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

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.

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.

With the rising incidence of colon cancer, several studies have indicated that aquaporin 1 (AQP1) expression is associated with the development of colon cancer. This study aims to elucidate the potential molecular mechanisms between them. Methods: We screened data from The Cancer Genome Atlas (TCGA) database and retrospectively examined AQP1 protein expression in 127 colon cancer patients to analyze the relationship between AQP1 expression and pathological stages, prognosis. We created stable colon cancer cell lines with differential AQP1 expression, the effect of AQP1 expression on the proliferation and migration of colon cancer cells was assessed by in vitro and in vivo studies, and explored potential molecular mechanisms through Western blotting. Results: High AQP1 expression was associated with poorer survival (overall survival [OS], p = .028) in colon cancer patients from the TCGA database. Similarly, retrospective clinical data indicated that high AQP1 expression was associated with reduced disease-free survival and OS (p = .036 and p = .017, respectively). The low-expressing AQP1 colon cancer cells exhibited a decrease in proliferation and migration ability of colon cancer cells compared to the overexpressing AQP1 group (p < .05) in vitro and in vivo. Immunohistochemistry and western blotting experiments validated heightened expression of N-cadherin, vimentin, and claudin- 1 in the tumor tissues of the overexpressing AQP1 group. Conversely, reduced AQP1 expression resulted in decreased expression of claudin- 1. Conclusions: AQP1 correlates with unfavorable prognosis in colon cancer and potentially enhances the proliferation and migration of colon cancer by up-regulating claudin-1 expression.

Premature ejaculation refers to a sexual dysfunction in which men experience a short intravaginal ejaculation latency and a lack of control over ejaculation during sexual activity. The onset of this condition is often accompanied by anxiety and depression, which can seriously affect the quality of the patient′s sexual life and the relationship between partners. Based on the "integration of body and spirit" theory in traditional Chinese medicine, our team believes that this condition is a comorbidity of physical and spiritual factors. We propose that the core pathogenesis of this disease lies in the "loss of form and essence, impairment of spirit, and depression of the mind, "while the primary treatment principle involves "nourishing form and regulating spirit." As a result, a new diagnosis and treatment approach of "four-dimensional integration" is summarized in this study. The disease is treated through the four dimensions of shape, body, spirit, and emotion. Traditional Chinese medicine is used to adjust the shape in cases where the physical form is damaged. For individuals with depression of heart and liver qi, the treatment focuses on soothing the heart and smoothing liver qi, and the modified Wangyou Powder and Xuanzhi Decoction is used. In cases where the heart and kidney function are compromised, the treatment involves nourishing both the heart and kidney while restoring interaction between the heart and the kidney, and modified Jihuo Yansi Elixir is used. To reduce the sensitivity of the glans penis, the patient′s body is washed with a traditional Chinese medicine formula, and a delicate fumigation formula is decocted for external washing. For those who are not in tune with their god, psychological counseling can be used to regulate their spirit and advocate "self-partner" and psychotherapy. If there are issues with intimacy, partners should focus on cooperating during foreplay, sexual intercourse, and post-coital interactions. Overall, the treatment aims to harmonize the body and spirit, addressing both physical and psychological factors through a comprehensive, multi-dimensional approach. This method provides new perspectives and ideas for the clinical diagnosis and treatment of this condition.

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.

Objective:To summarize the clinical phenotype and analyze genetic variant characteristics of hereditary pancreatitis (HP) in children.Methods:Eight families of children diagnosed with HP and admitted to the Children's Hospital Affiliated to Zhengzhou University from August 2022 to May 2024 were selected as the research subjects. A retrospective analysis was conducted on the clinical characteristics, pathogenic gene carrying status, and follow-up of the children. Whole exome sequencing was applied to conduct genetic testing on the 8 children and their relatives. Suspected variations were verified by Sanger sequencing and subjected to bioinformatics analysis.Results:This population was made up of 2 boys and 6 girls with the median onset age of 1.2(0.5-3.4) years. The median age at diagnosis was 2.9(1.5-5.7) years. The clinical symptoms and signs were abdominal pain (8/8), abnormal crying (6/8), vomiting (4/8), and bloating (2/8). None of them had jaundice, fever, hydrothorax or ascites. Pancreatitis generally occurred 4-6 times, and occurred 1-3 times before HP was diagnosed. 6 patients had family history of pancreatitis. Blood amylase and lipase in all 8 patients spiked by over 3 folds. Abdominal imaging showed enlarged pancreas with or without peripheral exudation (8/8), and pancreatic pseudocyst (1/8). The whole exome sequencing detected 2 splicing variant of SPINK1 gene c.194+2T>C(p.IVS3+2T>C), and 6 missense variations of PRSS1 gene c.86A>T(p.N29I) ( n=4) and c.365G>A(p.R122H) ( n=2). Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), all variants were assessed as pathogenic, including 6 inherited from father and 2 from mother. The predicted splicing model indicated that the splice site mutation c.194+2T>C can cause exon skipping, resulting in an unstable truncated protein. Analysis with PyMOL software suggested that the variants c.86A>T (p.N29I) and c.365G>A (p.R122H) may affect the structure of the encoded protein. Conventional conservative measures, including fasting, trypsin secretion inhibition by octreotide, were offered. One child underwent endoscopic retrograde cholangiopancreatogram plus pancreatic duct lithotomy and pancreatic duct stenting. Conclusions:For recurrent childhood pancreatitis, especially with family history, genetic testing is helpful for early diagnosis of HP.

Objective To analyze the application value of 3D Slicer software in endoscopic transsphenoidal surgery for pituitary adenoma resection.Methods A retrospective analysis was made on the clinical data of 36 patients with pituitary adenomas treated with 3D Slicer-assisted endoscopic transsphenoidal surgery(3D Slicer group)in the Department of Neurosurgery,The Second Affiliated Hospital of Xi'an Jiaotong University,from January 2024 to December 2024.Preoperatively,multimodal images were fused and reconstructed using 3D Slicer software to systematically evaluate bony anatomical structures such as sphenoid sinus ostia,intrasphenoidal septa,and sellar floor structures,design the size of pedicled nasoseptal flaps,and clarify the positional relationships between pituitary adenomas and surrounding vital structures including the internal carotid artery,pituitary gland,and optic chiasm,so as to provide real-time guidance for intraoperative procedures.Meanwhile,45 patients with pituitary adenomas treated with neuronavigation-assisted endoscopic transsphenoidal surgery from January 2023 to December 2023 were included as the control group(neuronavigation group).The surgical outcomes and postoperative complications were compared between the two groups.Results Compared with the neuronavigation group,the 3D Slicer group demonstrated higher identification rates of the optic nerve groove and carotid artery impression(94.4％vs.77.8％),shorter operative time[(2.9±0.6)h vs.(3.5±0.9)h],less intraoperative bleeding[(159.7±70.5)mL vs.(237.8±96.0)mL],and a lower incidence of postoperative olfactory dysfunction(8.3％vs.26.7％),with statistically significant differences(P＜0.05).However,there were no statistically significant differences between the two groups in the identification rate of the sphenoid sinus ostium(100.0％vs.97.8％),gross total resection rate(75.0％vs.64.4％),and the incidence of other postoperative complications,including cerebrospinal fluid leakage(0.0％vs.6.7％),intracranial infection(2.8％vs.11.1％),transient diabetes insipidus(30.6％vs.22.2％),and hypopituitarism(38.9％vs.37.8％,P＞0.05).Conclusion 3D Slicer software helps improve the mastery of anatomical basics in endoscopic transsphenoidal approach among junior and primary physicians,enhancing the clinical efficacy and safety of pituitary adenoma resection,and thus is worthy of clinical promotion.

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