The clinical application of chemotherapeutic drugs has been limited due to the lack of tumor selectivity which causes different degrees of adverse reactions. Transferrin receptor(TfR) is one of the targets for tumor targeted drug delivery system because it is over-expressed in many kinds of tumor cells and tumor-associated blood vessels, but is low-expressed in normal cells. By modifying drug carriers or coupling antitumor drugs with ligands that have high specific affinity for TfR, it is expected to achieve targeted therapy of TfR over-expressed tumors. In this paper, the application progress of TfR functional ligands in tumor targeted drug delivery in recent years is summarized, in order to provide reference for the research of TfR targeted drug delivery systems.

OBJECTIVE To investigate the effect of Guanxinning tablets(GXN) on early heart failure model rats, and to explore the protective mechanism of GXN on heart failure rats from the perspective of intestinal flora. METHODS Six rats who underwent sham operation were set as sham operation group. Took 80 SD rats to undergo aortic arch stenosis and established a heart failure rat model. The surviving rats were divided into 4 groups, namely the model control group, the positive control group(captopril tablets 12.5 mg·kg–1), high-dose and low-dose of GXN group(600, 1 200 mg·kg–1). The 4 groups were administered continuously for 8 weeks. Cardiac ultrasonography was performed every 4 week. Serum NT-proBNP, hs-CRP, IL-6, TNF-α, SOD and MDA levels were measured. The effects of GXN on the structure and function of intestinal flora were observed based on the high-throughput sequencing technology and bioinformatics analysis of 16S gut microbiome. RESULTS Compared to the model control group, after giving different doses of GXN, the survival rate of rats increased, and the thickness of the ventricular wall decreased to varying degrees. The weight of the heart and coefficient of the heart were all reduced. GXN could also reduce the level of inflammatory factors, inhibit the level increase of NT-proBNP in rats, and increase the activity of serum SOD. In addition, GXN intervention could significantly improve the intestinal flora diversity of rats with heart failure, the possible target genera of GXN were Akkermansia genera, Phascolarctobacterium genera and Oxalobacter genera. The effect of GXN on intestinal function in rats with heart failure might be concentrated in non-homologous end-joining, influenza A, carotenoid synthesis, indole alkaloids biosynthesis, betalain biosynthesis, renin-angiotensin system and other biological pathways. CONCLUSION The protective effect of GXN on early heart failure rats may be related to the regulation of intestinal flora pathway.

Objective:To investigate the effects of intravenous thrombolysis combined with Xingnaojing injection on hemodynamic indexes and neurological function in patients with cerebral infarction. Methods:A total of 142 patients with cerebral infarction who were treated in Xing An Meng Hospital from April 2020 to May 2021 were included in this study. They were randomly divided into a control group ( n = 71, intravenous thrombolysis) and a Xingnaojing injection group ( n = 71, intravenous thrombolysis + Xingnaojing injection). Intracranial arterial hemodynamic indexes, National Institutes of Health Stroke Scale score, Fugl-Meyer Assessment Scale score, serum inflammatory factors, oxidative stress indexes, brain injury markers, and the incidence of adverse reactions were compared between the two groups. Results:After treatment, serum levels of interleukin-1β, interleukin-6, and tumor necrosis factor-α were significantly lower in the Xingnaojing injection group than the control group [interleukin-1β: (4.05 ± 0.83) ng/L vs. (6.85 ± 1.02) ng/L, interleukin-6: (43.61 ± 5.14) ng/L vs. (60.31 ± 7.04) ng/L, tumor necrosis factor-α: (35.93 ± 4.25) ng/L vs. (20.93 ± 3.11) ng/L, t = 17.94, 16.14, 15.37, all P < 0.001]. After treatment, the mean blood flow velocities of the anterior cerebral artery, middle cerebral artery, and posterior cerebral artery in the Xingnaojing injection group were significantly higher than those in the control group [anterior cerebral artery: (49.36 ± 5.28) cm/s vs. (41.15 ± 5.12) cm/s, middle cerebral artery: (61.27 ± 7.02) cm/s vs. (50.19 ± 6.08) cm/s, posterior cerebral artery: (44.92 ± 5.63) cm/s vs. (37.26 ± 4.93) cm/s, t = 9.40, 10.05, 8.62, all P < 0.001]. After treatment, the National Institutes of Health Stroke Scale score and Fugl-Meyer Assessment Scale score in the Xingnaojing injection group were superior to those in the control group [National Institutes of Health Stroke Scale score: (10.36 ± 1.52) points vs. (14.62 ± 2.05) points, Fugl-Meyer Assessment Scale score: (76.19 ± 8.08) points vs. (65.28 ± 7.14) points, t = 14.06, 8.52, both P < 0.05]. After treatment, the serum level of malondialdehyde in the Xingnaojing injection group was significantly higher than that in the control group [(6.35 ± 1.02) μmol/L vs. (10.05 ± 1.63) μmol/L), t = 16.21, P < 0.001]. The serum level of superoxide dismutase in the Xingnaojing injection group was significantly lower than that in the control group [(114.31 ± 13.69) U/L vs. (92.25 ± 10.16) U/L), t = 10.90, P < 0.001]. Serum levels of neuron-specific enolase and S100β in the Xingnaojing injection group were significantly lower than those in the control group [neuron-specific enolase: (24.01 ± 3.24) IU/L vs. (30.31 ± 4.02) IU/L, S100β: (0.73 ± 0.17) ng/L vs. (1.13 ± 0.22) ng/L, t = 10.28, 12.12, both P < 0.001). There was a significant difference in the incidence of adverse reactions between the two groups ( P > 0.05). Conclusion:Intravenous thrombolysis combined with Xingnaojing injection for the treatment of cerebral infarction can improve intracranial hemodynamics, reduce the inflammatory response and oxidative stress, and alleviate brain tissue injury. The combined therapy is beneficial to protect the neurological function of patients with cerebral infarction and is highly safe.

Chinese medicine self-assembly nano-strategies（CSAN） is to utilize the self-assembly property of Chinese medicine components， so that the Chinese medicine components can self-assemble to form structurally stable nano-preparations through non-covalent interactions. The formation of Chinese medicine self-assembly nano-preparations is often a synergistic result of a variety of non-covalent interactions， and many Chinese medicine monomers are susceptible to self-assembly due to their structural characteristics， and the phenomenon of self-assembly of Chinese medicine is also common in the decoction of single or compound Chinese medicine， which has attracted the attention of researchers. It is found that CSAN can improve the solubility and bioavailability of active components in Chinese medicine， which is of positive significance for the development and application of insoluble components of Chinese medicine. The self-assembly phenomenon of Chinese medicine decoction is closely related to the therapeutic efficacy， and the study of self-assembly phenomenon of Chinese medicine will bring a new perspective for the explanation of the mechanism of Chinese medicine decoction. At the same time， traditional Chinese medicine（TCM） has unique advantages in the field of anti-tumor. The application of CSAN in the field of oncology can not only exert the anti-tumor effect of the active components of Chinese medicine directly， but also act as a natural nano-carrier to carry chemotherapy drugs for combination chemotherapy， improve the targeting of drugs， enhance the anti-tumor efficacy， and reduce the side effects of chemotherapy， which has excellent anti-tumor potential. The preparation method of Chinese medicine self-assembly nano-preparations is simple， low cost， and has better safety than traditional nano-preparations， which is conducive to the promotion of the clinical transformation of nano-preparations， and also helps to provide new strategies and perspectives for promoting the modernization of TCM. Therefore， based on a large number of researches in this field in recent years， this paper reviewed the formation mechanism， different assembly forms， formation conditions and stability of Chinese medicine self-assembly nano-preparations by searching databases such as China national knowledge infrastructure（CNKI）， PubMed， WanFang data and VIP， and summarized the application of CSAN in different tumor therapies， providing a reference for further research on CSAN.

Objective:Taking emergency department (ED) as a starting point, to analyze the epidemiological characteristics and mortality risk factors of sepsis, and to provide evidences for ED to carry out the strategy of "three early and two lower" for sepsis.Methods:Based on the ED and inpatient medical record management information platform of Tianjin Medical University Gernal Hospital, adult ED patients with sepsis from January 1, 2017 to December 31, 2020 were included according to the third international consensus definitions for sepsis and septic shock in 2016 and the consensus of Chinese experts on early prevention and blocking of sepsis in 2020. The epidemiological characteristics of patients were retrospectively analyzed. Chi-square test was used to compare the difference of age, sex, hospitalization times, length of stay, hospitalization cost and infection location between dead patients and survival patients, and a stepwise logistic regression model was used to analyze the influencing factors of mortality in hospitalized patients with ED sepsis.Results:A total of 7 494 patients with sepsis in ED were included in this study, and the annual and monthly component ratios varied from 3.8‰ to 6.1‰ and 2.0‰ to 9.0‰, respectively. The main characteristics of patients with sepsis in ED were as follows: 40-69 years old (46.0%), male (59.0%), mostly diagnosed with sepsis (96.8%), mainly treated with urban health insurance (59.6%), and ED diagnosis and treatment fees of 2 000-8 000 Yuan (51.1%). The mortality of hospitalized patients with ED sepsis was 24.4% and that of hospitalized patients with septic shock was 28.8%. The main characteristics of hospitalized patients with ED sepsis were as follows: most of them were male (56.2%) patients over 70 years old (56.0%), most of them were diagnosed with sepsis (94.0%) and hospitalized for the first time (76.0%), the median hospitalization time was 15 d, most of them were hospitalized under urban health insurance (65.2%), and the median hospitalization fees was 47 000 Yuan. The risk factors of death were influenced by age and length of stay. Patients aged 70 years or older had a higher risk of death than those aged from 18 to 39 years, and patients with a length of stay of more than 7 d had a lower risk of death than those with a length of stay of shorter than 7 d. The primary infection focus were mainly respiratory and urinary systems, while the death rate of patients with hematological and abdominal infections was relatively high, and the difference was statistically significant ( P<0.01). Respiratory and abdominal infections were risk factors for death in patients with ED sepsis. Conclusions:The composition ratio of sepsis in ED patients is not regular in time, so vigilance of sepsis in elderly men and patients with respiratory system, blood system, urinary system and abdominal infections should be constantly raised. Patients with sepsis who are older, hospitalized more frequently, hospitalized for a shorter time, and infected in the respiratory system or abdomen have a higher risk of death.

ABSTRACT: Meningiomas are the most common primary intracranial neoplasm with diverse pathological types and complicated clinical manifestations. The fifth edition of the WHO Classification of Tumors of the Central Nervous System (WHO CNS5), published in 2021, introduces major changes that advance the role of molecular diagnostics in meningiomas. To follow the revision of WHO CNS5, this expert consensus statement was formed jointly by the Group of Neuro-Oncology, Society of Neurosurgery, Chinese Medical Association together with neuropathologists and evidence-based experts. The consensus provides reference points to integrate key biomarkers into stratification and clinical decision making for meningioma patients. REGISTRATION Practice guideline REgistration for transPAREncy (PREPARE), IPGRP-2022CN234.
Humans ; Meningioma/pathology* ; Consensus ; Neurosurgical Procedures ; Meningeal Neoplasms/pathology*

Objective:To explore the role of parental origin verification in chromosomal microarray analysis (CMA) on the determination of the clinical significance of copy number variations (CNVs).Methods:This retrospective study collected clinical information from 73 core families who underwent prenatal diagnosis at Peking University First Hospital from November 2017 to December 2019. Indications for prenatal diagnosis included ultrasound abnormality in 54 cases (including 12 with thickened nuchal translucency (≥2.5 mm), four with fetal growth restriction, seven with abnormal pregnancy history, and 31 with isolated ultrasound abnormality), NIPT indicated high-risk in four cases, advanced age in nine cases, abnormal pregnancy history alone in three cases, intrauterine death in two cases and one with maternal mental retardation. Genomic DNA of amniotic fluid sample, chorionic villi, cord blood, fetal tissues, and fetal heart blood were extracted using genomic DNA extraction kit. The CNVs of prenatal samples in 73 subjects were analyzed using array-based comparative genomic hybridization (array-CGH) analysis and single nucleotide polymorphism array (SNP-array). Peripheral blood DNA of the couples, and relevant families if necessary, were collected and analyzed in the same way. The results of parental origin detection in CMA were summarized.Results:A total of 76 CNVs were detected in these 73 samples, out of which nine were pathogenic and parental origin detection revealed that six were de novo, two were maternally, and one was paternally inherited; six CNVs were likely pathogenic, including three de novo, two maternally inherited and one paternally inherited; 20 CNVs were variants of uncertain significance, including five paternally inherited, three maternally inherited and 12 de novo; 41 CNVs were likely benign, among which 38 were inherited from parents with normal phenotype. Conclusions:Parental origin verification plays an important role in explaining the clinical significance of detected fetal CNVs and thereby can help to analyze its clinical effect and reproductive risk.

Objective:To investigate the clinical application of 3-dimensional CT angiography(3D-CTA) in the repair of mandibular defects with deep circumflex iliac arterial flaps.Methods:From January 2019 to January 2020, 5 patients with postoperative defects of mandibular tumors were treated in the Department of Stomatology of the First Affiliated Hospital of Bengbu Medical College, including 2 males and 3 females. The ages of the patients ranged from 30 to 70 years, with an average of 52 years. CT angiography of both lower limbs was performed before operation. Data were processed using the CT workstation. According to the size and shape of the defect in the recipient site, the 3D model of the deep circumflex iliac arterial flap(DCIA) was constructed. the contour of the DCIA was observed and measured, and the data was recorded, including the diameter of the vassel at the starting point, the angle between the line from the starting point to the anterior superior iliac spine and the line between the bilateral anterior superior iliac spine, and the distance from the starting point to the anterior superior iliac spine. According to the 3D model, a composite tissue flap pedicled with DCIA was designed and prepared for mandibular defect repair. The actual situation during the procedure was compared with the preoperative 3D model simultaneously.Results:The diameter of the DCIA at the starting point was (2.30±0.24) mm. The angle between the line from the starting point to the anterior superior iliac spine and the line between the bilateral anterior superior iliac spine was 39.3°±6.1°, and the distance from the starting point to the anterior superior iliac spine was (5.83±0.24) cm. The shape and position of the DCIA were basically consistent with the three-dimensional model. All the flaps survived well after operation. All the patients were followed up for 3 to 6 months, the bilateral maxillofacial region were basically symmetrical. The postoperative imaging examination showed that the iliac osteocutaneous flap healed well, and the height and width of mandibular alveolar ridge were restored satisfactorily. There were no complications such as numbness in the donor site, abdominal hernia and gait abnormality.Conclusions:The 3D model of the DCIA produced by 3D-CTA can accurately locate the position and route of the vessel, clearly display the three-dimensional spatial relationship between the skin, muscles and bones around the target blood vessel, and significantly reduce the complications and operative time.

Objective:To investigate the clinical application of 3-dimensional CT angiography(3D-CTA) in the repair of mandibular defects with deep circumflex iliac arterial flaps.Methods:From January 2019 to January 2020, 5 patients with postoperative defects of mandibular tumors were treated in the Department of Stomatology of the First Affiliated Hospital of Bengbu Medical College, including 2 males and 3 females. The ages of the patients ranged from 30 to 70 years, with an average of 52 years. CT angiography of both lower limbs was performed before operation. Data were processed using the CT workstation. According to the size and shape of the defect in the recipient site, the 3D model of the deep circumflex iliac arterial flap(DCIA) was constructed. the contour of the DCIA was observed and measured, and the data was recorded, including the diameter of the vassel at the starting point, the angle between the line from the starting point to the anterior superior iliac spine and the line between the bilateral anterior superior iliac spine, and the distance from the starting point to the anterior superior iliac spine. According to the 3D model, a composite tissue flap pedicled with DCIA was designed and prepared for mandibular defect repair. The actual situation during the procedure was compared with the preoperative 3D model simultaneously.Results:The diameter of the DCIA at the starting point was (2.30±0.24) mm. The angle between the line from the starting point to the anterior superior iliac spine and the line between the bilateral anterior superior iliac spine was 39.3°±6.1°, and the distance from the starting point to the anterior superior iliac spine was (5.83±0.24) cm. The shape and position of the DCIA were basically consistent with the three-dimensional model. All the flaps survived well after operation. All the patients were followed up for 3 to 6 months, the bilateral maxillofacial region were basically symmetrical. The postoperative imaging examination showed that the iliac osteocutaneous flap healed well, and the height and width of mandibular alveolar ridge were restored satisfactorily. There were no complications such as numbness in the donor site, abdominal hernia and gait abnormality.Conclusions:The 3D model of the DCIA produced by 3D-CTA can accurately locate the position and route of the vessel, clearly display the three-dimensional spatial relationship between the skin, muscles and bones around the target blood vessel, and significantly reduce the complications and operative time.

Objective: To analyze variants of PRRT2 gene in two children with paroxysmal kinesigenic dyskinesia. Methods: Genomic DNA of the two children and their parents was extracted from peripheral venous blood samples. All exons and their flanking regions of the PRRT2 gene were subjected to PCR and Sanger sequencing. Results: The two children were found to respectively harbor a c. 282dupA and a c. 715_716dupCC variant in exon 2 of the PRRT2 gene, which were both inherited from their mothers. Pooling together their frequencies in general population, genetic models, related literature and impact on protein function, the two novel variants were both predicted to be pathogenic. Conclusion The c. 282dupA and c. 715_716dupCC variants probably underlie the disease in the two children.