFAs increase the current amplitude, meanwhile, differential molecular and biophysical mechanisms are associated with the current increase. In K_V7 channels the currents increasement are associated with a shift in the voltage dependence of channel opening and increased maximum conductance in K_V7 channels, while in BK_Ca channels, they are associated with destabilization the pore domain closed conformation. Furthermore, PUFA effects are influenced by auxiliary subunits of K_V7 and BK_Ca channels, associate with channels in certain tissues. although findings are conflicting. A better understanding of how PUFAs regulate K_V7 and BK_Ca channels may offer insight into their physiological regulation and may lead to new therapeutic strategies and approaches.

Tumor is one of the major diseases that endanger people’s health. At present, the treatments used for tumor include surgery, chemotherapy, radiotherapy and so on. Nonetheless, the traditional treatments have some disadvantages, such as insufficient treatment effect, liable to cause multidrug resistance, toxicity and side effect. Further research and exploration of tumor treatment schemes are still necessary. As the energy converter of cells, mitochondria are currently considered to be one of the most important targets for the design of new drugs for tumor, cardiovascular and neurological diseases. Nano-drug delivery carriers have the characteristics of being easily modified with active targeting groups, and it can achieve accurate targeted drug delivery to cells and organelles. This paper reviews the application of mitochondrial targeted nanoparticles in tumor diagnosis and treatment from the aspects of inhibiting tumor cell proliferation, promoting tumor cell apoptosis, inhibiting tumor recurrence and metastasis, and inducing cell autophagy.

[Objective] To investigate the functional differences and potential effects of chromatin spatial structure in patients with normal karyotype and complex karyotype multiple myeloma. [Methods] High-throughput chromosome conformational capture (Hi-C) analysis was performed on plasma cells of 1 case with 1q21 complex karyotype and 1 case with normal karyotype multiple myeloma, and the differences in three-dimensional genome structure between the two patients were analyzed, and the transcriptome characteristics of plasma cells were combined to investigate the differential features through gene functional enrichment. [Results] A/B switch occurred in 36% of the chromatin compartments in two cases, and 1 041 genes in patient with complex karyotype had B/A switch. About 3 500 topological association domains (TADs) were identified in each sample, and there was no significant difference. The number of loops identified in complex karyotype sample was 1 069, which was 1/6 of the normal sample, and there were significant differences in the number of three different types of loops, which to some extent reflected the loss of genome stability. Transcriptome analysis showed significant differences in expression profiles between the two patients, and a total of 6 150 differentially expressed genes (3 303 up-regulated genes and 2 847 down-regulated genes) were identified. [Conclusion] Compared with patient with normal karyotype, patient with 1q21 complex karyotype multiple myeloma exhibit significant changes in the spatial structure of plasma cell chromatin at different levels, which leads to changes in gene expression and activation of pathways related to cancer progression.

The etiology of short stature is multifaceted and influenced by various potential factors including genetics，nutrition，endocrine and psychology. Research has shown that psychological factors can contribute to growth disorders，impacting the behavioral，emotional，and neuropsychological well-being of children with short stature. These growth disorders may lead to language problems，social disorders，etc. Additionally，physical limitations and environmental barriers can pose practical challenges in the daily lives of children with short stature，potentially leading to a decrease in their health-related quality of life（HrQoL）. Moreover，growth disorders can increase parental care burden，further impacting their HrQoL. This article offers a literature review on the challenges faced by children with short stature and the neuropsychological implications of various types of short stature.

Objective To explore the role of breast/ovarian cancer susceptibility gene 1 associated protein 1(BAP1)in the occurrence and progression of human malignant glioma and the feasibility of BAP1 as a clinical diagnostic marker for malignant glioma.Methods The differential expression of BAP1 in normal and glioma tissue was analyzed based on the GSE4290 and GSE90598 sub-datasets from the gene expression omnibus(GEO)database.Receiver operating characteristic(ROC)curve analysis was conducted to assess the early diagnostic value of BAP1 for malignant glioma.Primary lesion tissues from 28 nonpaired malignant glioma patients and non-tumor brain tissues removed by internal decompression surgery in 5 patients with traumatic brain injury collected independently were collected,and the expression levels of BAP1 were measured using quantitative real-time polymerase chain reaction(qRT-PCR).Specific small interfering RNAs(siRNAs)targeting BAP1 were transiently transfected into U251 cells to further evaluate their interference efficiency.Flow cytometry was employed to analyze changes in the cell cycle and apoptosis of U251 cells with BAP1 knockdown.Results The results of bioinformatics showed that the expression of BAP1 in malignant glioma tissues was lower than that in normal brain tissues(GSE 4290:1 209±18.49 vs 1 476±53.90,GSE 90598:5.19±0.10 vs 5.65±0.21),and the differences were significant(t=5.115,2.267,all P<0.05).ROC curve showed that BAP1 could efficiently differentiate malignant glioma tissue from normal brain tissue(GSE4290:AUC=0.78,GSE90598:AUC=0.75,all P<0.05).The expression level of BAP1 in primary malignant glioma tissue was lower than that in normal brain tissue(0.27±0.04 vs 1.06±0.07),and the difference was significant(t=10.22,P<0.001).After down-regulating the expression of BAP1 in U251 cells,the proportion of S phase cells increased from 17.59%to 27.21%(siBAP1-1)and 25.79%(siBAP1-2),respectively,and the differences were significant(t=6.576,6.642,all P<0.01).However,the apoptosis levels decreased from 10.17%to 2.70%(siBAP-1)and 3.00%(siBAP-2),respectively,and the differences were significant(t=10.31,9.428,all P<0.01).Conclusion Histone H2A deubiquitinase BAP1 could exert the function of tumor suppressor genes by inhibiting rapid cell cycle progression and promoting apoptosis in malignant glioma,and could serve as a potential clinical diagnostic biomarker for malignant glioma.