BACKGROUND:Type 2 diabetes mellitus is a secondary causative factor for osteoporosis.As highly heterogeneous innate immune cells,macrophages may be polarized in a hyperglycemic environment,which affects osteogenesis-angiogenesis coupling.This may be a research target for improving bone quality in patients with type 2 diabetic osteoporosis.OBJECTIVE:To explore the role of modulating macrophage M1/M2 polarization to influence osteogenesis-angiogenesis coupling in type 2 diabetic osteoporosis and to summarize the effects of commonly used anti-glucose and anti-osteoporosis drugs and bone biorepair materials on bone osteogenesis-angiogenesis coupling by regulating macrophage M1/M2 polarization.METHODS:The keywords of"macrophage polarization,type 2 diabetes,osteoporosis,osteogenesis-angiogenesis coupling"in Chinese and"macrophages,macrophage polarization,osteogenesis-angiogenesis coupling"in English were used to search for relevant literature in CNKI and PubMed,respectively.Seventy-nine pieces of literature were screened and analyzed.RESULTS AND CONCLUSION:(1)Type 2 diabetes mellitus causes the body to be in a hyperglycemic environment and increases the secretion of inflammatory-related factors in the body,which promotes macrophage polarization towards M1 and decreases the number of M2 macrophages.(2)In type 2 diabetes,promoting M2 macrophage polarization is beneficial for osteogenesis-angiogenesis coupling.(3)Some anti-glycemic drugs,active ingredients in traditional Chinese medicine and bone biorepair materials can improve type 2 diabetic osteoporosis by regulating macrophage M1/M2 polarization,reducing M1/M2 ratio,and promoting osteogenesis-angiogenesis coupling.

OBJECTIVE To investigate the mechanism of Xihuang pill （XHP） against diffuse large B-cell lymphoma （DLBCL）. METHODS The active ingredients of XHP and potential therapeutic targets for DLBCL were identified using TCMSP， GeneCards and DisGeNET databases. Protein-protein interaction networks were constructed using the String database and Cytoscape software to screen core components and core targets. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were then performed. The clinical relevance of core targets was analyzed using the GEPIA and PanCanSurvPlot databases. Molecular docking and molecular dynamics （MD） simulation were conducted to verify the interactions between core components and core targets， and the binding free energy was calculated using the molecular mechanics Poisson-Boltzmann surface area （MM-PBSA） method. The effects of XHP on DLBCL and the related molecular mechanisms were validated using CCK-8 assay， flow cytometry and Western blot. RESULTS Network pharmacology analysis identified 108 active ingredients of XHP and 410 potential therapeutic targets for DLBCL. Six core components （e.g.， 17 beta-estradiol， quercetin） and ten core targets [e.g.， tumor protein 53 （TP53）， proto-oncogene tyrosine-protein kinase Src （SRC）] were obtained. Enrichment analysis indicated that the anti-DLBCL effects of XHP were primarily associated with the apoptotic signaling pathway， the phosphoinositide 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway and so on. Clinical correlation analysis revealed that TP53 and SRC expression were significantly up-regulated in DLBCL tissues and associated with poor patient prognosis （P＜0.05）. Molecular docking， MD simulations and MM-PBSA calculations confirmed that the SRC-quercetin complex had a mail：stronger and more stable binding affinity. In vitro experiments demonstrated that XHP concentration-dependently inhibited the proliferation of DLBCL cells； compared with control group， XHP medium- and high-dose groups could significantly induce the apoptosis of SU-DHL2 and SU-DHL4 cells， and significantly down- regulated the expressions of SRC protein， phosphorylated （p）-PI3K/PI3K and p-Akt/Akt in SU-DHL4 cells （P＜0.05）. CONCLUSIONS XHP may inhibit the proliferation and induce the apoptosis of DLBCL cells by regulating the SRC/PI3K/Akt signaling pathway.

BACKGROUND:Type 2 diabetes mellitus is a secondary causative factor for osteoporosis.As highly heterogeneous innate immune cells,macrophages may be polarized in a hyperglycemic environment,which affects osteogenesis-angiogenesis coupling.This may be a research target for improving bone quality in patients with type 2 diabetic osteoporosis.OBJECTIVE:To explore the role of modulating macrophage M1/M2 polarization to influence osteogenesis-angiogenesis coupling in type 2 diabetic osteoporosis and to summarize the effects of commonly used anti-glucose and anti-osteoporosis drugs and bone biorepair materials on bone osteogenesis-angiogenesis coupling by regulating macrophage M1/M2 polarization.METHODS:The keywords of"macrophage polarization,type 2 diabetes,osteoporosis,osteogenesis-angiogenesis coupling"in Chinese and"macrophages,macrophage polarization,osteogenesis-angiogenesis coupling"in English were used to search for relevant literature in CNKI and PubMed,respectively.Seventy-nine pieces of literature were screened and analyzed.RESULTS AND CONCLUSION:(1)Type 2 diabetes mellitus causes the body to be in a hyperglycemic environment and increases the secretion of inflammatory-related factors in the body,which promotes macrophage polarization towards M1 and decreases the number of M2 macrophages.(2)In type 2 diabetes,promoting M2 macrophage polarization is beneficial for osteogenesis-angiogenesis coupling.(3)Some anti-glycemic drugs,active ingredients in traditional Chinese medicine and bone biorepair materials can improve type 2 diabetic osteoporosis by regulating macrophage M1/M2 polarization,reducing M1/M2 ratio,and promoting osteogenesis-angiogenesis coupling.

Based on the theory of traditional Chinese medicine （TCM） chronomedicine， this paper explores the pathogenesis and treatment strategies of colorectal cancer mediated by circadian rhythm disorders. It is believed that the imbalance of yin and yang is isomorphic to the disorder of biological clock genes， which is the root cause of the disease. The disharmony of ying and wei （营卫） corresponds to the imbalance of immunity and metabolism， which is the pivot of the disease. The disorder of qi movement is related to the imbalance of intestinal barrier， which is the manifestation of the disease. Accordingly， relevant strategies are proposed， including chronochemotherapy regimen that aligns with biological rhythms to enhance efficacy and reduce toxicity， acupuncture based on the ebb and flow of midnight and midday which selects acupoints along meridians to harmonize qi and blood， and a timed medication strategy that matches the disease mechanism by administering drugs at optimal times. These strategies aim to deepen the understanding of the pathogenesis of colorectal cancer mediated by circadian rhythm disorders from the perspective of TCM chronomedicine， thereby providing new ideas for clinical practice.

Objective:To examine the effect of cumulative hemoglobin A 1c (HbA 1c) levels and insulin dosage on insulin resistance (IR)-related metabolic disturbances in newly diagnosed patients with type 1 diabetes (T1D). Methods:This retrospective cohort study included T1D patients admitted to the Second Xiangya Hospital of Central South University from November 2015 to March 2023. Clinical data collected comprised age, sex, disease duration, insulin dosage, body mass index, waist circumference, blood pressure, HbA 1c levels, islet autoantibodies, and fasting blood lipid profiles. IR-related metabolic disturbances assessed were overweight, obesity, central obesity, hypertension, and dyslipidemia. Cox regression and cluster analyses were applied to assess the influence of cumulative HbA 1c and insulin dosage on these metabolic disturbances. Results:A total of 235 patients were included, with 97 males (41.3%) and 138 females (58.7%). The median age was 19.8 (13.3, 31.1) years, and the median follow-up duration was 30.8 (20.8, 45.6) months. During follow-up, 41.6% (72/173) of patients developed IR-related metabolic disturbances. Multivariate Cox regression analysis revealed that a cumulative HbA 1c ≥60 mmol/mol was an independent risk factor for any IR-related metabolic disturbance [ HR (95% CI): 1.739 (1.067-2.835) ] and for triglyceride abnormalities [ HR (95% CI): 3.277 (1.176-9.127)]. Additionally, a cumulative insulin dosage ≥0.5 U·kg -1·d -1 was identified as an independent risk factor for overweight, obesity, or central obesity [ HR (95% CI): 2.374 (1.059-5.323)]. Cluster analysis further identified that patients with higher levels of cumulative HbA 1c and insulin dosage, particularly those with adolescent-onset diabetes, had the highest likelihood of developing hypertension ( HR=2.460, 95% CI 1.008-6.005), overweight/obesity/central obesity ( HR=2.707, 95% CI 1.062-6.900), triglyceride abnormalities ( HR=5.495, 95% CI 1.842-16.391), high-density lipoprotein cholesterol abnormalities ( HR=11.054, 95% CI 4.107-29.751), and any IR-related metabolic disturbance ( HR=5.833, 95% CI 2.602-13.077). Conclusions:Elevated cumulative HbA 1c and insulin dosage levels in T1D patients are associated with an increased risk of developing IR-related metabolic disturbances. These findings underscore the urgent need for novel therapeutic strategies tailored to this population.

Objective To explore the effect of low-frequency repetitive transcranial magnetic stimulation(rTMS)combined with unilateral upper limb mirror training on contralateral limb strength in patients with hemiplegia after ischemic stroke.Methods A total of 196 patients with hemiplegia after ischemic stroke were selected.All patients were divided into study group and control group via a random number table method,with 98 patients in each group.The control group received mirror training,while the study group received low-frequency rTMS treatment in addition to the control group.The neuroelectrophysiology,neurological function,limb motor function,and clinical efficacy of all patients were observed before and after treatment,and all patients were performed the resting-state functional MRI examination.A generalized estimating equation(GEE)model were used to analyze the improvement of contralateral limb strength.Results After treatment,the seed points in the study group showed a significant enhancement in connectivity with the whole brain function.The overall efficiency of the study group was significantly better than that of the control group.After treatment,the central motor conduction time(CMCT),neuron specific enolase(NSE),cortical latency(CL),and S100β of the two groups of patients were significantly reduced compared with before treatment,while the neurotrophin-3(NT-3),nerve growth factor(NGF),Fugl-Meyer assessment upper extremities(FMA-UE),Wolf motor function test(WMFT),modified Barthel index(MBI),and Berg balance scale(BBS)scores were significantly increased.Moreover,the study group showed a more significant improvement compared to the control group(P＜0.05).The GEE model analysis results showed that the improvement of contralateral limb strength in the study group was significantly better than that in the control group.Conclusion Low-frequency rTMS combined with unilateral upper limb mirror training can improve cortical excitability and upper limb motor function in hemiplegic patients after ischemic stroke,with good therapeutic effects.

Objective:To investigate whether there is a causal relationship between atopic dermatitis(AD)and ankylosing spondylitis(AS).Methods:Genetic data of AD and AS were extracted from genome-wide association studies(GWAS)by Mendelian randomization(MR),and inverse variance-weighted(IVW)analysis was used as main analysis,supplemented by weighted median,MR-Egger,weighted mode,etc,and verified by a series of sensitivity analyses.Results:IVW analysis of AD by AS:OR=1.015,95％CI:1.005～1.025,P=0.004.IVW analysis of AD for AS:OR=1.001,95％CI:1.000～1.002,P=0.120.Conclusion:AS has a statisti-cally small causal relationship on AD,and AD has no causal effect on AS.

Objective To establish a performance evaluation index system for fixed asset management in public hospitals provides a scientific basis for the performance evaluation of fixed asset management in public hospitals in Hainan Province.Methods Utilizing the literature review method,an initial framework of evaluation index was established.This framework was then adjusted and optimized through expert consultation.The Analytic Hierarchy Process was employed to quantify the weights of each evaluation index,leading to the construction of the final evaluation index system.Results The results indicated that the active coefficient of expert consultation was 100％,the authority coefficient was 0.83,and the variation coefficient range for the second round of expert consultation was 0.06 to 0.20.The Kendall's W coefficient of concordance for the comprehensive indicators evalation indexs 0.486,with P<0.001.The established performance evaluation index system for fixed asset management in public hospitals in Hainan Province encompasses three primary indicators,seven secondary indicators,and 33 tertiary indicators.The weights allocated to these three primary indicators are 0.4705,0.3051 and 0.2244,respectively.Conclusion The performance evaluation index system for fixed asset management in public hospitals in Hainan Province is scientifically and reasonably designed,providing a theoretical basis and reference for the performance evaluation of fixed asset management in public hospitals in Hainan Province.

Objective:To investigate the drug resistance of newly diagnosed HIV-1 infected patients in Shanghai and to provide reference value for clinical antiretroviral therapy (ART).Methods:The peripheral venous blood plasma of 196 newly diagnosed HIV-1 infected patients screened according to the inclusion and exclusion criteria at the Shanghai Public Health Clinical Center from April to June 2023 was collected, HIV-1 RNA was extracted, the pol region was amplified by reverse transcription-polymerase chain reaction (RT-PCR) for sequencing, the mutation sites and ART drug resistance were analyzed.Results:The plasma of 196 newly diagnosed HIV-1 infected patients was amplified successfully in 162 cases (amplification success rate was 82.65%). The subtypes consisted of CRF07_BC(51.23%), CRF01_AE (27.78%), and others (6.79%), CRF55_01B (5.56%), B (3.70%), CRF01_AE/B (3.70%) and CRF08_BC (1.23%). The overall transmitted drug resistance rate was 7.41%, the protease inhibitors (PIs), non-nucleoside/nucleotide reverse transcriptase inhibitors (NNRTIs), nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), integrase inhibitors (INSTIs) resistance rates were 3.09%, 3.70%, 0.00% and 0.62%, respectively. The proportion of NNRTIs-related mutation sites in B (66.67%) and CRF55_01B (88.89%) was higher than that in CRF07_BC (13.25%); the proportion of NNRTIs-related mutation sites in CRF55_01B (88.89%) was higher than that in CRF01_AE (22.22%) and other subtypes (18.18%), the difference was statistically significant (all P<0.05). Multivariate logistic regression analysis showed that the probability of PIs-related mutation sites in CRF01_AE/B was 21.71 times that of CRF07_BC[odds ratio ( OR)=21.71, 95% confidence interval ( CI): 3.36-140.27, P=0.001]. Conclusions:The transmitted drug resistance among newly diagnosed HIV-1 infected patients in Shanghai is at the moderate epidemic level, mainly NNRTIs and PIs-related drug resistance, and the INSTIs resistance rate is low, the use of INSTIs in ART regimens should be considered.

Objective:To examine the effect of cumulative hemoglobin A 1c (HbA 1c) levels and insulin dosage on insulin resistance (IR)-related metabolic disturbances in newly diagnosed patients with type 1 diabetes (T1D). Methods:This retrospective cohort study included T1D patients admitted to the Second Xiangya Hospital of Central South University from November 2015 to March 2023. Clinical data collected comprised age, sex, disease duration, insulin dosage, body mass index, waist circumference, blood pressure, HbA 1c levels, islet autoantibodies, and fasting blood lipid profiles. IR-related metabolic disturbances assessed were overweight, obesity, central obesity, hypertension, and dyslipidemia. Cox regression and cluster analyses were applied to assess the influence of cumulative HbA 1c and insulin dosage on these metabolic disturbances. Results:A total of 235 patients were included, with 97 males (41.3%) and 138 females (58.7%). The median age was 19.8 (13.3, 31.1) years, and the median follow-up duration was 30.8 (20.8, 45.6) months. During follow-up, 41.6% (72/173) of patients developed IR-related metabolic disturbances. Multivariate Cox regression analysis revealed that a cumulative HbA 1c ≥60 mmol/mol was an independent risk factor for any IR-related metabolic disturbance [ HR (95% CI): 1.739 (1.067-2.835) ] and for triglyceride abnormalities [ HR (95% CI): 3.277 (1.176-9.127)]. Additionally, a cumulative insulin dosage ≥0.5 U·kg -1·d -1 was identified as an independent risk factor for overweight, obesity, or central obesity [ HR (95% CI): 2.374 (1.059-5.323)]. Cluster analysis further identified that patients with higher levels of cumulative HbA 1c and insulin dosage, particularly those with adolescent-onset diabetes, had the highest likelihood of developing hypertension ( HR=2.460, 95% CI 1.008-6.005), overweight/obesity/central obesity ( HR=2.707, 95% CI 1.062-6.900), triglyceride abnormalities ( HR=5.495, 95% CI 1.842-16.391), high-density lipoprotein cholesterol abnormalities ( HR=11.054, 95% CI 4.107-29.751), and any IR-related metabolic disturbance ( HR=5.833, 95% CI 2.602-13.077). Conclusions:Elevated cumulative HbA 1c and insulin dosage levels in T1D patients are associated with an increased risk of developing IR-related metabolic disturbances. These findings underscore the urgent need for novel therapeutic strategies tailored to this population.