ObjectiveThis paper aims to investigate the efficacy and related actions of Guizhi Fulingwan in intervening in the mice with colitis-associated colon cancer （CAC） based on the immunosuppressive microenvironment associated with myeloid-derived suppressor cells （MDSCs）. MethodsSixty male C57BL/6 mice were randomly assigned to a blank group， a model group， an aspirin group （0.04 g·kg^-1）， and low-， medium-， and high-dose Guizhi Fulingwan groups （4.87， 9.75， and 19.50 g·kg^-1）， with ten mice per group. The CAC mouse model was established via combined induction of azoxymethane （AOM）/dextran sulphate sodium （DSS）. Drug intervention commenced in week five， with continuous intragastric administration for nine weeks. The food intake， body weight， fecal characteristics， and haematochezia were observed and recorded， and disease activity index （DAI） scores were calculated according to scoring criteria. Hematoxylin and eosin （HE） staining was used to observe the histopathological changes in the colon tissues of the mice. Immunohistochemistry was used to determine proliferating cell nuclear antigen-67 （Ki67） expression in the colon tissues， and enzyme-linked immunosorbent assay （ELISA） was used to detect the contents of interleukin-6 （IL-6）， IL-1β， and tumor necrosis factor-α （TNF-α） in the serum of the mice. Flow cytometry was employed to determine the proportion levels of MDSCs， CD4⁺ T cells， and CD8⁺ T cells in the spleen tissues of the mice. The mRNA expressions of MDSC-associated effector molecules， including arginase 1 （Arg1） and inducible nitric oxide synthase （iNOS）， were detected by real-time quantitative polymerase chain reaction （Real-time PCR）. After that， an in vitro co-culture model of MDSCs and CD8⁺ T cells was established， and drug-containing serum of Guizhi Fulingwan was used for intervention. The Flow cytometry was employed to assess the effects of drug-containing serum of Guizhi Fulingwan with different concentrations on the levels of reactive oxygen species （ROS） and iNOS in MDSCs and the proliferation of CD8⁺ T cells. The levels of granzyme B （GZMB） and interferon-γ （IFN-γ） in cell supernatant were detected by ELISA. ResultsCompared with those in the control group， the mice in the model group exhibited significantly reduced body weight， elevated DAI scores， shortened colon length （P<0.01）， increased number of tumors and Ki67 expression （P<0.01）， and significantly elevated contents of IL-6， IL-1β， and TNF-α in the serum （P<0.01）. Significant increases in the number of MDSCs were observed in mouse spleens， alongside marked reductions in the levels of CD4⁺ T and CD8⁺ T cells （P<0.01）. Furthermore， the mRNA expressions of MDSC function-associated effector molecules Arg1 and iNOS were significantly upregulated （P<0.01）. Compared with those in the model group， the mice in the middle-dose Guizhi Fulingwan group exhibited increased body weight and significantly decreased DAI scores （P<0.05， P<0.01）. The mice in the middle- and high-dose Guizhi Fulingwan groups exhibited significantly improved colon shortening， significantly decreased number of tumors and Ki67 expression （P<0.05， P<0.01）， and significantly decreased contents of IL-6， IL-1β， and TNF-α in the serum （P<0.05， P<0.01）. Furthermore， administration of Guizhi Fulingwan markedly reduced MDSC infiltration in the spleen of the mice， with different degrees of increase in the levels of both CD4⁺ T and CD8⁺ T cells （P<0.05， P<0.01）， alongside significant decreases in the mRNA expressions of Arg1 and iNOS （P<0.05， P<0.01）. In vitro cell co-culture shows that administration of drug-containing serum of Guizhi Fulingwan significantly decreases the activity levels of ROS and iNOS in MDSCs and promotes the proliferation of CD8⁺ T cells and the secretion of GZMB and IFN-γ （P<0.05， P<0.01）. ConclusionGuizhi Fulingwan can reduce pro-inflammatory cytokine secretion and inhibit tumor proliferation in the colon tissues of CAC mice. Its potential mechanism may involve reducing MDSC infiltration， enhancing effector T cells， particularly CD8⁺ T cell response， and improving the tumor immunosuppressive microenvironment.

Objective The aim of this study is to examine the Chinese version of Visual Prostate Symptom Score(CVPSS)and the International Prostate Symptom Score(IPSS)in the assessment of lower urinary tract symptoms in BPH pa-tients.Methods By using convenient sampling,inpatients in the urology department of a tertiary grade A hospital in Shanghai were selected as the survey subjects from March 2023 to March 2024.The lower urinary tract symptoms of the patients were eval-uated using the self-designed general information questionnaire.And the CVPSS and IPSS with their urine flow rate were meas-ured.A comparative analysis was conducted from aspects such as internal consistency,correlation of item scores,completion time of the scale,and assistance rate.Results A total of 246 patients with BPH were recruited.The total score and life quality score were 13.93±3.55 and 4.23±1.02 by CVPSS.And the total score and life quality by IPSS was 18.33±7.55 and 4.36±1.02,respectively.The Cronbach's α coefficient were 0.761 and 0.787,respectively.The time taken on CVPSS was less than that on IPSS(P＜0.01).And the rate of needing assistance was 23.58％for CVPSS,which was significantly lower than that(65.24％)for IPSS.Conclusion CVPSS is significantly correlated with the corresponding items and total scores of IPSS,as well as the quality of life.Moreover,it takes less time and can be used as a simple and effective self-assessment tool for lower urinary tract symptoms in elderly BPH patients with lower education levels.It reduces the burden of medical staffs as well.

AIM To study the chemical constituents from Stelmatocrypton khasianum.(Benth.)Baill.and their in vitro anti-inflammatory activity and cytotoxic activity.METHODS Separation and purification were performed using thin layer chromatography,silica gel,semi-preparative HPLC and Sephadex LH-20,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The in vitro anti-inflammatory activity was evaluated by RAW264.7 model,and the cytotoxic activity was determined by CCK-8 method.RESULTS Fifteen compounds were isolated and identified as 2α,3β,19α,23-tetrahydroxy-urs-12-en-28-oic acid-3-O-β-D-glucopyranosyl-28-O-β-D-glucopyranosyl ester(1),dalzienoside(2),benzyl-(6-O-α-L-rhanmopyranosyl)O-β-D-glucopyranoside(3),corchorusoside C(4),cyclo(Ala-Tyr)(5),thymidine(6),(4S,5S)-5-hydroxy-4-hexanolide(7),2-methylpyridin-3-ol(8),butyl isobutyl phthalate(9),bis-(2-ethylhexyl)terephthalate(10),p-hydroxybenzaldehyde(11),vanilic acid(12),salicylic acid(13),isovanilic acid(14),3-hydroxy-p-anisaldehyde(15).The IC50 values of compounds 1,2 and 4 for NO were(27.69±5.51),(25.82±3.58)and(23.35±7.09)μmol/L,respectively.The IC50 value of compound 1 on MCF-7 cells was(18.15±6.45)μmol/L.The IC50 values of compound 4 on MCF-7 and HCCC-9810 cells were(19.43±2.66)and(21.76±5.81)μmol/L,respectively.CONCLUSION Compounds 2-11 are isolated from S.khasianum for the first time.Compounds 1,2 and 4 exhibit good in vitro anti-inflammatory activity,and 1,4 have cytotoxic activity.

Objective:To evaluate the effectiveness and safety of belumosudil for the treatment of chronic graft-versus-host disease (cGVHD) .Methods:We retrospectively collected data on patients with cGVHD who received belumosudil at Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine from May 2023 to March 2024. The study endpoints were overall response rate (ORR), organ-specific response rates, time to response (TTR), changes in Lee Symptom Scale (LSS) scores, tapering or discontinuation of corticosteroid treatment, failure-free survival (FFS), and adverse events.Results:The study included 20 patients with cGVHD who received belumosudil, of whom 15 were men and 5 women. The median age was 34.5 (12-67) years, and three patients were under 18 years old. The median follow-up duration was 5.0 (1.4 - 9.8) months. All patients had severe cGVHD, and 18 (90.0%) showed involvement of at least four organs. The median number of prior treatment lines was 4, and 15 patients (75%) had previously received ruxolitinib. All patients received 200 mg of belumosudil once daily in combination with other cGVHD systemic therapies. The ORR was 90.0% (95% CI: 68.3%-98.8%), and all responses were partial responses. The median TTR was 1.6 (0.9 - 8.4) months. The LSS scores improved in a clinically meaningful way in 80.0% (16/20) of the patients within 3 months. The corticosteroid dose was reduced in 42.6% (6/14) of the patients. The 3-month FFS was 79.6% (95% CI: 61.4%-100.0%). Most adverse events were grade 1 or grade 2, and two patients (10.0%) experienced grade 3 or higher-grade adverse events. Conclusions:In the real-world setting, belumosudil demonstrated good effectiveness and safety in patients with cGVHD with a history of severe disease and multiorgan involvement.

Based on the concept of"two-stage,four-phase,and three-phase treatments"of in vitro fertilization and embryo transfer(IVF-ET)assisted the whole-course management of TCM by national TCM master You Zhaoling,this article analyzed the treatment strategy assisted by acupuncture in five aspects:principle,method,prescription,acupoint,and technique.Principle:syndrome differentiation and treatment follow different cases;method establish guiding methods based on principles,while following stage diagnoses and treatments;prescription:determine the prescriptions based on therapeutic principles within the context of overall regulation;acupoint:precise acupoint taking and rational acupoint matching;technique:the primary method is acupuncture,supported by various therapeutic modalities,providing a comprehensive framework and evidence-based support for the clinical application of acupuncture and moxibustion in IVF-ET.

Cardiogenic shock(CS)is a disease characterized by reduced cardiac output leading to inadequate end-organ perfusion and remains a significant issue in cardiovascular medicine.Despite significant therapeutic advancements in recent years,the mortality rate associated with CS remains high.Mechanical circulatory support(MCS)has emerged as an innovative therapeutic strategy,capable of maintaining hemodynamic stability and ensuring systemic perfusion of vital organs,thereby effectively improving patient prognosis and lowering mortality rates.This review summarizes the latest research progress on commonly used MCS devices,both domestically and internationally,covering aspects of CS overview,left and right heart assist,bicardial and total heart assist,as well as the selection and limitations of MCS devices.We provide an overview of the types of MCS devices currently available and their indications for use,aiming to offer better clinical guidance to physicians and enhance the treatment level of CS.

Objective To investigate the effect of Huangqi Shengmai Yin(HSY)on myocardial fibrosis in rats with acute myocardial infarction(AMI)by adjusting P2X purinoceptor 7(P2X7R)/NOD-like receptor protein 3(NLRP3)pathway.Methods Sixty rats were divied into a sham operation group and model group(5 groups),with 10 rats in each group.The AMI rat model was constructed by ligating the left anterior descending branch and randomly grouped into AMI group,the HSY-low group(intragastric administration of 1.6 ml/kg HSY),the HSY group(intragastric administration of 6.2 ml/kg HSY),the compound miltiorhiza group(intragastric administration of 300 mg/kg),and the HSY-high+P2X7R agonist-ATP group(intragastric administration of 6.2 ml/kg HSY,and tail vein administration of 10 mmol/L ATP).After the intervention,cardiac function,myocardial injury and inflammatory factor markers were detected.The tissue sections were prepared to examine pathological changes,myocardial fibrosis,type Ⅰ and type Ⅲ collagen(COL1A1,COL3A1).Western blotting was performed to detecte the protein expression of P2X7R,NLRP3,tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),and the expression of activated Caspase-1.Results Compared with the sham surgery group,the AMI group showed an increase in the left ventricular end diastolic diameter(LVEDD),the coatent of brain natriuretic peptide(BNP)and cardiac troponin I(cTn I),fibrosis volume fraction,the positive expression of COL1A1,COL3A1,TNF-α,IL-1β,P2X7R,NLRP3,and activated Caspase-1 proteins(P＜0.05),and a decrease in left ventricular ejection fraction(LVEF)(P＜0.05).The HSY-low group,HSY-high groups,and compound miltiorhiza group showed a decrease in LVEDD,the content of BNP and cTn I,fibrosis volume fraction,the positive expression of COL1A1 and COL3A1,TNF-α,IL-1β,P2X7R,NLRP3,and activated Caspase-1 proteins(P＜0.05),and an increase in LVEF than these in the AMI group(P＜0.05).The HSY-high+ATP group showed an increase in LVEDD,the content of BNP,cTn I,fibrosis volume fraction,the positive expression of COL1A1 and COL3A1,TNF-α,IL-1β,P2X7R,NLRP3,and activated Caspase-1 proteins(P＜0.05),and a decrease in LVEF than those in the HSY-high group(P＜0.05).Conclusion HSY inhibits P2X7R/NLRP3 pathway to alleviate myocardial fibrosis in AMI rats.

Objective:To analyze the development trend of medical institution bed allocation in OECD countries and provide insights for optimizing bed resources allocation in China.Methods:Data on indicators of bed allocation and related factors from 1991 to 2022 were collected from the OECD online database.Bed allocation impact dimensions were identified based on health needs and demand theories.The random effect model and correlation analysis were used to explore influencing pathways of bed allocation.Results:The number of beds per 1 000 population and average life expectancy showed a significant positive correlation in countries below the average bed level,while an inverse trend was observed in countries above the average level.The number of long-term care beds per 1000 population showed positive correlation with average life expectancy.Multidimensional factors such as the disease spectrum and bed utilization efficiency were significant correlated with the bed allocation levels.The greater the gap in inpatient and outpatient reimbursement rations,the higher the demand for hospitalization among patients with chronic disease.Conclusions:An optimal number of beds is essential for achieving higher health outcomes.The bed classification planning system should be designed to adapt to demographic changes and strengthen the medical security support system.

Objective:To explore the neurophysiological features of the prefrontal-limbic-striatal circuit in patients with early-stage bipolar disorder without manic or hypomanic episodes, and its role in identifying early-stage bipolar disorder.Methods:From 2009 to 2019, a total of 155 hospitalized patients with major depressive disorder (MDD) from Nanjing Brain Hospital were selected after at least 5 years of follow-up, 31 patients with depression transitioned to bipolar disorder(ctBD group) and 76 patients remained the diagnosis of MDD(MDD group) were recruited.Sixty-two healthy controls matched for age, gender, and education years were selected as control group(HC group). Resting-state magnetoencephalography (MEG) data in eyes-open state of all subjects were collected.Data were analyzed based on the fieldtrip toolkit on the MATLAB platform. The key brain area of the prefrontal-limbic-striatal circuit were selected. Inter-group statistical analysis were conducted on the spectral energy and power-correlated functional connectivity at the theta, alpha, beta, and gamma frequency bands in the brain area of interest. In addition, the prediction model was constructed to early recognize bipolar disorder.Results:(1)There were statistically significant differences in the spectral energy of theta and alpha frequency bands in the prefrontal-limbic-striatal circuit among the 3 groups (cluster- F=120.50, 112.39, both P<0.05). The spectral energy of theta and alpha frequency bands in interest brain regions of prefrontal-limbic-striatal circuit in MDD group was lower than that in HC group (cluster- t=89.52, P<0.05). The spectral energy of theta band in prefrontal-limbic-striatal circuit in ctBD group was lower than that in HC group(cluster- t=105.82, P<0.05), and the spectral energy of alpha band in inferior frontal gyrus, orbitofrontal gyrus and caudate nucleus was lower than that in HC group (cluster- t=75.78, P<0.05), while there was no significant difference between the MDD group and the ctBD group ( P>0.05).(2)After FDR correction, there were statistically significant differences in functional connectivity between the left orbitofrontal gyrus and the right ventral striatum among the three groups (0.26 (0.13, 0.34), 0.12 (0.09, 0.24), 0.27 (0.20, 0.37), H=13.51, P<0.05, FDR correction). The strength of functional connectivity between the left orbitofrontal gyrus and the right ventral striatum in the MDD group was weaker than that in the HC group and the ctBD group (all P<0.05).(3)Binary Logistic regression analysis showed that the functional connectivity of beta frequency band between the left orbitofrontal gyrus and the right ventral striatum ( B=1.50, OR=4.50, 95% CI=1.73-11.70), the functional connectivity between the right orbitofrontal gyrus and the right amygdala( B=0.98, OR=2.68, 95% CI=1.18-6.13), the total HAMD score ( B=0.80, OR=2.28, 95% CI=1.36-3.67), the body weight factor score ( B=-1.99, OR=0.14, 95% CI=0.04-0.45), the anxiety factor score ( B=-0.99, OR=0.37, 95% CI=0.19-0.71), and sleep factor score( B=-1.14, OR=0.32, 95% CI=0.16-0.65)were the influencing factors for depression transitioned to bipolar disorder. Conclusion:The decreased resting low-frequency energy in the prefrontal-limbic-striatal circuit may be the common neural basis for the onset of unipolar and bipolar depression, and enhanced functional connectivity may be a potential neural circuit mechanism for depression transitioned to bipolar disorder. Functional connectivity combined with clinical manifestations is helpful for early recognition of bipolar disorder.

Aim To explore the possible regulatory effect of leptin on acyl-CoA synthetase long chain fami-ly member ACSL5 and their effect on migration and in-vasion of breast cancer cell,and to explore the underly-ing mechanism.Methods The expression of leptin receptor was detected by immunofluorescence assay.The migration and invasion ability of MCF-7 cells were detected by wound healing assay and Transwell assay respectively.The downstream target gene of leptin was analyzed by PCR microarray data.The expression of ACSL5 in breast cancer and its correlation with the staging and prognosis of breast cancer patients were as-sessed uing bioinformatics methods.The expression of ACSL5 in MCF-7 cells treated with different concentra-tions of leptin was detected using real time fluorescence quantitative polymerase chain reaction(RT-qPCR).Overexpressing ACSL5 was constructed by lentiviral transfection;the expressions of EMT related proteins,AMPK-α and p-AMPK-α were detected by Western blot.Results Leptin promoted breast cancer cell mi-gration and invasion and EMT.ACSL5 was significant-ly low expressed in breast cancer and related to progno-sis.Leptin downregulated the expression of ACSL5 through OBR.Leptin activated AMPK pathway to downregulate ACSL5 and promote migration,invasion and EMT of breast cancer cells.Conclusions Leptin may promote the migration,invasion and EMT of breast cancer by downregulating ACSL5 through activating AMPK pathway.