Objective To systematically analyze the clinical advantageous diseases and core acupoint combinations of Jin's Three-Needle Therapy,providing data support for its broader clinical application.Methods The relevant literature from the China National Knowledge Infrastructure(CNKI),Wanfang Academic Journal Full-text Database,VIP Chinese Sci-Tech Journal Database,and China Biology Medicine(CBM)database were retrieved,covering all publications since the establishment of Jin's Three-Needle Therapy.A database of acupoint combinations was constructed,and statistical analyses were performed using SPSS Modeler,Cytoscape,Review Manager,Stata,and R software to evaluate literature quality,sensitivity,disease spectrum,therapeutic efficacy,high-frequency acupoint combinations,association rules,and combined therapies.Results A total of 228 eligible studies were included.The results indicate that Jin's Three-Needle Therapy has been applied to 11 disease categories and 63 specific conditions,with post-stroke hemiplegia and autism spectrum disorder identified as its primary advantageous diseases.The Temporal Three-Needle and Four-Spirit Needle emerged as the core acupoint combinations.The overall clinical efficacy rate reached 91.1％,and the therapy was frequently combined with rehabilitation training.Conclusion The unique three-needle prescription pattern of Jin's Three-Needle Therapy demonstrates significant clinical advantages.However,potential publication bias may exist,and further exploration is needed to elucidate its mechanisms and optimize clinical efficacy.

Prostate cancer is the most prevalent malignant tumor among men, ranking first in incidence and second in mortality globally. Novel hormone therapies (NHT) targeting the androgen receptor (AR) pathway have become the standard of care for metastatic prostate cancer. This review offers a comprehensive overview of NHT, including abiraterone, enzalutamide, apalutamide, darolutamide, and rezvilutamide, which have demonstrated efficacy in delaying disease progression and improving patient survival and quality of life. Nevertheless, resistance to NHT remains a critical challenge. The mechanisms underlying resistance are complex, involving AR gene amplification, mutations, splice variants, increased intratumoral androgens, and AR-independent pathways such as the glucocorticoid receptor, neuroendocrine differentiation, DNA repair defects, autophagy, immune evasion, and activation of alternative signaling pathways. This review discusses these resistance mechanisms and examines strategies to counteract them, including sequential treatment with novel AR-targeted drugs, chemotherapy, poly ADP-ribose polymerase inhibitors, radionuclide therapy, bipolar androgen therapy, and approaches targeting specific resistance pathways. Future research should prioritize elucidating the molecular basis of NHT resistance, optimizing existing therapeutic strategies, and developing more effective combination regimens. Additionally, advanced sequencing technologies and resistance research models should be leveraged to identify novel therapeutic targets and improve drug delivery efficiencies. These advancements hold the potential to overcome NHT resistance and significantly enhance the management and prognosis of patients with advanced prostate cancer.

The aim of this study is to determine the effects of Inonotus obliquus polysaccharides on the main organs and hormones of male mice infected with Neosporidium.The animal model of neosporidiosis in BALB/c mice was established.After intragastric administration,the pathological changes of brain,liver and spleen were observed by histopathology,the worm load in brain,liver and spleen was detected by qPCR,and the levels of FSH,LH and T4 in serum of male mice were detected by ELISA.The results showed that compared with the blank control group,granular spherical lesions could be seen in the brain tissue of mice in the model group,with patchy necrosis of hepatocytes,splenic hemorrhage,red pulp hyperemia and a large number of red blood cell infil-tration.Inonotus obliquus polysaccharides can improve the injury of brain,liver,spleen and other organs and tissues.The worm load in the brain of the Inonotus obliquus polysaccharide group was significantly lower than that of the model group on the 14th day and 21st day(P＜0.01),and that of the liver and spleen on the 21st day was significantly lower than that of the model group(P＜0.01).The level of FSH in the model group and Inonotus obliquus polysaccharide group was signif-icantly lower than that in the blank control group(P＜0.05 or P＜0.01),while that in the Inono-tus obliquus polysaccharide group was significantly higher than that in the model group(P＜0.05 or P＜0.01).The level of LH in the model group was significantly higher than that in the blank control group(P＜0.01),while that in the Inonotus obliquus polysaccharide group was significant-ly higher than that in the blank control group on the 7th day and 42nd day(P＜0.05).There was significant difference in T4 level between the model group and the blank group(P＜0.05 or P＜0.01),while the Inonotus obliquus polysaccharide group was similar to the blank control group on the 21st and 35th day(P＞0.05).Inonotus obliquus polysaccharides can improve the damage of Neosporidium on brain,liver and spleen of male rats,reduce the insect load in brain,liver and spleen,regulate the levels of FSH,LH and T4 hormones,and maintain the stability of reproductive system.

The aim of this study is to determine the effects of Inonotus obliquus polysaccharides on the main organs and hormones of male mice infected with Neosporidium.The animal model of neosporidiosis in BALB/c mice was established.After intragastric administration,the pathological changes of brain,liver and spleen were observed by histopathology,the worm load in brain,liver and spleen was detected by qPCR,and the levels of FSH,LH and T4 in serum of male mice were detected by ELISA.The results showed that compared with the blank control group,granular spherical lesions could be seen in the brain tissue of mice in the model group,with patchy necrosis of hepatocytes,splenic hemorrhage,red pulp hyperemia and a large number of red blood cell infil-tration.Inonotus obliquus polysaccharides can improve the injury of brain,liver,spleen and other organs and tissues.The worm load in the brain of the Inonotus obliquus polysaccharide group was significantly lower than that of the model group on the 14th day and 21st day(P＜0.01),and that of the liver and spleen on the 21st day was significantly lower than that of the model group(P＜0.01).The level of FSH in the model group and Inonotus obliquus polysaccharide group was signif-icantly lower than that in the blank control group(P＜0.05 or P＜0.01),while that in the Inono-tus obliquus polysaccharide group was significantly higher than that in the model group(P＜0.05 or P＜0.01).The level of LH in the model group was significantly higher than that in the blank control group(P＜0.01),while that in the Inonotus obliquus polysaccharide group was significant-ly higher than that in the blank control group on the 7th day and 42nd day(P＜0.05).There was significant difference in T4 level between the model group and the blank group(P＜0.05 or P＜0.01),while the Inonotus obliquus polysaccharide group was similar to the blank control group on the 21st and 35th day(P＞0.05).Inonotus obliquus polysaccharides can improve the damage of Neosporidium on brain,liver and spleen of male rats,reduce the insect load in brain,liver and spleen,regulate the levels of FSH,LH and T4 hormones,and maintain the stability of reproductive system.

Objective:To investigate the efficacy and safety of daratumumab (Dara) - combination regimens for newly diagnosed multiple myeloma (NDMM).Methods:A retrospective case series study was conducted. The clinical data of 34 patients with NDMM receiving treatment regimen including Dara from Qilu Hospital of Shandong University, Yantai Yuhuangding Hospital, Huangdao Branch of Affiliated Hospital of Qingdao University and Taian City Central Hospital between April 2020 and March 2022 were retrospectively collected. The efficacy, survival and adverse reactions of patients were analyzed. Cox proportional risk model was used to analyze the factors affecting overall survival (OS) and minimal residual disease (MRD) turning negative.Results:Among 34 patients with NDMM, there were 19 males and 15 females, with 21 cases aged < 65 years and 13 cases aged ≥65 years. The median follow-up duration [ M ( Q1, Q3)] was 22 months (19 months, 26 months), the median of Dara treatment cycles was 7 (5, 11), and the overall response rate (ORR) reached 97.1% (33/34). There were statistically significant differences in the optimal efficacy of patients stratified by receiving hematopoietic stem cell transplantation or not and receiving different treatment cycles (all P ≤ 0.05), while there were no statistically significant differences in patients stratified by other clinical features (all P > 0.05). The 1-year progression-free survival rate was 79.4% and the 1-year OS rate was 94.1%. Multivariate Cox regression analysis showed that the cycle number of treatment regimens containing Dara was an independent influencing factor of MRD turning negative (6 cycles vs. 2 cycles, HR = 0.267, 95% CI: 0.076-0.935, P = 0.039); age ≥ 65 years was an independent risk factor for OS ( HR = 35.313, 95% CI: 1.709-729.669, P = 0.021). The incidence of hematological adverse reactions grade 3 or above was 20.6% (7/34), and the non-hematological adverse reactions primarily included infection [44.1% (15/34)] and edema of extremity and trunk [41.2% (14/34)]. Conclusions:The Dara-based regimens for NDMM exhibit a high ORR. The remission depth accelerated with the increasing number of treatment cycle, and the adverse reactions are mild.

The maintenance of hematopoietic stem cells (HSCs) is a complex process involving numerous cell-extrinsic and -intrinsic regulators. The first member of the cyclin-dependent kinase family of inhibitors to be identified, p21, has been reported to perform a wide range of critical biological functions, including cell cycle regulation, transcription, differentiation, and so on. Given the previous inconsistent results regarding the functions of p21 in HSCs in a p21-knockout mouse model, we employed p21-tdTomato (tdT) mice to further elucidate its role in HSCs during homeostasis. The results showed that p21-tdT+ HSCs exhibited increased self-renewal capacity compared to p21-tdT- HSCs. Zbtb18, a transcriptional repressor, was upregulated in p21-tdT+ HSCs, and its knockdown significantly impaired the reconstitution capability of HSCs. Furthermore, p21 interacted with ZBTB18 to co-repress the expression of cKit in HSCs and thus regulated the self-renewal of HSCs. Our data provide novel insights into the physiological role and mechanisms of p21 in HSCs during homeostasis independent of its conventional role as a cell cycle inhibitor.
Animals ; Hematopoietic Stem Cells/cytology* ; Cyclin-Dependent Kinase Inhibitor p21/genetics* ; Mice ; Cell Self Renewal ; Repressor Proteins/genetics* ; Mice, Inbred C57BL ; Mice, Knockout ; Humans ; Gene Expression Regulation

Objective:To provide theoretical basis for the relevant mechanisms in diabetic retinopathy by bioinformatics methods.Methods:Proliferative diabetic retinopathy(PDR)datasets GSE60439 and GSE94019 were screened through GEO database.Expres-sion data of GSE60439 dataset was extracted using R language,and the differential genes were determined,with the screening condi-tions of P<0.05 and|log2FC|≥1;WGCNA was used to select the important modules related to PDR in GSE94019 dataset;key genes were obtained by intersecting differential genes and genes in important modules.Key genes were subjected to GO and KEGG enrich-ment analysis;PPI network was constructed to identify high-risk key proteins.Finally,CIBERSORTx was used to analyze the infiltra-tion of immune cells in PDR,and Pearson correlation analysis was used to screen key genes related to immune cells as core genes.Results:Three core genes were finally obtained,namely Col1a1,Col1a2 and Col3a1,their expressions were positively correlated with M2 macrophages,and the core genes were enriched in the AGEs-RAGE signaling pathway.Conclusion:Positive feedback may be formed between M2 macrophages,AGEs-RAGE signaling pathway and collagen genes(Col1a1,Col1a2,Col3a1),even without the stimulation of high glucose,this vicious circle may continue to damage retinal tissue.

Objective To establish the analysis method of 13 Paralytic shellfish toxins(PSTs)in human whole blood by high-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS).Methods 13 kinds of PSTs were extracted from the whole blood using acetonitrile with 1%acetate(1︰3,v︰v)solution,and separated by UPLC BEH Amide chromatographic column(100mm×2.1mm,1.7μm).The samples were detected by an electrospray ionization source(ESI)and positive and negative ion multiple reaction monitoring(MRM)mode,and quantified by matrix matching curve external standard method.Results The results showed that 13 kinds of PSTs in blood samples were linear well in the ranges of 1～100 ng/mL,with the correlation coefficient(r2)>0.995.The limit of detection(LODs)of the method were 0.5～2 ng/mL,the limit of quantitation(LOQs)were 1～4 ng/mL,and the recoveries of the method were 65.55%～114.12%.Conclusion The method is highly sensitive,reproducible,and can qualify and quantify thirteen toxins at the same time,which is suitable for the rapid detection of PSTs in whole blood samples.

Shegan Mahuang Decoction is a classic formula for the treatment of asthma, which has the efficacy of dissipating cold and reducing phlegm, relieving cough and relieving asthma, and can be used clinically alone to control acute attacks, or to assist Western medical methods to improve the efficacy, and can also to combine with other classical prescriptions for the pathogenesis, which can improve the symptoms of cough and asthma, expectoration, and lung function indexes. The mechanism of Shegan Mahuang Decoction in the treatment of asthma is mainly related to reducing inflammatory response and inhibiting airway remodeling, and it mainly regulates immune inflammatory pathways to play a role.

We reported a 54-year-old female patient with severe tricuspid regurgitation, who received mechanic valve in the mitral position 15 years ago. The patient’s Society of Thoracic Surgeons score was 8.27%, and was intolerant to open heart surgery, so she was recommended for transcatheter tricuspid valve replacement via right vena jugularis interna. The procedures were guided by echocardiography and X ray fluoroscopy on November 13, 2021, the prosthesis was implanted successfully, and the patient was recoved without any adverse events. After 1 month follow-up, her general condition was apparently improved.