This paper summarizes Professor DING Ying's clinical experience in the treatment of systemic lupus erythematosus （SLE） through differentiation of three states， yin fire， latent fire， and fire toxin. It is proposed that fire pathogenic factors constitute a key pathological element running throughout the entire disease course of SLE. The evolution of its pathogenesis centers on these three states， spleen-kidney deficiency with the initial emergence of yin fire as the onset of disease， damage to yin by medicinal toxicity with internal blazing of latent fire as the driver of disease progression， and the interlocking of blood stasis and heat with intense scorching by fire toxin as the critical factor leading to severe and life-threatening conditions. Corresponding to these three stages， targeted prescriptions are formulated， Jiuwei Yishen Formulation （九味益肾方） to tonify the spleen and kidney， raise yang， and disperse fire； Ziyin Xiehuo Decoction （滋阴泄火汤） to nourish yin and fluids while clearing latent fire； and Santeng Changluo Jiedu Decoction （三藤畅络解毒汤） to dispel blood stasis， unblock the collaterals， detoxify， and restrain fire. This staged and integrated therapeutic strategy aims to address both root and branch and to achieve overall regulation， providing valuable guidance for the clinical differentiation and treatment of SLE.

Aim To verify the mechanism of action of Carthami Flos-Lycopodii Herba in treating KOA carti-lage inflammation based on network pharmacology and in vitro and in vivo experiments.Methods The effec-tive ingredients of Carthami Flos-Lycopodii Herba were screened through the database,the core targets of"drug disease"were analyzed,and pathway enrichment analy-sis and molecular docking verification were conducted.Experimental verification:Primary chondrocytes were extracted from mice and divided into the control group,IL-1β group,treatment group,and treatment+TLR4 agonist group.CCK-8 method was used to screen the optimal intervention concentration of Carthami Flos-Ly-copodii Herba.ELISA was used to detect the content of inflammatory factors in chondrocytes.Western blot was employed to detect the protein expression related to cellular pathways.Subsequently,a KOA mouse model was constructed using the DMM method.After admin-istration,the knee joint injury of mice was evaluated u-sing safranin O-green staining.ELISA was used to de-tect the levels of inflammatory factors in serum.West-ern blot was employed to detect collagen Ⅱ,MMP13,Aggrecan,and apoptosis related protein expression in cartilage tissue.TUNEL staining was used to detect the apoptosis rate of cells.Results A total of 26 active ingredients of Carthami Flos-Lycopodii Herba were screened,as well as 123 potential targets for treating KOA.The enrichment analysis results indicated that it mainly involved mechanisms such as Toll like receptors and cell apoptosis.The experimental results showed that Carthami Flos-Lycopodii Herba alleviated the in-flammatory response of chondrocytes and affected the expression of pathway related proteins.Compared with KOA mice,safflower stretched muscle grass could im-prove cartilage damage and reduce the concentration of serum inflammatory factors,regulate the expression of collagen Ⅱ,MMP13,Aggrecan,and apoptosis related proteins in cartilage tissue,and reduce the fluorescence intensity of TUNEL staining in the tissue.Conclusions Carthami Flos-Lycopodii Herba can improve KOA cartilage inflammation,and its mechanism may be relat-ed to the TLR4/MyD88/NF-κB signaling pathway.

Aim To explore the mechanisms of PM2.5 exposure exacerbating bleomycin(BLM)-induced idio-pathic pulmonary fibrosis(IFP)by regulating ferropto-sis via nuclear factor 2 related factor 2(Nrf2)/solute carrier family 7 member 11(SLC7A11)/glutathione peroxidase(GPX)4 axis.Methods Forty C57BL/6J mice were randomized into the control,BLM,PM2.5,BLM+PM2.5 and sulforaphane(SFN,Nrf2 agonist)groups,with eight mice in each group.PM2.5 expo-sures were conducted to the BLM-induced IPF mice for two weeks.The lung function was measured,and the content of hydroxyproline(HYP)in lung tissue and the pathomorphology of lungs were observed.Reactive oxygen species(ROS),malondialdehyde(MDA),ferrous ion(Fe2+)and glutathione(GSH)of the lung tissue were measured by ELISA.The mRNA and pro-teins levels of Nrf2,SLC7A11,GPX4,collagen typeⅠ(COL-1),α-smooth muscle actin(α-SMA)were measured by quantitative polymerase chain reaction(qPCR)and Western blot.Results Compared with the control group,the lung function of mice was signif-icantly reduced(P＜0.01)in the BLM and PM2.5 groups,while lung tissue showed the characteristic pathological changes of pulmonary fibrosis such as a large number of inflammatory cell infiltration,alveolar wall fracture,thickening,collagen deposition,and sig-nificantly increased HYP,Fe2+,ROS,MDA(P＜0.05,P＜0.01),genes and proteins of COL-1,α-SMA(P＜0.01);and decreased GSH,Nrf2,SLC7A11,GPX4 genes and proteins(P＜0.05,P＜0.01).The above-mentioned lesions were markedly aggravated in the BLM+PM2.5 group compared with the BLM(P＜0.05)and PM2.5 groups(P＜0.01),and were also improved in the SFN group(P＜0.05,P＜0.01).Conclusions PM2.5 exposures can exac-erbate IPF-induced IPF in mice,and the regulating of Nrf2/SLC7 A1 1/GPX4 axis and ferroptosis might be in-volved in the related mechanisms.

Objective To investigate the effect of joint of Zishen Anshen Tang and growth hormone on the clinical outcomes of in vitro fertilization embryo transfer(IVF-ET)in patients with decreased ovarian reserve function(DOR).Methods A clinical trial was conducted on 108 DOR patients who underwent IVF-ET at the Reproductive Center of from January 2023 to August 2024.They were randomly assigned to a control group and a experimental group,each with 54.The control group was given growth hormone(GH),while the experimental group was additionally given Zishen Anshen Tang.The ovulation induction status,trigger day hormone levels,egg retrieval and embryo development,and clinical outcomes were compared.Results The duration of gonadotropin(Gn)use showed no great difference between two groups(P>0.05).The experimental group had lower Gn dosage,early LH peak rate,and luteinizing hormone(LH),higher estradiol(E2),progesterone(P),egg retrieval,2PN fertilization,available embryos,number of high-quality embryos on day 3,blastocyst formation rate,clinical pregnancy rate,and cumulative pregnancy rate,and a lower cycle cancellation rate than control group(P<0.05).Conclusion The joint of Zishen Anshen Tang and growth hormone for IVF-ET in DOR patients can improve their sex hormone and have a positive impact on clinical outcomes.

Aim To explore the therapeutic effect and mechanism of Qingjie Huagong decoction in modulating PI3K/AKT/NF-κB signaling pathway in inflammatory response of acute pancreatitis(AP)mice.Methods Twenty-four mice were randomly divided into Blank group,Model group,Ustekin group,and Qingjie Hua-gong decoction group,with six mice in each group.The AP model was prepared by using rain frogin.Serum α-AMS,PNLP,IL-1β,IL-6,IL-8,IL-18,and TNF-α lev-els were detected by ELISA;the pancreatic pathology was detected by HE staining;the expressions of PI3K,AKT,and NF-κB-related proteins and mRNAs were de-tected by immunohistochemistry,Western blot,and RT-qPCR.Results Compared with the blank group,the model group showed obvious pathological damage to the pancreas,with significantly higher serum α-AMS,PN-LP,IL-1β,IL-6,IL-8,IL-18,and TNF-α levels(P＜0.01),and significantly higher levels of PI3K,AKT,and NF-κB-related proteins and mRNA expression(P＜0.01).Compared with the model group,both the Qingjie Huagong decoction group and the ustekin group improved the histopathological changes in the pancreas of AP mice,decreased the serum α-AMS,PNLP,IL-1β,IL-6,IL-8,IL-18,and TNF-α levels,and down-reg-ulated the expression levels of pancreatic PI3K,AKT,NF-κB-related proteins and mRNA(P＜0.05 or P＜0.01).Conclusion Qingjie Huagong decoction may inhibit the inflammatory response and protect pancreat-ic tissues by regulating the expression of PI3K/AKT/NF-κB signaling pathway.

Objective To investigate the regulation of macrophage polarization and foaminess by homocysteine(Hcy)and its potential underlying mechanisms.Methods ELISA and flow cytometry were used to detect the effect of Hcy treatment on the polarization of macrophages.The contents of various forms of intracellular cholesterol were detected,and the effects of Hcy on intracellular lipid accumulation and ox-LDL uptake were evaluated by oil red O staining and Dil-oxLDL.RT-qPCR and Western blot were used to detect mRNA and pro-tein expression of key genes modified by N6-methyladenosine(m6 A).Results Hcy promoted M1 polarization of macrophages and ox-LDL-induced foam macrophages and promoted ox-LDL uptake as well as intracellular lipid accumulation.In addition,Hcy upregulated methyltransferase like 3(METTL3)expression,and the tendency of Hcy to promote macrophage M1 polarization and foaminess was markedly reduced after inhibition or knockdown of METTL3 expression.Conclusions Hcy significantly promotes macrophage M1 polarization and foaminess,an effectthat may be attenuated by METTL3 silencing.

Objective To investigate the mechanism by which Senegenin(SEN)alleviates microglial inflammatory response through the nuclear factor erythroid 2-related factor 2(Nrf2)/NOD-like receptor protein 3(NLRP3)pathway.Methods BV2 mouse microglia cells were randomly divided into control group,model group,SEN group and MCC950 group.Cells in control group were not treated,and cells in model group were added with 1 μg/ml lipopolysaccharide(LPS);Cells in SEN group were added with 1 μg/ml LPS+4 μmol/L SEN,and cells in MCC950 group were added with 1 μg/ml LPS+10 μmol/L MCC950 for 24 hours.CCK-8 method was used to detect the effect of different concentrations of SEN on the viability of BV2 cells.Griess method was used to determine the release amount of nitric oxide(NO)in the supernatant.Real-time fluorescent quantitative PCR was used to determine the mRNA expression levels of NLRP3,lymphocyte apoptosis-associated spect-like protein containing a CARD(ASC),caspase-1,interleukin(IL)-1β and IL-18 mRNA.Immunofluorescence staining was used to detect the expression levels of ASC,IL-1β,Nrf2 and heme oxygenase-1(HO-1).Western blotting was used to detect the expression levels of NLRP3,caspase-1,ASC,IL-1β,IL-18,Nrf2,HO-1,nuclear factor kappa B(NF-κB)and inducible nitric oxide synthase(iNOS).Results The results of CCK-8 method showed that there was no significant difference in the viability of BV2 cells treated with 2～20 μmol/L SEN compared with control group(P>0.05).Compared with control group,the viability of BV2 cells in model group decreased significantly(P<0.05).Compared with model group,the viability of BV2 cells in 4 μmol/L SEN group was significantly restored(P<0.05).Compared with control group,the results of Griess method showed that the release amount of NO in cells of model group increased significantly(P<0.05);the results of real-time PCR showed that the expression levels of NLRP3,ASC,caspase-1,IL-1β and IL-18 mRNA in cells of model group increased significantly(P<0.05);the results of Western blotting showed that the protein expression levels of NLRP3,ASC,caspase-1,IL-1β and IL-18 proteins in cells of model group increased significantly(P<0.05),and the immunofluorescence staining results showed that the expression levels of iNOS and NF-κB protein in cells of model group increased,and the expression levels of Nrf2 and HO-1 decreased,with statistically significant differences(P<0.05).Compared with model group,the release amount of NO in cells of SEN group and MCC950 group decreased,and the expression levels of NLRP3,ASC,caspase-1,IL-1β and IL-18 mRNA and proteins decreased,with statistically significant differences(P<0.05);in the SEN group,the expression levels of iNOS and NF-κB decreased,and immunofluorescence staining showed that Nrf2 was translocated into the nucleus,and the expression levels of Nrf2 and HO-1 proteins increased significantly,with statistically significant differences(P<0.05).Conclusions SEN could alleviate the inflammatory response of mouse microglia cells induced by LPS and inhibit the activation and expression of NLRP3 inflammasome,with an effect comparable to that of the inflammasome inhibitor MCC950.The mechanism may be related to the regulation of the expression of upstream factors Nrf2 and HO-1.

Objective To report a case of tibial synovial sarcoma and review relevant literature to enhance understanding of this disease.Methods The clinical data of a patient with tibial synovial sarcoma treated at Kaifeng Central Hospital were retrospectively analyzed.A literature search was conducted in domestic and international databases,including China National Knowledge Infrastructure(CNKI),Wanfang Data,PubMed,Web of Science,and Embase,up to July 2024.Relevant literature was comprehensively reviewed to summarize the imaging and pathological characteristics,treatment,and prognosis of synovial sarcoma.Results A 29-year-old female patient was admitted with left lower extremity pain.X-ray examination revealed a proximal tibia space-occupying lesion suggestive of malignancy,and a mid-tibial space-occupying lesion considered benign.Contrast-enhanced computed tomography(CT)and plain magnetic resonance imaging(MRI)of the proximal tibial lesion also suggested malignancy.Ultrasound-guided biopsy of the proximal tibial tumor revealed a poorly differentiated malignant tumor.Immunohistochemistry results indicated monophasic synovial sarcoma,requiring genetic testing for definitive diagnosis.The patient underwent wide resection of the proximal left tibial malignancy with tumor-type artificial joint replacement,combined with curettage and bone cement filling for the left mid-tibial lesion under anesthesia.Postoperative pathology of space-occupying lesions in the proximal tibia confirmed monophasic synovial sarcoma,and fluorescence in situ hybridization(FISH)demonstrated a rupture of the synovial sarcoma translocation gene(SYT)(i.e.,SS18 positive).There was no recurrence or metastasis found in the patient during the reexamination 6 months after postoperative chemotherapy.As of July 2024,15 cases of genetically confirmed primary intraosseous synovial sarcoma have been reported internationally.Symptoms included pain and swelling,with a medical history of 1-2 years.The X-ray and CT findings showed osteolytic destruction with bone cortical discontinuity.In 13 cases,the intraosseous masses extended to the extraosseous area;in 2 cases,punctate calcifications were detected within the masses.Plain MRI scan showed iso-signal or hypo-signal on T1WI and hyper-signal,iso-signal,and hypo-signal on fat-suppressed T2WI,and enhanced MRI scan demonstrated heterogeneous enhancement.Pathological examination showed spindle-shaped cells under microscopy.Immunohistochemistry results showed positive epithelial membrane antigen(EMA),broad-spectrum cytokeratin(AE1/AE3),Ewing's sarcoma marker(CD99),and transducin-like enhancer of Split 1(TLE1).Twelve patients underwent surgical treatment;6 patients received adjuvant chemotherapy after surgery,of whom 4 developed local recurrence or distant metastasis at initial diagnosis,and 3 died during follow-up.Among the 6 patients who did not receive adjuvant chemotherapy,3 suffered from recurrence or distant metastasis.Conclusions Primary intraosseous synovial sarcoma is a rare malignant tumor with non-specific clinical manifestations.Imaging features typically include osteolytic destruction and intraosseous masses extending extraosseously,suggesting an intraosseous origin.Pathology and immunohistochemistry aid diagnosis,but definitive confirmation relies on further genetic testing.At present,the main treatment regimens for synovial sarcoma involve comprehensive therapies such as surgery and adjuvant chemotherapy,and the prognosis of patients is poor.

Objective:To explore the effect of repetitive transcranial magnetic stimulation (rTMS) on the cognition and ability in the activities of daily living (ADL) of persons with cerebral small vessel disease.Methods:A total of 71 patients with cognitive impairment due to cerebral small vessel disease were randomly divided into a control group ( n=35) and a treatment group ( n=36). The treatment group was further divided into a group with mild cognitive impairment (a score of 21 to 26 on the mini-mental state exam, n=23) and a moderate cognitive impairment group (scoring 10 to 20, n=13). The treatment groups received 10Hz rTMS, while the control group received sham rTMS. Before and after 90 days of treatment, all were assessed using the mini-mental state examination (MMSE) and the cognitive subscale of the vascular dementia assessment scale (VaDAS-cog). Ability in the activities of daily living was quantified using the Barthel Index (BI). Results:After treatment, significantly increased MMSE and BI scores, but significantly decreased VaDAS-cog scores were observed in both groups. At that point the treatment group showed a significantly higher average post-treatment MMSE score (25.61±2.94) and BI score (80.00±7.85), but a significantly lower average VaDAS-cog score (44.06±3.41) than the control group. The average MMSE scores were not significantly different between the mild and moderate cognitive impairment subgroups. No severe adverse reactions were observed during the rTMS treatment.Conclusions:The 10Hz rTMS can effectively improve the cognition and daily living ability of persons with cerebral small vessel disease.

Objective:To investigate the effect of brain-computer interface (BCI) training on the upper limb function of stroke survivors and to observe any changes in cortical activation patterns after such training.Methods:Thirty ischemic stroke survivors with upper limb dysfunction were randomized into a treatment group ( n=15) and a control group ( n=15). Both groups were given conventional upper limb rehabilitation training, while the treatment group additionally underwent 30 minutes of upper limb BCI training daily, five days a week for four consecutive weeks. Their upper limb motor functioning was assessed using the Fugl-Meyer assessment (FMA) and their ability in the activities of daily living (ADL) was quantified using the modified Barthel Index (MBI) before the experiment and after two and four weeks. the functional near infrared spectroscopy (fNIRS) was employed to measure oxygenated hemoglobin (HbO 2) levels in six regions of interest: the premotor cortex (PMC), the supplementary motor area (SMA), and the sensorimotor cortex (SMC) of the affected and unaffected hemispheres. Changes in brain network topology and network efficiency during the upper limb training were also analyzed. Results:After two and four weeks of the treatment, both groups showed significant improvement in their average FMA and MBI scores. The improvement was significantly greater in the treatment group than among the controls, on average. Before the treatment, HbO 2 levels in the affected SMA were significantly lower than in the other regions of interest in both groups. However, after 4 weeks the treatment group had significantly increased HbO 2 in the affected PMC and SMA, with higher concentrations in the affected PMC than among the control group. The network efficiency in the treatment group was also significantly better than in the control group after four weeks. Conclusions:Supplementing conventional neuropharmacological and rehabilitation therapies with BCI training can significantly improve upper limb motor function and the ADL ability of stroke survivors. It enhances cortical activation in the affected PMC and SMA and increases inter-regional brain networks.