Methylation of the Selected TP53 Introns in Advanced-Stage Ovarian Carcinomas.

Objective: Advanced-stage ovarian cancer (OC) is among the most fatal female genital tract neoplasms worldwide. Although different genetic mechanisms have been shown to be involved in ovarian carcinogenesis, the role of TP53 introns methylation is still unresolved. We performed methylation analysis of introns 1, 3, and 4 of the TP53 to identify patterns in primary stage III OCs, corresponding metastases, and healthy tissues. Methods: The study involved samples of paraffin-embedded tissues obtained from 80 patients with stage III OCs, who underwent surgery at the Department of Gynecology and Gynecologic Oncology of the Military Institute of Medicine in Warsaw, Poland. Altogether, 40 serous-type G2/3 OCs and 40 endometrioid-type G2/3 OCs were included. From the same patient, metastatic and normal tissues were simultaneously analyzed. As a control group, 80 tissue samples were collected from patients after bariatric operations. Human ovarian cancer A2780 cell line was also investigated. Total genomic DNA was isolated from paraffin-embedded tissue blocks and the methylation analysis was performed by bisulfite DNA conversion, DNA amplification with specific primers, cloning, and DNA sequencing. Results: All of the samples of intron 1 of TP53 were un-methylated in OCs, metastatic tissues, and in healthy tissues from the same patient. Also, no methylation of TP53 intron 1 was detected in cells from the human A2780 ovarian cancer cell line and in all samples from control group. In all samples, introns 3 and 4 of the TP53 were methylated in primary tumors, metastatic tissue, and in healthy tissue from the same patient, in human A2780 ovarian cell line, and in DNA samples from healthy patients. None of the clinicopatholocal features was related to the TP53 introns methylation status. Conclusions: Our data on TP53 introns methylation sheds new light on the mechanism of p53 activity for a better understanding of cancer biology. The study suggests the existence of an additional regulation rule of TP53 activity that involves demethylation-methylation mechanisms. Methylation at introns 3 and 4 may also overall help in protecting TP53 against damage by viral restrictases or viral DNA integration.

Perspective of Calcium Imaging Technology Applied to Acupuncture Research / 中国结合医学杂志

Acupuncture, a therapeutic treatment defined as the insertion of needles into the body at specific points (ie, acupoints), has growing in popularity world-wide to treat various diseases effectively, especially acute and chronic pain. In parallel, interest in the physiological mechanisms underlying acupuncture analgesia, particularly the neural mechanisms have been increasing. Over the past decades, our understanding of how the central nervous system and peripheral nervous system process signals induced by acupuncture has developed rapidly by using electrophysiological methods. However, with the development of neuroscience, electrophysiology is being challenged by calcium imaging in view field, neuron population and visualization in vivo. Owing to the outstanding spatial resolution, the novel imaging approaches provide opportunities to enrich our knowledge about the neurophysiological mechanisms of acupuncture analgesia at subcellular, cellular, and circuit levels in combination with new labeling, genetic and circuit tracing techniques. Therefore, this review will introduce the principle and the method of calcium imaging applied to acupuncture research. We will also review the current findings in pain research using calcium imaging from in vitro to in vivo experiments and discuss the potential methodological considerations in studying acupuncture analgesia.

Synchronously occurring endometrioid carcinomas of the uterine corpus and uterine cervix preceded by different precancerous lesions: A case study and a literature review.

The incidence of two synchronous carcinomas originating from the uterine corpus and uterine cervix, both endometrioid subtypes, is exceedingly rare. Herein, we presented synchronous early stage G1 adenocarcinoma of the uterine corpus with cervical G2 endometrioid adenocarcinoma. Although both neoplasms displayed the same histological subtype, they differed significantly according to the histological grading or clinical stage of the disease. Finally, it is worth emphasizing that both tumors were preceded by different precancerous lesions, atypical endometrial hyperplasia (AEH) and foci of endometriosis localized within the uterine cervix. Although AEH is a well-known precancerous condition of endometrioid carcinoma, the mechanisms resulting in the malignant transformation of endometriosis foci to the cervical endometrioid carcinoma are still a matter of controversy. We briefly summarized the impact of different precancerous lesions on the development of synchronous female genital tract neoplasms with the same histotype.

The most likely but largely ignored triggering factor for breast (or all) cancer invasion.

Breast cancer development and progression are believed to be a sequential process, from normal to hyperplastic, to in situ, and to invasive and metastatic stages. Given that over 90% of cancer deaths are caused by invasive and metastatic lesions, countless factors and multiple theories have been proposed as the triggering factor for the cascade of actions of cancer invasion. However, those factors and theories are largely based on the studies of cell lines or animal models. In addition, corresponding interventions based on these factors and theories have failed to reduce the incidence rate of invasive and metastatic lesions, suggesting that previous efforts may have failed to arm at the right target. Considering these facts and observations, we are proposing "A focal aberrant degeneration in the myoepithelial cell layer (MECL) as the most likely triggering factor for breast cancer invasion". Our hypothesis is based on our recent studies of breast and multiple other cancers. Our commentary provides the rationale, morphologic, immunohistochemical, and molecular data to support our hypotheses. As all epithelium-derived cancers share a very similar architecture, our hypothesis is likely to be applicable to invasion of all cancer types. We believe that human tissue-derived data may provide a more realistic roadmap to guide the clinic practice.

Predicting cerebral white matter lesions based on the platelet-to-white blood cell ratio in hypertensive patients.

Hypertension is a common chronic disease affecting many people. White matter lesions (WMLs) are one of the imaging features of cerebrovascular disease. Predicting the possibility of developing syncretic WMLs in patients with hypertension may contribute to the early identification of serious clinical conditions. This study aims to build a model to identify patients who suffered from moderate-to-severe WMLs by using recognized WMLs risk factors including age and history of diabetes and a new factor named platelet-to-white blood cell ratio (PWR). A total of 237 patients were included in this study. The Affiliated ZhongDa Hospital of Southeast University Research Ethics Committee approved this study (Ethics No. 2019ZDSYLL189-P01). We developed a nomogram to predict the risk of syncretic WMLs in patients with hypertension using the above factors. Higher total scores on the nomogram indicated a higher risk of syncretic WMLs. This means older age, smaller PWR, and patients suffering from diabetes contributed to a greater chance for the patient to suffer from syncretic WMLs. We used a decision analysis curve(DCA) to determine the net benefit of the prediction model. The DCA we constructed showed that using our model to decide whether patients suffered from syncretic WMLs or not was better than assuming they all suffered from syncretic WMLs or all WMLs-free. As a result, the area under the curve of our model was 0.787. By integrating PWR, history of diabetes, and age, we could estimate integrated WMLs in hypertensive patients. This study provides a potential tool to identify cerebrovascular disease in patients with hypertension.

Imaging characteristics and postoperative pathological analysis of bronchiolar adenoma / 中国胸心血管外科临床杂志

@#Objective    To analyze the pathological manifestations and imaging characteristics of bronchiolar adenoma (BA). Methods    The clinical data of 11 patients with BA who received surgeries in our hospital from January 2019 to September 2020 were retrospectively analyzed, including 5 males and 6 females aged 40-73 (62.40±10.50) years. The intraoperative rapid freezing pathological diagnosis, postoperative pathological classification, cell growth pattern, nuclear proliferation index Ki-67 and other immunohistochemical staining combined with preoperative chest CT imaging characteristics were analyzed. Results    The average preoperative observation time was 381.10±278.28 d. The maximum diameter of imaging lesions was 5-27 (10.27±6.34) mm. Eight (72.7%) patients presented with irregular morphology of heterogeneous ground-glass lesions, and 3 (27.3%) patients presented with pure ground-glass lesions. There were 10 (90.9%) patients with vascular signs, 8 (72.7%) patients with vacuolar signs, 1 (9.1%) patient with bronchus sign, 3 (27.3%) patients with pleural traction and 9 (81.8%) patients with burr/lobular sign. The surgical methods included sub-lobectomy in 10 patients and lobectomy in 1 patient. Five (45.5%) patients were reported BA by intraoperative frozen pathology. The postoperative pathological classification included 8 patients with distal-type and 3 patients with proximal-type, and the maximum diameter of the lesions was 4-20 (8.18±5.06) mm. Eight (72.7%) patients showed characteristic bilayer cell structure under microscope, and 10 (90.9%) patients showed thyroid transcription factor 1 expression in pathological tissues. The expression of NapsinA in intracavity cells was found in 9 (81.8%) patients. The Ki-67 index of the lesion tissue was 1%-5% (3.22%±1.72%). Conclusion    The pathological features and imaging findings of BA confirm the premise that BA is a neoplastic lesion. However, to identify BA as a benign or inert tumor needs more clinical data and evidence of molecular pathological studies.

Cryo-EM structures for the Mycobacterium tuberculosis iron-loaded siderophore transporter IrtAB

The adenosine 5'-triphosphate (ATP)-binding cassette (ABC) transporter, IrtAB, plays a vital role in the replication and viability of Mycobacterium tuberculosis (Mtb), where its function is to import iron-loaded siderophores. Unusually, it adopts the canonical type IV exporter fold. Herein, we report the structure of unliganded Mtb IrtAB and its structure in complex with ATP, ADP, or ATP analogue (AMP-PNP) at resolutions ranging from 2.8 to 3.5 Å. The structure of IrtAB bound ATP-Mg2+ shows a "head-to-tail" dimer of nucleotide-binding domains (NBDs), a closed amphipathic cavity within the transmembrane domains (TMDs), and a metal ion liganded to three histidine residues of IrtA in the cavity. Cryo-electron microscopy (Cryo-EM) structures and ATP hydrolysis assays show that the NBD of IrtA has a higher affinity for nucleotides and increased ATPase activity compared with IrtB. Moreover, the metal ion located in the TM region of IrtA is critical for the stabilization of the conformation of IrtAB during the transport cycle. This study provides a structural basis to explain the ATP-driven conformational changes that occur in IrtAB.

A case of acute severe cryptogenic organic pneumonia with secondary hemophilia / 中南大学学报(医学版)

Cryptogenic organic pneumonia (COP) refers to organic pneumonia that has not been identified a clear cause by current medical methods. A small proportion of COP can exhibit severe and progressive characteristics, while severe COP can cause systemic inflammatory storms and can be secondary to hemophilia. This article reported a case of acute severe COP secondary to hemophilia. A 67-year-old male patient was admitted to the hospital due to cough, shortness of breath, and fever. At first, he was misdiagnosed as severe pneumonia, but failed to receive anti infection treatments. Sputum pathogenetic examination and Macrogene testing of alveolar lavage fluid were performed, and no etiology was found to explain the patient's condition. The condition was gradually worsened and hemophilia occurred to explain, suggesting that acute severe COP was relevant. After receiving hormone treatment, the condition gradually relieved and the absorption of lung lesions improved. Hemophilia secondary to COP is rare, and the specific mechanism needs further study.

Animal DNA Typing and Its Research Progress in Forensic Medicine / 法医学杂志

With the advance of molecular biology, DNA analysis technology has been widely applied in forensic science. Non-human DNA analysis can be used in some special cases and has unique forensic value to provide investigation clues and trial basis. Animal DNA typing plays a more prominent role in the detection of all kinds of non-human DNA related cases and is the main content of forensic non-human DNA analysis. This paper reviews the development history, present situation, advantages and disadvantages of animal DNA typing according to its technology, characteristic, challenges facing forensic science application scenarios, and also its future development.

Molecular features of 109 patients with chronic myelomonocytic leukemia in a single center / 中华血液学杂志

Objective: To explore the molecular features of chronic myelomonocytic leukemia (CMML) . Methods: According to 2022 World Health Organization (WHO 2022) classification, 113 CMML patients and 840 myelodysplastic syndrome (MDS) patients from March 2016 to October 2021 were reclassified, and the clinical and molecular features of CMML patients were analyzed. Results: Among 113 CMML patients, 23 (20.4%) were re-diagnosed as acute myeloid leukemia (AML), including 18 AML with NPM1 mutation, 3 AML with KMT2A rearrangement, and 2 AML with MECOM rearrangement. The remaining 90 patients met the WHO 2022 CMML criteria. In addition, 19 of 840 (2.3%) MDS patients met the WHO 2022 CMML criteria. At least one gene mutation was detected in 99% of CMML patients, and the median number of mutations was 4. The genes with mutation frequency ≥ 10% were: ASXL1 (48%), NRAS (34%), RUNX1 (33%), TET2 (28%), U2AF1 (23%), SRSF2 (21.1%), SETBP1 (20%), KRAS (17%), CBL (15.6%) and DNMT3A (11%). Paired analysis showed that SRSF2 was frequently co-mutated with ASXL1 (OR=4.129, 95% CI 1.481-11.510, Q=0.007) and TET2 (OR=5.276, 95% CI 1.979-14.065, Q=0.001). SRSF2 and TET2 frequently occurred in elderly (≥60 years) patients with myeloproliferative CMML (MP-CMML). U2AF1 mutations were often mutually exclusive with TET2 (OR=0.174, 95% CI 0.038-0.791, Q=0.024), and were common in younger (<60 years) patients with myelodysplastic CMML (MD-CMML). Compared with patients with absolute monocyte count (AMoC) ≥1×10(9)/L and <1×10(9)/L, the former had a higher median age of onset (60 years old vs 47 years old, P<0.001), white blood cell count (15.9×10(9)/L vs 4.4×10(9)/L, P<0.001), proportion of monocytes (21.5% vs 15%, P=0.001), and hemoglobin level (86 g/L vs 74 g/L, P=0.014). TET2 mutations (P=0.021) and SRSF2 mutations (P=0.011) were more common in patients with AMoC≥1×10(9)/L, whereas U2AF1 mutations (P<0.001) were more common in patients with AMoC<1×10(9)/L. There was no significant difference in the frequency of other gene mutations between the two groups. Conclusion: According to WHO 2022 classification, nearly 20% of CMML patients had AMoC<1×10(9)/L at the time of diagnosis, and MD-CMML and MP-CMML had different molecular features.

Research progress of m 6A methylation modification in respiratory viruses replication and host immune response / 中华临床感染病杂志

N 6-methyladenosine (m 6A) modification is the most prevalent internal modification of eukaryotic mRNA and is dynamically regulated by a variety of m 6A modifying enzymes, including methylation transferases, demethylases and specific binding proteins. Respiratory viral infections have received much attention in recent years, and the process of virus replication and metabolism in host cells is regulated by m 6A. This article reviews the mechanism of m 6A-regulated enzymes, the roles of m 6A modifications in respiratory viruses replication and the host immune response to viruses, including adenovirus, influenza A virus, severe acute respiratory syndrome coronavirus 2, respiratory syncytial virus, and human metapneumovirus. It would provide a reference for exploring the regulatory role of viral episodic transcriptome modifications and antiviral targets or vaccine development.

Clinical characteristics and antiviral therapy of influenza in immunosuppressed hospitalized patients / 中华临床感染病杂志

Objective:To analyse the clinical characteristics and antiviral therapy in immunosuppressed hospitalized patients with influenza.Methods:The clinical data of 273 patients with positive influenza A or B virus nucleic acid admitted in Peking University People’s Hospital from November 2015 to March 2022 were retrospectively analyzed. Among them, 123 were immunosuppressed and 150 were non-immunosuppressed. The clinical characteristics and antiviral therapy in immunosuppressed patients with influenza were analyzed. SPSS 22.0 software was used to analyze the data.Results:Chemotherapy for malignancies was the most common cause of immunosuppression (61.8%, 76/123), followed by haemopoietic stem cell transplantation (24.4%, 30/123). The common symptoms were fever (93.5%, 115/123) and cough (41.5%, 51/123). The proportions of co-infections (22.8%, 28/123) and complications (43.9%, 54/123) in immunosuppressed hospitalized patients were higher than those in non-immunosuppressed patients ( χ2=9.365 and 7.496, both P<0.01). Compared with single drug therapy, combination of antiviral drugs did not shorten the fever time, negative conversion time of virus nucleic acid and the length of hospital stay, and reduce the death ( U/ χ2=312.5, 356.0, 749.5 and 0.185, all P>0.05). Compared to patients without corticosteroids use, the use of corticosteroids did not increase mortality in immunosuppressed patients ( χ2=2.508, P=0.113). Conclusions:Classical symptoms may be absent in immunosuppressed patients with influenza, and early detection of influenza virus is still an important means of early diagnosis. Co-infections and complications are more common in immunosuppressed influenza patients. Immunosuppressed influenza patients did not benefit from the combination of antiviral therapy.

Assessment of 3D-printed tissue compensators for superficial tumor X-ray radiation compensation / 中华放射医学与防护杂志

Objective:To investigate the advantage of three dimensional(3D)-printed tissue compensators in radiotherapy for superficial tumors at irregular sites.Methods:A subcutaneous xenograft model of prostate cancer in nude mice was established. Mice were randomly divided into no tissue compensator group( n=6), common tissue compensator group( n=6), and 3D-printed tissue compensator group( n=6). Computed tomography (CT) images of nude mice in the 3D-printed tissue compensator group were acquired. Compensator models were made using polylactic acid, and material properties were evaluated by measuring electron density. CT positioning images of the three groups after covering the corresponding tissue compensators were acquired to delineate the gross tumor volume (GTV). Nude mice in the three groups were irradiated with 6 MV X-rays at the prescribed dose. The prescribed dose for the three groups was 1 500 cGy. The dose distribution in the GTV of the three groups was calculated and compared using the analytical anisotropic algorithm in the Eclipse 13.5 treatment planning system. The metal-oxide-semiconductor field-effect transistor was used to verify the actual dose received on the skin surface of nude mice. Results:The air gap in the 3D-printed tissue compensator group and the common tissue compensator group was 0.20±0.07 and 0.37±0.07 cm 3, respectively ( t=4.02, P<0.01). For the no tissue compensator group, common tissue compensator group, and 3D-printed tissue compensator group, the D95% in the target volume was (1 188.58±92.21), (1 369.90±146.23), and (1 440.29±45.78) cGy, respectively ( F=9.49, P<0.01). D98% was (1 080.13±88.30), (1 302.76±158.43), and (1 360.23±48.71) cGy, respectively ( F=11.17, P<0.01). Dmean was (1 549.08±44.22), (1 593.05±65.40), and (1 638.87±40.83) cGy, respectively ( F=4.59, P<0.05). The measured superficial dose was (626.03±26.75), (1 259.83±71.94), and (1 435.30±67.22) cGy, respectively ( F=263.20, P<0.001). The percentage variation in tumor volume growth after radiation was not significantly different between the common tissue compensator group and the 3D-printed tissue compensator group ( P>0.05). Conclusions:3D-printed tissue compensators fit well to the body surface, which reduces air gaps, effectively increases the dose on the body surface near the target volume, and provides ideas for radiotherapy for superficial tumors at some irregular sites.

A case of combined oxidative phosphorylation deficiency 32 caused by MRPS34 gene variation and literature review / 中华儿科杂志

Objective: To investigate the clinical features and genetic features of combined oxidative phosphorylation deficiency 32 (COXPD32) caused by MRPS34 gene variation. Methods: The clinical data and genetic test of a child with COXPD32 hospitalized in the Department of Neurology, Children's Hospital, Capital Institute of Pediatrics in March 2021 were extracted and analyzed. A literature search was implemented using Wanfang, China biology medicine disc, China national knowledge infrastructure, ClinVar, human gene mutation database (HGMD) and Pubmed databases with the key words "MRPS34" "MRPS34 gene" and "combined oxidative phosphorylation deficiency 32" (up to February 2023). Clinical and genetic features of COXPD32 were summarized. Results: A boy aged 1 year and 9 months was admitted due to developmental delay. He showed mental and motor retardation, and was below the 3rd percentile for height, weight, and head circumference of children of the same age and gender. He had poor eye contact, esotropia, flat nasal bridge, limbs hypotonia, holding instability and tremors. In addition, Grade Ⅲ/6 systolic murmur were heard at left sternal border. Arterial blood gases suggested that severe metabolic acidosis with lactic acidosis. Brain magnetic resonance imaging (MRI) showed multiple symmetrical abnormal signals in the bilateral thalamus, midbrain, pons and medulla oblongata. Echocardiography showed atrial septal defect. Genetic testing identified the patient as a compound heterozygous variation of MRPS34 gene, c.580C>T (p.Gln194Ter) and c.94C>T (p.Gln32Ter), with c.580C>T being the first report and a diagnosis of COXPD32. His parents carried a heterozygous variant, respectively. The child improved after treatment with energy support, acidosis correction, and "cocktail" therapy (vitaminB1, vitaminB2, vitaminB6, vitaminC and coenzyme Q10). A total of 8 cases with COXPD32 were collected through 2 English literature reviews and this study. Among the 8 patients, 7 cases had onset during infancy and 1 was unknown, all had developmental delay or regression, 7 cases had feeding difficulty or dysphagia, followed by dystonia, lactic acidosis, ocular symptoms, microcephaly, constipation and dysmorphic facies(mild coarsening of facial features, small forehead, anterior hairline extending onto forehead,high and narrow palate, thick gums, short columella, and synophrys), 2 cases died of respiratory and circulatory failure, and 6 were still alive at the time of reporting, with an age range of 2 to 34 years. Blood and (or) cerebrospinal fluid lactate were elevated in all 8 patients. MRI in 7 cases manifested symmetrical abnormal signals in the brainstem, thalamus, and (or) basal ganglia. Urine organic acid test were all normal but 1 patient had alanine elevation. Five patients underwent respiratory chain enzyme activity testing, and all had varying degrees of enzyme activity reduction. Six variants were identified, 6 patients were homozygous variants, with c.322-10G>A was present in 4 patients from 2 families and 2 compound heterozygous variants. Conclusions: The clinical phenotype of COXPD32 is highly heterogenous and the severity of the disease varies from development delay, feeding difficulty, dystonia, high lactic acid, ocular symptoms and reduced mitochondrial respiratory chain enzyme activity in mild cases, which may survive into adulthood, to rapid death due to respiratory and circulatory failure in severe cases. COXPD32 needs to be considered in cases of unexplained acidosis, hyperlactatemia, feeding difficulties, development delay or regression, ocular symptoms, respiratory and circulatory failure, and symmetrical abnormal signals in the brainstem, thalamus, and (or) basal ganglia, and genetic testing can clarify the diagnosis.

Role of blood markers in predicting the failure of prosthesis removal and antibiotic-loaded bone cement spacer implantation for treatment of periprosthetic joint infection / 中华外科杂志

Objective: To investigate the value of inflammation,coagulation and nutrition markers in predicting the failure of prosthesis removal and antibiotic-loaded bone cement spacer implantation for treatment of periprosthetic joint infection(PJI). Methods: A retrospective study was conducted on 70 patients who undertook prosthesis removal and antibiotic-loaded bone cement spacer implantation due to PJI from June 2016 to October 2020 in the Department of Orthopedics,Henan Provincial People's Hospital. There were 28 males and 42 females,aged (65.5±11.9) years (range: 37 to 88 years). Patients were divided into two groups as the successful group and the failed group depended on whether reinfection occurred after prosthesis removal and antibiotic-loaded bone cement spacer implantation at the last follow up. Patient demographics,laboratory values (C-reactive protein (CRP),erythrocyte sedimentation rate (ESR),ESR and CRP ratio (ESR/CRP),white blood cell count(WBC),platelet count(PLT),hemoglobin(HB),total lymphocyte count(TLC),albumin、fibrinogen(FIB),CRP and albumin ratio (CAR),prognostic nutritional index(PNI)),and reinfection rates were assessed. Comparison between groups was conducted by the independent sample t test or χ2 test. Receiver operating characteristic (ROC) curve was plotted,and the area under the curve (AUC),optimal diagnostic threshold,sensitivity,and specificity were analyzed to predict the failure of prosthesis removal and antibiotic-loaded bone cement spacer implantation. Results: All patients were followed up for at least two years,and the follow-up time was (38.4±15.2) months (range: 24 to 66 months). Fifteen patients suffered failure after prosthesis removal and antibiotic-loaded bone cement spacer implantation,while the other 55 patients succeeded. The overall failure rate of prosthesis removal and antibiotic-loaded bone cement spacer implantation in PJI treatment was 21.4%. Level of preoperative CRP(35.9±16.2)mg/L,PLT(280.0±104.0)×109/L and CAR 1.3±0.8 in successful group were lower than CRP (71.7±47.3)mg/L,PLT (364.7±119.3)×109/L and CAR 2.5±2.0 in failed group (all P<0.05).Whereas,level of preoperative ESR/CRP (3.3±3.1), Albumin (35.3±5.2)g/L and PNI 43.6±6.2 in successful group were higher than ESR/CRP (1.6±1.4),Albumin(31.3±4.8)g/L and PNI (39.2±15.1) in failed group (all P<0.05). AUC of ROC curve,optimal threshold value,sensitivity and specificity of CRP,ESR/CRP, PLT, Albumin,CAR and PNI for the predicting failure of prosthesis removal and antibiotic-loaded bone cement spacer implantation were 0.776(95%CI:0.660 to 0.867),35.4 mg/L,86.7%,67.3%;0.725(95%CI:0.605 to 0.825),1.0,60.0%,78.2%;0.713(95%CI:0.593 to 0.815),253,93.3%,47.3%;0.721(95%CI:0.601 to 0.822),35.7,93.3%,49.1%;0.772(95%CI:0.656 to 0.863),1.1,86.7%,67.3%;0.706(95%CI:0.585 to 0.809),45.7,100%,41.8% respectively. Conclusion: In patients with PJI,CRP>35.4,ESR/CRP≤1.0 and CAR>1.1 could predict the failure of prosthesis removal and antibiotic-loaded bone cement spacer implantation.

Analysis of the characteristics of viral infections in children with diarrhea in Beijing from 2018 to 2022 / 中华预防医学杂志

Objective: To explore the characteristics of viral infections in children with diarrhea in Beijing from 2018 to 2022. Methods: Real-time PCR and enzyme-linked immunosorbent assay were used to detect viral nucleic acid of Norovirus (NoV), Sappovirus (SaV), Astrovirus (AstV), Enteric Adenovirus (AdV) or antigen of Rotavirus (RV) in 748 stool samples collected from Beijing Capital Institute of Pediatrics from January 2018 to December 2021. Subsequently, the reverse transcription PCR or PCR method was used to amplify the target gene of the positive samples after the initial screening, followed by sequencing, genotyping and evolution analysis, so as to obtain the characteristics of these viruses. Phylogenetic analysis was performed using Mega 6.0. Results: From 2018 to 2021, the overall detection rate of the above five common viruses was 37.6%(281/748)in children under 5 years old in Beijing. NoV, Enteric AdV and RV were still the top three diarrhea-related viruses, followed by AstV and SaV, accounting for 41.6%, 29.2%, 27.8%, 8.9% and 7.5%, respectively. The detection rate of co-infections with two or three diarrhea-related viruses was 4.7% (35/748). From the perspective of annual distribution, the detection rate of Enteric AdV was the highest in 2021, while NoV was predominant in the other 4 years. From the perspective of genetic characteristics, NoV was predominant by GⅡ.4, and after the first detection of GⅡ.4[P16] in 2020, it occupied the first two gene groups together with GⅡ.4[P31]. Although the predominant RV was G9P[8], the rare epidemic strain G8P[8] was first detected in 2021. The predominant genotypes of Enteric AdV and AstV were Ad41 and HAstV-1. SaV was sporadic spread with a low detection rate. Conclusion: Among the diarrhea-related viruses infected children under 5 years of age in Beijing, the predominant strains of NoV and RV have changed and new sub-genotypes have been detected for the first time, while the predominant strains of AstV and Enteric AdV are relatively stable.

Effects of breast milk intake ratio during hospitalization on antibiotic therapy duration in preterm infants less than 34 gestational weeks: a multicenter retrospective cohort study / 中华围产医学杂志

Objective:To investigate the effects of breast milk to total milk intake ratio during hospitalization on the duration of antibiotic therapy in preterm infants less than 34 weeks of gestation.Methods:Clinical data of preterm infants ( n=1 792) less than 34 gestational weeks were retrospectively collected in 16 hospitals of Jiangsu Province Neonatal-Perinatal Cooperation Network from January 1, 2019, to December 31, 2021. The days of therapy (DOT) were used to evaluate the duration of antibiotic administration. The median DOT was 15.0 d (7.0-27.0 d). The patients were divided into four groups based on the quartiles of DOT: Q 1 (DOT≤7.0 d), Q 2 (7.0 d<DOT≤15.0 d), Q 3 (15.0 d<DOT≤27.0 d) and Q 4 (DOT>27.0 d) groups. According to the breast milk intake ratio (breast milk intake to total milk intake during hospitalization×100%), they were also divided into four groups: very-low-ratio breastfeeding group (breast milk intake ratio≤25%), low-ratio breastfeeding group (25%<breast milk intake ratio≤50%), medium-ratio breastfeeding group (50%<breast milk intake ratio≤75%) and high-ratio breastfeeding group (breast milk intake ratio>75%). Univariate analysis ( Chi-square test and Kruskal-Wallis rank-sum test) was used to analyze the factors influencing DOT. Spearman correlation analysis and trend Chi-square test were used to explore the relationship between breast milk intake ratio and DOT. After using multiple imputations to address missing data, two models were constructed after adjusting for different factors, and multinomial logistic regression model was applied to evaluate the effects of the breast milk intake ratio on DOT. Finally, sensitivity analysis was conducted to assess the stability of the models. Results:(1) Of the 1 792 preterm infants, there were 507 (28.3%) in the Q 1 group, 422 (23.5%) in the Q 2 group, 438 (24.4%) in the Q 3 group and 425 (23.7%) in the Q 4 group. (2) The median values of DOT in the very-low-ratio, low-ratio, medium-ratio and high-ratio breastfeeding groups were 20.0 d (11.0-31.0 d), 20.0 d (11.0-32.0 d), 13.0 d (6.0-25.8 d) and 10.0 d (4.0-21.0 d), respectively. Compared with the very-low-ratio and low-ratio breastfeeding groups, the medium-ratio and high-ratio breastfeeding groups had shorter DOT (all P<0.05). (3) After adjusting for factors with P<0.1 (prenatal glucocorticoid exposure, antimicrobial use within 24 h before delivery, gestational age at delivery, birth weight, Apgar score≤7 at 1 min, neonatal respiratory distress syndrome, infectious pneumonia and early-onset neonatal sepsis) between the DOT quartile groups, it showed that medium-ratio and high-ratio breastfeeding were protective factors in contrast to very-low-ratio breastfeeding in the Q 2, Q 3 and Q 4 groups as compared with the Q 1 group [Q 2 group: OR=0.50 (95% CI: 0.30-0.85) and OR=0.36 (95% CI: 0.26-0.51); Q 3 group: OR=0.31 (95% CI: 0.18-0.55) and OR=0.20 (95% CI: 0.14-0.29); Q 4 group: OR=0.22 (95% CI: 0.12-0.42) and OR=0.17 (95% CI: 0.12-0.26)]. Conclusion:Breast milk intake accounting for over 50% of total milk intake has a positive impact on reducing DOT in premature infants requiring antibiotics, which suggests that breastfeeding should be actively encouraged.

Functions of CRABP2 in tumorigenesis and progression / 中国临床药理学与治疗学

Retinoic acid (RA) is a metabolic intermediate of vitamin A, which plays an important role in embryonic development and cell growth and differentiation. Cellular retinoic acid-binding proteins 2 (CRABP2) are a group of low-molecular weight intracellular proteins whose primary physiological function is to transport RA to the nucleus. Generally, CRABP2 binds to the retinoic acid receptor (RAR), then regulates specific downstream signaling pathways to function. Abnormal expression of CRABP2 was closely related to several human malignant tumors, and could affect the tumor occurrence and development through regulating multiple growth or apoptosis associated pathways or key biological molecules. Therefore, CRABP2 may be considered as a new diagnostic and prognostic marker for cancer, and a new therapeutic target for malignant tumors. Our present article summarizes the relationship between CRABP2 and tumor progression, drug resistance and prognosis, so as to provide reference for the future research.

Ginsenoside Rgl inhibits neuronal ferroptosis caused by ischemic stroke through activating of Nrf2/xCT/GPX4 axis / 中国药理学通报

Aim To study the inhibitory effect of ginsenoside Rgl on neuronal ferroptosis after ischemic stroke and its mechanism. Methods A model of oxygen glucose deprivation/reoxygenation (OGD/R) was established in HT22 cells, and the effect of Rgl on the viability of HT22 cells after OGD/R injury was detected by CCK-8. The effect of Rgl on ferroptosis in HT22 cells after OGD/R injury was detected by the test of ferroptosis markers GSH/GSSG, SOD, MDA, and Fe

Clinical characteristics of epileptic seizure in neurofibromatosis type 1 in 15 cases / 中华儿科杂志

Objective: To summarize the clinical characteristics of epileptic seizure associated with neurofibromatosis type 1 (NF1). Methods: From January 2017 to July 2023 at Children's Hospital Capital Institute of Pediatrics, medical records of patients with both NF1 and epileptic seizure were reviewed in this case series study. The clinical characteristics, treatment and prognosis were analyzed retrospectively. Results: A total of 15 patients(12 boys and 3 girls) were collected. Café-au-lait macules were observed in all 15 patients. There were 6 patients with neurodevelopmental disorders and the main manifestations were intellectual disability or developmental delay. The age at the first epileptic seizure was 2.5 (1.2, 5.5) years. There were various seizure types, including generalized tonic-clonic seizures in 8 patients, focal motor seizures in 6 patients, epileptic spasm in 4 patients, tonic seizures in 1 patient, absence in 1 patient, generalized myoclonic seizure in 1 patient and focal to bilateral tonic-clonic seizure in 1 patient. Among 14 patients whose brain magnetic resonance imaging results were available, there were abnormal signals in corpus callosum, basal ganglia, thalamus or cerebellum in 6 patients, dilated ventricles of different degrees in 3 patients, blurred gray and white matter boundary in 2 patients, agenesis of corpus callosum in 1 patient and no obvious abnormalities in the other patients. Among 13 epilepsy patients, 8 were seizure-free with 1 or 2 antiseizure medications(ASM), 1 with drug resistant epilepsy was seizure-free after left temporal lobectomy, and the other 4 patients who have received 2 to 9 ASM had persistent seizures. One patient with complex febrile convulsion achieved seizure freedom after oral administration of diazepam on demand. One patient had only 1 unprovoked epileptic seizure and did not have another seizure without taking any ASM. Conclusions: The first epileptic seizure in NF1 patients usually occurs in infancy and early childhood, with the main seizure type of generalized tonic-clonic seizure and focal motor seizure. Some patients have intellectual disability or developmental delay. Most epilepsy patients achieve seizure freedom with ASM.