Objective: To investigate the effects and mechanisms of Astragalus Polysacharin(APS) on the proliferation and metastasis of breast cancer cells by regulating miR-107 and miR-346-mediated macrophage polarization in breast cancer-derived exosomes. Methods: Forty 8-week-old female BALB/c mice were selected and breast cancer xenograft models and 4T1 transplanted tumor models were established. The mice were divided into the control group and the APS group. The APS group mice received daily intragastric administration of APS for 25 days, while the control group mice were given the same amount of normal saline. After all treatments were completed, the mice were euthanized, and tumor tissues were isolated. Western blot and flow cytometry were used to detect the expressions of proliferating cell nuclear antigen(PCNA), Ki-67, CD206, CD163, inducible nitric-oxide synthase(iNOS), and CD86. The apoptosis of single-cell suspensions in tumor tissues was analyzed. Human breast cancer cell line MDA-MB-231 was cultured and stimulated with APS, and exosomes from the cell culture medium were collected. The proliferation, migration, and invasion of cells were detected by CCK-8 assay, scratch assay, permeability chamber cell invasion assay, and qRT-PCR. Differentially expressed genes were screened by bioinformatics. Results : By measuring the expressions of molecules related to breast cancer cell proliferation and metastasis, it was shown that APS treatment reduced the expressions of proliferation-related proteins(PCNA and Ki-67) and metastasis-related proteins(Vimentin) in MDA-MB-231 xenograft tumor tissues; and the polarization of tumor-associated macrophages was observed. APS treatment of 4T1 transplanted tumor tissues could reduce the number of M2 macrophages and increase the number of M1 macrophages, resulting in a decrease in the ratio of M2/M1 macrophages and an increase in cell apoptosis in 4T1 transplanted tumor tissues. The expressions of related proteins iNOS and CD86 increased, and CD206 and CD163 decreased. After APS treatment, the exosomes produced by MDA-MB-231 reduced the polarization of M2 macrophages and affected the expressions of miR-107 and miR-346. Conclusion APS inhibits the polarization of M2 macrophages by regulating the expression of miR-107 or miR-346 in breast cancer cell-derived exosomes, ultimately inhibiting the proliferation and metastasis of breast cancer cells.

A 35-year-old female patient with advanced lung cancer was treated with paclitaxel(albumin-bound)and carboplatin chemotherapy,combined with tislelizumab immunotherapy for one cycle.After 6 days of treatment,the patient developed sagging of the right eyelid compared to the leftside,mild morning and heavy evening,systemic muscle soreness,abnormal transaminases and myocardial enzymes,and abnormal electrocardiogram.It is suspected that there may be a correlation between tislelizumab and myasthenia gravis or related myositis.After admission,patients were treated with methylprednisolone,intravenous immunoglobulin,plasma exchange,mycophenolate mofetil,temporary pacemaker installation,and tracheal intubation.After more than a month of treatment,the patient's indicators decreased,but the patient became unconscious,the patient's family requested discharge.The association between the multisystem adverse reactions and tislelizumab was evaluated using the Naranjo's Assessment Scale,the correlation score was 7 and evaluated as probably relevant.It is suggested that when using tislelizumab in clinical practice,risk factor assessment and medication monitoring should be strengthened to ensure drug safety.

A 55-year-old male patient received immunotherapy combined with chemotherapy regimen(intravenous infusions of tislelizumab 200 mg on day 1, paclitaxel protein-bound 470 mg, and carboplatin 500 mg on day 1) after surgery for left upper lung squamous cell carcinoma, with 21 days as a treatment cycle. After more than half a month of medication in the 1st cycle, the patient developed multiple symmetrical purple red bruises on both lower limbs, which did not fade when pressed. The purple red bruising disappeared the next day after treatment with anti-allergic drugs. After 3 days of medication in the 3rd cycle, the patient developed a large number of scattered red papules on both lower limbs, protruding from the surface of the skin and accompanied by itching, a small number of red papules were scattered on both upper limbs and the face; after 15 days, the patient felt poor appetite; after 16 days, the patient experienced abdominal pain accompanied by vomiting and loose yellow stool. Laboratory tests showed a blood creatinine level of 204 μmol/L and occult blood in urine (+++). Pathological examination of skin tissue at the lesion site of the patient suggested IgA vasculitis (IgAV). After excluding other factors such as primary disease and infection, it was considered that the IgAV was probably related to tislelizumab. Tislelizumab was discontinued, anti-allergic and anti-inflammatory drugs, and glucocorticoid were given. After 2 weeks of treatments, the skin purpura gradually disappeared, and the abdominal pain and renal function indicators were improved. After fully aware of the risks, the patient was restarted tislelizumab immunotherapy combined with chemotherapy, and anti-allergic drugs were add at the same time. IgVA did not recur.

A 35-year-old female patient with advanced lung cancer was treated with paclitaxel(albumin-bound)and carboplatin chemotherapy,combined with tislelizumab immunotherapy for one cycle.After 6 days of treatment,the patient developed sagging of the right eyelid compared to the leftside,mild morning and heavy evening,systemic muscle soreness,abnormal transaminases and myocardial enzymes,and abnormal electrocardiogram.It is suspected that there may be a correlation between tislelizumab and myasthenia gravis or related myositis.After admission,patients were treated with methylprednisolone,intravenous immunoglobulin,plasma exchange,mycophenolate mofetil,temporary pacemaker installation,and tracheal intubation.After more than a month of treatment,the patient's indicators decreased,but the patient became unconscious,the patient's family requested discharge.The association between the multisystem adverse reactions and tislelizumab was evaluated using the Naranjo's Assessment Scale,the correlation score was 7 and evaluated as probably relevant.It is suggested that when using tislelizumab in clinical practice,risk factor assessment and medication monitoring should be strengthened to ensure drug safety.

A 55-year-old male patient received immunotherapy combined with chemotherapy regimen(intravenous infusions of tislelizumab 200 mg on day 1, paclitaxel protein-bound 470 mg, and carboplatin 500 mg on day 1) after surgery for left upper lung squamous cell carcinoma, with 21 days as a treatment cycle. After more than half a month of medication in the 1st cycle, the patient developed multiple symmetrical purple red bruises on both lower limbs, which did not fade when pressed. The purple red bruising disappeared the next day after treatment with anti-allergic drugs. After 3 days of medication in the 3rd cycle, the patient developed a large number of scattered red papules on both lower limbs, protruding from the surface of the skin and accompanied by itching, a small number of red papules were scattered on both upper limbs and the face; after 15 days, the patient felt poor appetite; after 16 days, the patient experienced abdominal pain accompanied by vomiting and loose yellow stool. Laboratory tests showed a blood creatinine level of 204 μmol/L and occult blood in urine (+++). Pathological examination of skin tissue at the lesion site of the patient suggested IgA vasculitis (IgAV). After excluding other factors such as primary disease and infection, it was considered that the IgAV was probably related to tislelizumab. Tislelizumab was discontinued, anti-allergic and anti-inflammatory drugs, and glucocorticoid were given. After 2 weeks of treatments, the skin purpura gradually disappeared, and the abdominal pain and renal function indicators were improved. After fully aware of the risks, the patient was restarted tislelizumab immunotherapy combined with chemotherapy, and anti-allergic drugs were add at the same time. IgVA did not recur.

To summarize the clinical experience of the diagnosis and treatment of Hashimoto's thyroiditis based on the theory of "loss of nourishment in bright essence". It is believed that damages of the seven emotions and loss of nourishment in bright essence are the root cause of Hashimoto's thyroiditis， so the overall therapeutic principle was proposed as fortifying brain and tranquillizing mind. For patients with Hashimoto's thyroiditis combined with hypothyroidism， the self-prescribed Jiaan Mixture Formula （甲安合剂） with modification is used to fortify brain and tranquillize mind， emolliate the liver and nourish the kidneys； for patients with Hashimoto's thyroiditis combined with hyperthyroidism， the self-prescribed Xinnao Kang Formula （心脑康） with modification is used to fortify brain and tranquillize mind， boost qi， invigorate blood， and unblock the collaterals； and for patients with Hashimoto's thyroiditis combined with nodularity， the self-prescribed Xiaopi Shu Formula （消癖舒） with modification is used to boost qi and nourish yin， and invigorate blood and dissipate masses.

Objective To compare the contents of alkaloid in Aconiti Kusnezoffii Radix with different degrees of processing and their effects on electrocardiogram and vagus nerve action potential in SD rats;To establish a toxicity evaluation method for Aconiti Kusnezoffii Radix and its processed products.Methods HPLC was used to determine the contents of six alkaloid components,including benzoyl neoaconitine,benzoyl aconitine,benzoyl subeaconitine,neoaconitine,subeaconitine and aconitine in Aconiti Kusnezoffii Radix and Aconiti Kusnezoffii Radix Cocta of soaking and boiled for 30 minutes,boiled for 4 h without soaking,soaking and boiled for 4 h,and soaking and boiled for 8 h.SD rats were subjected to sublingual drainage with Aconiti Kusnezoffii Radix and four types of processed products.The vagus nerve action potential and electrocardiogram of rats before and after administration were recorded,and the correlation analysis between alkaloid content and vagus nerve action potential and heart rate was conducted.Results The contents of alkaloid of the four processed products showed that the content of diester alkaloids was soaking and boiled for 30 min>boiled for 4 h without soaking>soaking and boiled for 4 h>soaking and boiled for 8 h;monoester alkaloid content:boiled for 4 h without soaking>soaking and boiled for 30 min>soaking and boiled for 4 h>soaking and boiled for 8 h.After the administration of each sample,compared with the basal discharge,the vagus nerve discharge of rats with different processed products was changed by sublingual administration,heart rate increased,the degree of arrhythmia increased,and it varied with the degree of processing;the results of correlation analysis showed that there was a significant correlation between the nerve discharge area and the contents of diester alkaloids and total alkaloids.Conclusion The action potential of the vagus nerve and electrocardiogram of rats after sublingual drainage administration can reflect the degree of numbness in the tongue,which can provide reference for the study of tongue sensation of Aconiti Kusnezoffii Radix.

During the process of dairy farming,various factors such as physical injury and bacterial infection act upon body tissues or organs,leading to the disruption of skin or mucous tissue integ-rity and subsequent tissue injury and trauma.The healing of these injuries is a complex process that necessitates the coordinated efforts of different cells and involvement of diverse cytokines.A-mong them,the interaction between macrophages and myofibroblasts is indispensable for efficient tissue repair.Nod-like receptor protein 3(NLRP3),a pattern recognition receptor in the innate im-mune system,may play a regulatory role in modulating this intricate process.In this study,cow myofibroblasts and M1 type bone marrow-derived macrophages were cultured in vitro,followed by collection of cell culture supernatant for co-culture analysis.Both cytokine secretion levels in M1 type bone marrow-derived macrophages as well as expression patterns levels of myofibroblast growth factor protein and mRNA were detected.The regulatory mechanism underlying NLRP3 in-volvement in mediating interactions between these two cell types was investigated using NLRP3 inhibitor MCC950.The results showed that an effective method for culturing cow muscle fibroblasts in vitro was successfully established and myofibroblast conditioned medium(MFbCM)could regulate M1 macrophage secretion profiles.Moreover,M1 macrophage conditioned medium(M1?CM)was found to influence myofibroblast growth factor expression levels.Our findings sug-gest that NLRP3 plays a significant regulatory role during crosstalk between myofibroblasts and M1-type pro-inflammatory macrophages.

Objective To identify the astaxanthin, a major secondary metabolite produced by Rhodotorula sp, and to optimize the culture conditions for the production of astaxanthin. Methods The marine red yeast preservation strain was subjected to activation culture and fermentation culture. Single factor and response surface test was designed to optimize fermentation conditions. Secondary metabolites of marine red yeast were analyzed by HPLC, and secondary metabolites of marine red yeast were identified by standard samples. The antioxidant activity of marine red yeast astaxanthin was detected in the study. Results A strain of marine red yeast Rhodotorula sp isolated from a polar separation source was found to produce a variety of metabolites, the main metabolite of which was astaxanthin. Single factor experiments showed that the amount of added zinc sulfate was 100. 00 mg/L, and the highest yield of astaxanthin was 24. 10 mg/ml. The added amount of acetylsalicylic acid was 100. 00 mg/L, and the highest yield of astaxanthin was 25. 00 mg/ml. When fermentation time lasted for 5 days, the highest yield of astaxanthin was 25. 30 mg/mL. The surface response experiments indicated that the fermentation time was 6. 64 days, when the added amount of zinc sulfate was 113. 50 mg/L, and when the added amount of acetyl chloride was 111. 00 mg/L, the astaxanthin output in Rhodotorula sp. fermentation broth was 27. 00 mg/ml. The marine red yeast astaxanthin and other antioxidants have significant antioxidant activity. Conclusion Astaxanthin discovered from the polar separation source, the polar marine red yeast, Rhodotorula sp. is a main secondary metabolite. The use of zinc sulfate and acetylsalicylic acid to regulate the biosynthesis of astaxanthin could enrich the production of astaxanthin. The research results might provide an acess for large-scale production of astaxanthin.