This article systematically reviews and verifies the name， origin， production area， quality evaluation， harvesting， processing and other aspects of Cynanchi Atrati Radix et Rhizoma（CARR） by consulting relevant ancient and modern literature， in order to provide a basis for the development and utilization of famous classical formulas containing this herb. Through textual research， Baiwei has been the official name for CARR， though it also bears alternative names such as Chuncao， Popo Zhenxianbao， Longdan Baiwei. The mainstream base is the roots and rhizomes of Cynanchum atratum. Historical records indicate primary producing areas include Shandong， Anhui， Jiangsu， Shaanxi and Shanxi. Since the late Ming dynasty， varieties from Juxian， Yishui and Rizhao in Shandong have been highly regarded as authentic， commonly known as eastern Baiwei. Since modern times， its quality has been summarized as fine， slender， and straight fibrous roots， pale yellow exterior， whiter interior， and dryness with easy breakability are considered superior. The harvesting time before the Song dynasty was on the third day of the third lunar month， but after the Song dynasty， harvesting was possible in both spring and autumn. The initial processing methods of CARR in ancient times included drying in the shade， removing Lu（the little rhizomes which are on tap of roots）， and removing mustaches， modern methods involve washing and sun-drying. During the Northern and Southern dynasties， processing methods included steaming. In the Song dynasty， drying and light stir-frying were predominant， while wine washing emerged in the Ming dynasty. Modern practices primarily involve using raw， stir-frying or honey processing. Regarding the medicinal properties of CARR， both ancient and modern texts agree it has a bitter and salty taste and is non-toxic. Records prior to the Qing dynasty predominantly describe its nature as extremely cold， while mainstream herbal texts after the Qing dynasty generally characterize it as cold. Before the Ming dynasty， there were no records of its meridian tropism. It was not until the Qing dynasty that it was recorded in the lung meridian. Modern records mainly refer to the stomach， liver， and kidney meridians. Throughout history， its main functions have been to clear heat， diuresis， nourish Yin， and replenish essence， primarily treating Yin deficiency and fever syndrome. Based on the research results， it is suggested that when developing famous classical formulas containing CARR， the dried roots and rhizomes of C. atratum can be selected as its medicinal source. If there are no specific processing requirements， raw products can be selected as medicine. If the processing requirements are specified， corresponding processed products can be selected as medicine according to the original formula requirements.

Neurocritical care involves complex pathophysiological mechanisms, and its incidence is higher, injuries are more severe, and treatment is more challenging in high-altitude environments. This consensus, based on the latest domestic and international evidence-based medical data, establishes a standardized, goal-oriented framework for neurocritical care management applicable in high-altitude regions and nationwide. The consensus was developed following international standards for evidence quality assessment and underwent two rounds of Delphi expert consultation, resulting in 32 recommendation statements covering three parts: management systems, monitoring and assessment, and core strategies. Key updates include: advocating for the establishment of independent neurocritical care units and implementing precise tiered diagnosis and treatment based on the "Five Differences in Critical Care" concept; constructing a "trinity" multimodal brain monitoring system centered on cerebral blood flow, cerebral oxygenation, and brain function, emphasizing routine bedside transcranial Doppler ultrasound, cerebral oximetry, and continuous electroencephalography monitoring; shifting management strategies from mild hypothermia therapy to targeted temperature management, and defining the "446" target management pathway for the supercritical stage; emphasizing the assessment of static and dynamic cerebrovascular autoregulation functions through multimodal methods to achieve individualized optimal mean arterial pressure management; elevating cerebrospinal fluid management goals to the level of "glymphatic system" function maintenance; implementing a multidisciplinary collaborative, whole-process management model focusing on patients' long-term neurological functional outcomes; de-escalation criteria include multidimensional indicators such as recovery of brain structure, restoration of cerebrovascular autoregulation, improvement in cerebrospinal fluid dynamics, and reduction in biomarker levels; and integrating cutting-edge technologies like artificial intelligence into post-critical care management and rehabilitation planning. This consensus systematically integrates the entire process of neurocritical care management, reflecting the modern connotation of goal-oriented, dynamic, and multimodal integration in neurocritical care medicine. It aims to adapt to new trends such as deepening understanding of pathophysiological mechanisms, the integration of medicine and engineering, and the empowerment of artificial intelligence, thereby further advancing the discipline of critical care medicine.

Objective To introduce the causes of accidents and the diagnosis and treatment of two patients with radiation-induced skin injury admitted to our hospital in 2023, and to provide a reference for the clinical treatment of subsequent radiation-induced skin injury. Methods The clinical treatment process of two patients with acute skin injury caused by external radiation exposure were summarized and analyzed. Results The exposure history of the two patients was reconstructed, the flaw detection scenario was simulated, the biological dose and hand skin exposure dose were estimated, and the infrared thermal imaging device was used for dynamic monitoring. A comprehensive analysis was conducted based on clinical manifestations and other data. The diagnosis of “Xie” was excessive exposure combined with acute radiation-induced skin injury on both hands (Grade IV for the right hand palm, index finger, and middle finger and Grade II for the left hand little finger). The diagnosis of “Hao” was acute radiation-induced skin injury on both hands (Grade I). The two patients received different clinical treatment measures: “Xie” was treated with both local and systemic therapies, while “Hao” was mainly treated with systemic therapy. Conclusion After systematic and effective treatment, the radiation-induced skin injuries healed in both patients.

Objective To gain insights into the biological characteristics of different populations of Culex tritaeniorhynchus within and around the Yellow Sea wetland from the perspective of the occurrence of resistance, we investigated the levels of resistance to deltamethrin and kdr gene mutation in the wetland and its peripheral areas. Methods Specimens were collected from Cx. tritaeniorhynchus populations at two monitoring sites in the Rare Bird National Nature Reserve and Tiaozi Ni Wetland Scenic Area, and also from two populations in Yancheng City and the Liuhe District of Nanjing, and the resistance of these mosquitoes to deltamethrin was determined using the CDC biotest bottle method. For each concentration of deltamethrin assessed, a random subset of exposed specimens was selected for amplification of the kdr gene fragment, followed by Sanger sequencing to identify and analyze resistance-associated mutations. Results The LC50 levels of deltamethrin among mosquitoes from the four populations in Luhe, Yancheng, the Rare Bird National Nature Reserve and the Tiaozi Ni Wetland Scenic Area were 2.048 5, 7.798 2, 3.473 3, and 17.695 5 mg/mL, respectively, with corresponding concentrations of deltamethrin ranging from 0.005 to 5.000,0.050 to 50.000,0.050 to 25.000 and 0.050 to 50.000 mg/mL, respectively. Furthermore, the ranges of the KT50 values were 11.76-107.43, 67.05-216.30,29.77-107.43 and 28.40-329.51 min; the 1-h knockdown rates were 34.58%-99.15%, 9.52%-43.80%, 55.09%-73.01%, and 10.09%-68.07%; and the 24-h mortality rates were 12.15%-67.52%,9.52%-79.56%,13.17%-82.21%, and 11.01%-78.99%, respectively. With respect to kdr gene mutation, we assayed a total of 63,70,59, and 57 mosquitoes for the four populations, for which we detected L1014F mutation frequencies of 14.29%, 35.00%, 20.34%, and 31.58%, respectively, with a majority of these mutations being heterozygous for resistance. In addition, five adult mosquitoes were identified has having synonymous mutations at site 1011[i. e. , AAT(asparagine)mutation to AAC(asparagine)]. Conclusions Our findings revealed the clear resistance of Cx. tritaeniorhynchus to deltamethrin in the Yancheng region of the Yellow Sea wetland, and the resistance phenotype and kdr frequency of Cx. tritaeniorhynchus in the wetland environment were comparable to those of Cx. tritaeniorhynchus in the wetland environment, thereby indicating that the resistance of different populations of Cx. tritaeniorhynchus was homogeneous under the pressure of different insecticide selection within and around the wetland. However, the underlying mechanisms need to be further studied.

BACKGROUND:Osteoarthritis is now considered a metabolic disease.Previous studies have shown that glycolysis plays an important role in the occurrence and development of osteoarthritis.Compound 3k,as a novel small molecule inhibitor of glycolysis,has anti-inflammatory and anti-tumor effects.Therefore,it can target glycolysis and is expected to provide new ideas for the treatment of osteoarthritis. OBJECTIVE:To explore the role of Compound 3k in osteoarthritis caused by glycolytic overactivity based on the hypoxia-inducible factor 1 alpha(HIF-1α)/reactive oxygen species(ROS)pathway. METHODS:ATDC5 chondroblasts at logarithmic growth phase were taken to induce osteoarthritis in an in vitro cellular model by the action of 10 ng/mL interleukin-1β for 24 hours.The cytotoxicity of Compound 3k at different concentrations(0.25,0.5,1,2.5,5,10,15 μmol/L)was detected by cell counting kit-8 assay,and the appropriate concentrations were selected for the subsequent experiments.The chondrocytes were randomly divided into control,model and treatment groups.The model group was induced with 10 ng/mL interleukin 1β,and the treatment group was pre-stimulated with Compound 3k for 2 hours and then co-cultured with interleukin 1β.The proliferation of the cells in each group was detected by the cell counting kit-8 assay;the inflammatory level of the cells in each group was detected by the ELISA kit;the ROS,extracellular lactate and glucose contents were detected using the kit;qRT-PCR and western blot were used to detect the levels of related inflammatory factors,interleukin-6 and tumor necrosis factor-α,glycolysis-related genes glucose transporter protein-1,glyceraldehyde 3-phosphate dehydrogenase,monocarboxylate transporter protein-1 and HIF-1α. RESULTS AND CONCLUSION:Compared with the control group,the model group showed a decrease in cell proliferative activity,active glycolysis level,manifested by an increase in extracellular lactate content(P<0.001)and a decrease in glucose content(P<0.001),interleukin-6(P<0.000 1)and tumor necrosis factor-α(P<0.001).The expression levels of glycolysis-related genes glucose transporter protein-1(P<0.001),glyceraldehyde 3-phosphate dehydrogenase(P<0.001),monocarboxylic acid transporter protein-1(P<0.001)and HIF-1α(P<0.001)in the model group were all up-regulated,accompanied by oxidative stress and overproduction of ROS.Compared with the model group,Compound 3k treatment effectively increased cell proliferation activity and inhibited the level of overactive glycolysis(P<0.001),while suppressing the expression of genes related to inflammation(P<0.001)and glycolysis in osteoarthritic chondrocytes,inhibiting oxidative stress,downregulating the expression level of HIF-1α(P<0.000 1)and decreasing the content of ROS.To conclude,Compound 3k inhibits interleukin-1β induced chondrocyte inflammation,and its mechanism may be related to glycolysis and HIF-1α/ROS mediated oxidative stress.

This paper explored the specific mechanism of ginsenoside Rg_1 in regulating mitochondrial fusion through the neurogenic gene Notch homologous protein 1(Notch1) pathway to alleviate hypoxia/reoxygenation(H/R) injury in HL-1 cells. The relative viability of HL-1 cells after six hours of hypoxia and two hours of reoxygenation was detected by cell counting kit-8(CCK-8). The lactate dehydrogenase(LDH) activity in the cell supernatant was detected by the lactate substrate method. The content of adenosine triphosphate(ATP) was detected by the luciferin method. Fluorescence probes were used to detect intracellular reactive oxygen species(Cyto-ROS) levels and mitochondrial membrane potential(ΔΨ_m). Mito-Tracker and Actin were co-imaged to detect the number of mitochondria in cells. Fluorescence quantitative polymerase chain reaction and Western blot were used to detect the mRNA and protein expression levels of Notch1, mitochondrial fusion protein 2(Mfn2), and mitochondrial fusion protein 1(Mfn1). The results showed that compared with that of the control group, the cell activity of the model group decreased, and the LDH released into the cell culture supernatant increased. The level of Cyto-ROS increased, and the content of ATP decreased. Compared with that of the model group, the cell activity of the ginsenoside Rg_1 group increased, and the LDH released into the cell culture supernatant decreased. The level of Cyto-ROS decreased, and the ATP content increased. Ginsenoside Rg_1 elevated ΔΨ_m and increased mitochondrial quantity in HL-1 cells with H/R injury and had good protection for mitochondria. After H/R injury, the mRNA and protein expression levels of Notch1 and Mfn1 decreased, while the mRNA and protein expression levels of Mfn2 increased. Ginsenoside Rg_1 increased the mRNA and protein levels of Notch1 and Mfn1, and decreased the mRNA and protein levels of Mfn2. Silencing Notch1 inhibited the action of ginsenoside Rg_1, decreased the mRNA and protein levels of Notch1 and Mfn1, and increased the mRNA and protein levels of Mfn2. In summary, ginsenoside Rg_1 regulated mitochondrial fusion through the Notch1 pathway to alleviate H/R injury in HL-1 cells.
Ginsenosides/pharmacology* ; Receptor, Notch1/genetics* ; Signal Transduction/drug effects* ; Mice ; Animals ; Mitochondrial Dynamics/drug effects* ; Mitochondria/metabolism* ; Cell Line ; Reactive Oxygen Species/metabolism* ; Oxygen/metabolism* ; Cell Hypoxia/drug effects* ; Cell Survival/drug effects* ; Membrane Potential, Mitochondrial/drug effects* ; Humans

The genome tagging project (GTP) plays a pivotal role in addressing a critical gap in the understanding of protein functions. Within this framework, we successfully generated a human influenza hemagglutinin-tagged sperm-specific protein 411 (HA-tagged Ssp411) mouse model. This model is instrumental in probing the expression and function of Ssp411. Our research revealed that Ssp411 is expressed in the round spermatids, elongating spermatids, elongated spermatids, and epididymal spermatozoa. The comprehensive examination of the distribution of Ssp411 in these germ cells offers new perspectives on its involvement in spermiogenesis. Nevertheless, rigorous further inquiry is imperative to elucidate the precise mechanistic underpinnings of these functions. Ssp411 is not detectable in metaphase II (MII) oocytes, zygotes, or 2-cell stage embryos, highlighting its intricate role in early embryonic development. These findings not only advance our understanding of the role of Ssp411 in reproductive physiology but also significantly contribute to the overarching goals of the GTP, fostering groundbreaking advancements in the fields of spermiogenesis and reproductive biology.
Animals ; Female ; Humans ; Male ; Mice ; Spermatids/metabolism* ; Spermatogenesis/physiology* ; Spermatozoa/metabolism* ; Thioredoxins/genetics*

OBJECTIVES: To investigate the genomic characteristics and prognostic factors of juvenile myelomonocytic leukemia (JMML) with RAS mutations. METHODS: A retrospective analysis was conducted on the clinical data of JMML children with RAS mutations treated at the Hematology Hospital of Chinese Academy of Medical Sciences, from January 2008 to November 2022. RESULTS: A total of 34 children were included, with 17 cases (50%) having isolated NRAS mutations, 9 cases (27%) having isolated KRAS mutations, and 8 cases (24%) having compound mutations. Compared to children with isolated NRAS mutations, those with NRAS compound mutations showed statistically significant differences in age at onset, platelet count, and fetal hemoglobin proportion (P<0.05). Cox proportional hazards regression model analysis revealed that hematopoietic stem cell transplantation (HSCT) and hepatomegaly (≥2 cm below the costal margin) were factors affecting the survival rate of JMML children with RAS mutations (P<0.05); hepatomegaly was a factor affecting survival in the non-HSCT group (P<0.05). CONCLUSIONS Children with NRAS compound mutations have a later onset age compared to those with isolated NRAS mutations. At initial diagnosis, children with NRAS compound mutations have poorer peripheral platelet and fetal hemoglobin levels than those with isolated NRAS mutations. Liver size at initial diagnosis is related to the prognosis of JMML children with RAS mutations. HSCT can improve the prognosis of JMML children with RAS mutations.
Humans ; Leukemia, Myelomonocytic, Juvenile/therapy* ; Mutation ; Male ; Female ; Child, Preschool ; Retrospective Studies ; Child ; Infant ; GTP Phosphohydrolases/genetics* ; Membrane Proteins/genetics* ; Adolescent ; Hematopoietic Stem Cell Transplantation ; Proportional Hazards Models ; Proto-Oncogene Proteins p21(ras)/genetics* ; Prognosis