Inflammatory diseases (IDs) are a general term of diseases characterized by chronic inflammation as the primary pathogenetic mechanism, which seriously affect the quality of patient′s life and cause significant social and medical burden. Current drugs for IDs include nonsteroidal anti-inflammatory drugs, corticosteroids, immunomodulators, biologics, and antioxidants, but these drugs may cause gastrointestinal side effects, induce or worsen infections, and cause non-response or intolerance. Given the outstanding performance of metal polyphenol network (MPN) in the fields of drug delivery, biomedical imaging, and catalytic therapy, its application in the diagnosis and treatment of IDs has attracted much attention and significant progress has been made. In this paper, we first provide an overview of the types of IDs and their generating mechanisms, then sort out and summarize the different forms of MPN in recent years, and finally discuss in detail the characteristics of MPN and their latest research progress in the diagnosis and treatment of IDs. This research may provide useful references for scientific research and clinical practice in the related fields.

Tumor is one of the serious problems threatening human health. There are some limitations in the delivery of commonly used tumor therapy technologies, and the therapeutic effect is not satisfactory, so new anti-tumor strategies need to be developed. The process of tumor cells using glycolysis to produce energy under aerobic conditions is called aerobic glycolysis, which is closely related to tumor growth, proliferation and metastasis, and can provide a new target spot for tumor treatment. Nano drug delivery system has been widely used in targeted tumor therapy because of its advantages of targeted drug delivery, improved anti-tumor efficacy and reduced toxic side effects. Numerous studies have shown that more and more nano drug delivery systems regulates aerobic glycolytic metabolism by targeting to potential targets such as signaling factors or reaction products of aerobic glycolytic process in tumors, and therefore enhance the anti-tumor effect. This paper reviews the application of nano drug delivery system in regulating tumor aerobic glycolysis, and provides theoretical references for realizing efficient targeted tumor therapy.

Objective:To explore the clinical characteristics and genetic variants in three children with late-onset Multiple acyl-Coenzyme A dehydrogenase deficiency (MADD type Ⅲ).Methods:Clinical data of three children diagnosed with late-onset MADD at the Children′s Hospital Affiliated to Zhengzhou University between March 2020 and March 2022 were retrospectively analyzed. All children were subjected to whole exome sequencing (WES), and candidate variants were verified by Sanger sequencing. All children had received improved metabolic therapy and followed up for 1 ~ 3 years.Results:The children had included 2 males and 1 female, and aged from 2 months to 11 years and 7 months. Child 1 had intermittent vomiting, child 2 had weakness in lower limbs, while child 3 had no symptom except abnormal neonatal screening. Tandem mass spectrometry of the three children showed elevation of multiple acylcarnitines with short, medium and long chains. Children 1 and 2 showed increased glutaric acid and multiple dicarboxylic acids by urine Gas chromatography-mass spectrometry (GC-MS) analysis. All children were found to harbor compound heterozygous variants of the ETFDH gene, including a paternal c. 1211T>C (p.M404T) and a maternal c. 488-22T>G variant in child 1, a paternal c. 1717C>T (p.Q573X) and a maternal c. 250G>A (p.A84T) variant in child 2, and a paternal c. 1285+ 1G>A and maternal c. 629A>G (p.S210N) variant in child 3. As for the treatment, high-dose vitamin B2, levocarnitine and coenzyme Q 10 were given to improve the metabolism, in addition with a low fat, hypoproteinic and high carbohydrate diet. All children showed a stable condition with normal growth and development during the follow-up. Conclusion:The compound heterozygous variants of the ETFDH gene probably underlay the muscle weakness, remittent vomiting, elevated short, medium, and long chain acylcarnitine, as well as elevated glutaric acid and various dicarboxylic acids in the three children with type Ⅲ MADD.

Objective To investigate the impact of matrine(Mat)on renal injury in rats with chronic glomerulonephritis by regulating the monocyte chemotactic protein-1(MCP-1)/chemokine C-C-motif receptor 2(CCR2)signaling pathway.Methods The rat model of chronic glomerulonephritis was established by subcutaneous injection of bovine serum albumin,the rats were randomly grouped into control group,model group,low and high dose matrine groups(Mat-L group,Mat-H group),and matrine+CCR2 group(Mat+CCR2 group),with 10 rats in each group.After continuous gavage for 4 weeks,24-hour urine protein excretion was measured;spleen and thymus were removed and organ index was calculated;The levels of blood urea nitrogen(BUN)and serum creatinine(Scr)in the serum of each group were detected,the pathological changes of renal tissue were observed by HE staining;the levels of tumor necrosis factor α(TNF-α)and interleukin(IL)-6 in renal tissue were detected by ELISA;Flow cytometry was applied to detect the proportion of T lymphocyte subsets in peripheral blood of rats in each group;Western blotting was applied to determine the expression of MCP-1 and CCR2 proteins.Results The spleen index and thymus index of rats in the model group rats were obviously reduced,and there were a large number of inflammatory cell infiltration in the renal tissue,the 24-hour urine protein,BUN,Scr,TNF-α,IL-6,and the expression of MCP-1 and CCR2 obviously increased,the peripheral blood T cell subpopulations CD3+,CD4+,and CD4+/CD8+ratio obviously reduced,the proportion of CD8+obviously increased(P＜0.05);The spleen index and thymus index of rats in the Mat-L and Mat-H groups of rats increased,and the phenomenon of renal tissue inflammation and infiltration improved,the 24-hour urine protein,BUN,Scr,TNF-α,IL-6,and the expression of MCP-1 and CCR2 obviously decreased,the peripheral blood T cell subpopulations CD3+,CD4+,and CD4+/CD8+ratio obviously increased,the proportion of CD8+obviously decreased(P＜0.05);CCR2 attenuated the effect of Mat-H on immune function in rats with chronic glomerulonephritis.Conclusion Matrine can alleviate the inflammatory damage and improve the peripheral immune function of rats with chronic glomerulonephritis,and its mechanism may be related to the inhibition of MCP-1/CCR2 signaling pathway.

Objective To explore clinical effect of distal tibial tubercle-high tibial osteotomy(DTT-HTO)in treating knee osteoarthritis(KO A)with medial meniscus posterior root tear(MMPRT).Methods A retrospective analysis was performed on 21 patients with varus KOA with MMPRT from May 2020 to December 2021,including 3 males and 18 females,aged from 49 to 75 years old with an average of(63.81±6.56)years old,the courses of disease ranged from 0.5 to 18.0 years with an average of(5.9±4.2)years,and 4 patients with grade Ⅱ,14 patients with grade Ⅲ,and 3 patients with grade Ⅳ according to Kellgren-Lawrence;14 patients with type 1 and 7 patients with type 2 according to MMPRT damage classification.The distance of medi-al meniscusextrusion(MME)and weight-bearing line ratio(WBLR)of lower extremity were compared before and 12 months after operation.Visual analogue scale(V AS),Western Ontarioand and McMaster Universities(WOMAC)osteoarthritis index,and Lysholm knee score were used to evaluate knee pain and functional improvement before operation,1,6 and 12 months after operation,respectively.Results Twenty-one patients were followed up for 12 to 18 months with an average of(13.52±1.72)months.MME distance was improved from(4.99±1.05)mm before operation to(1.87±0.76)mm at 12 months after operation(P＜0.05).WBLR was increased from(15.49±7.04)％before operation to(62.71±2.27)％at 12 months after operation(P＜0.05).VAS was decreased from(7.00±1.14)before operation to(2.04±0.80),(0.90±0.62)and(0.61±0.50)at 1,6 and 12 months after operation.WOMAC were decreased from preoperative(147.90±9.88)to postoperative(103.43±8.52),(74.00±9.54)and(47.62±9.53)at 1,6 and 12 months,and the difference were statistically significant(P＜0.05).Lysholm scores were increased from(46.04±7.34)before oepration to(63.19±8.93),(81.10±6.41)and(89.29±3.04)at 1,6 and 12 months after operation(P＜0.05).Conclusion For the treatment of varus KOA with MMPRT,DTT-HTO could reduce medial meniscus pro-trusion distance,improve the ratio of lower limb force line,and effectively reduce knee pain and improve knee joint function.

Objective:To investigate the prognostic factors for liver transplantation for hepatocellular carcinoma beyond UCSF criteria but without macrovascular invasion.Methods:A retrospective analysis was performed for the clinical data of the hepatocellular carcinoma patients without macrovascular invasion beyond UCSF criteria who underwent liver transplantation at our center from Jan 2018 to Jun 2023. The receiver operating characteristic curve analysis was performed to assess the predictive power of potential prognosis factors.Results:With this criteria, the 1-, 3-year overall survival rates were 94.1% and 75.0%, respectively, and the 1-, 3-year tumor free survival rates were 82.4% and 38.1%, respectively. The maximum tumor size, number of tumors, AFP, PIVKA-Ⅱ before transplantation, and whether undergo pretransplant down-stage therapy were significant prognostic factors ( P<0.05). Combining the above prognostic factors to construct the receiver operating characteristic curve yielded an area under the curve of 0.967, with a sensitivity and specificity of 0.932, 0.952, respectively. Further, the differentiation, MVI and Ki-67 were significant prognostic factors ( P<0.05). Combining pathological factors to construct the receiver operating characteristic curve yielded an area under the curve of 0.927, with a sensitivity and specificity of 0.769, 1, respectively. Conclusion:The maximum tumor diameter, number of tumors, AFP, PIVKA-Ⅱ before transplantation, and pretransplant down-stage therapy and tumor differentiation, MVI and Ki-67 are all prognostic factors of liver transplantation for hepatocellular carcinoma without macrovascular invasion beyond UCSF criteria.

Objectives: This study aimed to present the Asia-Pacific consensus on long-term and sequential therapy for osteoporosis, offering evidence-based recommendations for the effective management of this chronic condition.The primary focus is on achieving optimal fracture prevention through a comprehensive, individualized approach. Methods: A panel of experts convened to develop consensus statements by synthesizing the current literature and leveraging clinical expertise. The review encompassed long-term anti-osteoporosis medication goals, first-line treatments for individuals at very high fracture risk, and the strategic integration of anabolic and anti resorptive agents in sequential therapy approaches. Results: The panelists reached a consensus on 12 statements. Key recommendations included advocating for anabolic agents as the first-line treatment for individuals at very high fracture risk and transitioning to anti resorptive agents following the completion of anabolic therapy. Anabolic therapy remains an option for in dividuals experiencing new fractures or persistent high fracture risk despite antiresorptive treatment. In cases of inadequate response, the consensus recommended considering a switch to more potent medications. The consensus also addressed the management of medication-related complications, proposing alternatives instead of discontinuation of treatment. Conclusions This consensus provides a comprehensive, cost-effective strategy for fracture prevention with an emphasis on shared decision-making and the incorporation of country-specific case management systems, such as fracture liaison services. It serves as a valuable guide for healthcare professionals in the Asia-Pacific region, contributing to the ongoing evolution of osteoporosis management.

BACKGROUND: Progressive lipid loss of adipose tissue is a major feature of cancer-associated cachexia. In addition to systemic immune/inflammatory effects in response to tumor progression, tumor-secreted cachectic ligands also play essential roles in tumor-induced lipid loss. However, the mechanisms of tumor-adipose tissue interaction in lipid homeostasis are not fully understood. METHODS: The yki -gut tumors were induced in fruit flies. Lipid metabolic assays were performed to investigate the lipolysis level of different types of insulin-like growth factor binding protein-3 (IGFBP-3) treated cells. Immunoblotting was used to display phenotypes of tumor cells and adipocytes. Quantitative polymerase chain reaction (qPCR) analysis was carried out to examine the gene expression levels such as Acc1 , Acly , and Fasn et al . RESULTS: In this study, it was revealed that tumor-derived IGFBP-3 was an important ligand directly causing lipid loss in matured adipocytes. IGFBP-3, which is highly expressed in cachectic tumor cells, antagonized insulin/IGF-like signaling (IIS) and impaired the balance between lipolysis and lipogenesis in 3T3-L1 adipocytes. Conditioned medium from cachectic tumor cells, such as Capan-1 and C26 cells, contained excessive IGFBP-3 that potently induced lipolysis in adipocytes. Notably, neutralization of IGFBP-3 by neutralizing antibody in the conditioned medium of cachectic tumor cells significantly alleviated the lipolytic effect and restored lipid storage in adipocytes. Furthermore, cachectic tumor cells were resistant to IGFBP-3 inhibition of IIS, ensuring their escape from IGFBP-3-associated growth suppression. Finally, cachectic tumor-derived ImpL2, the IGFBP-3 homolog, also impaired lipid homeostasis of host cells in an established cancer-cachexia model in Drosophila . Most importantly, IGFBP-3 was highly expressed in cancer tissues in pancreatic and colorectal cancer patients, especially higher in the sera of cachectic cancer patients than non-cachexia cancer patients. CONCLUSION Our study demonstrates that tumor-derived IGFBP-3 plays a critical role in cachexia-associated lipid loss and could be a biomarker for diagnosis of cachexia in cancer patients.
Humans ; Insulin-Like Growth Factor Binding Protein 3/metabolism* ; Culture Media, Conditioned/pharmacology* ; Cachexia/pathology* ; Gastrointestinal Neoplasms ; Somatomedins/metabolism* ; Insulins/metabolism* ; Lipids

BACKGROUND: In the present study, a novel tissue engineering bone graft including platelet rich plasma gel (PRP gel), human umbilical mesenchymal stem cells (HUMSCs) and nanohydroxyapatite/polyamide 66 (nHA-PA66) was constructed. We explored whether the composite scaffolds could enhance the angiogenesis and bone repair capacity in rat femoral large bone defect (LBD). This study aimed to provide evidence for the clinical application of the composite scaffold in LBD treatment. METHODS: PRP was prepared, the platelets and growth factors were measured. HUMSCs were isolated and identified.the osteogenic capacity of PRP in vitro was measured. Then HUMSCs-PRP-gelHA-PA66 composite scaffolds were synthesized and observed. The proliferation and osteogenesis differentiation of HUMSCs on the composite scaffold was measured. The angiogenic capacity of PRP in vitro was measured by capillary-like tube formation assay. Finally, the angiogenesis and bone repair capacity of the composite scaffolds was measured in rat LBD. RESULTS: PRP contained high level of platelets and growth factors after activation, and promoted osteogenic and angiogenic differentiation in vitro. The HUMSCs-PRP-gelHA-PA66 composite scaffold was porosity and promoted the proliferation and osteogenesis differentiation of HUMSCs. At 12th weeks, more micro-vessels and new bone were formed around the composite scaffolds compared with other groups, the defect was almost repaired. CONCLUSION Our study for the first time identified that the combination of PRP gel, HUMSCs and nHA-PA66 scaffold could significantly promote angiogenesis and bone regeneration in rat LBD, which may have implications for its further application in clinical LBD treatment.

This study aims to explore the factors influencing the success rate of the microdissection testicular sperm extraction (Micro-TESE) in patients with nonobstructive azoospermia (NOA) and cryptorchidism. Clinical data of 162 patients with cryptorchidism who underwent Micro-TESE due to infertility from December 2015 to May 2020 in the First Affiliated Hospital of Nanjing Medical University were analyzed retrospectively. In the univariate analysis, significant differences in the age of patient at the time of orchidopexy (median [interquartile range, IQR]: 7.0 [4.0-11.0] years vs 11.5 [9.0-14.5] years, P < 0.001), interval between orchidopexy and Micro-TESE (mean ± standard deviation: 17.5 ± 5.0 years vs 14.4 ± 4.4 years, P < 0.001), severity of cryptorchidism (unilateral [62.8%] vs bilateral [31.6%], P < 0.001; location of cryptorchidism, intra-abdominal [27.3%] vs inguinal [44.8%] vs suprascrotal [66.7%], P < 0.001), volume of the dominant testis (median [IQR]: 17.00 [15.00-19.00] ml vs 14.50 [11.75-16.25] ml, P < 0.001), and levels of follicle-stimulating hormone (FSH; P = 0.004) and testosterone (P = 0.006) were observed between the successful and failed sperm extraction groups. After conducting the multivariate analysis, four of these factors, including unilateral/bilateral cryptorchidism (P < 0.001), location of cryptorchidism (P = 0.032), age of orchidopexy (P < 0.001), and dominant testicular volume, were adopted in the clinical prediction model to evaluate preoperatively the success rate of Micro-TESE for patients with NOA and cryptorchidism. The likelihood of successful sperm retrieval by Micro-TESE in men with NOA and cryptorchidism increased in patients with mild forms of cryptorchidism.
Azoospermia ; Child ; Cryptorchidism ; Humans ; Male ; Microdissection ; Models, Statistical ; Prognosis ; Retrospective Studies ; Semen ; Sperm Retrieval ; Spermatozoa ; Testis