Objective To evaluate the value of tripartite motif-containing protein 21(TRIM21)mRNA expression in alveolar macrophages for the serverity and prognosis of patients with severe pneumonia complicated by acute respiratory distress syndrome(SP-ARDS).Methods A retrospective analysis was conducted on 42 SP-ARDS patients(SP-ARDS group)and 15 outpatient healthy controls(control group)admitted to the Department of Respiratory and Critical Care Medicine,Jinling Hospital Affilicated to Medical School of Nanjing University,from November 2023 to June 2024.Bronchoalveolar lavage fluid was collected,and alveolar macrophages were isolated.The expression levels of TRIM21 mRNA were quantified using qPCR.Differences in TRIM21 mRNA expression levels,clinical characteristics,and relevant laboratory test results were compared between the two groups.Correlations between TRIM21 mRNA expression and SP-ARDS severity,28-day mortality,inflammatory indicators,acute physiology and chronic health evaluation Ⅱ(APACHE Ⅱ)scores,duration of mechanical ventilation,and ICU stay were analyzed using Pearson or Spearman correlation analysis.Logistic regression analysis was used to identify risk factors for 28-day mortality,and the predictive value of each factor was evaluated using receiver operating characteristic(ROC)curves.Results Compared with control group,the expression levels of TRIM21 mRNA,white blood cell counts,neutrophil-to-lymphocyte ratio(NLR),and C-reactive protein(CRP),and procalcitonin(PCT)levels increased(P<0.05),and hemoglobin levels decreased(P<0.05)in SP-ARDS group.No significant differences were observed in gender,age,smoking history,alcohol consumption,underlying disease history,and platelet count between the two groups(P>0.05).TRIM21 mRNA expression level in SP-ARDS patients was positively correlated with ARDS severity(P<0.05).Additionally,non-survivors within 28 days had a significantly higher expression level of TRIM21 mRNA compared to survivors(P<0.001).Correlation analysis indicated that the relative expression level of TRIM21 mRNA in SP-ARDS patients was positively correlated with CRP(r=0.309,P<0.05),NLR(r=0.422,P<0.01),PCT(r=0.561,P<0.001),APACHE Ⅱ score(r=0.615,P<0.001),and duration of mechanical ventilation(r=0.665,P<0.001).Logistic regression analysis revealed that elevated expression levels of TRIM21 mRNA(OR=2.886,P=0.043)and higher APACHE Ⅱ scores(OR=1.546,P=0.037)were independent risk factors for 28-day mortality in SP-ARDS patients.The areas under the ROC curves(AUCs)for predicting 28-day mortality using TRIM21 mRNA expression level and APACHE Ⅱ score were 0.889 and 0.874,respectively,with optimal cut-off values of 5.21 and 20.5 points,respectively.The combined AUC for prediction was 0.962.Conclusion Increased TRIM21 mRNA expression in alveolar macrophages of SP-ARDS patients is positively correlated with disease severity and may serve as a potential predictive marker for 28-day survival in SP-ARDS patients.

Peptide-based radiopharmaceuticals targeting integrin α5β1 show promise for precise tumor diagnosis and treatment. However, current peptide-based radioligands that target α5β1 demonstrate inadequate in vivo performance owing to limited tumor retention. The use of PEGylation to enhance the tumor retention of radiopharmaceuticals by prolonging blood circulation time poses a risk of increased blood toxicity. Therefore, a PEGylation strategy that boosts tumor retention while minimizing blood circulation time is urgently needed. Here, we developed a PEGylation-enabled peptide multidisplay platform (PEGibody) for PR_b, an α5β1 targeting peptide. PEGibody generation involved PEGylation and self-assembly. [⁶⁴Cu]QM-2303 PEGibodies displayed spherical nanoparticles ranging from 100 to 200 nm in diameter. Compared with non-PEGylated radioligands, [⁶⁴Cu]QM-2303 demonstrated enhanced tumor retention time due to increased binding affinity and stability. Importantly, the biodistribution analysis confirmed rapid clearance of [⁶⁴Cu]QM-2303 from the bloodstream. Administration of a single dose of [¹⁷⁷Lu]QM-2303 led to robust antitumor efficacy. Furthermore, [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 exhibited low hematological and organ toxicity in both healthy and tumor-bearing mice. Therefore, this study presents a PEGibody-based radiotheranostic approach that enhances tumor retention time and provides long-lasting antitumor effects without prolonging blood circulation lifetime. The PEGibody-based radiopharmaceutical [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 shows great potential for positron emission tomography imaging-guided targeted radionuclide therapy for α5β1-overexpressing tumors.

The activation proteins released by fibroblasts in the tumor microenvironment regulate tumor growth, migration, and treatment response, thereby influencing tumor progression and therapeutic outcomes. Owing to the proliferation and metastasis of tumors, fibroblast activation protein (FAP) is typically highly expressed in the tumor stroma, whereas it is nearly absent in adult normal tissues and benign lesions, making it an attractive target for precision medicine. Radiolabeled agents targeting FAP have the potential for targeted cancer diagnosis and therapy. This comprehensive review aims to describe the evolution of FAPI-based radiopharmaceuticals and their structural optimization. Within its scope, this review summarizes the advances in the use of radiolabeled small molecule inhibitors for tumor imaging and therapy as well as the modification strategies for FAPIs, combined with insights from structure-activity relationships and clinical studies, providing a valuable perspective for radiopharmaceutical clinical development and application.

OBJECTIVE: To investigate the relationship between physical activity and genetic risk and their combined effects on the risk of developing chronic obstructive pulmonary disease. METHODS: This prospective cohort study included 318,085 biobank participants from the UK. Physical activity was assessed using the short form of the International Physical Activity Questionnaire. The participants were stratified into low-, intermediate-, and high-genetic-risk groups based on their polygenic risk scores. Multivariate Cox regression models and multiplicative interaction analyses were used. RESULTS: During a median follow-up period of 13 years, 9,209 participants were diagnosed with chronic obstructive pulmonary disease. For low genetic risk, compared to low physical activity, the hazard ratios ( HRs) for moderate and high physical activity were 0.853 (95% confidence interval [ CI]: 0.748-0.972) and 0.831 (95% CI: 0.727-0.950), respectively. For intermediate genetic risk, the HRs were 0.829 (95% CI: 0.758-0.905) and 0.835 (95% CI: 0.764-0.914), respectively. For participants with high genetic risk, the HRs were 0.809 (95% CI: 0.746-0.877) and 0.818 (95% CI: 0.754-0.888), respectively. A significant interaction was observed between genetic risk and physical activity. CONCLUSION Moderate or high levels of physical activity were associated with a lower risk of developing chronic obstructive pulmonary disease across all genetic risk groups, highlighting the need to tailor activity interventions for genetically susceptible individuals.
Humans ; Pulmonary Disease, Chronic Obstructive/epidemiology* ; Exercise ; Male ; Female ; Middle Aged ; Prospective Studies ; Aged ; Genetic Predisposition to Disease ; Risk Factors ; United Kingdom/epidemiology* ; Incidence ; Adult

To explore the common irritant components in different base sources of Polygonati Rhizoma(PR). A rabbit eye irritation experiment was conducted to compare the irritant effects of raw products of Polygonatum kingianum, P. officinale, and P. multiflorum. The irritant effects of different solvent extraction parts and needle crystals of PR were compared, and the irritant components were screened. The morphology and structure of the purified needle crystal of PR were observed by microscope and scanning electron microscope and characterized by X-ray diffraction. Rabbit eye irritation and mouse abdominal inflammation model were used to evaluate rabbit eye irritation scores, inflammatory mediators, inflammatory factors levels in the peritoneal exudate of mice, with the peritoneal pathological section used as indicators. The inflammatory effect of needle crystals of PR was studied, and the content of calcium oxalate in three kinds of PR was determined by HPLC. The common protein in three kinds of PR was screened and compared by double enzymatic hydrolysis in solution combined with mass spectrometry. The results showed that three kinds of PR raw products had certain irritant effects on rabbit eyes, among which P. kingianum had the strongest irritant effect. There were no obvious irritant effects in the different solvent extraction parts of P. kingianum. Compared with the blank group, the needle crystal of PR had a significant irritant effect on rabbit eyes, and the inflammatory mediators and inflammatory factors in the peritoneal exudate were significantly increased(P<0.05) in a dose-dependent manner. Meanwhile, the peritoneal tissue of mice was damaged with significant inflammatory cell infiltration after intraperitoneal injection of needle crystal, indicating that needle crystal had an inflammatory effect. Microscope and scanning electron microscope observations showed that the needle crystals of PR were slender, with a length of about 100-200 μm and sharp ends. X-ray diffraction analysis showed that the needle crystals of PR were calcium oxalate monohydrate crystals. The results of HPLC showed that the content of calcium oxalate in P. kingianum was the highest among the three kinds of PR. It was speculated that the content of needle crystal in P. kingianum was higher than that in P. officinale and P. multiflorum, which was consistent with the results of the rabbit eye irritation experiment. The results of mass spectrometry showed that ribosome inactivating protein and mannose/sialic acid binding lectin were related to inflammation and cell metabolism in all three kinds of PR. There was no obvious irritant effect in different solvent extracts of PR. The calcium oxalate needle crystal contained was the main irritant component of PR, and three kinds of PR contained common ribosome inactivating protein and mannose/sialic acid binding lectin, which may be related to the inflammatory irritant effect of PR.
Animals ; Rabbits ; Mice ; Polygonatum/chemistry* ; Drugs, Chinese Herbal/toxicity* ; Rhizome/chemistry* ; Male ; Eye/drug effects* ; Female ; Humans

This study aimed to investigate the correlation between changes in intestinal toxicity and compositional alterations of Euphorbiae Ebracteolatae Radix(commonly known as Langdu) before and after milk processing, and to explore the detoxification mechanism of milk processing. Mice were intragastrically administered the 95% ethanol extract of raw Euphorbiae Ebracteolatae Radix, milk-decocted(milk-processed), and water-decocted(water-processed) Euphorbiae Ebracteolatae Radix. Fecal morphology, fecal water content, and the release levels of inflammatory cytokines tumor necrosis factor-α(TNF-α) and interleukin-1β(IL-1β) in different intestinal segments were used as indicators to evaluate the effects of different processing methods on the cathartic effect and intestinal inflammatory toxicity of Euphorbiae Ebracteolatae Radix. LC-MS/MS was employed to analyze the small-molecule components in the raw product, the 95% ethanol extract of the milk-processed product, and the milky waste(precipitate) formed during milk processing, to assess the impact of milk processing on the chemical composition of Euphorbiae Ebracteolatae Radix. The results showed that compared with the blank group, both the raw and water-processed Euphorbiae Ebracteolatae Radix significantly increased the fecal morphology score, fecal water content, and the release levels of TNF-α and IL-1β in various intestinal segments(P<0.05). Compared with the raw group, all indicators in the milk-processed group significantly decreased(P<0.05), while no significant differences were observed in the water-processed group, indicating that milk, as an adjuvant in processing, plays a key role in reducing the intestinal toxicity of Euphorbiae Ebracteolatae Radix. Mass spectrometry results revealed that 29 components were identified in the raw product, including 28 terpenoids and 1 acetophenone. The content of these components decreased to varying extents after milk processing. A total of 28 components derived from Euphorbiae Ebracteolatae Radix were identified in the milky precipitate, of which 27 were terpenoids, suggesting that milk processing promotes the transfer of toxic components from Euphorbiae Ebracteolatae Radix into milk. To further investigate the effect of milk adjuvant processing on the toxic terpenoid components of Euphorbiae Ebracteolatae Radix, transmission electron microscopy(TEM) was used to observe the morphology of self-assembled casein micelles(the main protein in milk) in the milky precipitate. The micelles formed in casein-terpenoid solutions were characterized using particle size analysis, fluorescence spectroscopy, ultraviolet spectroscopy, and Fourier-transform infrared(FTIR) spectroscopy. TEM observations confirmed the presence of casein micelles in the milky precipitate. Characterization results showed that with increasing concentrations of toxic terpenoids, the average particle size of casein micelles increased, fluorescence intensity of the solution decreased, the maximum absorption wavelength in the UV spectrum shifted, and significant changes occurred in the infrared spectrum, indicating that interactions occurred between casein micelles and toxic terpenoid components. These findings indicate that the cathartic effect of Euphorbiae Ebracteolatae Radix becomes milder and its intestinal inflammatory toxicity is reduced after milk processing. The detoxification mechanism is that terpenoid components in Euphorbiae Ebracteolatae Radix reassemble with casein in milk to form micelles, promoting the transfer of some terpenoids into the milky precipitate.
Animals ; Mice ; Milk/chemistry* ; Drugs, Chinese Herbal/chemistry* ; Male ; Tumor Necrosis Factor-alpha/immunology* ; Intestines/drug effects* ; Interleukin-1beta/immunology* ; Tandem Mass Spectrometry ; Female

Liver ischemia-reperfusion injury (LIRI) is a pathological process involving multiple injury factors and cell types, with different stages. Currently, protective drugs targeting a single condition are limited in efficacy, and interventions on immune cells will also be accompanied by a series of side effects. In the current bottleneck research stage, the multi-target and obvious clinical efficacy of Chinese medicine (CM) is expected to become a breakthrough point in the research and development of new drugs. In this review, we summarize the roles of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in various stages of hepatic ischemia-reperfusion and on various types of cells. Combined with the current research progress in reducing ROS/RNS with CM, new therapies and mechanisms for the treatment of hepatic ischemia-reperfusion are discussed.
Reperfusion Injury/drug therapy* ; Reactive Oxygen Species/metabolism* ; Reactive Nitrogen Species/metabolism* ; Humans ; Liver/drug effects* ; Animals ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/pharmacology*

Osteoporotic proximal humeral fracture (OPHF) is one of the common osteoporotic fractures in the aged, with an incidence only lower than vertebral compression fracture, hip fracture, and distal radius fracture. OPHF, secondary to osteoporosis and characterized by poor bone quality, comminuted fracture pattern, slow healing, and severely impaired shoulder joint function, poses a big challenge to the current clinical diagnosis and treatment. In the field of diagnosis, treatment, and rehabilitation of OPHF, traditional Chinese and Western medicine have accumulated rich experience and evidence from evidence-based medicine and achieved favorable outcomes. However, there is still a lack of guidance from a relevant consensus as to how to integrate the advantages of the two medical systems and achieve the integrated diagnosis and treatment. To promote the diagnosis and treatment of OPHF with integrated traditional Chinese and Western medicine, relevant experts from Orthopedic Expert Committee of Geriatric Branch of Chinese Association of Gerontology and Geriatrics, Youth Osteoporosis Group of Orthopedic Branch of Chinese Medical Association, Osteoporosis Group of Orthopedic Surgeon Branch of Chinese Medical Doctor Association, and Osteoporosis Committee of Shanghai Association of Integrated Traditional Chinese and Western Medicine have been organized to formulate Expert consensus on the diagnosis and treatment of osteoporotic proximal humeral fracture with integrated traditional Chinese and Western medicine ( version 2024) by searching related literatures and based on the evidences from evidence-based medicine. This consensus consists of 13 recommendations about the diagnosis, treatment and rehabilitation of OPHF with integrated traditional Chinese medicine and Western medicine, aimed at standardizing, systematizing, and personalizing the diagnosis and treatment of OPHF with integrated traditional Chinse and Western medicine to improve the patients ′ function.

AIM To investigate the effects of Xinyue Capsules on the expression of glycerophospholipid metabolizing enzymes in isoproterenol(ISO)-induced rat heart tissue and primary myocardial cells of neonatal rats.METHODS The SD rats were randomly divided into the normal group,the model group,the Xinyue Capsules intervention group and Xinyue Capsules control group,with 8 rats in each group.The rat model of cardiac hypertrophy was established by 14 days consecutive intraperitoneal injection of ISO(30 mg/kg).Prior to the modeling,once daily administration of 0.393 g/kg Xinyue Capsules was given by gavage from 3 days in advance to the end of the experiment.After the last administration,the procurement of blood from abdominal aorta,the left and right ventricles were processed.And the rats had their indices levels of the heart,the left ventricle and the right ventricle measured;their pathomorphological changes of myocardial tissue observed using HE staining;their expressions of cardiac hypertrophy-related myocardial embryonic genes ANP,β-MHC and α-SKA mRNA detected using RT-qPCR method;and their serum TC,TG,LDL-C and HDL-C levels detected by biochemical method.In in vitro experiment,the neonatal rat model of myocardial hypertrophy was induced by exposure to ISO 1 μmol/L for 24 h.The investigation of the effect of Xinyue Capsules 12.5 μg/mL on ISO-induced myocardial hypertrophy was conducted by detection of myocardial cell area,embryo genes related to cardiac hypertrophy and myocardial cells protein cuntent.The further anti-cardiac hypertrophy mechanism of Xinyue Capsules research was conducted using RT-qPCR and Western blot to detect the gene and protein expressions of phospholipase A2(PLA2G6),phospholipase A1 member A(PLA1A)and lecithin cholesterol acyltransferase(LCAT)in left ventricle tissue and myocardial cells of each group.RESULTS The in vivo experimental result showed that compared with the normal group,the model group displayed increased indices levels of the heart,the left ventricle and the right ventricle and cross-sectional area of left ventricular myocytes(P＜0.05);and up-regulated expressions of ANP,β-MHC,α-SKA mRNA and PLA2G6,PLA1A and LCAT mRNA and proteins in the left ventricle(P＜0.05);and increased levels of serum TC,TG and LDL-C(P＜0.05);and decreased HDL-C level(P＜0.05).However,the intervention of Xinyue Capsules inhibited the changes of the aforementioned indices(P＜0.05).The in vitro experimental result revealed that Xinyue Capsules inhibited the ISO-induced increases of myocardial cell surface area and myocardial cell protein level,the up-regulation of ANP,β-MHC,α-SKA mRNA expressions and the PLA2G6,PLA1A,LCAT mRNA and protein expressions as well(P＜0.05).CONCLUSION Xinyue Capsules can improve the ISO-induced cardiac hypertrophy in rats,and its mechanism may be associated with its regulation upon the expressions of glycerophospholipid metabolism-related enzymes PLA2G6,PLA1A and LCAT.

Objective:To explore the surgical techniques and effects of transfer of the free chimeric functional thoracodorsal artery perforator flap (TDAPF) with latissimus dorsi in reconstruction of dynamic muscle and soft tissue defects in forearm.Methods:From January 2014 to December 2020, a total of 13 transfer surgery of free chimeric functional TDAPF with vascularised latissimus dorsi were performed in the Department of Hand Surgery, Plastic & Reconstructive Surgery, Ningbo Sixth Hospital, to reconstruct forearm composite defects. The patients were 12 males and 1 female with an average age of 33.2 years old. They all had open forearm injuries, with 5 in the left and 8 in the right. Removal of inactivated muscles, exploration and repair of blood vessels and nerves were performed in emergency surgery, and VSD were applied after the surgery. Phase II reconstructive surgery were completed within 4 to 12 days, with 7.5 days in average. The wounds and flaps sized were 9.0 cm×8.0 cm - 21.0 cm×11.0 cm and were 10.0 cm×9.0 cm - 22.0 cm×12.0 cm, respectively. The volume of transferred muscles ranged were 9.0 cm × 2.0 cm × 1.5 cm - 19.0 cm × 9.0 cm × 1.5 cm. Free chimeric functional muscular flaps were transferred to reconstruct the musculus flexor digitorum profundus in 4 patients, the musculus extensor digitorum communis in 8 patients, the musculus flexor carpi radialis in 3 patients, and the musculus flexor pollicis longus in 1 patient. Reconstruction of both of musculus flexor carpi radialis and musculus extensor digitorum communis with 2 functional sub-blocks of latissimus dorsi were performed in 3 patients. All donor sites were closed primarily. All patients were included in the postoperative follow-up to evaluate the appearance of flaps, range of motion of the digits, recovery of muscle strength and gripping power, at the outpatient clinics or through the telephone interview.Results:A total of 12 flaps survived uneventfully after reconstructive surgery. One flap developed a vascular crisis and it was rectified after surgical exploration. Postoperative follow-up ranged from 17 to 52 months, with a mean of 34.1 months. Appearances of limbs and flaps were good without obvious bulky, hyperpigmentation or scar contracture. Four patients with reconstructed musculus flexor digitorum profundus showed muscle strength recovery of M 4, with the fingertips measured lower than 2.0 cm from the centre of palm when clenching a fist, and the average gripping strength of the hand reached 27.5% (20%-35%) to the healthy side. Five patients with reconstructed musculus extensor digitorum communis showed muscle strength recovery of M 4, and there was no obvious limitation in fingers flexion and extension, with the average gripping strength of the hand reached 75.4% (65%-80%) to the healthy side. Of the 3 patients with reconstruction of both power muscles, the recovery of muscle strength of musculus flexor carpi radialis was at M 4 in all the 3 patients, and the musculus extensor digitorum communis was at M 4 in 1 and M 3 in 2 patients. However, the patient who received reconstruction of musculus flexor pollicis had no significant recovery in muscle strength. Conclusion:Transfer of free chimeric functional TDAPF combines the benefits of a perforator flap and a functional muscle transfer together. This surgical technique can effectively reconstruct damaged muscle groups in forearm and resulting in good hand movement. Additionally, it can also restore the aesthetic appearance of forearm, hence makes it an excellent option for complex wound coverage.