[摘 要] 目的：基于公开的卵巢癌（OC）单细胞测序数据并利用生物信息学方法构建OC上皮细胞亚型，探究上皮细胞异质性及其对OC肿瘤微环境（TME）的影响。方法：使用GSE118828卵巢癌单细胞数据集的分析得到的8种细胞类型及基因表达矩阵结果，使用反卷积方法估计整体转录组测序（bulk RNA-seq）数据中的细胞组成，依据上皮细胞丰度将OC分为高上皮细胞亚型（C1型）和低上皮细胞亚型（C2型）。分析C1型与C2型患者的生存时间及免疫微环境差异。基于C1、C2型及OC早期（Ⅰ~Ⅱ期）、晚期（Ⅲ~Ⅳ期）组间的差异表达基因（DEG），筛选与OC进展相关的上皮细胞相关基因并分析其对TME的影响。通过人类蛋白质图谱（HPA）数据库数据验证OC进展中上皮细胞相关基因的蛋白表达水平。结果：C1型患者的OS明显优于C2型患者（P < 0.05）。C1、C2型具有完全不同的免疫微环境浸润特性，C1型中辅助性T（Th）细胞、M1型巨噬细胞和激活的树突状细胞浸润程度显著高于C2型（均P < 0.05）。晚期高上皮细胞OC患者HAS1、DAPL1、ADH1B基因表达增加（均P < 0.05），同时，DAPL1基因在OC中的表达与巨噬细胞、Treg细胞的浸润程度呈正相关（P < 0.05）。HPA数据库数据证实，DAPL1蛋白在OC组织中表达显著增加。结论：卵巢癌高上皮细胞亚型可能由于Th细胞、M1型巨噬细胞和激活的树突状细胞的高度浸润发挥抗肿瘤作用；上皮细胞相关基因DAPL1的高表达可能会诱导巨噬细胞、Treg细胞的浸润程度，从而促进OC的进展。

OBJECTIVE To evaluate the safety of fondaparinux in pregnancy and provide reference for its rational clinical application. METHODS A search was conducted in databases including CNKI， Wanfang， PubMed， Embase， and Elsevier （the search time was from the construction of the database to December 17， 2024） to collect case report literature on fondaparinux use during pregnancy. Patient demographic information， fondaparinux use during pregnancy， concomitant medications， clinical manifestations， and treatment details were extracted for descriptive statistical analysis. RESULTS A total of 17 case reports regarding the use of fondaparinux during pregnancy were collected， involving 42 patients from 11 countries and 47 pregnancy records. Among these， 20 cases involved the use of fondaparinux for the prevention of pregnancy-related venous thromboembolism （VTE）， while 27 cases were fondaparinux treatment due to related conditions. A total of 29 occurrences of the patients were treated with fondaparinux due to a （family） history of VTE. Nine occurrences of complicated pregnancies were reported， and 35 patients had records of comorbidities or relevant medical histories. The adverse events that occurred during pregnancy with the use of fondaparinux include postpartum hemorrhage （7 cases） and excessive anticoagulation caused by inappropriate dosage （1 case）. Among the 7 cases of postpartum hemorrhage， 3 cases had a blood loss of no less than 1 000 mL （including 2 cases with uterine atony）， 3 cases had a drug discontinuation time of ≤12 h. CONCLUSIONS Based on the existing literature， the safety of fondaparinux during pregnancy is generally manageable， with the main adverse event being postpartum hemorrhage. The dosage， interval between discontinuation，comorbidities/medical history， and concomitant medications of fondaparinux may be the main causes of its adverse events.

In January 2023,the American Heart Association(AHA)released A Scientific Statement:Cancer Therapy Related Hypertension,provided an overview of the mechanisms and clinical management of anticancer therapy related hypertension.Contemporary anticancer drugs are mostly at the expense of cardiovascular toxicities,one of the most common side effects is hypertension,especially vascular endothelial growth factor inhibitors,as well as tyrosine kinase inhibitors and proteasome inhibitors.Cancer therapy related hypertension is often dose limiting,and is usually reversible after interruption or discontinuation of treatment.The exact molecular mechanisms underlying hypertension are unclear,recent discoveries indicate an important role for decreased nitric oxide,increased endothelin-1,endothelial dysfunction,increased sympathetic outflow,and microvascular rarefaction.Based on the International Cardio Oncology Society(IC-OS),this article provides an interpretation of the diagnosis and management of hypertension related to cancer treatment.Insufficient evidence exists supporting an antihypertensive medication strategy specific to patients with anticancer therapy induced hypertension,therefore,antihypertensive management should follow current guidelines for the general population..Multidisciplinary cooperation is needed to optimize management to ensure the optimal therapeutic effect from cancer treatment while minimizing competing cardiovascular toxicities.

Patients with gastric cancer are at high risk for venous thromboembolism(VTE)and bleeding,and patients who develop VTE are often associated with poor outcomes,making it clinically challenging to identify and manage the risk of thrombosis in patients with gastric cancer.Risk factors for VTE in gastric cancer patients include age,obesity,surgery,chemotherapy,etc.It is essential to identify high-risk patients and adopt aggressive prevention strategies.The main strategy to prevent and treat VTE is the use of anticoagulant drugs.This article discusses guidelines and recent studies for the prevention and treatment of VTE in patients with gastric cancer to help clinicians make individualized decisions for their patients and maximize clinical outcomes for their patients.

Patients with primary membranous nephropathy(PMN)tend to develop thrombosis,especially in the early phase of the disease.The pathogenesis of thrombosis is multifactorial,with hypoalbuminemia being widely regarded as an inde-pendent risk factor.Other factors include proteinuria,M-type phospholipase A2 receptor antibody,and D-dimer.Although prophy-lactic anticoagulation therapy is frequently used in clinical practice to prevent thrombosis in PMN patients,there are still many un-resolved issues regarding the optimal prevention of thrombosis in this condition.The timing of prophylactic anticoagulation,the threshold of serum albumin level,and the choice of treatment regimen are still lacking consensus.This article reviewed the relevant literature on these topics,aiming to establish a standard for thrombosis prevention and treatment for this population in the future and provide guidance for clinical practice.

ObjectiveTo investigate the effect of Shugan Quyu Jiedu prescription （SGQYJDF） on inducing ferroptosis in hepatocellular carcinoma cells based on the tumor protein 53 （p53）/solute carrier family 7 member 11 （SLC7A11）/glutathione peroxidase 4 （GPX4） pathway. MethodMHCC97H cells were divided into the blank serum group （10% blank serum medium）， SGQYJDF-containing serum low concentration group （5% SGQYJDF-containing serum and 5% blank serum medium）， SGQYJDF-containing serum medium concentration group （7.5% SGQYJDF-containing serum and 2.5% blank serum medium）， SGQYJDF-containing serum high concentration group （10% SGQYJDF-containing serum medium） and sorafenib group （sorafenib concentration of 10 μmol·L^-1 in 10% blank serum medium）. After 24 hours of intervention， the cell survival rate was detected by cell counting kit-8 （CCK-8） assay. The cell proliferation ability was detected by 5-ethynyl-2′-deoxyuridine （EdU） staining. The intracellular ferrous ion （Fe²⁺） level was detected by ferrous ion fluorescent probe （FerroOrange） staining. The intracellular malondialdehyde （MDA） and glutathione （GSH） levels were detected by colorimetric assays. The ultrastructure of mitochondria was observed by transmission electron microscopy. The expression levels of ferroptosis-related proteins p53， SLC7A11 and GPX4 were detected by Western blot. ResultIn terms of cell viability， compared with the blank serum group， the SGQYJDF group showed a dose-dependent decrease in the survival rate of MHCC97H cells. Effect of the medium and high concentrations of SGQYJDF on the survival rate of MHCC97H cells were significantly decreased （P<0.01）. Additionally， the results of the EdU assay showed that both the medium and high concentrations of SGQYJDF were able to inhibit the proliferation ability of MHCC97H cells （P<0.05， P<0.01）. Regarding the biochemical indicators of ferroptosis， compared to the blank serum group， the medium and high concentrations of SGQYJDF were able to dose-dependently increase the intracellular Fe²⁺ level （P<0.01）. The low， medium， and high concentrations of SGQYJDF were able to dose-dependently decrease the level of GSH in MHCC97H cells （P<0.01） and increase the level of MDA in the cells （P<0.05， P<0.01）. In terms of pathway-related protein expression， compared to the blank serum group， the medium and high concentrations of SGQYJDF could significantly increase the expression of p53 （P<0.01）. The low， medium， and high concentrations of SGQYJDF could significantly decrease the expression of GPX4 （P<0.01）. The high concentration of SGQYJDF could decrease the expression of SLC7A11 （P<0.01）. In terms of the cell morphology of ferroptosis， compared with the blank serum group， transmission electron microscopy revealed that the low concentration of SGQYJDF caused mitochondrial deformation， while the medium and high concentrations of SGQYJDF resulted in reduced mitochondrial volume， increased double-layer membrane density， and decreased mitochondrial cristae. These features were similar to those of sorafenib-induced ferroptosis. Furthermore， compared with the sorafenib group， the high concentration of SGQYJDF showed no statistically significant differences in cell survival rate， proliferation ability， Fe²⁺ level， MDA level， and GSH level. ConclusionThe results suggest that SGQYJDF may induce ferroptosis and inhibit proliferation in hepatocellular carcinoma MHCC97H cells by upregulating the expression of p53， suppressing the expressions of GPX4 and SLC7A11， downregulating the level of GSH， and leading to the accumulation of intracellular Fe²⁺ and MDA.

In order to strengthen the supervision of the use of drugs in hospitals，the Sichuan Academy of Medical Sciences· Sichuan Provincial People’s Hospital took the lead in compiling the Principles for the Rational Use of National Key Monitoring Drugs （the Second Batch） with a number of experts from multiple medical units in accordance with the Second Batch of National Key Monitoring Rational Drug Use List （hereinafter referred to as “the List”） issued by the National Health Commission. According to the method of the WHO Guidelines Development Manual， the writing team used the Delphi method to unify expert opinions by reading and summarizing the domestic and foreign literature evidence of related drugs， and applied the evaluation， formulation and evaluation method of recommendation grading （GRADE） to evaluate the quality of evidence formed， focusing on more than 30 drugs in the List about the evaluation of off-label indications of drugs， key points of rational drug use and key points of pharmaceutical monitoring. It aims to promote the scientific standardization and effective management of clinical medication， further improve the quality of medical services， reduce the risk of adverse drug reactions and drug abuse， promote rational drug use， and improve public health.

Aim To investigate the effeot of Shenqi Fuzheng injection on the prevention of immune myocarditis induced by anti-PD-1 antibody by reducing the production of inflammatory factors and the expression of myocardial injury markers. Methods Thirty-two maie PD-1 humanized mice with C57BL/6 genetic background were randomly divided into control group, myocarditis model group, anti-PD-1 antibody group and Shenqi Fuzheng injection group (n = 8). Except the control group, mice in other groups were intraperitoneally injected with myocardial myosin heavy chain peptide (5 mg • kg

Objective:To summarize the clinical manifestations and gene mutation features of patients with nucleotide excision repair (NER) disorders.Methods:A retrospective analysis was made on clinical data of patients with NER disorders who were admitted to the Chinese People′s Liberation Army General Hospital from October 2008 to February 2022 and diagnosed in the Outpatient Department of Beijing Children′s Hospital, Capital Medical University from October 2015 to February 2022.Literature on previously reported Chinese patients with NER disorders was reviewed.Results:(1)A total of 16 patients with NER disorders were enrolled, including 6 males and 10 females.The onset age was 7.5 (4.0, 12.0) months and the age at diagnosis was 42.0 (21.5, 77.0) months.There were 3 types of NER disorders: Cockayne syndrome (CS) in 13 cases, Xeroderma Pigmentosum (XP) in 2 cases and Cerebro-Oculo-Facio-Skeletal syndrome (COFS) in 1 case.Four disease-causing genes were detected: CSA gene in 11 cases, CSB gene in 3 cases, XPG gene in 1 case, and XPD gene in 1 case.The first symptoms of the 16 patients were photosensitivity and developmental delay, and neurological symptoms were observed in all the 3 NER disorder types.XP and CS patients had skin symptoms.CS patients presented typical facial features, visual and auditory impairment, microcephaly and changes in neuroimaging features.COFS patients showed intrauterine growth retardation.(2)Results of literature review: a total of 96 Chinese patients reported were retrieved, involving 6 disease types, including CS in 45 cases, XP in 44 cases, trichothiodystrophy in 4 cases, COFS in 1 case, XP-CS in 1 case, and ultraviolet sensitive syndrome in 1 case.Nine mutated genes were identified: CSA in 33 cases, XPA in 15 cases, CSB in 13 cases, XPV in 10 cases, XPC in 9 cases, XPG in 7 cases, XPD in 7 cases, XPF in 1 case, and MPLKIP in 1 case.The common symptoms were growth failure (62 cases), skin photosensitivity (61 cases), typical facial features (52 cases), mental retardation (49 cases) and microcephaly (48 cases). Among 36 cases had imaging data 33 cases(91.7%)had calcification of basal nucleus or globus pallidus.Three cases had intrauterine growth retardation and microcephaly during pregnancy. Conclusions:Patients with such prenatal manifestations as intrauterine growth retardation and microcephaly or with typical symptoms like skin photosensitivity, typical facial features, growth failure, mental retardation, hypertonia, and calcifications of basal ganglia should be suspected of NER disorders.Early genetic testing is recommended to confirm the diagnosis.

Purpose: This study explored the performance of prenatal ultrasonography in the differential diagnosis of cystic biliary atresia (CBA) and choledochal cyst (CC). Methods: Fetuses diagnosed with hepatic hilar cyst in the second trimester were included in this study. A series of prenatal ultrasound examinations were performed in the second and third trimesters. The diameter of the gallbladder (GB) and hepatic cyst were measured, as well as the wall thickness of the GB. The GB-cyst connection, visibility of the right hepatic artery (RHA), and other concomitant abnormalities were carefully evaluated. A neonatal transabdominal ultrasound examination was performed within 1 week after birth, and clinical data were followed up to 6 months after birth. Results: Between January 1, 2016 and January 31, 2020, 53 fetuses diagnosed with hepatic hilar cyst were recruited. Eight were excluded because they were lost to follow-up. Among the 45 cases included in this study, 10 were diagnosed with CBA and 35 with CC after birth. Statistically significant differences were found in GB width, wall thickness, change in GB width, change in cyst length, GB-cyst connection, and RHA visibility between the CBA and CC groups. GB width showed the best diagnostic performance with an area under the curve (AUC) of 0.899. The combination of GB width, GB wall thickness, and GB-cyst connection yielded a comparable AUC of 0.971. Conclusion The GB should be carefully evaluated in fetuses with hepatic hilar cyst. Prenatal ultrasound findings could provide suggestive parameters for the differential diagnosis of CBA from CC.