Objective: To report the antibody identification, blood management during pregnancy and the monitoring process of fetal hemolytic disease of fetus and newborn (HDFN) in a pregnant woman with a history of blood transfusion and pregnancy who developed anti-Jr . Methods: Saline tube technique and anti-human globulin technique were used for maternal blood typing, unexpected antibody screening and identification, as well as for determining antibody titer and IgG subclasses. PCR-SSP was employed for genotyping of 18 blood group systems. Next-generation sequencing (NGS) was utilized for gene sequencing of 38 blood group systems. Sanger sequencing was applied to verify rare blood group mutations detected by NGS and to investigate the corresponding rare blood group genes in family members. Blood preparation was achieved through anemia management in prenatal clinics and autologous blood collection during pregnancy. The newborn underwent the three primary tests for HDFN and plasma IgG subclass testing. Results: The pregnant woman's blood type was B, RhD positive, with a positive unexpected antibody screen, and the antibody identification pattern was consistent with a high-frequency antigen antibody. Gene sequencing revealed a homozygous ABCG2 c.376C>T mutation in the woman, resulting in the Jr(a-) phenotype, and anti-Jr antibody was present in her plasma. No compatible Jr(a-) blood was found among family members. The maternal anti-Jr IgG titer remained stable at 256 during pregnancy, with no detectable IgG1 or IgG3 subclasses against the Jr antigen. A total of 800 mL of autologous blood was collected in two stages during pregnancy. The newborn was B, RhD positive, Jr(a+), with a positive unexpected antibody screen (anti-Jr ). IgG subclass typing detected no IgG1 or IgG3. The direct antiglobulin test was positive, while the acid elution test was negative. Conclusion: The combination of serology and blood group genetic analysis provides a diagnostic basis for identifying antibodies to high-frequency antigens. Managing perinatal anemia and implementing staged autologous blood storage can secure blood supply for the perioperative period. IgG antibody subclass typing offers a reference for clinical assessment and prevention of HDFN.

Poly(lactic-co-glycolide)(PLGA)is a key excipient in long-acting sustained-release preparations,and its degradation properties directly affect the drug release behavior.In this study,PLGA microspheres were prepared by microfluidic techniques,and the morphology changes of the microspheres were observed by scanning electron microscopy(SEM).In alkaline environment,due to the accelerated hydrolysis of ester bonds,the surface of the microspheres was rapidly dissolved and eroded,and the degradation rate was significantly higher than that in acidic environment.High temperature accelerated the degradation of PLGA microspheres.Under neutral and alkaline conditions,the microspheres showed aggregation and adhesion.Under acidic conditions,the microspheres gradually decomposed into irregular fragments.The high ionic strength further promoted the surface corrosion of the microspheres,especially under extreme pH conditions.Simultaneously,PLGA microspheres encapsulating coumarin were prepared to simulate the microsphere formulation.The release rate of coumarin after degradation of the microspheres under different conditions was observed by measuring the absorbance with ultraviolet-visible spectrophotometry.The results were consistent with those of the blank microspheres.This study revealed that the degradation of PLGA microspheres was significantly pH-dependent,temperature sensitive and ion strength responsive.These findings not only helped to understand and optimize the long-term stability and controlled release performance of drug-carrying microspheres,but also provided a theoretical basis for further improvement of PLGA-based drug carrier design.

Near infrared spectroscopy(NIRS)analysis technology has become an important process analysis tool in industrial and agricultural production,and has been widely used for qualitative and quantitative analysis in the fields of tobacco,agriculture,and pharmaceuticals.To address issues such as poor generalization ability and low prediction accuracy in NIRS modeling,a two-dimensional convolutional neural network(2DCNN)quantitative analysis model based on competitive adaptive reweighted sampling(CARS)and Gramian angular difference field(GADF)(CARS-GADF-2DCNN)was proposed.CARS-GADF-2DCNN used the CARS method to select an optimal wavelength set from the full spectrum,then employed GADF to encode the selection results into two-dimensional images,and finally used 2DCNN for prediction analysis.The 2DCNN model consisted of convolutional layers,parallel convolution modules,flattening layer,and fully connected layers.Simulation experiments were conducted on three public near-infrared(NIR)spectral datasets encompassing soil,tablet,and grain datasets to evaluate the CARS-GADF-2DCNN model.The results demonstrated that,compared to the one-dimensional convolutional neural network(1DCNN),the GADF-2DCNN model achieved 16.74％,23.40％,and 7.13％improvement in prediction accuracy for the soil,tablet,and grain datasets,respectively.Compared to GADF-2DCNN,VCPA-GADF-2DCNN,and IRIV-GADF-2DCNN models,the CARS-GADF-2DCNN model further improved prediction accuracy.For the soil dataset,prediction accuracy improved by 39.00％,30.78％and 4.13％;for the tablet dataset,the improvements were 9.52％,6.94％and 2.56％;for the grain dataset,the improvements were 20.57％,9.85％and 15.66％.In conclusion,CARS-GADF-2DCNN effectively selected the optimal wavelength subset from near infrared spectra,and revealed the latent features between different wavelengths.CARS-GADF-2DCNN addresses the issues of high complexity in prediction models and low prediction accuracy in near infrared spectral modeling,and could be effectively applied to near infrared spectral prediction analysis of different substances.

Rubi Fructus has a long history of medicinal and edible use in China. It contains chemical components such as terpenes, flavonoids, phenolic acids, fatty acids, and alkaloids, and possesses various pharmacological activities, including antioxidant, anti-inflammatory, hypoglycemic, anti-tumor, anti-osteoporosis, and liver-protective effects. Rubi Fructus is widely applied in medical, health, and food fields. The quality of Rubi Fructus can directly affect the safety and effectiveness of clinical medication. Therefore, this article reviews the research progress on the chemical constituents and pharmacological effects of Rubi Fructus. Based on the concept of traditional Chinese medicine(TCM) quality markers(Q-markers), the article explores the screening and determination of Q-markers for Rubi Fructus from various aspects, including plant kinship, traditional efficacy, medicinal properties, measurability of chemical composition, different processing methods, producing areas, harvesting periods, and planting conditions. The components ellagic acid, kaempferol, quercetin, kaempferol-3-O-rutinoside, rutin, astragalin, tiliroside, and hyperoside are preliminarily proposed as Q-markers for Rubi Fructus, providing a reference for the quality control of Rubi Fructus.
Drugs, Chinese Herbal/pharmacology* ; Humans ; Rubus/chemistry* ; Fruit/chemistry* ; Quality Control ; Animals

Proanthocyanidin B_2(PAC-B_2), a polyphenolic dimeric compound comprising two epicatechin molecules linked by a C-C bond, is extensively found in traditional Chinese medicines, with anti-tumor and anti-oxidant activities. Given the limited bioavailability, a thorough investigation and comprehensive understanding of PAC-B_2 metabolism in vivo are essential for elucidating therapeutic forms and mechanisms. In the present study, ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS) in the negative ion mode was employed to acquire the MS/MS information of PAC-B_2 and metabolites in urine and feces samples of the rats administrated with PAC-B_2. Online energy-resolved MS(ER-MS) was applied as supplementary to obtain the full collision energy ramp-MS~2 spectra(FCER-MS~2) of isomers-of-interest, which implied comprehensive MS~2 information of targeted compounds. Finally, the possible metabolic pathways of PAC-B_2 in rats were proposed. The primary fragmentation behaviors of PAC-B_2 in the negative ion mode included quinone methide fission between C_4-C_8 bond, retro Diels-Alder cracking of F-ring, heterocyclic ring fission of C-ring, and neutral loss of small molecules such as H_2O. A total of 25 metabolites were tentatively elucidated in urine and feces samples of rats administrated with PAC-B_2 by fragmentation pattern and reported literature. Two groups of isomers, M3/M4/M5 and M9/M11, were confirmatively differentiated based on the relationships between optimal collision energy provided by FCER-MS~2 and bond properties, including bond length and bond dissociation energy. In addition to the ring-opening and methylation, PAC-B_2 could also be metabolized into epicatechin and low molecular weight phenolic acids, which were subsequently subjected to dehydroxylation, ring-opening, methylation, sulfation, and glucuronidation. The structural information provided by online ER-MS and FCER-MS~2 enabled the differentiation of isomers and improved the identification confidence. More importantly, the present study deeply analyzes the in vivo metabolic pathways of PAC-B_2, providing a basis for the research on the pharmacological mechanism of this compound.
Animals ; Proanthocyanidins/urine* ; Rats ; Male ; Drugs, Chinese Herbal/chemistry* ; Rats, Sprague-Dawley ; Tandem Mass Spectrometry ; Chromatography, High Pressure Liquid ; Feces/chemistry* ; Molecular Structure

ObjectiveTo investigate the triglyceride-glucose (TyG) index and the level of serum homocysteine (Hcy) in association with the incidence of stroke in type 2 diabetes mellitus (T2DM) patients. MethodsBased on the chronic disease risk factor surveillance cohort in Pudong New Area, Shanghai, excluding those with stroke in baseline survey, T2DM patients who joined the cohort from January 2016 to October 2020 were selected as the research subjects. During the follow-up period, a total of 318 new-onset ischemic stroke patients were selected as the case group, and a total of 318 individuals matched by gender without stroke were selected as the control group. The Cox proportional hazards regression model was used to adjust for confounding factors and explore the serum TyG index and the Hcy biochemical indicator in association with the risk of stroke. ResultsThe Cox proportional hazards regression results showed that after adjusting for confounding factors, the risk of stroke in T2DM patients with 10 μmol·L⁻¹-¹ and Hcy>15 μmol·L⁻¹ was 1.532 times (95%CI: 1.017‒2.309 times, P=0.041) and 1.738 times (95%CI: 1.119‒2.699 times, P=0.014) higher respectively, compared to T2DM patients with Hcy≤10 μmol·L⁻¹. T2DM patients with TyG>9.074 had 1.396 times higher risk of stroke (95%CI: 1.091‒1.787, P=0.008) compared to those with TyG≤9.074. The study found that urea and α1-antitrypsin (α1-AT) were independent risk factors for the incidence of stroke in T2DM patients. For every unit increase in urea andα1-AT, the risk of stroke in T2DM patients increased by 233.6% (HR=3.336, 95%CI: 1.588‒7.009, P=0.001) and 11.3% (HR=1.113, 95%CI: 1.028‒1.205, P=0.008), respectively. Cumulative risk curves showed that Hcy>10 μmol·L⁻¹ and TyG>9.074 accelerated the time to stroke occurrence in T2DM patients. ConclusionElevated levels of Hcy>10 μmol·L⁻¹ and a higher TyG index are risk factors for stroke in T2DM patients. Effective interventions for Hcy and TyG should be conducted for diabetic patients to reduce the incidence of stroke.

Garcinol, a benzenetriol compound extracted from Garcinia cambogia, has antitumor activity, however, its antitumor mechanism remains unclear. The aim of this study was to investigate the role and mechanism of garcinol as a novel potential proteasome inhibitor. We applied the drug affinity responsive target stability (DARTS) method coupled to mass spectrometry to determine the binding protein of garcinol; the proteasome activity assay was used to determine the effect of garcinol on its hydrolase activity; immunofluorescence and proximity ligation assay (PLA) were used to detect the effects of garcinol on ubiquitin and RPN6; and flow cytometry were used to determine the effects of garcinol on cell apoptosis; and the anti-cancer effect was studied in organoid models. The results showed that RPN6 was a direct binding protein of garcinol; garcinol inhibited the hydrolase activity of proteasome, and induced the accumulation and aggregation of ubiquitin protein, and its proteasomal inhibitory effect was dependent on RPN6; further studies showed that garcinol induced oligomerization of RPN6 and formation of granules in the nucleus; finally, it was verified that garcinol induced apoptosis of tumor cells, and inhibited the growth of organoids of Apc^min/+ small intestine mice. These results suggest that garcinol is a potential proteasome inhibitor, which inhibits proteasome activity by directly targeting RPN6 on proteasome 19S, which in turn induces cell apoptosis and inhibits tumor growth.

OBJECTIVE To investigate the effects of Tripterygium wilfordii multiglycoside （TWM） on renal injury in diabetic nephropathy （DN） rats through tumor protein p53/microRNA-214 （miR-214）/UNC-51-like kinase 1 （ULK1） axis. METHODS Male SD rats were randomly divided into normal group （n＝6） and modeling group （n＝28）； the modeling group was fed with high fat and high glucose plus intraperitoneal injection of streptozotocin to establish DN model. The modeled rats were randomly divided into model group， valsartan group [8.33 mg/（kg·d）] and TWM group[6.25 mg/（kg·d）]， with 8 rats in each group. Rats in each group were gavaged with the corresponding medication or normal saline， once a day， for 6 consecutive weeks. After the last medication， liver and renal function indexes [24 h urinary total protein （24 h-UTP）， blood urea nitrogen （BUN）， serum creatinine （SCr）， albumin （ALB）， alanine transaminase （ALT）]， blood lipid indexes （triglycerides， total cholesterol） and blood glucose index （fasting blood glucose） in urine/blood sample of rats were detected in each group. Renal pathologic change was observed， protein and mRNA expressions of p53， ULK1， Beclin-1 and microtubule-associated protein 1 light chain 3 （LC3）， and expression of miR-214 in renal tissue were also determined. RESULTS Compared with the normal group， the renal tubular epithelium of rats in the model group showed obvious edema， cell swelling， accompanied by lymphocyte infiltration； the levels of 24h-UTP， BUN， SCr， ALT and glycolipid indexes， the expressions of p53 protein and mRNA， as well as the expression of miR-214 in rats in the model group and administration groups were significantly increased or up-regulated， while ALB level， LC3-Ⅱ/LC3-Ⅰ， the expressions of LC3 mRNA， the expressions of ULK1， Beclin-1 protein and mRNA were significantly decreased or down-regulated （P＜0.01）. Compared with the model group， the histopathological damage of the kidney in rats was improved in administration groups； the levels of 24 h-UTP， BUN， SCr， ALT and glycolipid indexes， the expressions of p53 protein and mRNA， as well as the expression of miR-214 were all significantly decreased or down-regulated， while ALB level， LC3-Ⅱ/LC3-Ⅰ， the expressions of LC3 mRNA， the expressions of ULK1 and Beclin-1 protein and mRNA were significantly increased or up-regulated （P＜0.01）. CONCLUSIONS TG can alleviate renal damage in DN rats， and improve their liver and renal function， as well as glucose and lipid levels. These effects may be related to the regulation of the p53/miR-214/ULK1 axis and the restoration of cellular autophagy.

Fibrosis, the pathological scarring of vital organs, is a severe and often irreversible condition that leads to progressive organ dysfunction. It is particularly pronounced in organs like the liver, kidneys, lungs, and heart. Despite its clinical significance, the full understanding of its etiology and complex pathogenesis remains incomplete, posing substantial challenges to diagnosing, treating, and preventing the progression of fibrosis. Among the various molecular players involved, platelet-derived growth factor-C (PDGF-C) has emerged as a crucial factor in fibrotic diseases, contributing to the pathological transformation of tissues in several key organs. PDGF-C is a member of the PDGFs family of growth factors and is synthesized and secreted by various cell types, including fibroblasts, smooth muscle cells, and endothelial cells. It acts through both autocrine and paracrine mechanisms, exerting its biological effects by binding to and activating the PDGF receptors (PDGFRs), specifically PDGFRα and PDGFRβ. This binding triggers multiple intracellular signaling pathways, such as JAK/STAT, PI3K/AKT and Ras-MAPK pathways. which are integral to the regulation of cell proliferation, survival, migration, and fibrosis. Notably, PDGF-C has been shown to promote the proliferation and migration of fibroblasts, key effector cells in the fibrotic process, thus accelerating the accumulation of extracellular matrix components and the formation of fibrotic tissue. Numerous studies have documented an upregulation of PDGF-C expression in various fibrotic diseases, suggesting its significant role in the initiation and progression of fibrosis. For instance, in liver fibrosis, PDGF-C stimulates hepatic stellate cell activation, contributing to the excessive deposition of collagen and other extracellular matrix proteins. Similarly, in pulmonary fibrosis, PDGF-C enhances the migration of fibroblasts into the damaged areas of lungs, thereby worsening the pathological process. Such findings highlight the pivotal role of PDGF-C in fibrotic diseases and underscore its potential as a therapeutic target for these conditions. Given its central role in the pathogenesis of fibrosis, PDGF-C has become an attractive target for therapeutic intervention. Several studies have focused on developing inhibitors that block the PDGF-C/PDGFR signaling pathway. These inhibitors aim to reduce fibroblast activation, prevent the excessive accumulation of extracellular matrix components, and halt the progression of fibrosis. Preclinical studies have demonstrated the efficacy of such inhibitors in animal models of liver, kidney, and lung fibrosis, with promising results in reducing fibrotic lesions and improving organ function. Furthermore, several clinical inhibitors, such as Olaratumab and Seralutinib, are ongoing to assess the safety and efficacy of these inhibitors in human patients, offering hope for novel therapeutic options in the treatment of fibrotic diseases. In conclusion, PDGF-C plays a critical role in the development and progression of fibrosis in vital organs. Its ability to regulate fibroblast activity and influence key signaling pathways makes it a promising target for therapeutic strategies aiming at combating fibrosis. Ongoing research into the regulation of PDGF-C expression and the development of PDGF-C/PDGFR inhibitors holds the potential to offer new insights and approaches for the diagnosis, treatment, and prevention of fibrotic diseases. Ultimately, these efforts may lead to the development of more effective and targeted therapies that can mitigate the impact of fibrosis and improve patient outcomes.

Abstract In recent years, the prevalence of overweight and obesity among children and adolescents has risen rapidly, posing a serious threat to their physical and mental health. To provide scientific, systematic, and standardized weight management guidance for overweight and obese children and adolescents, the study focuses on the core concept of healthy lifestyle intervention, integrates multidisciplinary expert opinions and research findings,and proposes a comprehensive multidisciplinary intervention framework covering scientific exercise intervention, precise nutrition and diet, optimized sleep management, and standardized psychological support. It calls for the establishment of a multi agent collaborative management mechanism led by the government, implemented by families, fostered by schools, initiated by individuals, optimized by communities, reinforced by healthcare, and coordinated by multiple stakeholders. Emphasizing a child and adolescent centered approach, the consensus advocates for comprehensive, multi level, and personalized guidance strategies to promote the internalization and maintenance of a healthy lifestyle. It serves as a reference and provides recommendations for the effective prevention and control of overweight and obesity, and enhancing the health level of children and adolescents.