ObjectiveTo observe the effects of Dihuang Yinzi （DY） on motor dysfunction in rats with advanced Parkinson's disease （PD） and to investigate the mechanisms by which DY improves advanced PD symptoms through the "gut microbiota-short-chain fatty acids （SCFAs）-inflammation-neuroprotection pathway". MethodsAn advanced PD rat model was induced by rotenone. Rats were divided into a normal group， model group， positive drug group （levodopa， 50 mg·kg^-1）， and DY low-， medium-， and high-dose groups （5.2， 10.4， 20.8 g·kg^-1）. After 7 days of administration， motor function was evaluated using the open-field， pole-climbing， and inclined plate tests. Hematoxylin-eosin （HE） staining was used to observe pathological changes in the substantia nigra and colon， and immunohistochemistry was performed to detect α-Synuclein （α-Syn） and tyrosine hydroxylase （TH） expression in the substantia nigra. Enzyme-linked immunosorbent assay （ELISA） was used to measure levels of dopamine （DA）， 5-hydroxytryptamine （5-HT）， 3，4-dihydroxyphenylacetic acid （DOPAC）， Levodopa， homovanillic acid （HVA）， tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and interleukin-1β （IL-1β）. Western blot analysis was used to detect the expression of zonula occludens-1 （ZO-1） and occludin. Gut microbiota diversity was analyzed by 16S rRNA sequencing， and gas chromatography （GC） was used to determine the content of SCFAs in colonic contents. ResultsCompared with the normal group， the model group showed significantly decreased movement speed and distance in the open-field test， prolonged pole-climbing time， and reduced retention angle on the inclined plate （P<0.01）， accompanied by increased α-Syn expression （P<0.01） and decreased TH expression （P<0.01） in the brain. Compared with the model group， all DY dose groups improved motor dysfunction in advanced PD rats to varying degrees （P<0.05， P<0.01） and alleviated pathological damage in the brain and colon. High-dose DY significantly reduced α-Syn aggregation in the substantia nigra （P<0.01） and increased TH expression （P<0.01）. ELISA and Western blot results showed that， compared with the normal group， the model group exhibited decreased levels of DA， 5-HT， DOPAC， Levodopa， and HVA in the striatum （P<0.01）， increased levels of TNF-α， IL-6， and IL-1β in the colon and striatum （P<0.01）， and significantly reduced expression of ZO-1 （P<0.05） and occludin in the colon （P<0.01）. Compared with the model group， all DY dose groups increased the levels of DA， 5-HT， DOPAC， Levodopa， and HVA in the striatum to varying degrees （P<0.05， P<0.01）. In the high-dose DY group， the levels of TNF-α， IL-6， and IL-1β in the colon and striatum were reduced （P<0.01）， while the expression of ZO-1 （P<0.05） and occludin in the intestine was increased. The 16S rRNA sequencing results indicated that the relative abundances of Actinobacteriota， Enterobacteriaceae， and Erysipelotrichaceae were increased in the model group， whereas the relative abundances of Bacteroidota， class Clostridia， Lachnospiraceae， and Akkermansia muciniphila were decreased. These changes were effectively reversed after high-dose DY intervention. GC analysis showed that the content of SCFAs in the colonic contents of rats in the model group was decreased （P<0.05， P<0.01）， while after high-dose DY intervention， the levels of acetate， propionate， isobutyrate， and butyrate were significantly increased （P<0.05， P<0.01）. ConclusionDY may exert therapeutic effects in advanced PD by regulating the gut microbiota-SCFAs-inflammation pathway.

The coinfection of respiratory viruses and bacteria is a major cause of morbidity and mortality worldwide, despite the development of vaccines and powerful antibiotics. As a macromolecule that is difficult to absorb in the gastrointestinal tract, a homogeneous polysaccharide from Houttuynia cordata (HCPM) has been reported to exhibit anti-complement properties and alleviate influenza A virus (H1N1)-induced lung injury; however, the effects of HCPM without in vitro antiviral and antibacterial activities on more complicated pulmonary diseases resulting from viral-bacterial coinfection remains unclear. This study established a representative coinfection murine pneumonia model infected with H1N1 (0.2 LD₅₀) and methicillin-resistant Staphylococcus aureus (MRSA, 10⁷ CFU). HCPM significantly improved survival rate and weight loss, and ameliorated gut-lung damage and inflammatory cytokine production. Interestingly, the therapeutic effect of HCPM on intestinal damage preceded that in the lungs. Mechanistically, HCPM inhibited the overactivation of the intestinal complement (C3a and C5a) and suppressed the activation of the NLR family pyrin domain-containing 3 (NLRP3) pathway, which contributes to the regulation of the Treg/Th17 cell balance in the gut-lung axis. The results indicate the beneficial effects of an anti-complement polysaccharide against viral-bacterial coinfection pneumonia by modulating crosstalk between multiple immune regulatory networks.

Thyroid cancer is the most common endocrine malignancy. Although most patients achieve good prognosis through surgery and conventional treatments, approximately 15%-20% of patients with papillary thyroid cancer and the anaplastic and medullary thyroid cancers still lack effective treatment options. The tumor immune microenvironment plays a critical role in the occurrence, progression, and drug resistance of thyroid cancer. This review focused on the key immune cells in thyroid cancer, including tumor-associated macrophages, myeloid-derived suppressor cells, mast cells, natural killer cells, and T lymphocytes, and explored their roles and mechanisms in tumor immune evasion. Immunotherapy has become an emerging treatment strategy for advanced thyroid cancer, we summarized the attempts and advances in immune checkpoint inhibitors, targeted macrophage therapy and tumor vaccines.

ObjectiveTo investigate the possible mechanism of Huatan Sanjie Formula （化痰散结方， HSF） in treating Graves' disease （GD） from the perspective of thyroid angiogenesis. MethodsThirty-six BALB/c female mice were randomly divided into a normal control group （n=9） and a modeling group （n=27）. Mice in the modeling group were injected with 2.0×10⁹ PFU/ml of Ad-TSHR289 adenovirus into the tibialis anterior muscle to build GD model. Nine weeks after immunization， the successfully modeled mice were randomly divided into model group， methimazole （MMI） group and HSF group， with 9 mice in each group. The MMI group was given 5.2 mg/（kg·d） of methimazole tablets by gavage， while the HSF group was given HSF at a relative crude drug dosage of 7.02 g/（kg·d） by gavage. The normal control group and the model group were given 0.1 ml/10 g of pure water by gavage. All groups were administered intragastrically once a day for a total of 4 weeks. The levels of thyroxine （T4） and thyrotropin receptor autoantibodies （TRAb） in serum were detected by radioimmunoassay， while the pathological changes of the thyroid gland were assessed by HE staining. The vascular morphology of thyroid tissue was observed by CD34 immunohistochemical staining， and the microvessel density （MVD） was counted. The protein expression of vascular endothelial growth factor A （VEGFA） and vascular endothelial growth factor receptor 2 （VEGFR2） in thyroid was detected by Western-blot. ResultsCompared to those in the normal control group， the thyroid volume of the mice in the model group significantly increased with excessive congestion， and the pathology showed significant thyroid follicular hyperplasia， columnar and proliferated epithelial cells， and enlarged follicle size； serum T4 and TRAb significantly increased， as well as the count of thyroid MVD， and the protein expressions of thyroid VEGFA and VEGFR2 （P＜0.01）. Compared to those in the model group， the thyroid glands of the mice in the MMI group and the HSF group were significantly reduced， and the congestion was improved； pathology showed that thyroid follicular hyperplasia and epithelial cell proliferation were reduced， with smooth edges of the follicles and the significantly reduced inward protrusion； serum T4 and TRAb significantly decreased， as well as the thyroid MVD， thyroid VEGFA and VEGFR2 protein expressions （P＜0.05 or P＜0.01）. There was no significant difference in all indicators between the MMI group and the HSF group （P＞0.05）. ConclusionHSF may inhibit thyroid angiogenesis by down-regulating thyroid VEGFA/VEGFR2 signaling pathway， thereby improving goitre and hyperfunction in GD mice.

The classical prescription Yangweitang， derived from Zhengzhi Zhunsheng， is specialized in treating syndromes of chill and fever due to exogenous pathogens， inner-cooling， and malaria， and it has been included in the Catalogue of Ancient Classical Formulas （the First Batch） published by the National Administration of Traditional Chinese Medicine （TCM） in 2018. Through bibliographical research， the relevant ancient books and modern documents were systematically sorted out， and it was found that there were many prescriptions related to the Yangweitang from Zhengzhi Zhunsheng. They were interwoven with Yangweitang from Zhengzhi Zhunsheng and widely used in clinical practice. In order to clarify their history and evolution， this paper combed the historical origin of Yangweitang and its related prescriptions and conducted textual analysis on key information such as semantic composition， herb origin， processing method， and efficacy. A total of 896 pieces of data on Yangweitang from Zhengzhi Zhunsheng were collected. 26 pieces of effective data were included after the screening， involving 17 ancient TCM books. Then， a total of 28 pieces of data on prescriptions related to the Yangweitang from Zhengzhi Zhunsheng were included， involving 23 ancient TCM books for reference. The textual analysis showed that Yangweitang originated from the Renshen Yangweitang recorded in Taiping Huimin Heji Jufang in the Song dynasty. Based on the original formula， medical experts from later generations have modified it into many different versions. A comparative analysis showed that Yangweitang from different generations had similar compositions， and the herb origin and processing method were basically clear. The recommended prescriptions are as follows： 37.3 g of Pinelliae Rhizoma Praeparatum Cum Alumine， Magnoliae Officinalis Cortex（fried with ginger juice）， and frying with rice water Atractlodis Rhizoma， 27.98 g of Citri Exocarpium Rubrum， 18.65 g of Pogostemon cablin leaf， Tsaoko Fructus， Poria， and Ginseng Radix et Rhizoma， and 9.33 g of Glycyrrhizae Radix et Rhizoma. They could be ground into a coarse powder， with 14.92 g for every dose， and they could be orally taken after being decocted with 450 mL of water， 7 g of fresh ginger， and 2 g of Mume Fructus to 270 mL in warm conditions. Yangweitang from Zhengzhi Zhunsheng has the effect of warming the middle and releasing the external， and it can treat many syndromes including spleen and stomach disharmony caused by chill and fever due to exogenous pathogens and inner-cooling， as well as all kinds of malaria. Modern clinical applications mainly focus on chronic atrophic gastritis and other digestive system diseases.

Objective To investigate the expression of circRAF1 in primary ovarian insufficiency(POI)and explore its effect on cell proliferation and apoptosis of human ovarian granulosa cells(GCs)line(KGN cells).Methods The expression of circRAF1 in GCs and serum of patients with normal ovarian reserve function(n = 50)and patients with POI(n = 50)were detected with RT-qPCR.The correlation of circRAF1 with ovarian reserve function indexes was analyzed.Small interfering RNA(siRNA)targeting circRAF1 was constructed and trans-fected into KGN cells,with the cell proliferation detected by CCK-8 and EdU assay,and the cell apoptosis detected by JC-1 and Tunel assay.The mRNA and protein levels of genes related to cell proliferation and apoptosis(FSHR,PCNA,Bcl-2,Casp-9,Bax)were detected by RT-qPCR and WB.Results The expression of circRAF1 decreased in GCs and serum of POI patients.The expression of circRAF1 was positively correlated with serum E2 and AMH levels(P<0.001),but negatively correlated with serum FSH and LH levels(P<0.001).At the same time,the expression of circRAF1 was positively correlated with AFC(P<0.001).Interfering with the expression of circRAF1 could inhibit the proliferation of KGN cells and promote their apoptosis.Conclusion The expression of circRAF1 in the GCs and serum of POI patients is down-regulated,which is correlated with the decline of ovarian reserve function.Interfering with circRAF1 can inhibit the proliferation of GCs and promote their apoptosis.

Objective:To investigate the effects of the Y-box binding protein 1(YBX1)on the proliferation and apoptosis of granulosa cells by regulating silent information regulator 1(SIRT1),and explore the differential ex-pression of YBX1 and SIRT1 of premature ovarian insufficiency(POI)patients and health controls,as well as its clinical significance.Methods:We recruited patients with POI and patients with normal ovarian function during in vitro fertilization(IVF)/intracytoplasmic sperm injection(ICSI)assisted pregnancy in the Department of Reproduc-tive Medical Center of the Fourth Affiliated Hospital of Jiangsu University from June 2022 to July 2023.The granu-losa cells and serum were collected.Western-Blot(WB)to detect YBX1 protein expression.Real-time quantitative polymerase chain reaction(RT-qPCR)to detect YBX1 and SIRT1 mRNA levels,and the correlation between the abundance of YBX1 and SIRT1 in serum and follicle stimulating hormone(FSH),luteinizing hormone(LH),estra-diol(E2),anti-Mullerian Hormone(AMH),and antral follicle count(AFC)were analyzed.5-bromo-2-deoxyuracil(EdU)and cell counting Kit-8(CCK8)were applied to detect cell proliferation;TdT-mediated dUTP-biotin nick end labeling assay(TUNEL)to detect cell apoptosis;RT-qPCR to detect cell proliferating cell nuclear antigen(PC-NA),B cell lymphoma 2(Bcl2),Bcl2 associated X protein(BAX),and cysteine-aspartate protease 3(Caspase-3)mRNA expression;RNA Immunoprecipitation(RIP)experiment to detect the interaction between YBX1 and SIRT1.Results:The expression of YBX1 protein and SIRT1 mRNA in granulosa cells and serum of POI patients were significantly lower than that of the control group(P＜0.05).The expression of YBX1 and SIRT1 mRNA in serum were negatively correlated with FSH,LH(r＜0,P＜0.05),and positively correlated with E2,AMH and AFC(r＞0,P＜0.05).Upregulating YBX1 in granulosa cells increased SIRT1 protein expression,SIRT1 mRNA stabili-ty,EdU positive rate,cell viability,PCNA mRNA expression level,Bcl2/BAX ratio(P＜0.05),while decreased Caspase-3 mRNA expression level,TUNEL positive rate(P＜0.05).Conclusions:The expression levels of YBX1 and SIRT1 in POI patients were significantly reduced and correlated with clinical ovarian function indicators.YBX1 can bind to SIRT1 mRNA and enhance its stability,which may promote the proliferation of granulosa cells,and in-hibit apoptosis.These findings suggested that YBX1 and SIRT1 are expected to become new targets for POI diag-nosis and treatment.

Osteoarthritis(OA)is the most common degenerative disease in clinical practice.Joint pain is the main manifestation of OA,and in severe cases,it can lead to joint deformity.The main pathological changes include destruction of articular cartilage,synovitis,thickening of subchondral bone,bone redundancy,degeneration of articular ligaments,and enlargement of articular periosteum.Clinicopathological changes and pain degrees in OA patients vary from person to person,and treatment options vary from person to person.Clinically,non-steroidal anti-inflammatory drugs are used to treat the pain of OA patients now,but the effect is not ideal,and long-term use of these drugs will bring obvious toxic and side effects.Traditional Chinese medicine obtains good results in relieving the pain of OA patients.Therefore,this paper reviews the research on traditional Chinese medicine treatment and pain mechanisms of OA,with a view to providing ideas and references for clinical relief of pain in OA patients.

Cognition is the most basic human mental process,and is a higher neural function of the brain.Cognitive dysfunction caused by various neuropsychiatric diseases may involve one or more cognitive domains such as working memory,attention and executive function,which can seriously affect the quality of patients'survival.Transcranial alternating current stimulation(tACS)can directly modulate cortical oscillations as well as intrinsic oscillatory activity,thereby affecting sensory,perceptual and cognitive processes.This paper analyses and summarizes domestic and international studies on tACS applied to cognitive disorders based on evidence-based medicine methods,to provide the theoretical basis for future scientific application of tACS in cognitive disorders.

Objective:To investigate the effects of the Y-box binding protein 1(YBX1)on the proliferation and apoptosis of granulosa cells by regulating silent information regulator 1(SIRT1),and explore the differential ex-pression of YBX1 and SIRT1 of premature ovarian insufficiency(POI)patients and health controls,as well as its clinical significance.Methods:We recruited patients with POI and patients with normal ovarian function during in vitro fertilization(IVF)/intracytoplasmic sperm injection(ICSI)assisted pregnancy in the Department of Reproduc-tive Medical Center of the Fourth Affiliated Hospital of Jiangsu University from June 2022 to July 2023.The granu-losa cells and serum were collected.Western-Blot(WB)to detect YBX1 protein expression.Real-time quantitative polymerase chain reaction(RT-qPCR)to detect YBX1 and SIRT1 mRNA levels,and the correlation between the abundance of YBX1 and SIRT1 in serum and follicle stimulating hormone(FSH),luteinizing hormone(LH),estra-diol(E2),anti-Mullerian Hormone(AMH),and antral follicle count(AFC)were analyzed.5-bromo-2-deoxyuracil(EdU)and cell counting Kit-8(CCK8)were applied to detect cell proliferation;TdT-mediated dUTP-biotin nick end labeling assay(TUNEL)to detect cell apoptosis;RT-qPCR to detect cell proliferating cell nuclear antigen(PC-NA),B cell lymphoma 2(Bcl2),Bcl2 associated X protein(BAX),and cysteine-aspartate protease 3(Caspase-3)mRNA expression;RNA Immunoprecipitation(RIP)experiment to detect the interaction between YBX1 and SIRT1.Results:The expression of YBX1 protein and SIRT1 mRNA in granulosa cells and serum of POI patients were significantly lower than that of the control group(P＜0.05).The expression of YBX1 and SIRT1 mRNA in serum were negatively correlated with FSH,LH(r＜0,P＜0.05),and positively correlated with E2,AMH and AFC(r＞0,P＜0.05).Upregulating YBX1 in granulosa cells increased SIRT1 protein expression,SIRT1 mRNA stabili-ty,EdU positive rate,cell viability,PCNA mRNA expression level,Bcl2/BAX ratio(P＜0.05),while decreased Caspase-3 mRNA expression level,TUNEL positive rate(P＜0.05).Conclusions:The expression levels of YBX1 and SIRT1 in POI patients were significantly reduced and correlated with clinical ovarian function indicators.YBX1 can bind to SIRT1 mRNA and enhance its stability,which may promote the proliferation of granulosa cells,and in-hibit apoptosis.These findings suggested that YBX1 and SIRT1 are expected to become new targets for POI diag-nosis and treatment.