Objective To investigate the disease spectrum and pathogenic genes of inherited metabolic disorder(IMD)among neonates in Gansu Province of China.Methods A retrospective analysis was conducted on the tandem mass spectrometry data of 286 682 neonates who received IMD screening in Gansu Provincial Maternal and Child Health Hospital from January 2018 to December 2021.A genetic analysis was conducted on the neonates with positive results in tandem mass spectrometry during primary screening and reexamination.Results A total of 23 types of IMD caused by 28 pathogenic genes were found in the 286 682 neonates,and the overall prevalence rate of IMD was 0.63‰(1/1 593),among which phenylketonuria showed the highest prevalence rate of 0.32‰(1/3 083),followed by methylmalonic acidemia(0.11‰,1/8 959)and tetrahydrobiopterin deficiency(0.06‰,1/15 927).In this study,166 variants were identified in the 28 pathogenic genes,with 13 novel variants found in 9 genes.According to American College of Medical Genetics and Genomics guidelines,5 novel variants were classified as pathogenic variants,7 were classified as likely pathogenic variants,and 1 was classified as the variant of uncertain significance.Conclusions This study enriches the database of pathogenic gene variants for IMD and provides basic data for establishing an accurate screening and diagnosis system for IMD in this region.

Ceria nanoparticles(CeO2 NPs)have become popular materials in biomedical and industrial fields due to theirpotential applications in anti-oxidation,cancer therapy,photocatalytic degradation of pollutants,sensors,etc.Many methods,including gas phase,solid phase,liquid phase,and the newly proposed green synthesis method,have been reported for the synthesis of CeO2 NPs.Due to the wide application of CeO2 NPs,concerns about their adverse impacts on human health have been raised.This review covers recent studies on the biomedical applications of CeO2 NPs,including their use in the treatment of various diseases(e.g.,Alzheimer's disease,ischemic stroke,retinal damage,chronic inflammation,and cancer).CeO2 NP toxicity is discussed in terms of the different systems of the human body(e.g.,cytotoxicity,genotoxicity,respiratory toxicity,neurotoxicity,and hepatotoxicity).This comprehensive review covers both fundamental discoveries and exploratory progress in CeO2 NP research that may lead to practical developments in the future.

Objective Viral encephalitis is an infectious disease severely affecting human health.It is caused by a wide variety of viral pathogens,including herpes viruses,flaviviruses,enteroviruses,and other viruses.The laboratory diagnosis of viral encephalitis is a worldwide challenge.Recently,high-throughput sequencing technology has provided new tools for diagnosing central nervous system infections.Thus,In this study,we established a multipathogen detection platform for viral encephalitis based on amplicon sequencing. Methods We designed nine pairs of specific polymerase chain reaction(PCR)primers for the 12 viruses by reviewing the relevant literature.The detection ability of the primers was verified by software simulation and the detection of known positive samples.Amplicon sequencing was used to validate the samples,and consistency was compared with Sanger sequencing. Results The results showed that the target sequences of various pathogens were obtained at a coverage depth level greater than 20×,and the sequence lengths were consistent with the sizes of the predicted amplicons.The sequences were verified using the National Center for Biotechnology Information BLAST,and all results were consistent with the results of Sanger sequencing. Conclusion Amplicon-based high-throughput sequencing technology is feasible as a supplementary method for the pathogenic detection of viral encephalitis.It is also a useful tool for the high-volume screening of clinical samples.

Objective To investigate the long-term incidence of in-stent stenosis(ISS)in patients with intracranial aneurysms receiving pipeline embolization device(PED)who showed no ISS at short-to-medium term follow-up examination.Methods The clinical data of patients,who received PED treatment at the Department of Neurointervention,First Affiliated Hospital of Zhengzhou University of China between April 2015 and June 2022,were retrospectively collected.The patients with intracranial aneurysms,who showed no ISS at the initial follow-up with DS A and completed＞12 months long-term follow-up check after treatment at the same hospital,were screened out,and their relevant clinical data and imaging materials were collected.The incidence of ISS occurring in postoperative＞12 months long-term follow-up was calculated.The ISS was defined as a＞25％lumen loss of the parent artery when compared with its lumen size measured immediately after PED implantation.Results A total of 57 patients with 61 aneurysms were enrolled in this study,and a total of 68 PEDs were implanted.Forty-one(67.21％)aneurysms were treated by PED implantation only,and 20(32.79％)aneurysms by PED plus spring coils.The median initial follow-up time was 184.0 days(119.0,212.5).At postoperative＞12 months long-term follow-up visit,DSA was employed for 35(57.38％)aneurysms,CTA was adopted for 22(36.07％)aneurysms,and 3D-SPACE sequence MR scan was performed in 4(6.56％)aneurysms.The median follow-up time was 538.0 days(407.5,678.0),and the incidence of ISS was 0％.No ISS-related neurological symptoms occurred in all patients.Conclusion In treating intracranial aneurysms with PED,the postoperative incidence of ISS is low.No ISS is found during the short-term follow-up period,and long-term follow-up results tend to indicate that no ISS events have occurred.

Objective:To investigate the relationship between serum soluble CD155 (sCD155), soluble CD163 (sCD163) and chemotherapy efficacy and prognosis in patients with diffuse large B-cell lymphoma (DLBCL).Methods:A total of 126 patients with DLBCL admitted to Handan Central Hospital from May 2018 to May 2020 (DLBCL group) and 126 healthy subjects (control group) were prospectively selected to compare serum sCD155 and sCD163 levels. According to the chemotherapy effect of DLBCL patients, they were divided into effective group and ineffective group, and the serum sCD155 and sCD163 levels were compared before and after treatment. The effective rate of chemotherapy in patients with different serum sCD155 and sCD163 levels was compared. Kaplan-Meier method was used to analyze the relationship between serum sCD155 and sCD163 levels and 3-year overall survival (OS) and progression-free survival (PFS) of DLBCL patients. Cox proportional risk regression model was used to analyze the prognostic factors of DLBCL patients.Results:The serum levels of sCD155 and sCD163 in DLBCL group were higher than those in control group before treatment (all P<0.05). The effective rate of chemotherapy in 126 DLBCL patients in this group was 69.8%(88/126). Compared with the effective group, the serum levels of sCD155 and sCD163 were higher in the ineffective group before and after treatment (all P<0.05). Compared with before treatment, serum sCD155 and sCD163 levels in the effective group were decreased after treatment (all P<0.05). The effective rate of DLBCL patients in sCD155 and sCD163 high level groups was lower than that in sCD155 and sCD163 low level groups (all P<0.05). Kaplan-Meier analysis showed that the 3-year OS and PFS of DLBCL patients in the low level group of sCD155 and sCD163 were higher than those in the high level group (all P<0.05). The high level of sCD155 and sCD163 were independent risk factors for 3-year PFS and OS in DLBCL patients (all P<0.05). Conclusions:Abnormal levels of serum sCD155 and sCD163 in DLBCL patients may reduce the efficacy of chemotherapy and lead to poor prognosis.

ObjectiveTo observe the impacts of electroacupuncture （EA） on the expression of hippocampal brain-derived neurotrophic factor （BDNF） and acetylated histone （AcH3） in the rat model of spared nerve injury （SNI）， so as to explore the analgesic and antidepressant effects of EA. MethodsTwenty-four Male SD rats were randomly divided into 4 groups， with 6 in each group. SNI was used to establish the model of pain and depression. All the groups were intervened one week after SNI surgery and persisted 5 weeks. The EA group was treated with EA （2 Hz） for 30 min every other day and imipramine drug group （IMP） group with peritoneal imipramine injection （10 mg/kg） per day. The sham surgery group （SS） and model group （SNI） received the same grasping stimulation. The paw mechanical withdrawal threshold （PWT） test was performed before the SNI surgery， 1， 2， 3， 4， 5， and 6 weeks after surgery， respectively. The forced swimming test （FST） and the sucrose preference test （SPT） were performed 6 weeks after SNI surgery. The Western blot method was employed to detect the expression of BDNF and AcH3 from the rat hippocampal tissue at the end of the behavioral tests. ResultsCompared with the SS group， the SNI group had significantly decreased PWT and sucrose consumption， prolonged FST immobility time （all P<0.01）， down-regulated BDNF and AcH3 expression （P<0.05 & P<0.01） in the hippocampus， which indicated the successful construction of the pain-depression model. Compared with the SNI group， 6 weeks after SNI surgery， the EA and IMP groups had significantly increased PWT and sucrose consumption， and reduced FST immobility time （all P<0.01）； the EA group had up-regulated BDNF and AcH3 expression （both P<0.05） in the hippocampus， the IMP group had up-regulated AcH3 （P<0.05） expression but no difference in BDNF expression. ConclusionEA could relieve pain and depressive behavioral symptoms in SNI rats. And its analgesic and antidepressant mechanisms may relate to the up-regulation of hippocampal AcH3 and BDNF expression.

OBJECTIVE: To investigate the causes of ineffectiveness of platelet transfusion with monoclonal antibody solid phase platelet antibody test (MASPAT) matching in patients with allogeneic hematopoietic stem cell transplantation and explore the strategies of platelet transfusion. METHODS: A case of donor-specific HLA antibodies (DSA) induced by transfusion which ultimately resulted in transplantation failure and ineffective platelet transfusion with MASPAT matching was selected, and the causes of ineffective platelet transfusion and platelet transfusion strategy were retrospectively analyzed. RESULTS: The 32-year-old female patient was diagnosed as acute myeloid leukemia (high risk) in another hospital with the main symptoms of fever and leukopenia, who should be admitted for hematopoietic stem cell transplantation after remission by chemotherapy. In the course of chemotherapy, DSA was generated due to platelet transfusion, and had HLA gene loci incompatible with the donor of the first transplant, leading to the failure of the first transplant. The patient received platelet transfusion for several times before and after transplantation, and the results showed that the effective rate of MASPAT matched platelet transfusion was only 35.3%. Further analysis showed that the reason for the ineffective platelet transfusion was due to the missed detection of antibodies by MASPAT method. During the second hematopoietic stem cell transplantation, the DSA-negative donor was selected, and the matching platelets but ineffective transfusion during the primary transplantation were avoided. Finally, the patient was successfully transplanted and discharged from hospital. CONCLUSIONS DSA can cause graft failure or render the graft ineffective. For the platelet transfusion of patients with DSA, the platelet transfusion strategy with matching type only using MASPAT method will miss the detection of antibodies, resulting in invalid platelet transfusion.
Female ; Humans ; Adult ; Platelet Transfusion ; Antibodies, Monoclonal ; Retrospective Studies ; HLA Antigens ; Hematopoietic Stem Cell Transplantation

Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.
Female ; Humans ; Adolescent ; SARS-CoV-2 ; Smell ; COVID-19/complications* ; Cross-Sectional Studies ; COVID-19 Vaccines ; Incidence ; Olfaction Disorders/etiology* ; Taste Disorders/etiology* ; Prognosis

This study primarily concentrated on scientific problems of poor taste caused by unclear critical quality attributes of oral preparations manufactured by Chinese materia medica, successfully established an identification method for taste critical quality attribute and a taste improvement method combining electronic tongue with human senses, and determined the optimal taste formula, to improve patients' oral medication compliance. The study received ethical approval from the Review Committee of the Beijing University of Chinese Medicine. The results showed that the proportion of bitterness of Xiaoer Qingrening Granule was 61.8%, and its bitterness grade was 3.70, it was determined that bitterness is the critical quality attribute that caused the poor taste of Xiaoer Qingrening Granule. Additionally, the optimal taste formula per milliliter of Xiaoer Qingrening sugar-free intermediate was determined with allowable daily intake, solubility, and sweetness as the limiting conditions, which was 40 mg hydroxypropyl β-cyclodextrin, 180 mg trehalose, and 1.5 mg acesulfame potassium. Compared with the Xiaoer Qingrening Granule, the sensory evaluation score of the optimal taste formula was increased by 37.5 points. In conclusion, this study achieved the taste improvement of Xiaoer Qingrening Granule and formed a set of taste improvement strategies including the identification of taste critical quality attribute, the selection of the type and dosage of corrigent, and the optimization of taste formula, which provided a thought reference for the taste improvement of other oral preparations and a new perspective for quality control of intelligent manufacturing of traditional Chinese medicines.

There is still a serious challenge of the measurement of critical quality attributes (CQAs) related to clinical efficacy for Chinese materia medica manufacturing. To overcome this challenge, an integrated strategy of biosensor and ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) was proposed using Tongren niuhuang qingxin pills as a trial. Firstly, an original biosensor was created using a semiconductor chip material high electron mobility transistor (HEMT) as the transducer and the macrophage migration inhibitory factor (MIF) as the identification element. By this MIF-HEMT biosensor, the efficacy on stoke of different components from Tongren niuhuang qingxin pills was measured. It was clear that all three components of Tongren niuhuang qingxin pills had strong therapeutic effects on stroke, especially the section A, the K_D of which reached to 8.722×10^-10 g·mL^-1. Furthermore, MIF-HEMT biosensor integrated UPLC-MS/MS was introduced to identify the efficacy CQAs of different components of Tongren niuhuang qingxin pills. As a result, 19 potential CQAs, such as albiforin, paeoniflorin, and prim-O-glucosylcimifugin, were measured as the efficacy CQAs of Tongren niuhuang qingxin pills on stroke treatment by MIF. These results provided vital measurement techniques and methodological guidance for the CQAs study of Tongren niuhuang qingxin pills intervention in MIF-induced stroke treatment. This also provided an essential guideline for the efficient utilization and quality control measurement of high-quality classical recipes.