Prostate cancer is one of the most common male urological malignancies,in which bone metastasis of desmo-plasia-resistant prostate cancer is an important stage in the progression of the disease,which seriously affects the quality of life and survival of patients.With the development of nuclide therapy technology in recent years,223-Ra,as a new type of alpha-targeted therapy,has shown good efficacy in the treatment of desmoplasia-resistant prostate cancer bone metastasis.The purpose of this pa-per is to review the characteristics,mechanism of action,treatment,and the main research results of its treatment of desmoplasia-resistant prostate cancer bone metastasis,and provide a comprehensive review of the clinical application of 223-Ra in the treatment of desmoplasia-resistant prostate cancer bone metastasis for the clinical application of 223-Ra in prostate cancer bone metastasis.

Objective:To explore the short-term effect of drug-coated balloon angioplasty (DCBA) and common plain old balloon angioplasty (POBA) in the isolated popliteal artery chronic total occlusion (CTO), and to analyze the factors affecting the postoperative primary patency rate.Methods:A retrospective cohort study approach was used in this study. A total of 42 isolated popliteal CTO patients admitted to the First Affiliated Hospital of Bengbu Medical University from January 2020 to June 2022 were divided into two groups according to their different balloons: 24 as POBA group and 18 as DCBA group. The primary patency rate of target lesions, the clinically-driven target lesion revascularization(CD-TLR) rate, amputation and toe amputation rate, and the improvement of ankle-brachial index (ABI) and Rutherford grade at 6 and 12 months after surgery were compared.Measurement data with normal distribution was expressed as xˉ± s and means between two groups were compared using independent samples t-test. The percentage of counting data was calculated, and the rate between groups was compared by χ2 test or Fisher's exact probability method. Kaplan-Meier survival curve method was used to plot the survival curves of primary patency rate and CD-TLR free rate at 12 months after surgery, and Log rank test was used to compare the differences between groups . Univariate log rank test and multivariate Cox regression was used to analyze the factors affecting the primary patency rate at 12 months in patients with isolated popliteal CTO. Results:12 months after surgery, 4 patients in the DCBA group experienced lumen restenosis or occlusion while 12 patients in the POBA group experienced lumen restenosis or occlusion. The cumulative primary patency rate of target lesions in the DCBA group was higher than that in the POBA group (Log-rank χ2=4.03, P=0.045). ABI in the DCBA group at 6 and 12 months was greater than that in the POBA group [(0.91±0.11) vs (0.83±0.09), (0.84±0.11) vs (0.70±0.12), t=2.40, P=0.021, t=3.64 and P=0.001].There were no significant difference in cumulative CD-TLR exemption, amputation and amputation at 12 months, and Rutherford grade at 6 and 12 months for both groups(all P>0.05). The results of univariate analysis showed that DCBA as surgical method, hypertension and coronary heart disease were the influencing factors of the primary patency rate after chronic occlusion of the isolated popliteal artery (all P<0.05). The results of multivariate Cox regression analysis indicated that DCBA as surgical method was a protective factor for primary patency at 12 months (odds ratio =0.31,95% confidence interval: 0.10~0.870., P=0.038), while hypertension was an independent risk factor( OR=5.63,95% confidence interval: 1.54~20.56, P=0.009). Conclusions:The cumulative primary patency rate of target lesions 12 months after isolated popliteal CTO was higher than that of POBA. DCBA as surgical method was a protective factor for primary patency rate 12 months in patients with isolated popliteal CTO, while hypertension was an independent risk factor.

OBJECTIVES: To explore the relationship between white matter injury (WMI) and cerebral perfusion in preterm infants using arterial spin labeling (ASL). METHODS: A total of 293 preterm infants (gestational age <34 weeks) hospitalized at the Third Affiliated Hospital of Zhengzhou University between June 2022 and June 2024 were included. After achieving clinical stability, the infants underwent brain magnetic resonance imaging (MRI) and ASL. Based on MRI findings, infants were classified into WMI (n=66) and non-WMI (n=227) groups. Cerebral perfusion parameters were compared between groups, and the association between WMI and perfusion alterations was evaluated. RESULTS: The WMI group showed a higher incidence of mild intraventricular hemorrhage (IVH) than the non-WMI group (P<0.05). Significantly lower cerebral perfusion was observed in the WMI group across bilateral frontal, temporal, parietal, and occipital lobes, as well as the basal ganglia and thalamus (P<0.05). After adjusting for gestational age, corrected gestational age at ASL scan, and mild IVH, WMI remained significantly associated with reduced regional perfusion (P<0.05). CONCLUSIONS WMI in preterm infants correlates with localized cerebral hypoperfusion. ASL-detected perfusion abnormalities may provide novel insights into WMI pathogenesis.
Humans ; White Matter/blood supply* ; Infant, Newborn ; Spin Labels ; Infant, Premature ; Female ; Male ; Cerebrovascular Circulation ; Magnetic Resonance Imaging

Objective To investigate the protective effects of paeonol(PAE)on autophagy in human neuroblastoma cells(SH-SY5Y)induced by overexpression of α-synuclein(α-Syn),and to explore its related mechanism.Methods SH-SY5Y cells served as control group,while those induced with A53T-α-Syn mutation were used as model group.Additional groups included PAE(150 μg/ml)group,3-MA(1 mmol/L)group,and PAE(150 μg/ml)+3-MA(1 mmol/L)group.Cell viability was assessed using CCK-8 method,cell morphology was observed under an optical microscope,and protein expressions of α-Syn,LC3-Ⅱ,p62,Beclin-1,phosphorylated c-Jun N-terminal kinase(p-JNK),and p-Bcl-2 were determined by Western blotting.Results Compared with control group,model control exhibited decreased cell survival(P＜0.01),increased α-Syn expression(P＜0.001),reduced expression of autophagy-related proteins LC3-Ⅱ and Beclin-1(P＜0.01,P＜0.05),elevated autophagy substrate protein p62(P＜0.05),and decreased expression of autophagy pathway-related proteins p-JNK and Bcl-2(P＜0.05,P＜0.01).Compared with model group,PAE group showed increased cell survival(P＜0.01),decreased α-Syn and p62 protein expression(P＜0.01,P＜0.05),and increased expression of LC3-Ⅱ,Beclin-1,p-JNK and Bcl-2(P＜0.05).Compared with PAE group,3-MA+PAE group demonstrated increased α-Syn expression(P＜0.05).Conclusions PAE could attenuate the injury of SH-SY5Y cells induced by A53T-α-Syn and eliminate over-expressed α-Syn by activating autophagy pathway,which may be associated with the upregulation of JNK/Bcl-2 mediated autophagy pathway.

Traditional Chinese medicine （TCM） has long recognized metabolism-associated fatty liver disease （MASLD）. The Classic of Difficulties （Nan Jing） records that "the accumulation of the liver is called obese Qi". ZHANG Jingyue also stated， "People with spleen and stomach deficiency and weakness or imbalance often suffer from diseases of accumulation". According to syndrome differentiation of the Zang-fu organs， modern physicians generally believe that the key pathogenesis of MASLD lies in the deficiency of spleen and stomach functions. However， MASLD is a chronic and complex disease， and its pathological characteristics cannot be fully explained by a single Zang-Fu syndrome differentiation. The concepts of sweat pores and collateral vessels emerged as early as the Huangdi's Internal Classic （Huang Di Nei Jing）， and later TCM scholars， based on the idea that "sweat pore is the gateway of collateral vessels" proposed the concept of Xuanluo （sweat pores-collateral vessels）. Xuanluo refers to fine structures widely distributed throughout the human body， serving as hubs and channels that regulate the movement and distribution of Qi， blood， and body fluids. By linking the Zang-Fu organs with Xuanluo， a theoretical framework of Qi， blood， and body fluid circulation centered on the "spleen and stomach-Xuanluo" as a whole was established， providing a new perspective for analyzing the essential pathogenesis of MASLD. Combined with the mechanisms involved in the formation and progression of MASLD， the intrinsic correlations between TCM pathogenesis and modern microscopic mechanisms are further analyzed. Modern studies have shown that intestinal microbial dysbiosis and mitochondrial dysfunction are pathological mechanisms involved in the occurrence and development of MASLD， but few have discussed the two as an integrated system. Existing research has confirmed that intestinal microorganisms can affect mitochondrial energy metabolism and oxidative stress through their metabolites， leading to hepatic energy metabolism disorders， oxidative stress （OS）， and inflammation， thereby promoting MASLD progression. Focusing on the correspondence between the "spleen and stomach-Xuanluo" theory and the intestinal microorganism-mitochondrion micro-pathological mechanism， it is proposed that the spleen and stomach share similarities with intestinal microorganisms in the generation of Qi， blood， and body fluids as well as in the regulation of Qi movement， while Xuanluo and mitochondria have commonalities in energy regulation. Moreover， harmonizing the spleen and stomach to ensure unobstructed Xuanluo is the key to maintaining the normal interaction mechanism between intestinal microorganisms and mitochondria. Based on the correlation between the "spleen and stomach-Xuanluo" theory and the intestinal microorganism-mitochondrion interaction， this paper reveals that the essence of MASLD pathogenesis lies in spleen and stomach dysfunction， specifically， failure of the spleen to ascend the clear and failure of the stomach to descend the turbid， resulting in insufficient transformation of Qi and blood， impaired nourishment of Xuanluo， stagnation of Qi and blood， and the long-term formation of phlegm and blood stasis in the liver. Furthermore， it explores the preventive and therapeutic effects of tonifying the spleen and stomach， dredging Xuanluo and collaterals， unblocking the bowels， and regulating Qi in the treatment of MASLD， thereby providing new insights for its prevention and therapy.

This study assessed the role and mechanism of the recombinant Bacillus Calmette-Gue?rin vaccine(rBCG)with c-di-AMP adjuvant in regulating metabolism and immunity in epididymal white adipose(eWAT)in mice.Male C57BL/6 mice were intravenously immunized with BCG and rBCG,and their body weights were monitored.eWAT was isolated from the mice,and the stromal vascular fractions(SVFs)cell number was counted with a hemocytometer.Sections of mouse adipose tissue were prepared,and the size,number,and morphology of eWAT adipocytes and crown-like structure(CLS)formation were compared under a microscope after HE staining.The transcription levels of lipid metabolism-associated factors,cytokines and aging-associated genes in each group were determined with qRT-PCR.The body weights of mice gradually increased after immunization with BCG and rBCG.The proportions of eWAT increased,and the SVFs cell number decreased,in rBCG immunized mice.HE staining indicated that BCG immunization promoted hyperplasia,whereas rBCG immunization promoted hypertrophy of eWAT adipocytes;moreover,both BCG and rBCG immunization induced CLS formation in eWAT.The qRT-PCR results indicated that rBCG immunization inhibited the expression of genes associated with lipolysis and energy expenditure in eWAT.BCG immunization had little effect on cytokine transcription,whereas rBCG significantly induced the transcription of IFN-γ and IL-1Ra,and inhibited that of IL-15 and IL-2,but did not induce the expression of aging-associated genes.Thus,rBCG immunization induced eWAT adipocyte hypertrophy,which was associated with the inhibition of eWAT lipolysis and the regulation of cytokine expression.

Aim To evaluate the bioequivalence of two oral preparations of rivaroxaban tablets(test preparation T and refe-rence preparation R)in fasting/postprandibular state in healthy Chinese subjects.Methods A randomized,open,single-dose,four-cycle,completely repeated crossover experiment was used in this study.A total of 70 healthy male and female subjects were enrolled,including 38 subjects in the fasting group and 32 sub-jects in the postprandial group.Rivaroxaban tablets(2.5 mg/tablet)were taken orally once per cycle and their reference preparations were tested.The plasma rivaroxaban concentration was determined by LC-MS/MS method.The pharmacokinetic parameters of rivaroxaban tablets were calculated by WinNonlin software,and the parameters were analyzed and processed.Re-sults The PK parameters of rivaroxaban tablets and reference preparations in fasting group were as follows:Cmax was(72.48±17.08)and(66.36±15.64)μg·L-1,respectively.AUC0-t were(383.49±101.06)and(370.43±102.16)h·ng·mL-1,and AUC0-inr were(389.58±102.28)and(375.84±103.01)h·μg·L-,respectively.Main PK parameters of subjects taking rivaroxaban tablets orally after meals:Cmax were(66.48±15.64 and 60.87±13.44)μg·L-1,AUC0-t were(404.44±72.58)and(381.80±79.93)h·μg·L-1,re-spectively.AUC0_inf was(410.88±73.55)and(393.64±69.71)h·μg·L-1,respectively.Under fasting and postmeal conditions,subjects took rivaroxaban test and reference prepara-tion orally,one tablet(2.5 mg/tablet)each time.The geometric mean of the main pharmacokinetic parameters of rivaroxaban in plasma(Cmax,AUC0-t,AUC0-inf)and their corresponding values had a 90％confidence interval ranging from 80.00％to 125.00％.No serious adverse events or unexpected adverse e-vents occurred in both groups.Conclusion Rivaroxaban tablets are bioequivalent and safe in vivo under fasting and postprandial conditions.

Tracheal intubation is the most commonly used way to establish artificial airway in intensive care unit patients, and it is the premise of respiratory support and treatment, the success of extubation is an important basis to measure the prognosis of patients. Influenced by many factors, extubation of patients may fail, resulting in prolonged hospitalization, increased medical expenses and increased incidence of complications. This article reviews the literature at home and abroad, and summarizes the main mechanism, risk factors and prevention strategies of extubation failure in intensive care unit patients, aiming at improving the recognition ability of clinical medical staff for extubation failure and providing reference for clinical management and follow-up research.