BACKGROUND:Lijin manipulation can promote skeletal muscle repair and treat skeletal muscle injury.However,the formation of fibrosis and scar tissue hyperplasia are closely related to the quality of skeletal muscle repair.To study the regulatory effect of Lijin manipulation on the formation of fibrosis and scar tissue hyperplasia is helpful to explain the related mechanism of Lijin manipulation to improve the repair quality of skeletal muscle injury. OBJECTIVE:To explore the mechanism of Lijin manipulation to improve the repair quality of skeletal muscle injury in rabbits,thereby providing a scientific basis for clinical treatment. METHODS:Forty-five healthy adult Japanese large-ear white rabbits were randomly divided into blank group,model group and Lijin group,with 15 rats in each group.Gastrocnemius strike modeling was performed in both model group and Lijin group.The Lijin group began to intervene with tendon manipulation on the 3rd day after modeling,once a day,and 15 minutes at a time.Five animals in each group were killed on the 7th,14th and 21st days after modeling.The morphology and inflammatory cell count of gastrocnemius were observed by hematoxylin-eosin staining,the collagen fiber amount was observed by Masson staining,the expression of interleukin-6 and interleukin-10 in gastrocnemius was detected by ELISA.The protein and mRNA expressions of paired cassette gene 7,myogenic differentiation factor,myoblastogenin,alpha-actin,transforming growth factor beta 1,and type Ⅰ collagen were detected by western blot and RT-PCR,respectively,and the expression of type Ⅰ collagen protein was detected by immunohistochemistry. RESULTS AND CONCLUSION:Hematoxylin-eosin staining and Masson staining showed that compared with the model group,inflammatory cell infiltration and collagen fiber content decreased in the Lijin group(P<0.01),and the muscle fibers gradually healed.ELISA results showed that compared with the model group,the expression of interleukin-6 in the Lijin group continued to decrease(P<0.05),and the expression of interleukin-10 increased on the 7th day after modeling(P<0.05)and then showed a decreasing trend(P<0.05).Western blot and RT-PCR results showed that compared with the model group,the protein and mRNA expressions of paired cassette gene 7,myogenic differentiation factor,myoblastogenin in the Lijin group were significantly increased on the 14th day after modeling(P<0.05),but decreased on the 21st day(P<0.05);the protein and mRNA expressions of alpha-actin,transforming growth factor beta 1,and type Ⅰ collagen in the Lijin group were significantly decreased compared with those in the model group(P<0.05).Immunohistochemical results showed that the expression of type Ⅰ collagen in the Lijin group was significantly lower than that in the model group(P<0.05).To conclude,Lijin manipulation could improve the repair quality of skeletal muscle injury by inhibiting inflammation,promoting the proliferation and differentiation of muscle satellite cells,and reducing fibrosis.

To investigate the effects of Pithecellobium clypearia extract on the tissue structure,in-flammatory lesions as well as microbial diversity in the intestinal of yellow-feathered broilers.2401-day-old yellow-feathered broilers were randomly divided into four groups(groups A,B,C and D),groups A,B and C were supplemented with Pithecellobium clypearia extract in basal diets with concentrations of 0.5,1.0 and 2.0 g/kg,respectively.Group D served as the control group without adding Pithecellobium clypearia extract in diets,and the full trial period lasted for 70 d.Duodenum and jejunum samples were collected on the 20th,40th and 70th days of the test,the vil-lous/crypt ratio of duodenum and jejunum were calculated,and the mRNA expression level of in-flammatory cytokine as well as related pathways were detected in each group,respectively.In addition,the contents of cecum were collected at 70 th day of the experiment and the microbial di-versity in cecum were also analysed by 16S rDNA sequencing.The results showed that adding 0.5 and 1.0 g/kg of Pithecellobium clypearia extract in the diet could significantly increase the veloci-ty height/crypt depth ratio of duodenum and jejunum(P＜0.05)compared to control group,as well as the mRNA expression level of tight junction protein(CLDN1 and CLDN5)in jejunum,which further improved the structure of mucous of intestinal.Pithecellobium clypearia extract could significantly(P＜0.05)decrease the mRNA expression level of inflammatory cytokine inclu-ding IL-1β,IL-8 and TNF-α,as well as the related pathway genes such as TLR4,MyD88 and NF-κB in jejunum,thus reduced the inflammatory lesions in intestinal.Pithecellobium clypearia ex-tract also could significantly increase the abundance of beneficial microbial such as Parabacteroide and Prevotellaceae,while significantly decrease the abundance of pathogenic microbial such as Proteobacteria in cecum(P＜0.05)and improve the microbial diversity in intestinal.In summary,Pithecellobium clypearia extract could improve the structure of intestinal tissue and the gut barri-er function,as well as the microbial diversity in cecum,and also decrease the inflammatory lesions in jejunum,which is helpful to the intestinal health for yellow-feathered broilers.The present study provides scientific basis for the development of Pithecellobium clypearia as a safe feed additive in the future.

Objective:To investigate the efficacy and safety of Venetoclax combined with CACAG regimen in treatment of patients with refractory/relapse acute myeloid leukemia(R/R AML).Methods:The study was a singlecenter prospective clinical trial.The enrolled patients met the criteria for R/R AML.Treatment included Azacidine(75mg/m2,d1-7),Ara-C(75-100 mg/m2,q12h,d1-5),Aclacinomycin(20 mg d1,d3,d5),Chidamide(30 mg d1,d4),Venetoclax(100 mg d1,200 mg d2,400 mg d3-d14,in combination with Triazole Drug,reduced to 100 mg/d),and granulocyte colony-stimulating factor(300 μg/d until neutrophil recovery).The primary endpoint of observation was overall response rate after 1 course of treatment.Results:A total of 19 patients were enrolled from January 2022 to April 2023.After 1 course of treatmen,the overall response rate was 81.3％(13/16),the CR rate was 68.8％(11/16),and the PR was 12.5％(2/16).Among the 11 patients who got CR/CRi,8 cases achieved CRm(minimal residual disease negative CR)and 3 cases did not.As of March 27,2023,the median follow-up time was 111(19-406)days.The six-month overall survival and progression-free survival rates were both 55.7％,the 1-year overall survival and progression-free survival rates were 46.4％and 47.7％,respectively.In addition,compared with the non-CRm group,CRm patients had a better PFS(377 days vsi11 days,P=0.046).Treatment-related adverse events were mainly 3-4 degrees of bone marrow suppression,complicated by various degrees of infection(n=12),hypokalemia(n=12)and hypocalcemia(n=10)and elevated liver enzymes(n=8),of which 3/4 degrees accounted for 47.4％(9/19).Conclusion:The Venetoclax combined with CACAG regimen is an effective salvage therapy for patients with R/R AML,with high remission rate and safety profile.

Objective:To investigate the relationship between IGF2BP3 gene expression and prognosis in patients with acute myeloid leukemia(AML).Methods:High throughput transcriptome sequencing was performed on bone marrow primary leukemia cells from 27 patients with AML in our center,the relationship between IGF2BP3 expression levels and clinical characteristics were analyzed and verify the samples from patients with newly treated AML and refractory AML.The expression level of IGF2BP3 gene were analyzed in 20 healthy subjects and 26 patients with AML.The expression of IGF2BP3 in two anthracycline-resistant cell lines(HL60/ADR,K562/ADR)was detected by RT-qPCR and Western blot,and the expression difference of IGF2BP3 was compared with that in sensitive cells(HL60,K562).The relationship between the expression level of IGF2BP3 in patients with AML and prognostic were analyzed through data analysis of 746 patients with AML,and the prognostic value of IGF2BP3 in AML was analyzed by multivariate Cox regression analysis.Results:In the bone marrow primary leukemia cells of 27 AML patients in our center,the expression level of IGF2BP3 in patients with refractory AML was significantly higher than that in chemotherapy sensitive patients(P=0.0343).The expression of IGF2BP3 in leukemia patients with extramedullary infiltration(EMI)was significantly higher than that in AML patients without extramedullary infiltration(P=0.0049).Compared with healthy subjects(n=20),IGF2BP3 expression in AML patients(n=26)was higher(P=0.0009).The expression of IGF2BP3 mRNA in the anthracycline resistant cell lines(HL60/ADR,K562/ADR)was significantly higher than that in the sensitive cell lines(K562/ADR vs K562,P=0.0430;HL60/ADR vs HL60,P=0.7369).Western blot results showed that the expression of IGF2BP3 protein in mycin resistant cells was significantly higher than that in sensitive cells(P＜0.001).qPCR results showed that the expression level of IGF2BP3 mRNA in refractory AML patients was significantly higher than that in patients with chemotherapy sensitive(P=0.002).High expression of IGF2BP3 was associated with poor prognosis in AML(P＜0.05)in 3 large sample cohorts of AML patients.Univariate and multivariate prognostic analyses demonstrated that high expression of IGF2BP3 was significantly associated with shorter event-free survival(EFS,HR=1.887,P=0.024)and overall survival(OS,HR=1.619,P=0.016).Conclusion:The high expression of IGF2BP3 gene may be an important factor in the poor prognosis of AML,suggesting that IGF2BP3 gene may be a new molecular marker for the clinical prognosis evaluation and treatment strategy of AML.

Objectives:To understand the current situation of the sense of uselessness of the elderly in China and the impact of Internet use on the sense of uselessness of the elderly,exploring the moderating role of age and social participation in it,so as to provide empirical evidence for improving the mental health of the elderly and promoting active aging.Method:T-test and analysis of variance were used for univariate analysis,multiple linear regression was used for multivariate analysis,and point selection and Johnson Neyman methods were used to analyze the moderating effects of age and social participation.Results:At present,the level of the sense of uselessness of the elderly in China is relatively high.Internet use affects the sense of uselessness of the elderly(b=-0.10,P<0.001);With the increase of age and the level of social participation,the alleviating effect of Internet use on the sense of uselessness of the elderly has gradually weakened(b=0.01,P<0.05;b=0.02,P<0.01).Internet use can alleviate the sense of uselessness of the elderly and is regulated by age and social participation.It is suggested that the Internet access intervention should be carried out as soon as possible for the elderly at a lower age,and the elderly with a lower level of social participation should be focused,so as to play the positive role of the Internet in reducing the sense of uselessness of the elderly and improving their mental health.

Objective:To investigate the therapeutic effect of Ningmitai Capsules(NMT)on chronic prostatitis/chronic pel-vic pain syndrome(CP/CPPS)and its action mechanism.Methods:We equally randomized fifteen 6-8 weeks old male Wistar rats into a sham operation,a model control and an NMT group,and established a CP/CPPS model in the rats by intra-prostatic injection of complete Freund adjuvant(CFA).We treated the rats in the sham operation and model control groups by injection of aseptic phosphate buffer saline(PBS)and 50 μl complete Freund adjuvant(CFA),respectively,into the ventral lobe of the prostate followed by gavage with purified water from the second day after surgery,and those in the NMT group with 50 μl CFA injected into the ventral lobe of the prostate followed by gavage with 3 ml NMT suspension at 400 mg/kg/d from the second day after surgery.After 4 weeks of treatment,we killed the animals and collected the serum and prostatic tissue samples for evaluation of the severity of prostatitis by histopathological grading of chronic prostatitis through HE staining,determination of the mRNA expressions of inflammatory factors by real-time quantita-tive PCR,measurement of the activities of related antioxidant enzymes with testing kits,and detection of the expressions of the related targets in the signaling pathways by Western blot.Results:Histopathological examination revealed different degrees of inflammatory cell infiltration in the mesenchyme,inflammatory vacuoles,irregularly shaped acini in the model control group,with a significantly higher inflammation score than in the sham operation group(P＜0.05),and reduced infiltrating lymphocytes,inflammatory vacuoles and inflammation score in the NMT group compared with those in the model controls(P＜0.05).Compared with the rats in the sham operation group,the model controls showed remarkably up-regulated expressions of IL-1 β,IL-6,IL-10,IL-17A,TNF-α and IFN-γ(P＜0.05),decreased contents of superoxide dismutase(SOD),catalase(CAT)and glutathione peroxidase(GSH-Px)(P＜0.05),and increased content of malondialdehyde(MDA)(P＜0.05).Compared with the model controls,the rats treated with NMT exhibited markedly reduced expressions of IL-1β,IL-6,IL-10,IL-17A,TNF-α and IFN-γ(P＜0.05),increased contents of SOD,CAT and GSH-Px(P＜0.05),decreased content of MDA(P＜0.05),up-regulated expressions of nuclear factor red 2-related factor 2(n-Nrf2)and heme oxygenase-1(HO-1)(P＜0.05),and down-regulated expression of NF-κB P-P65(P＜0.05).Conclusion:NMT plays anti-oxidation and anti-inflammation roles in the pathogenesis of CP/CPPS,possibly by activation of Nrf2 and suppression of NF-κB signaling pathways.

AIM To investigate the effects of Zuogui Jiangtang Tongmai Recipe on necroptosis pathway in a rat model of type 2 diabetes mellitus(T2DM)complicated with cerebral infarction(CI).METHODS The SD rats were randomly divided into the sham operation group,the model group,the metformin group(0.045 g/kg),and the low,medium and high dose Zuogui Jiangtang Tongmai Recipe groups(6.5,13,26 g/kg),with 9 rats in each group.In contrast to rats of the sham operation group,rats of the other groups were given 4 weeks feeding of high-sugar and high-fat diet combined with intraperitoneal injection of streptozotocin to establish a T2DM rat model with one week stable blood glucose,followed by gavage of corresponding drugs 3 days before the establishment of the middle cerebral artery occlusion(MCAO)model.After 7 days of administration,the rats had their CI injury assessed by mNSS method and TTC staining;their level of blood glucose detected by blood glucose meter;their levels of glycated serum protein,serum TNF-α and IL-1β detected by ELISA;their cerebral mRNA expressions of FADD,RIPK1,RIPK3 and MLKL detected by RT-qPCR;and their cerebral protein expressions of FADD,p-RIPK1,p-RIPK3 and p-MLKL detected by Western blot.RESULTS Compared with the sham operation group,the model group displayed increased levels of blood glucose value,glycosylated serum protein,neurological function score,cerebral infarction volume,cerebral FADD,RIPK1,RIPK3 and MLKL mRNA expressions,cerebral FADD,p-RIPK1,p-RIPK3 and p-MLKL protein expressions,serum TNF-α and IL-1β levels(P＜0.01);and more disordered and morphologically diverse neurons with smaller nucleus.Compared with the model group,the groups intervened with medium or high dose Zuogui Jiangtang Tongmai Recipe,or metformin shared improvement in terms of the aforementioned indices(P＜0.05,P＜0.01);and more neurons with regular morphology neat arrangement,and reduced cell gap.CONCLUSION Zuogui Jiangtang Tongmai Recipe can improve the neurological dysfunction of the rat model of T2DM complicated with CI,which may associate with the inhibited activation of necroptosis signaling pathway.

AIM To study the chemical constituents from n-butanol fraction of Corydalis impatiens(Pall.)Fisch.and their antioxidant activities.METHODS The n-butanol fraction was isolated and purified by silica gel,MCI,ODS,Sephadex LH-20 and semi-preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The antioxidant activities were determined by DPPH method and tyrosinase method.RESULTS Fourteen compounds were isolated and identified as nicotinamide(1),methyl L-pyroglutamate(2),bungeanoline F(3),monomethyl fumarate(4),5-hydroxymethylfurfural(5),4-hydroxybenzoic acid(6),hydroxybenzoate(7),methyl 3,4-dihydroxybenzoate(8),methyl ferulate(9),dimethylcaffeic acid(10),dimethyl feruloyl malate(11),(-)-4-O-feruloylquinic acid(12),syringaresinol(13)and(-)-loliolide(14).Compounds 1,8,11 and 13 showed strong antioxidant activites on DPPH free radicals,with IC50 values ranging from 54.47 to 97.4 μmol/L.Compound 13 had potential inhibitory effect on tyrosinase.CONCLUSION Compounds 4-14 are first isolated from Corydalis genus,and 3 is isolated from this plant for the first time.Compounds 1,8,11 and 13 have strong antioxidant activities.

Clinical data of 15 primary central nervous system lymphoma (PCNSL) children aged ≤18 years admitted to our hospital between May 2013 to May 2023 were retrospectively analyzed. Our goal was to summarize the clinical features of children and investigate the therapeutic effect of a high-dose methotrexate (HD-MTX) based chemotherapy regimen on this disease. The male-to-female ratio was 2.7∶1, and the median age was 7.2 (2.3-16.4) years at diagnosis. The initial clinical symptoms were primarily cranial hypertension, with imaging findings revealing multiple lesions. Pediatric PCNSL with normal immune function has a favorable prognosis with HD-MTX-based chemotherapy. Patients with a stable disease can be treated with minimal or no maintenance. HD-MTX-based chemotherapy remains effective when the disease progresses or recurs after an initial course of non-HD-MTX-based chemotherapy.

Non-communicable diseases(NCDs),including cardiovascular diseases,cancer,metabolic diseases,and skeletal diseases,pose significant challenges to public health worldwide.The complex pathogenesis of these diseases is closely linked to oxidative stress and inflammatory damage.Nuclear factor erythroid 2-related factor 2(Nrf2),a critical transcription factor,plays an important role in regulating antioxidant and anti-inflammatory responses to protect the cells from oxidative damage and inflammation-mediated injury.Therefore,Nrf2-targeting therapies hold promise for preventing and treating NCDs.Quercetin(Que)is a widely available flavonoid that has significant antioxidant and anti-inflammatory properties.It modulates the Nrf2 signaling pathway to ameliorate oxidative stress and inflammation.Que modulates mitochondrial function,apoptosis,autophagy,and cell damage biomarkers to regulate oxidative stress and inflammation,highlighting its efficacy as a therapeutic agent against NCDs.Here,we discussed,for the first time,the close association between NCD pathogenesis and the Nrf2 signaling pathway,involved in neurodegenerative diseases(NDDs),cardiovascular disease,cancers,organ damage,and bone damage.Furthermore,we reviewed the availability,pharmacokinetics,pharmaceutics,and therapeutic applica-tions of Que in treating NCDs.In addition,we focused on the challenges and prospects for its clinical use.Que represents a promising candidate for the treatment of NCDs due to its Nrf2-targeting properties.