Objective: To explore the laboratory testing methods and clinical management strategies for immune hemolytic anemia induced by Ceftizoxime sodium drug-dependent antibodies. Methods: Patient blood samples were subjected to blood typing, direct antiglobulin test, and unexpected antibody identification. Ceftizoxime sodium drug-dependent antibodies were detected using the immune complex method and drug-sensitized red cell method. The properties and titers of the drug antibodies were further assessed. Flow cytometry was used to assess the complement activation capacity of the drug antibodies in vitro. Results: Direct antiglobulin tests (IgG and C3d) were positive. Ceftizoxime sodium drug-dependent antibodies were identified using both the immune complex method and the sensitized red cell method, their titers significantly increased following the addition of the drug. Flow cytometry confirmed the complement activation capability of these antibodies and identified 30 minutes as the optimal time for activation in vitro. The patient's condition improved rapidly after drug withdrawal and supportive transfusion, resulting in a favorable outcome. Conclusion: Ceftizoxime sodium can cause drug-induced immune hemolytic anemia via complement activation mediated by drug-dependent antibodies. Serological testing is essential for diagnosing drug-induced hemolytic anemia. Clinicians should be vigilant for this adverse reaction. The offending drug must be promptly discontinued, and supportive care should be initiated upon the onset of symptoms.

Aim To explore the effect and mechanism of the artesunate(ART)on hepatocellular carcinoma(HCC).Methods The cell lines MHCC-97H and HCC-LM3 were used to be detected.MTT and clone formation were used to determine the cell proliferation;Wound healing was used to detect the cell migration;Transwell was used to test the cell invasion.Flow-cy-tometry was used to detect cell apoptosis and cell cy-cle.RNA-seq and qRT-PCR was used to detect the genes expression.Results The proliferation,migra-tion and invasion of treated cells were obviously inhibi-ted(P＜0.01).Moreover,the apoptosis rate in-creased significantly,so did the proportion of G2/M cells.Transcriptomic analysis identified GADD45A as a potential target of ART through RNA-sequencing da-ta,and suggested that ART might induce apoptosis and cell cycle arrest through regulating the expression of GADD45A.In addition,the results of mechanism studies and signaling analysis suggested that GADD45A had interaction with its upstream gene NACC1(nucle-us accumbens associated 1).Moreover,after ART treatment,the expressions of GADD45A and NACC1 were changed significantly.Conclusion ART may be a potential drug to resist HCC by affecting the expres-sion of GADD45A and its upstream gene NACC1,which provides a new drug,a new direction and a new method for the clinical treatment of HCC.

Objective:To explore the clinical characteristics and genetic etiology of a Chinese Hui family with nanophthalmos.Methods:A pedigree investigation was performed.The clinical features and genetic etiology analysis were conducted in this Chinese family with nanophthalmos who first visited Beijing Tongren Eye Center in October 2005 and were followed up until October 2023.This family included 25 individuals of 4 generations, among which there were 3 patients.All the patients underwent medical history collection and comprehensive ophthalmological examinations, including visual acuity, intraocular pressure, slit-lamp microscope, IOLMaster, ultrasound biomicroscopy, color fundus photography, B-scan ultrasonography, visual field, etc.Genomic DNA was extracted from the 3 patients and 3 phenotypically normal individuals.Disease-causing genes were screened by whole-exome sequencing.Bioinformatic analysis and prediction of pathogenicity of candidate variants were conducted, followed by further validation by Sanger sequencing and co-segregation analysis.All the included subjects were informed of the purpose and methods of the study and signed an informed consent form.The study protocol was reviewed and approved by the Ethics Committee of Beijing Tongren Hospital, Capital Medical University (No.TRECKY2021-241).Results:Nanophthalmos in this family was inherited in an autosomal recessive manner.The proband and his two sisters were diagnosed with nanophthalmos based on clinical evaluation of typical phenotypes including the reduction of visual acuity, hyperpresbyopia, short ocular axis, shallow anterior chamber, narrow anterior chamber angle, high intraocular pressure, crowded optic disc, tortuous retinal vessel, etc.companied by angle-closure glaucoma, exudative retinal detachment and uveal effusion and other common complications.Compound heterozygous variants c. 1010_1021del (p.His337_Glu340del) and c. 1486G>A (p.Glu496Lys) were detected in MFRP gene in all three patients, and c. 1010_1021del, one of the biallelic variants was first reported.Both variants were rare in healthy populations and were co-segregated within this pedigree.According to the standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology, the variants were predicted to have strong pathogenicity and were the genetic cause of the nanophthalmos in this pedigree. Conclusions:This study finds a novel pathogenic variant c.1010_1021del in a nanophthalmos pedigree.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective To investigate the prevalence of tension-type headache(TTH)in children and adolescents aged 0-19 years globally in 1990-2021,and to provide a basis for the prevention and treatment of TTH.Methods Based on the Global Burden of Disease Study data,the age-standardized prevalence distribution of TTH and its changing trend were analyzed among the children and adolescents aged 0-19 years,with different sexes,age groups,sociodemographic index(SDI)regions and countries/territories.Results The age-standardized prevalence rate(ASPR)of TTH in children and adolescents aged 0-19 globally in 2021 was 17 339.89/100 000,which was increased by 1.73%since 1990.The ASPR in females was slightly higher than that in males(1990:17 707.65/100 000 vs 16 403.78/100 000;2021:17 946.29/100 000 vs 16 763.09/100 000).The ASPR in adolescence was significantly higher than that in school-aged and preschool periods(1990:27 672.04/100 000 vs 10 134.16/100 000;2021:28 239.04/100 000 vs 10 059.39/100 000).Regions with high SDI exhibited a higher ASPR than the other regions,with significant differences in prevalence rates across different countries.From 1990 to 2021,there was a slight increase in global ASPR,with an average annual percentage change(AAPC)of 0.06%.Females experienced a smaller increase than males based on AAPC(0.04%vs 0.07%).There was reduction in ASPR in preschool and school-aged groups,with an AAPC of-0.02%,while there was a significant increase in ASPR in adolescence,with an AAPC of 0.07%.ASPR decreased in regions with low-middle and low levels of SDI,with an AAPC of-0.02%and-0.04%,respectively,while it increased in regions with middle SDI,with an AAPC of 0.24%.Conclusions There is a consistent increase in the ASPR of TTH in children and adolescents aged 0-19 years globally,with significant differences across sexes,age groups,SDI regions and countries/territories.

BACKGROUND:Combined radiation and wound injury appeared mainly in patients with tumor radiotherapy and nuclear radiation accidents.The radiation destroys the repair mechanism,resulting in delayed or prolonged wound healing.It still lacks an effective therapeutic strategy currently. OBJECTIVE:To prepare multifunctional wound dressings based on the multiple clinical symptoms of combined radiation and wound injury,which are designed to be antibacteria,promoted healing and analgesics. METHODS:Using levofloxacin,fibroin and lidocaine hydrochloride as raw materials,3D bioprinting technology was applied to prepare the multifunctional wound dressing.(1)The multifunctional dressing was placed on a fixed culture plate coated with Staphylococcus aureus,Escherichia coli and Pseudomonas aeruginosa,and incubated at 37 ℃ overnight to detect the diameter of the antibacterial zone.(2)40 Kunming mice were randomly divided into trauma group,radiation and trauma model group,treatment group and positive drug group,with 10 mice in each group.Mice in the radiation and trauma model group,treatment group and positive drug group were irradiated by 60Co gamma rays.After 1 hour of radiation,a full-layer skin defect wound with a diameter of 1 cm was made on the back of each mouse in the four groups.Normal saline was applied to the wounds of the trauma group and the radiation and trauma model group.Trethanolamine cream was applied to the wounds of the positive drug group.Multifunctional dressing was applied to the wounds of the treatment group.The dressing was changed every 2 days,and the treatment was continued for 14 days.Wound healing rate and serum interleukin-6 level were measured at 3,7 and 14 days after wound modeling.14 days after the wound modeling,the skin tissue of the wound was obtained and received hematoxylin-eosin staining,Masson staining and cytokeratin-14 immunohistochemical staining. RESULTS AND CONCLUSION:(1)3D-printed multifunctional wound dressing had good antibacterial activity.The antibacterial zone diameters against Staphylococcus aureus,Escherichia coli and Pseudomonas aeruginosa were(4.15±0.09),(4.18±0.23)and(4.35±0.13)cm,respectively.(2)With the extension of modeling time,the wound healed gradually.The wound healing rate of the treatment group and the positive drug group was higher than that of the radiation and trauma model group at 3,7 and 14 days after modeling(P<0.01,P<0.001).The wound healing rate of the treatment group was higher than that of the positive drug group.With the extension of modeling time,the serum interleukin level of mice increased first and then decreased.The serum interleukin level in the treatment group at 3,7 and 14 days after modeling was lower than that in the radiation and trauma model group.Hematoxylin-eosin staining and Masson staining exhibited that inflammatory cells infiltrated the granuloma tissue in the trauma group,and the dermal collagen fibers were densely arranged.The normal structure of epidermis and dermis was destroyed and inflammatory cells were infiltrated in the radiation and trauma model group.In the treatment group,normal skin mucosal tissue was observed,the epidermis was arranged closely,and the sweat glands,hair follicles and dermal collagen fibers were arranged regularly.In the positive drug group,the arrangement of epidermal layer was tight,and the arrangement of sweat glands,hair follicles and dermal collagen fibers was regular.Cytokeratin-14 immunohistochemical staining displayed that the epidermal tissue thickness in the treatment group was lower than that in the other three groups(P<0.01,P<0.001).(3)The results confirm that the 3D-printed multifunctional dressing has multiple functions of local anesthesia,anti-infection and promoting healing.

AIM To establish an HPLC method for the simultaneous content determination of gallic acid,protocatechuic acid,morroniside,loganin,sweroside,paeoniflorin,hypericin,astragalin,salvianolic acid B,salvianolic acid A,epimedin C and icariin in Bushen Huoxue Sanjie Capsules.METHODS The analysis was performed on a 30℃thermostatic Agilent 5 TC-C18 column(250 mm×4.6 mm,5 μm),with the mobile phase comprising of acetonitrile-0.1%phosphoric acid flowing at 1.0 mL/min in a gradient elution manner,and the detection wavelength was set at 240 nm.RESULTS Twelve constituents showed good linear relationships within their own ranges(r≥0.999 8),whose average recoveries were 97.11%-101.14%with the RSDs of 0.60%-2.65%.CONCLUSION This simple,accurate and reproducible method can be used for the quality control of Bushen Huoxue Sanjie Capsules.

AIM To determine the contents of aspartic acid,glutamic acid,serine,glycine,threonine,citrulline,arginine,alanine,γ-amino-butyric acid,tyrosine,valine,phenlalanine,isoleucine,ornithine,leucine,lysine and proline in Gualoupi Injection and its intermediates,and to analyze their change laws.METHODS The OPA-FMOC online derivatization analysis was performed on a 45℃ thermostatic Waters XBridge C18 column(4.6 mm×100 mm,3.5 μm),with the mobile phase comprising of phosphate buffer solution-[methanol-acetonitrile-water(45 : 45 : 10)]flowing at 1 mL/min in a gradient elution manner,and the detection wavelengths were set at 262,338 nm.Principal component analysis and heatmap analysis were adopted in chemical pattern recognition for the corresponding intermediates in ten processes of six batches of samples.RESULTS Seventeen amino acids showed good linear relationships within their own ranges(R2>0.998 0),whose average recoveries were 83.4％-119.5％with the RSDs of 0.91％-7.94％.Different batches of samples in the same process were clustered,and the corresponding intermediates in different processed were clustered into three groups.Alcohol precipitation and cation exchange column demonstrated the biggest influences on amino acid composition.CONCLUSION This experiment can provide important references for the critical factors on quality control of Gualoupi Injection,thus ensure the stability and uniformity of final product.

Zuoguiwan， one of the classic formulas of traditional Chinese medicine （TCM）， has the effects of nourishing genuine Yin， supplementing essence， and replenishing marrow， and it is widely used in the clinical treatment of diseases caused by congenital essence deficiency. This article systematically reviewed the ancient books involving congenital deficiency and the modern research reports on the treatment of congenital deficiency with Zuoguiwan. From the formulation principle of Zuoguiwan and the TCM concept of congenital deficiency， this article discussed the theoretical basis of treating congenital deficiency with Zuoguiwan based on the modern research results. Ancient physicians have discovered that the deficiency of parents can lead to abnormal physical development and weakness of the offspring. ZHANG Jingyue divided congenital essence Qi into genuine Yin and primordial Yang and formulated Zuoguiwan based on the principle of Yin-Yang mutual assistance for supplementing congenital genuine Yin. Experimental studies have shown that Zuoguiwan can up-regulate the expression of connexin 43 （Cx43） protein and improve gap junction intercellular communication （GJIC） function to promote osteogenic differentiation and maturation of bone marrow mesenchymal stem cells and ameliorate abnormal bone development caused by congenital essence deficiency. Zuoguiwan can enhance the expression and activity of Reelin to ameliorate abnormal brain development. It can upregulate the expression of Cx43 protein to intervene in the phosphatidylinositol 3 kinase/protein kinase B （PI3K/Akt） pathway， thus repairing the reproductive functions. Zuiguiwan can promote the development and maturation of T cells and activate the Wnt/β-catenin signaling pathway in the thymus to improve immune functions. In addition， it can promote the expression of β-catenin and inhibit the expression of microtubule-associated proteins 1 light chain 3 （LC3） to attenuate skin dysfunctions. Moreover， Zuoguiwan can guide the differentiation of stem cells via the correlation between essence and vitality in TCM. Zuoguiwan has demonstrated significant therapeutic effects on some diseases in the pediatric， andrological， gynecological， geriatric， internal medicine， orthopedic and skin disease departments. On the basis of the results of experiments and clinical applications， this paper analyzes the specific connotation of congenital deficiency proposes that congenital deficiency should be subdivided into the four aspects of essence， Qi， Yin， and Yang. Congenital essence deficiency as the deficiency of genuine Yin can lead to deficiency of kidney essence in the offspring and dysfunction of kidney storing essence. Pharmacological studies have discovered that Cuscutae Semen， Lycii Fructus， and Achyranthis Bidentatae Radix in Zuoguiwan contain active components such as quercetin and kaempferol， which act on the targets such as recombinant prostaglandin endoperoxide synthase 2 （PTGS2）， interleukin-6 （IL-6）， mitogen-activated protein kinases （MAPK14）， tumor necrosis factor （TNF）， TP53， Vascular permeability factor A （VEGFA）， and albumin （ALB） to play a role in reproductive system development and hormone responses. Zuoguiwan has unique advantages over Liuwei Dihuangwan in nourishing congenital genuine Yin in the kidney and can achieve better therapeutic effects on the syndromes and diseases caused by congenital essence deficiency. This review is expected to enrich the knowledge about the efficacy and clinical application of Zuoguiwan， provide new perspectives and methods for the prevention and treatment of congenital deficiency and congenital essence deficiency， and give insights into the application of Zuoguiwan in modern healthcare， especially in the nurturing of offspring.

The clinical medicine postdoctoral training program embodies a pioneering initiative in China's pursuit of excellence in medical education in the contemporary era. The establishment of the Department of Rare Diseases at Peking Union Medical College Hospital in 2023 signifies a momentous milestone, making it the nation's inaugural clinical department exclusively dedicated to diagnosis and treatment of patients with rare diseases. Aligned with the Consensus on Core Competency Framework for Residency Education Among China Consortium of Elite Teaching Hospitals for Residency Education, the clinical postdoctoral program in the Department of Rare Diseases underscores a holistic advancement of fundamental competencies within the framework of "three basics and three stricts". This approach is further complemented by the refinement of teaching evaluation and feedback systems. The program aspires to serve as an educational paradigm for cultivating elite talents in the field of rare disease medicine in China and nurture multifaceted talents equipped with exceptional clinical insight and comprehensive capabilities, thereby alleviating the acute shortage of adept professionals in the domain of rare diseases and propelling the field's progression in China.