Endometriosis is a common chronic gynecological disease with endometrial cell implantation outside the uterus.Angiogenesis is a major pathophysiology in endometriosis.Our previous studies have demon-strated that the prodrug of epigallocatechin gallate(ProEGCG)exhibits superior anti-endometriotic and anti-angiogenic effects compared to epigallocatechin gallate(EGCG).However,their direct binding targets and underlying mechanisms for the differential effects remain unknown.In this study,we demonstrated that oral ProEGCG can be effective in preventing and treating endometriosis.Additionally,1D and 2D Proteome Integral Solubility Alteration assay-based chemical proteomics identified metadherin(MTDH)and PX domain containing serine/threonine kinase-like(PXK)as novel binding targets of EGCG and ProEGCG,respectively.Computational simulation and BioLayer interferometry were used to confirm their binding affinity.Our results showed that MTDH-EGCG inhibited protein kinase B(Akt)-mediated angiogenesis,while PXK-ProEGCG inhibited epidermal growth factor(EGF)-mediated angiogenesis via the EGF/hypoxia-inducible factor(HIF-1a)/vascular endothelial growth factor(VEGF)pathway.In vitro and in vivo knockdown assays and microvascular network imaging further confirmed the involvement of these signaling pathways.Moreover,our study demonstrated that ProEGCG has superior therapeutic effects than EGCG by targeting distinct signal transduction pathways and may act as a novel anti-angiogenic therapy for endometriosis.

The traditional commodity specifications of Chinese medicinal materials are mainly divided into different grades based on macroscopic characteristics. As the basis for high quality and good price, there is still a lack of systematic evaluation on whether they are consistent with the current standards and whether they can reflect the internal quality of medicinal material. Panax notoginseng is a commonly used, large consumption of Chinese medicinal material. At present, it is divided into 8 grades in the market based on "Tou" (the number of crude drug /500 g), but it is not related to the standard of total saponins of Panax notoginseng (the sum of three saponins) in Chinese Pharmacopoeia. In this study, ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry (UPLC-Q-TOF-MS/MS) coupled with mass spectrometry molecular network were used for the rapid identification of saponins of Panax notoginseng with different "Tou" and a total of 64 saponins were identified. Seventeen saponins related to "Tou" were screened by orthogonal partial least squares discriminant analysis (OPLS-DA). The content of five saponins R₁, Rb₁, Rg₁, Rd, and Re in Panax notoginseng with different "Tou" was determined by high performance liquid chromatography (HPLC). The results of correlation analysis showed that Rd and R₁ with the largest VIP values among the differential saponins, which significantly negatively correlated with "Tou" (P < 0.05). Based on the determination results of 36 batches of samples, using Rd/Total Panax notoginseng saponins (TPNS) ratio ( > 0.08) as the index, Panax notoginseng can be divided into two grades: 20-60 "Tou" (superior) and 80-200 "Tou" (qualified). Based on the concept of "macroscopic characteristics and chemical profiling", this study integrates the non-targeted analysis and quantitative determination methods to provide a new strategy for quality evaluation of Panax notoginseng.

Objective To investigate the causes of a cluster of suspected neonatal carbapenem-resistant Klebsiella pneumoniae(CRKP)bloodstream infection(BSI)in the neonatal department of a hospital,and provide references for the effective control of the occurrence of healthcare-associated infection(HAI).Methods Epidemiological in-vestigation on 3 neonates with CRKP BSI in the neonatal department from January 31 to February 6,2023 was per-formed.Specimens from environmental object surfaces were taken for environmental hygiene monitoring,and effec-tive control measures were taken according to the risk factors.Results From January 31 to February 6,2023,a to-tal of 60 neonates were admitted in the neonatal department,including 16 with peripherally inserted central venous catheter(PICC).Three neonates had CRKP BSI,with a incidence of 5.00％.There were 33 hospitalized neonates on the day(February 7)when the cluster of HAI was reported,with a prevalence rate of 9.09％(3/33).CRKP BSI rate in the neonatal department of this hospital from January 31 to February 6,2023 was higher than that in 2022(P＜0.001).The incubators of the 3 neonates with CRKP BSI were in the same ward and adjacent to each other.The first neonate with CRKP BSI(who developed BSI on January 31)underwent PICC maintenance on Feb-ruary 4,and the other 2 neonates with PICC maintenance immediately following the first one also developed CRKP BSI.CRKP were isolated from blood culture of all 3 neonates,and antimicrobial susceptibility testing results were consistent.Conclusion The occurrence of the cluster event of neonatal CRKP BSI may be related to the failure of strict implementation of aseptic procedures during PICC maintenance and cross contamination among items.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Chirality is one of the fundamental properties of nature, and most of the important molecules in living organisms contain chiral structures. The efficacy and safety of drugs are often closely related to the chiral structure of compounds, however, there are relatively more studies on synthetic characterization, pharmacology, and toxicology of chiral small molecule chemical drugs, but relatively less studies on chiral compounds contained in natural drugs such as traditional Chinese medicines. Chiral separation, as the basis of chiral research, has a pivotal position in the study of chiral compounds. In this paper, we systematically describe the separation methods of chiral compounds from the classification of chiral splitting methods based on chromatographic and non-chromatographic methods, as well as chromatographic packing materials, chiral additives and chiral derivatization, and review the chiral compounds in natural drugs such as traditional Chinese medicines reported in the past ten years, in order to provide references for the splitting and evaluating the activity of chiral compounds, and the improvement of quality standards of traditional Chinese medicines.

Aim To explore the effect of androgen receptor AR on the proliferation and lipid synthesis of cardiac fibroblasts under high-glucose conditions and the possible molecular mechanism.Methods The hearts of neonatal rats were dissected for primary culture of cardiac fibroblasts. Then the growth status of CFs was observed under the inverted microscope, and the identification of CFs was performed by immunofluorescence staining using anti-vimentin. After cell adherence, the cells were divided into blank control group, high glucose model group, negative control group, and overexpressed AR group. The glucose concentration was 33.0 mmol·L-1 except that the blank control group was 5.5 mmol·L-1. After 24 hours of CFs culture, Western blot and RT-qPCR were used to detect the expression of AR, FASN, PCNA, cyclin D1, α-SMA, and collagen . Oil red O and CCK-8 were used to detect the changes in lipid synthesis and cell proliferation ability, respectively.Results Compared with the blank control group, the lipid synthesis and proliferation of CFs in the high glucose model group were enhanced. Western blot and RT-qPCR results showed that the expression of AR decreased, while the expression of fat lipid synthase(FASN), proliferation marker PCNA, cyclin D1 and fibrosis marker α-SMA and collagen increased. After AR overexpressed plasmid was transfected into the CFs treated by high glucose, AR overexpression markedly decreased the expression of FASN, PCNA, cyclin D1, α-SMA and collagen compared with the empty plasmid‐transfected group. Meanwhile, oil red O staining and CCK-8 results showed that the lipid synthesis and proliferation ability of the overexpressed AR group decreased compared with the empty vector group, respectively. Conclusions High glucose promotes the proliferation and lipid synthesis of cardiac fibroblasts. Besides, the mechanism may be related to the regulation of lipid synthesis regulated by AR.

Objective:To investigate the radiosensitization effect of low-dose sulfasalazine (SAS) on colorectal cancer (CRC) cells.Methods:Proliferation inhibition effect of SAS on CRC cells was detected by CCK-8 assay, and the concentration of SAS in vitro assays was based on its IC10 value. CRC cells were treated with SAS alone or combined with inhibitors of apoptosis, autophagy, ferroptosis and necroptosis, then cell viability was detected by CCK-8 assay. Trypan blue staining, clone formation assay and cell growth curves were used to verify the radiosensitization effect of SAS on CRC cells in vitro. CRC cells were treated with SAS and radiotherapy, then the intracellular contents of lipid peroxidation and the protein levels of GPX4, PTGS2, cleaved PARP and active caspase 3 were evaluated, respectively. Subcutaneous xenograft tumor mouse model was established to further verify the radiosensitization effect of SAS in vivo. Results:High dose (lethal dose) of SAS could induce apoptosis and ferroptosis in CRC cells. Low dose (non-lethal dose) of SAS enhanced the radiosensitivity of CRC cells in vitro, and the radiosensitivity effect of SAS could only be abolished by ferroptosis inhibitor (Fer-1). Low dose of SAS combined with radiotherapy significantly down-regulated the expression of GPX4, whereas increased the intracellular lipid peroxidation levels and the expression of PTGS2. SAS also showed significant radiosensitization effect in subcutaneous xenograft tumor model. Conclusion:Our findings suggest that low-dose SAS could increase the radiosensitivity of CRC cells by promoting ferroptosis.

Looking retrospectively at the development of humanity, vaccination is an unprecedented medical landmark that saves lives by harnessing the human immune system. During the ongoing coronavirus disease 2019 (COVID-19) pandemic, vaccination is still the most effective defense modality. The successful clinical application of the lipid nanoparticle-based Pfizer/BioNTech and Moderna mRNA COVID-19 vaccines highlights promising future of nanotechnology in vaccine development. Compared with conventional vaccines, nanovaccines are supposed to have advantages in lymph node accumulation, antigen assembly, and antigen presentation; they also have, unique pathogen biomimicry properties because of well-organized combination of multiple immune factors. Beyond infectious diseases, vaccine nanotechnology also exhibits considerable potential for cancer treatment. The ultimate goal of cancer vaccines is to fully mobilize the potency of the immune system as a living therapeutic to recognize tumor antigens and eliminate tumor cells, and nanotechnologies have the requisite properties to realize this goal. In this review, we summarize the recent advances in vaccine nanotechnology from infectious disease prevention to cancer immunotherapy and highlight the different types of materials, mechanisms, administration methods, as well as future perspectives.

Charcot-Marie-Tooth Disease/genetics* ; DNA-Binding Proteins/genetics* ; Humans ; Mutation ; Transcription Factors/genetics*

Diabetic cardiomyopathy (DCM) is described as abnormalities of myocardial structure and function in diabetic patients without other well-established cardiovascular factors. Although multiple pathological mechanisms involving in this unique myocardial disorder, mitochondrial dysfunction may play an important role in its development of DCM. Recently, considerable progresses have suggested that mitochondrial biogenesis is a tightly controlled process initiating mitochondrial generation and maintaining mitochondrial function, appears to be associated with DCM. Nonetheless, an outlook on the mechanisms and clinical relevance of dysfunction in mitochondrial biogenesis among patients with DCM is not completely understood. In this review, hence, we will summarize the role of mitochondrial biogenesis dysfunction in the development of DCM, especially the molecular underlying mechanism concerning the signaling pathways beyond the stimulation and inhibition of mitochondrial biogenesis. Additionally, the evaluations and potential therapeutic strategies regarding mitochondrial biogenesis dysfunction in DCM is also presented.