Macrophages play a pivotal role in host defense against Mycobacterium tuberculosis ( Mtb) infection. Their metabolic processes and metabolites are essential for maintaining immune homeostasis, responding to invading pathogens, and orchestrating subsequent immune responses. Therefore, a comprehensive understanding of macrophage metabolic reprogramming during Mtb infection is critical for deciphering the intricate mechanisms underlying the host immune response against tuberculosis. This review summarizes recent advances in how macrophages regulate immune responses through core metabolic pathways, including glucose metabolism, oxidative phosphorylation, lipid metabolism, and amino acid metabolism, in the context of Mtb infection. The insights provided here offer new perspectives and potential strategies for future tuberculosis prevention and targeted therapy.

Objective:To evaluate the clinical equivalence between a domestic calcipotriol/betamethasone dipropionate ointment and the originator product in the treatment of stable plaque psoriasis.Methods:A multicenter, randomized, double-blind, three-arm, parallel-group, active- and placebo-controlled study was conducted, and 449 patients aged 18 - 65 years with stable plaque psoriasis were enrolled from 25 hospitals (such as the First Affiliated Hospital of China Medical University). Eligible patients had a baseline physician's global assessment (PGA) score of ≥ 3 points, baseline body surface area (BSA) involvement of 5% - 30%, and a target lesion psoriasis area and severity index (TL-PASI) for plaque elevation of ≥ 3 points. Participants were randomly assigned in a 2:2:1 ratio to the test group ( n = 179), reference group ( n = 180), and placebo group ( n = 90), and applied the domestic calcipotriol/betamethasone dipropionate ointment, originator product, and ointment base respectively, once daily in the evening for 4 weeks. Efficacy and safety were assessed at weeks 1, 2, and 4. The primary efficacy endpoints were the treatment success rates and clinical success rates in each group at week 4. The per-protocol set (PPS) was used for the primary efficacy analysis, and the intention-to-treat (ITT) set for supplementary efficacy analysis. Equivalence between the test and reference preparations was tested using the Cochran-Mantel-Haenszel method adjusted for randomization strata. Superiority of the test and reference preparations over the placebo was also tested. Measurement data were compared among the 3 groups using analysis of variance or non-parametric tests, while treatment success rates, clinical success rates, and incidence rates of adverse reactions were compared using the chi-square test. Results:The ITT, PPS, and safety sets included 447, 420, and 448 patients, respectively. In the ITT set, patients were aged 43.6 ± 12.8 years, including 320 (71.6%) males and 127 (28.4%) females, and the disease duration was 11.21 ± 9.05 years; 316 (70.7%) had a PGA score of 3 points and 131 (29.3%) had a PGA score of 4 - 5 points. No significant differences in the baseline characteristics (including age, sex, disease duration and disease severity) were observed among the 3 groups (all P > 0.05). Based on the PPS analysis, the treatment success rates were 57.9% (99/171) in the test group, 50.3% (86/171) in the reference group, and 7.7% (6/78) in the placebo group, and the clinical success rates were 57.9% (99/171), 50.3% (86/171), and 10.3% (8/78), respectively; both the test and reference groups were superior to the placebo group in both treatment and clinical success rates (all P < 0.001) ; the rate differences for treatment success (90% confidence interval [ CI]: -1.3% - 16.4%) and clinical success (90% CI: -1.3% - 16.3%) between the test and reference groups were entirely within the pre-defined equivalence margin (-20% - 20%). Subgroup analyses by baseline PGA scores: for patients with a baseline PGA score of 3 points, the treatment success rates in the test, reference, and placebo groups were 60.8% (73/120), 52.1% (62/119), and 11.1% (6/54), respectively, and the corresponding clinical success rates were 61.7% (74/120), 53.8% (64/119), and 13% (7/54), respectively; the test and reference groups did not differ significantly in treatment or clinical success rates (both P > 0.05), but both showed higher success rates than the placebo group (all P < 0.001) ; the results of statistical comparisons among the 3 groups in patients with a baseline PGA score of 4 - 5 points were consistent with those observed in patients with a baseline PGA score of 3 points. The percentage reductions in PGA and TL-PASI scores from baseline to weeks 1, 2, and 4 showed significant differences among the 3 groups, which were significantly higher in the test and reference groups than in the placebo group (all P < 0.001), but did not differ between the test and reference groups (all P > 0.05). The primary adverse reactions were local skin reactions, such as pruritus, pain, and erythema. The incidence rates of adverse reactions were 8.9% (16/179) in the test group, 7.3% (13/179) in the reference group, and 7.8% (7/90) in the placebo group, with no significant difference among the 3 groups ( P > 0.05) . Conclusions:The domestic calcipotriol/betamethasone dipropionate ointment demonstrated clinical equivalence to the originator product in the treatment of stable plaque psoriasis, and the two agents exhibited comparable efficacy for patients with varying degrees of disease severity, and were comparable in the speed and degree of clinical improvement, with similar favorable safety profiles.

The study was a prospective observational study. A total of 24 patients who underwent maintenance hemodialysis (MHD) at Haidian Hospital in Beijing from May 2024 to June 2024 were included as the study subjects. The safety and efficacy of a new single-needle dialysis in MHD patients were evaluated. The reasons for using single-needle dialysis included waiting for the maturity of internal fistula(7 cases, 29.17%), autogenous arteriovenous fistula thrombosis occurred (6 cases, 25.00%), puncture difficulty occurred (7 cases, 29.17%), and pain sensitivity or elderly (4 cases, 16.67%). The results showed that the average blood flow was (155.65±5.90) ml/min, total blood volume was (35.92±2.65) L during single-needle dialysis. One patient had slight puncture leakage, and the puncture success rate was 95.83%. Relevant indicators of dialysis adequacy showed that the average urea clearance (Kt/V) was 0.90±0.42, urea reduction ratio was 58.31%±7.93%, and online real-time Kt/V monitoring average value was 0.98±0.55. The results suggest that the application of the new improved single-needle dialysis mode in MHD patients is safe and effective.

Objective To investigate the effects of electroacupuncture at Neiguan(PC6)combined with Buyang Huanwu Decoction on myocardial edema-related proteins and its cardioprotective role in mice with acute high-altitude hypoxic myocardial injury,and to explore the potential mechanisms by which this combined therapy ameliorates acute hypoxic myocardial damage.Methods Mice were randomly divided into control,hypoxia model,electroacupuncture at Neiguan,Buyang Huanwu Decoction,and electroacupuncture at Neiguan+Buyang Huanwu Decoction groups.Except for the normal control group,all other groups were subjected to the establishment of an acute high-altitude hypoxia-induced myocardial injury model.Four days before entering the low-pressure hypoxia animal simulation chamber,the electroacupuncture at Neiguan group was treated with bilateral electroacupuncture at Neiguan,the Buyang Huanwu Decoction group was treated with Buyang Huanwu Decoction by gavage,and the electroacupuncture at Neiguan+Buyang Huanwu Decoction group was treated with a combination of electroacupuncture at Neiguan and Buyang Huanwu Decoction.The intervention lasted for 7 days.The normal control group and the hypoxia model group were handled normally without any other treatment.Myocardial pathology and ultrastructure were evaluated using HE staining and transmission electron microscopy.Serum levels of creatine kinase-MB(CK-MB)and cardiac troponin I(cTn-I)were measured by ELISA.Western blot was performed to quantify β1-AR,cAMP,PKA,and AQP1 protein expression.Results Compared with normal control group,the hypoxia model group exhibited significant myocardial damage,elevated cardiac biomarkers,and upregulated β1-AR/cAMP/PKA pathway proteins with increased AQP1 expression(all P<0.01).The electroacupuncture at Neiguan+Buyang Huanwu Decoction group demonstrated attenuated myocardial injury,reduced biomarker levels,and downregulated target proteins(all P<0.01)versus the hypoxia model group.Conclusion Electroacupuncture at Neiguan combined with Buyang Huanwu Decoction alleviates myocardial edema and injury in acute hypobaric hypoxia by reducing vascular permeability,potentially via suppression of the β1-AR/cAMP/PKA pathway and subsequent inhibition of AQP1 expression.

Objective To evaluate the cost-effectiveness of low-dose steroid combined with tacrolimus or cyclophosphamide in treating adult idiopathic membranous nephropathy(IMN).Methods A prospective cohort design was used to collect clinical data on IMN patients admitted to the Affiliated Hospital of Hebei University from December 2018 to April 2022.The patients were divided into the exposure group(low-dose steroid combined with tacrolimus)and control group(low-dose steroid combined with cyclophosphamide)according to the treatment regimen.Propensity score matching was employed to balance the baseline characteristics between the two groups.The total response rate was taken as the effect index,cost-effectiveness analysis was conducted by using the decision tree model,and single factor sensitivity analysis and probabilistic sensitivity analysis were used to verify the robustness of the cost-effectiveness analysis results.Results A total of 112 patients with IMN were included.After propensity score matching,46 patients were included in the exposed and control groups,respectively.The total remission rate of the exposure group was 84.78％,with the cost of 13,352.64 yuan and the cost-effectiveness ratio of 157.50.In the control group,the total remission rate was 80.43％,the cost was 8,154.18 yuan,and the cost-effectiveness ratio was 101.38.The incremental cost-effectiveness ratio of the two groups was 1 195.05,and the sensitivity analysis results were consistent with those of the cost-effectiveness analysis.Conclusion The two treatment schemes have their own advantages in the treatment of IMN.The cost-effectiveness ratio of low-dose hormone combined with tacrolimus is relatively higher,and the combination of low-dose hormone with cyclophosphamide is more economical.Both schemes have certain clinical promotion value..

AIM:To investigate the therapeutic effects and potential mechanism of pachymic acid(PA)on li-popolysaccharide(LPS)-induced acute kidney injury(AKI)in mice.METHODS:(1)Genes related to AKI were screened using the DAVID database.Core genes were identified by intersecting related genes and analyzed using Cyto-scape software.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analyses were performed through the DAVID database for the cross-targets.Molecular docking and activity assays were conducted on the primary core targets.(2)A total of 100 C57BL/6J mice were randomly divided into five groups:normal control(NC),model(LPS),solvent control(LPS+DMSO),and treatment groups(LPS+PA-10 and LPS+PA-20),with 20 mice in each group.The LPS-AKI model was established by intraperitoneal injection of 18 mg/kg LPS.The treatment groups received 10 mg/kg and 20 mg/kg PA,respectively,and the solvent control group was administered an equivalent dose of DMSO.Mice were euthanized 24 h after injection.Serum was collected for biochemical analysis,and Western blot was used to detect neutro-phil gelatinase-associated lipocalin(NGAL),kidney injury molecule-1(KIM-1),caspase-3,cleaved caspase-3,interleu-kin-1β(IL-1β),and monocyte chemoattractant protein-1(MCP-1)protein expression.RT-qPCR was employed to detect inflammatory factor mRNA levels.Molecular docking was used to simulate the optimal binding site of PA to caspase-3.En-zyme activity assays were performed to assess caspase protein activity,and renal lesions were observed via hematoxylin and eosin(HE)staining.Apoptosis was detected by TUNEL staining.RESULTS:(1)Thirty-one potential targets of PA against AKI were identified through network pharmacology.GO and KEGG enrichment analyses indicated that these tar-gets were primarily involved in immune response,inflammatory processes,apoptosis and survival,angiogenesis and hemo-dynamics,oxidative stress,and endoplasmic reticulum stress.Key targets included CASP3(caspase-3),PTGS2,BCL2,CCL2,and CYP219.(2)PA treatment improved renal function and reduced tubular epithelial injury.It significantly de-creased NGAL,KIM-1,and cleaved caspase-3 protein levels,as well as inflammatory factors TNF-α,IL-1β,and MCP-1 mRNA and protein expression.PA also reduced apoptosis of renal tubular epithelial cells.Enzyme activity assays and mo-lecular docking revealed that PA exerted its anti-apoptotic effect by directly binding to caspase-3,thereby inhibiting its ac-tivation by caspase-8.CONCLUSION:PA demonstrated a therapeutic effect in LPS-AKI,potentially through the inhibi-tion of inflammatory factor synthesis and release,as well as the inhibition of caspase-3 activation by caspase-8,reducing apoptosis in renal tubular epithelial cells.

Objective To explore the relationship between IgA nephropathy(IgAN)and intestinal flora and mucosal immune response disorder based on the theory of"intestinal-kidney axis",and to summarize and enumerate the measures of Chinese and Western medicine in the treatment of IgAN by regulating intestinal flora,mucosal immune response and improving intestinal microecology.Methods Through literature search,the changes of intestinal flora between healthy people and IgAN patients and their effects on intestinal mucosal immunity were compared and analyzed,and then the relationship between different intestinal flora and IgAN was summarized.Results This paper summarizes that different floras including Firmicutes,Escherichia coli,Bifidobacterium and Enterococcus faecalis are closely related to the occurrence and development of IgAN.Conclusions Intestinal flora imbalance can negatively regulate IgAN,regulate intestinal flora and improve intestinal microecological environment,which may become a new target for the treatment of IgAN.

Objective: This study aims to investigate the therapeutic effects and underlying mechanisms of Xuanfei Baidu Decoction (XFBD) in a mouse model of dampness-heat toxin pneumonia. By exploring how XFBD exerts its effects, we seek to deepen our understanding of its role in treating pulmonary diseases and to address the current knowledge gap regarding its mechanisms of action, thereby supporting its clinical application. Methods: Ultra-high-performance liquid chromatography and high-resolution mass spectrometry (HRMS) were employed to analyze the chemical constituents of XFBD. The protective effects of XFBD were evaluated using a dampness-heat toxin-induced mouse model, established through dampness-heat exposure and HCoV-229E infection. XFBD was administered orally, followed by assessments including lung index measurement, micro-CT imaging, viral load quantification, cytokine analysis, and histological evaluation via hematoxylin-eosin staining. Proteomics and single-cell transcriptomic analyses were conducted to explore the potential mechanisms underlying XFBD’s pharmacological effects. A cellular model of HCoV-229E infection was developed to investigate changes in the cAMP/PKA signaling pathway. Molecular docking and surface plasmon resonance (SPR) experiments confirmed the strong binding affinity between key XFBD components and PKA. Finally, PKA activators and inhibitors were applied in vitro to validate these mechanistic findings. Results: In vivo studies demonstrated that XFBD significantly reduced the lung index, improved the structural integrity of lung and tongue tissues, and decreased levels of proinflammatory mediators, including IL-6, IL-8, and TNF-α. Proteomic and single-cell transcriptomic analyses showed that the differentially expressed proteins after XFBD treatment were primarily associated with inflammatory responses and immune regulation. The cAMP/PKA signaling pathway was identified as a key mechanism underlying these therapeutic effects. Notably, Western blot, ELISA, molecular docking, and SPR analyses confirmed that XFBD elevated cAMP levels and p-PKA expression, thereby activating the cAMP/PKA signaling pathway in vitro. Conclusion: This study demonstrated that XFBD significantly alleviates symptoms in mice with dampness-heat toxin pneumonia. Its therapeutic effects are mediated, at least in part, through activation of the cAMP/PKA signaling pathway. These findings provide compelling evidence that XFBD is an effective herbal remedy against HCoV-229E infection.

Objective To investigate iodine content in drinking water and clarify the distribution characteristics of iodine in water in Shaanxi Province.Methods A cross-sectional survey method was used to collect water samples from administrative villages in the province.Two tap water samples were taken from the centralized water supply villages,and 10％samples were taken from the decentralized water supply villages.Water iodine was detected by arsenic cerium catalytic spectrophotometry.Water iodine areas were divided according to national standards:＜40 μg/L was iodine deficiency area,40-100 μg/L was iodine adequate area,＞100 μg/L was high iodine area.According to the ecological regionification scheme of the Chinese Academy of Sciences,Shaanxi Province was divided into three types:the central and eastern Inner Mongolia Platea-Loess Plateau ecological region,the Fenwei Basin ecological region,and the Qinba Mountains ecological region.SPSS 25.0 was used for statistical analysis.Results The median of water iodine in Shaanxi Province was 6.66 μg/L.The survey of water iodine content was conducted in 22 848 administrative villages,1 309 townships,112 counties and 14 municipalities in the whole province.The median water iodine was less than 40 μg/L in 91.75％(20 963/22 848)of the administrative villages,between 40 and 100 μg/L in 7.40％(1 691/22 848)of the administrative villages,and more than 100 μg/L in 0.85％(194/22 848)of the administrative villages.The median of water iodine in the central and eastern Inner Mongolia Platea-Lose Plateau ecological zone,the Fenwei Basin ecological zone,and Qinba Mountains ecological zone was 12.35,8.88,and 2.00 μg/L,respectively,and the differences among different ecological zones were statistically significant(H=6 616.23,P＜0.001).The median of water iodine of centralized and decentralized water supply was 6.72 and 6.21 μg/L,respectively,and differences between different water supply methods were statistically significant(Z=5.638,P＜0.01).Conclusion The overall external environment of Shaanxi Province is iodine deficient,and most of the administrative villages are iodine deficient areas.There are a certain proportion of high iodine water source areas and suitable iodine areas.

Objective To investigate the effects of acteoside in a rat model on of diabetic nephropathy(DN)and high-glucose-induced glomerular mesangial cells(GMCs),focusing on the role of acteoside in the silent information regulator 1(SIRT1)/nuclear factor eryth-roid 2-related factor 2(Nrf2)signaling pathway.Methods GMCs were cultured under normal glucose conditions or stimulated with high glucose.Fibrosis,oxidative stress,SIRT1 and Nrf2 protein expression,and mitochondrial structure were assessed in four groups:normal glucose,high glucose,high glucose+acteoside,and high glucose+acteoside+SIRT1 inhibitor(hsa62).DN was induced in rats via intraperitoneal streptozotocin injection,and animals were divided into control,model,and acteoside-treated groups.Pathological kidney changes,blood glucose changes,renal function indices,and protein expression of SIRT1 and Nrf2 were evaluated.Results Compared with controls,DN model rats showed significantly elevated fasting blood glucose,serum creatinine,blood urea nitrogen,and 24-h urinary protein levels of rats in the model group were significantly increased(P＜0.01).GMCs exhibited increased fibrosis,oxidative stress,and mitochondrial damage.Acteoside treatment significantly improved all measured parameters(P＜0.01);and mitigated mitochondrial injury.In vitro,acteoside reduced high-glucose-induced fibrosis and oxidative stress in GMCs,effects that were reversed by SIRT1 inhibition.Western blotting confirmed upregulation of SIRT1 and Nrf2 expression in both treated rat kidney tissues and GMCs(P＜0.01).Conclusion Acteoside alleviates glomerular fibrosis and oxidative stress in DN by activating the SIRT1/Nrf2 signaling pathway,suggesting its potential therapeutic agent for DN.