OBJECTIVE: To explore the clinical and genetic features of a child with Pontocerebellar hypoplasia type 2B (PCH2B) due to compound heterozygous variants of the TSEN2 gene. METHODS: A PCH2B patient presented at Department of Pediatric Neurology, Xiangya Hospital of Central South University in June 2023 was selected as the study subject. Clinical data of the patient were retrospectively analyzed. The patient and her parents were subjected to whole exome sequencing and bioinformatic analysis. Pathogenicity of the candidate variants were classified based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). A literature review was also conducted by searching the China National Knowledge Infrastructure (CNKI), Wanfang Data, and PubMed databases from their establishment to May 2025 using keywords "TSEN2 gene" "PCH2B" and "Pontocerebellar Hypoplasia 2B" to summarize the clinical and genotypic features of patients with PCH2B due to variants of the TSEN2 gene. This study was approved by the Medical Ethics Committee of the Hospital (No.: #202310892). RESULTS: The patient, a 6-year-5-month-old girl, had exhibited severe global developmental delay, developmental regression, autism spectrum disorder, myoclonus of eyelids, feeding difficulty, irritability, progressive microcephaly, esotropia, and hypotonia. MRI showed reduced volume of bilateral cerebellar hemispheres and vermis. Genetic testing revealed that she has harbored compound heterozygous variants of the TSEN2 gene (NM_025265.4), namely c.1054A>T (p.Lys352*) and c.899G>T (p.Ser300Ile), which were inherited from her father and mother, respectively. Both variants were classified as likely pathogenic based on the ACMG guidelines and were previously unreported. Literature review has identified six PCH2B patients with missense, nonsense, frameshift, and splice site variants of the TSEN2 gene. Their main clinical manifestations included global developmental delay, progressive microcephaly, feeding difficulties, irritability, and vermis hypoplasia. Cranial MRI and genetic testing are crucial for definite diagnosis. CONCLUSION The c.1054A>T (p.Lys352*) and c.899G>T (p.Ser300Ile) compound heterozygous variants of the TSEN2 gene probably underlay the pathogenesis in this patient. Above findings has expanded the genotypic and phenotypic spectra of TSEN2-related PCH2B, and offered guidance for genetic counseling for this family.
Child ; Female ; Humans ; Cerebellar Diseases/genetics* ; Exome Sequencing ; Heterozygote ; Mutation

Parkinson's disease （PD） is a common neurodegenerative disorder characterized by motor impairments， with its pathological mechanisms involving multiple processes such as the degeneration of dopaminergic neurons and the abnormal aggregation of α-synuclein. Current Western medical treatments face challenges including diminished long-term efficacy and motor complications. In recent years， Traditional Chinese Medicine （TCM） has demonstrated advantages in the prevention and treatment of PD through its systematic regulatory capabilities， featuring multi-component， multi-target， and multi-pathway approaches.This article systematically reviews the roles of seven key signaling pathways-NF-κB， AMPK/mTOR， PI3K/Akt， MAPKs， Nrf2/ARE， Wnt/β-catenin， and BDNF/TrkB-in the pathological process of PD and the regulatory mechanisms of TCM. Research indicates that active ingredients of Chinese herbs and compound formulations can synergistically modulate these pathways， exerting comprehensive effects in inhibiting neuroinflammation， alleviating oxidative stress， promoting autophagy to clear abnormal proteins， and enhancing neurotrophic support. These signaling pathways form a complex regulatory network through crosstalk among key nodal molecules， constituting an intricate regulatory system in PD pathology. The multi-target intervention characteristics of TCM align well with this network-based regulatory requirement， achieving integrated anti-inflammatory， antioxidant， autophagy-regulating， and neurorestorative effects through synergistic multi-pathway modulation. This article systematically outlines the mechanisms of TCM in the coordinated regulation of multiple pathways， providing a theoretical basis for elucidating the pathological process of PD and the intervention mechanisms of TCM， while also offering new perspectives and directions for modern research on TCM in the prevention and treatment of PD.

Rheumatoid arthritis （RA） is a common chronic systemic autoimmune disease with synovitis as the main manifestation， which often causes joint swelling and pain or even deformity. It is considered to be an incurable lifelong disease. Although the current Western medicine treatment can alleviate the progression of the disease， it has the clinical limitations of liver injury， cardiovascular complications， and other adverse reactions， along with easy recurrence. Traditional Chinese medicine （TCM） has a long history and has the advantages of individualized treatment and fewer adverse reactions. It can effectively relieve the symptoms of joint swelling and pain in RA patients and slow down the progression of bone destruction， which has attracted wide concern in the medical community. Janus kinase （JAK）/signal transducer and activator of transcription （STAT） signaling pathway is an important intracellular pathway involved in cell proliferation， differentiation， apoptosis， immune regulation， and other biological behaviors， and plays an important role in the pathophysiological process of RA. In recent years， many studies have confirmed that TCM monomers and compounds can inhibit inflammation and angiogenesis by regulating the JAK/STAT signaling pathway， induce apoptosis and inhibit proliferation of fibroblast-like synoviocytes （FLS）， regulate immune response， and thus exert an effect in the treatment of RA. However， there is still a lack of comprehensive and systematic induction and overview. Therefore， by searching the relevant literature in China National Knowledge Infrastructure （CNKI） and PubMed databases from 2009 to 2024， this study described the mechanism of the JAK/STAT signaling pathway in the occurrence and development of RA and summarized the research progress of TCM monomers and compounds in regulating the JAK/STAT signaling pathway in RA intervention. The study aims to provide new ideas and strategies for the clinical treatment of RA with TCM and the research and development of new drugs.

Stratified diagnosis and treatment is a crucial approach in precision medicine， aiming to optimize medical care by grouping patients based on clinical manifestations， biomarkers， and pathological characteristics. Based on clinical stages， symptoms， age， gene expression， and pathology， research on Sjögren's syndrome （SS） has proposed various stratification methods， incorporating both traditional Chinese medicine （TCM） and Western medicine perspectives. These methods provide essential support for early diagnosis， risk assessment， and personalized treatment. Key strategies include moving SS intervention time forward， to leverage TCM's preventive principles， integrating TCM and Western tools to enhance precision， innovating clinical trial designs， developing multifactorial risk prediction models and digital imaging technologies， and constructing combined prognostic models for personalized follow-up and big data-driven treatment. These insights offer a comprehensive framework for advancing SS precision medicine.

OBJECTIVE To evaluate the efficacy and safety of rituximab （RTX） in the treatment of primary Sjögren syndrome （pSS）. METHODS Randomized controlled trials （RCTs） on the effects of RTX （trial group） versus placebo （control group） in the treatment of pSS were searched from the Cochran Library， PubMed， Embase， Medline， Web of Science， VIP， CNKI， Wanfang， and other databases during the inception to February 2024. After literature screening and quality evaluation， meta-analysis was performed by using RevMan 5.3 software. RESULTS Seven RCTs were finally included， involving a total of 518 patients. Results of meta-analysis showed that European League Against Rheumatism Sjögren syndrome disease activity index （ESSDAI） score [MD＝－1.17， 95%CI（－1.52， －0.82）， P＜0.000 01] and oral dryness visual analogue scale （VAS） score [MD＝－3.97， 95%CI （－5.08， －2.86）， P＜0.000 01] in the trial group were significantly lower than the control group； unstimulated salivary flow rate [SMD＝0.64， 95%CI（0.41， 0.87）， P＜0.000 01] and Schirmer score [MD＝0.19， 95%CI（0.18， 0.20）， P＜0.000 01] were significantly higher than the control group. There was no statistical significance in response rate [RD＝0.10， 95%CI（－0.04， 0.23）， P＝0.16]， fatigue VAS score [MD＝－12.50， 95%CI（－35.14， 10.15）， P＝0.28]， European League Against Rheumatism Sjögren syndrome patient reported index （ESSPRI） score [MD＝0.33， 95%CI（－0.53， 1.18）， P＝0.46]， Short-form 36 health survey physical component summary （SF36-PCS） score [MD＝0.90， 95%CI（－2.97， 4.78）， P＝0.65]， SF-36 mental component summary （SF36-MCS） score [MD＝0.11， 95%CI（－0.41， 0.63）， P＝0.68]， total salivary gland ultrasound score [SMD＝－1.91， 95%CI（－4.01， 0.19）， P＝0.07] or the incidence of adverse drug reactions [OR＝1.15，95%CI（0.62，2.13），P＝0.66] between 2 groups. CONCLUSIONS RTX has advantages in the improvement of ESSDAI score， unstimulated salivary flow rate， Schirmer score and oral dryness VAS score in pSS patients， and has a good safety profile. However， it did not exhibit significant improvement in fatigue VAS score， ESSPRI score， SF36-PCS score， SF36-MCS score or response rates.

Objective To investigate the clinical characteristics of hepatitis-associated aplastic anemia(HAAA)in pediatric patients.Methods A retrospective study was conducted on 212 children with aplastic anemia(AA)who were hospitalized at Henan Children's Hospital from September 2014 to February 2023.The patients were categorized into two groups based on etiology:the HAAA group and the non-HAAA group.The study group consisted of 23 patients in the HAAA group,while a control group of 115 children without HAAA was matched in a 1∶5 ratio based on age,sex,and severity of aplastic anemia.The clinical characteristics,treatment regimens,and outcomes of the 23 patients with HAAA were analyzed and compared with those of the control group comprising 115 patients.Results Among the 23 children with HAAA,there were 11 males and 12 females,with a median age of 6 years and 3 months(ranging from 1 year and 4 months to 12 years old).The onset of aplastic anemia in all HAAA children occurred after the initial presentation of acute hepatitis.Following gradual improvement in liver function,peripheral blood images showed a progressive decline by two or three lines,including platelets.Among these cases,very severe aplastic anemia was observed in 14 patients(60.9%),severe aplastic anemia in 7 patients(30.4%),and non-severe aplastic anemia in 2 patients(8.7%).The median interval between hepatitis onset and diagnosis of aplastic anemia was found to be 56 days(range:10～157 days).All 23 pediatric patients with HAAA presented with acute icteric hepatitis,accounting for 100%of the cohort.One patient(4.3%)was genetically diagnosed with X-linked lymphoproliferative disease type 2,while liver biopsy revealed drug-induced hepatitis/chemical liver injury in five patients(21.7%).Compared to the control group,HAAA patients exhibited significantly lower levels of CD4+cells[(1.2±0.3)vs.(1.5±0.1)]and CD4+/CD8+ratios[(-0.2±0.4)vs.(0.1±0.2)](P<0.05).Three patients received immunosuppressive therapy(IST),18 underwent hematopoietic stem cell transplantation(HSCT),and two non-severe cases were treated with methylprednisolone sodium succinate and compound Zapoan pill;all patients survived.Conclusions Children with HAAA present a critical condition and exhibit a poor prognosis,predominantly manifesting as severe or extremely severe aplastic anemia during the recovery phase of hepatitis.Reduction in CD4+cell count and inversion of CD4+/CD8+ratio may serve as early warning indicators for HAAA.Effective improvement in prognosis can be achieved through immunosuppressive therapy and hematopoietic stem cell transplantation.

Alzheimer disease(AD)is a progressive neurodegenerative disorder characterized by cognitive dysfunction and declining learning and memory abilities,significantly impacting daily lives and behavioral capacities of the patients.The mitogen-activated protein kinase(MAPK)signaling pathway,primarily composed of extracellular signal-regulated kinase,p38 MAPK,and c-Jun N-terminal kinase.Mounting evidence suggests that the MAPK signaling path-way is intimately linked to the pathogenesis of AD,providing crucial insights into the disease's progression.In recent years,traditional Chinese medicine(TCM)has demonstrated promising potential in treating AD,with its advantages of personalized therapy and multi-target regulation garnering increasing research attention.This study aims to review the ex-perimental research landscape of TCM interventions targeting the MAPK signaling pathway for the prevention and treat-ment of AD over the past five years.The findings reveal that effective compounds and herbal formulas in TCM,such as isorhamnetin,nobiletin,parthenolide,Glehnia littoralis,Ishige okamurae,shikonin,artemisinin,kaempferol,myrice-tin,and Tripterygium glycosides,can alleviate AD symptoms by modulating the MAPK signaling pathway.These interven-tions mitigate Aβ-induced neuronal damage,reduce Tau protein hyperphosphorylation,and suppress neuroinflammatory responses.The objective of this review is to provide a scientific and theoretical reference for the clinical prevention and treatment of AD and to inform the development of novel therapeutic agents.

Hypertension is one of the important causes of premature death worldwide,and the prevention and treatment of hypertension is of great significance in reducing the incidence and mortality rate of cardiovascular disease.Antihypertensive drugs and food homologous traditional Chinese medicine have the advantages of easy access,high safety,and minimal side effects.Based on the list of 101 traditional Chinese medicinal materials that are both medicinal and food substances released by the National Health Commission,a search was conducted on 101 Chinese medicinal materials related to hypertension using the China National Knowledge Infrastructure(CNKI).The screening criteria are single drug,extract,or monomer therapy for hypertension,and the number of literature is≥2,resulting in 14 medicinal and food homologous traditional Chinese medicines with antihypertensive effects.Search for 14 Chinese medicine names and hypertension keywords on PubMed,Web of Science,and Google Scholar to collect reports on the treatment of hypertension with medicinal and food homologous traditional Chinese medicine.Based on the search results of China National Knowledge Infrastructure,summarize their classification,drug properties,efficacy,antihypertensive effects,and mechanism of action,in order to provide inspiration for new prescriptions,drug development,and functional foods for treating hypertension.Most of the antihypertensive traditional Chinese medicines with the same origin as medicine and food belong to the categories of clearing heat and tonifying deficiency;Most drugs have a sweet and spicy taste,which belongs to the liver,spleen,and kidney meridians.The efficacy is mostly to clear the liver and brighten the eyes,tonify the liver and kidneys,promote qi circulation,dispel blood stasis,and disperse nodules.It mainly inhibits ACE activity;Reduce REN and AngⅡ levels;Upregulate SOD levels and reduce MDA expression;Improve the expression level of NO/NOS;Enhance antioxidant effects;Improve endothelial function;Relieve inflammatory reactions;Various methods such as reducing target organ damage can play a role in treating hypertension.

OBJECTIVE: To explore the clinical features and genetic characteristics of three patients with Infantile liver failure syndrome type 2 (ILFS2). METHODS: Three children who were diagnosed with ILFS2 at the Children's Hospital Affiliated to Zhengzhou University from February 2023 to February 2024 were selected as the study subjects. Clinical data of the children were collected. Peripheral blood samples of the children and their parents were collected and subjected to whole exome sequencing (WES). Candidate variants of the NBAS gene were verified by Sanger sequencing. This study was approved by the Ethics Committee of the Children's Hospital Affiliated to Zhengzhou University (Ethics No. 2024-k-069). RESULTS: The three children had presented with fever-triggered recurrent acute liver failure. All of them were found to harbor compound heterozygous variants of the NBAS gene, including c.3596G>A and c.1181A>T in child 1, c.2617C>T and c.2T>C in child 2, and c.3596G>A and c.2817_2818insT in child 3. Among these, the c.1181A>T and c.2817_2818insT variants were unreported previously. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), they were respectively classified as variants of uncertain significance (PM2_Supporting+PM3+PP3) and pathogenic (PVS1+PM2_Supporting+PM3). CONCLUSION Combined with the patient's clinical phenotype, the compound heterozygous variants of the NBAS gene probably underlay the pathogenesis of ILFS2 in the three children. For children with fever-related acute liver failure of unknown causes, the possibility of this disease should be suspected, and genetic testing may facilitate the diagnosis. Early diagnosis and timely intervention can significantly improve the prognosis. Discoveries of the c.1181A>T and c.2817_2818insT variants have enriched the mutational spectrum of the NBAS gene.
Humans ; Exome Sequencing ; Genetic Testing/methods* ; Liver Failure, Acute/etiology* ; Mutation ; Child ; Adult ; Neoplasm Proteins

OBJECTIVE: To explore the clinical and genetic characteristics of a boy with X-linked familial Behcet-like autoinflammatory syndrome-2 (AIFBL2). METHODS: A boy who was admitted to Children's Hospital Affiliated to Zhengzhou University in December 2023 due to recurrent oral ulcers for 2 years, intermittent abdominal pain and fever for more than 1 year was selected as the study subject. Clinical data of the patient was collected. Whole exome sequencing (WES) was carried out, and candidate variant was verified by Sanger sequencing and bioinformatic analysis. A literature search was conducted in OMIM, PubMed, Wanfang Data Knowledge Service Platform, China Biomedical Literature Service System, and the VIP database using the keywords "ELF4 gene" "deficiency in ELF4, X-linked" "ELF4 deficiency" and "DEX" to identify recently published studies. This study was approved by the Medical Ethics Committee of the Children's Hospital Affiliated to Zhengzhou University (Ethics No.: 2023-H-K44). RESULTS: The patient, a 12-year-old male, presented with recurrent mouth ulcers, fever and abdominal pain. Lymphocyte subsets showed a significant decrease in NK cells. Abdominal CT showed thickening of local intestinal wall in the lower right abdomen. Colonoscopy revealed a solitary deep longitudinal ulcer in the ileocecal region. Genetic testing revealed a hemizygote missense variant c.687C>G, with his mother showing the same mutation at this locus. According to the guidelines of the American College of Medical Genetics and Genomics (ACMG), the variant was considered likely pathogenic (PP1+PP2+PM2_Supporting+PP3+PP4). Literature review has found 19 AIFBL2 patients including 1 patient from this study. Mouth ulcer, fever, rash and abdominal pain were the primary clinical manifestations, for which genetic testing is the main diagnostic method. CONCLUSION The hemizygote c.687C>G missense variant of the ELF4 gene probably underlay the AIFBL2 in this child, which has provided a basis for his clinical diagnosis and genetic counseling.
Humans ; Male ; Behcet Syndrome/genetics* ; Child ; DNA-Binding Proteins/genetics* ; Exome Sequencing ; Hereditary Autoinflammatory Diseases/genetics* ; Mutation