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

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

Objective:To investigate variation and correlation of type 2 intrinsic lymphocyte(ILC2)and related factors in acute and chronic brucellosis,to identify immune role of ILC2 in chronic brucellosis.Methods:Forty-three patients with acute brucel-losis and 45 patients with chronic brucellosis were compared with 49 healthy controls.ILC2 level in each group was detected by flow cytometry.mRNA level of GATA3 in PBMC was detected by fluorescence quantitative PCR.Serum IL-33,ST2,IL-4 and IL-13 levels were detected by ELISA.ALT and AST levels were measured by fully automatic biochemical analyzer.Results:ILC2 level,GATA3 mRNA in PBMC,serum IL-33,IL-4 and IL-13 levels in chronic brucellosis group were significantly higher than healthy control group and acute brucellosis group(P<0.01).Correlation analysis showed that ILC2 level was positively correlated with GATA3 mRNA,IL-33,IL-4 and IL-13 levels,while negatively correlated with ST2 level.ROC curve suggested that ILC2,GATA3,IL-33 and ST2 had good predictive ability for severity of brucellosis patients(AUC>0.7).Conclusion:Increase of ILC2 and its related factors are closely related to chronic brucella infection,which may play an important immune role in pathogenesis of brucella infection.

Thoracolumbar spine fracture often leads to severe pain, functional impairments, and neurological deficits, for which open reduction and internal fixation can effectively restore the spinal structural stability. Open decompression and reduction with internal fixation can help relieve spinal cord compression and improve spinal function in cases of concomitant cord injury. Although spinal stability can be restored through surgery, patients often face chronic pain and functional impairments postoperatively. A postoperative rehabilitation program is critical in optimizing therapeutic outcomes, reducing complications, and minimizing the risk of secondary injuries. However, current rehabilitation methods, such as physical therapy, functional training, and pain management, are confronted with problems in clinical practice, including significant variation in efficacy, poor patient adherence, and prolonged rehabilitation period. There is an urgent need for a unified rehabilitation strategy to address these problems. To this end, the Spinal Trauma Group of the Orthopedic Physicians Branch of the Chinese Medical Association and the Spine Health Professional Committee of the Chinese Human Health Technology Promotion Association organized experts from relevant fields to formulate Evidence-based guidelines for rehabilitation treatment after internal fixation of thoracolumbar spine fracture in adults ( version 2025) by integrating evidences from clinical researches and advanced rehabilitation concepts at home and abroad. A total number of 14 recommendations concerning the rehabilitation treatment with multimodal analgesia, psychological intervention, deep vein thrombosis prevention, core muscle and extremity exercise, appropriate use of braces, early weight-bearing, device-aided rehabilitation exercise, neuroregulatory therapy, rehabilitation team were put forward, aiming to standardize the post-operative rehabilitation process following internal fixation, promote the functional recovery, and enhance patients′ quality of life.

Acute symptomatic osteoporotic thoracolumbar compression fracture (ASOTLF) can lead to chronic low back pain, kyphosis deformity, pulmonary dysfunction, loss of mobility, and even life-threatening complications. Vertebral augmentation is currently the mainstream treatment method for this condition. In 2019, the Editorial Board of Chinese Journal of Trauma and the Spinal Trauma Group of Orthopedic Surgeons Branch of Chinese Medical Doctor Association collaboratively led the development of Clinical guideline for vertebral augmentation for acute symptomatic osteoporotic thoracolumbar compression fractures. Six years later, with advances in clinical diagnosis and treatment techniques as well as accumulating evidence in related fields, the 2019 guideline requires updating. To this end, the Spinal Trauma Group of Orthopedic Surgeons Branch of Chinese Medical Doctor Association, the Spinal Health Professional Committee of China Human Health Science and Technology Promotion Association, and the Minimally Invasive Orthopedics Professional Committee of Shaanxi Medical Doctor Association have organized experts in the field to develop the Clinical guideline for vertebral augmentation of acute symptomatic osteoporotic thoracolumbar compression fractures ( version 2025) , based on the latest evidence-based medical researches. This guideline incorporates 3 recommendations retained from the 2019 version with updated strength of evidence, along with 12 new recommendations. It provides recommendations from six aspects of diagnosis, pain management, treatment option selection, prevention of postoperative complications, anti-osteoporosis therapy, and postoperative rehabilitation, aiming to provide a reference for standard treatment of vertebral augmentation for ASOTLF in hospitals at all levels.

Objective To investigate the prognostic value of thrombin-antithrombin III complex(TAT),plasmin-α2-plasmin inhibitor complex(PIC),thrombomodulin(TM)and tissue plasminogen activator-inhibitor complex(t-PAIC)in patients with myelodysplastic syndrome(MDS).Methods Selected 88 primary MDS patients diagnosed at the 521 Hospital of Ordnance Industry from January 2018 to January 2021.Plasma levels of TAT,PIC,TM,t-PAIC,fibrin degradation products(FDP)and D-dimer(D-D)were measured.A multivariate approach was used to analyze the association between overall survival(OS)and the levels of each coagulation marker.Coagulation markers significantly associated with OS were used to construct a coagulation prognostic scoring system.Based on the median coagulation marker score,MDS patients were divided into high and low score groups.Kaplan-Meier analysis was used to plot survival curves.Results TAT(OR=1.667),PIC(OR=0.734),TM(OR=1.294)and t-PAIC(OR=1.523)were independent factors influencing OS in MDS patients(Wald χ2=0.671～10.751,all P<0.05).The β-values were integrated as statistical weights to construct a coagulation marker score,calculated as follows:[TAT]×0.502-[PIC]×1.013+[TM]×0.181+[t-PAIC]×0.381.The OS(median 14.6 months)and leukemia free survival(LFS)(median 10.3 months)of patients in the high coagulation marker score group were significantly lower than those in the low score group(33.6 months,35.2 months)(Log rank=20.57,26.84,all P<0.001).Subgroup analysis indicated that in both the low-risk IPSS-R subgroup(very low,low,and intermediate risk)and the high-risk IPSS-R subgroup(high and very high risk),the OS(Log rank=9.12,4.30)and LFS(Log rank=4.54,8.51)of the high coagulation marker score group were lower than those of the low score group(all P<0.05).Bivariate analysis showed a moderate correlation between the coagulation marker score and Revise International Prognostic Scoring System(IPSS-R)(PCC=0.536,P<0.001).Multivariate analysis indicated that IPSS-R and high coagulation marker scores were independent risk factors for OS and LFS in MDS patients(P<0.05).Conclusion The coagulation marker score,based on TAT,PIC,TM and t-PAIC,can serve as an independent prognostic factor for OS and LFS in MDS patients.

Objective To investigate the prognostic value of thrombin-antithrombin III complex(TAT),plasmin-α2-plasmin inhibitor complex(PIC),thrombomodulin(TM)and tissue plasminogen activator-inhibitor complex(t-PAIC)in patients with myelodysplastic syndrome(MDS).Methods Selected 88 primary MDS patients diagnosed at the 521 Hospital of Ordnance Industry from January 2018 to January 2021.Plasma levels of TAT,PIC,TM,t-PAIC,fibrin degradation products(FDP)and D-dimer(D-D)were measured.A multivariate approach was used to analyze the association between overall survival(OS)and the levels of each coagulation marker.Coagulation markers significantly associated with OS were used to construct a coagulation prognostic scoring system.Based on the median coagulation marker score,MDS patients were divided into high and low score groups.Kaplan-Meier analysis was used to plot survival curves.Results TAT(OR=1.667),PIC(OR=0.734),TM(OR=1.294)and t-PAIC(OR=1.523)were independent factors influencing OS in MDS patients(Wald χ2=0.671～10.751,all P<0.05).The β-values were integrated as statistical weights to construct a coagulation marker score,calculated as follows:[TAT]×0.502-[PIC]×1.013+[TM]×0.181+[t-PAIC]×0.381.The OS(median 14.6 months)and leukemia free survival(LFS)(median 10.3 months)of patients in the high coagulation marker score group were significantly lower than those in the low score group(33.6 months,35.2 months)(Log rank=20.57,26.84,all P<0.001).Subgroup analysis indicated that in both the low-risk IPSS-R subgroup(very low,low,and intermediate risk)and the high-risk IPSS-R subgroup(high and very high risk),the OS(Log rank=9.12,4.30)and LFS(Log rank=4.54,8.51)of the high coagulation marker score group were lower than those of the low score group(all P<0.05).Bivariate analysis showed a moderate correlation between the coagulation marker score and Revise International Prognostic Scoring System(IPSS-R)(PCC=0.536,P<0.001).Multivariate analysis indicated that IPSS-R and high coagulation marker scores were independent risk factors for OS and LFS in MDS patients(P<0.05).Conclusion The coagulation marker score,based on TAT,PIC,TM and t-PAIC,can serve as an independent prognostic factor for OS and LFS in MDS patients.

Objective:To investigate variation and correlation of type 2 intrinsic lymphocyte(ILC2)and related factors in acute and chronic brucellosis,to identify immune role of ILC2 in chronic brucellosis.Methods:Forty-three patients with acute brucel-losis and 45 patients with chronic brucellosis were compared with 49 healthy controls.ILC2 level in each group was detected by flow cytometry.mRNA level of GATA3 in PBMC was detected by fluorescence quantitative PCR.Serum IL-33,ST2,IL-4 and IL-13 levels were detected by ELISA.ALT and AST levels were measured by fully automatic biochemical analyzer.Results:ILC2 level,GATA3 mRNA in PBMC,serum IL-33,IL-4 and IL-13 levels in chronic brucellosis group were significantly higher than healthy control group and acute brucellosis group(P<0.01).Correlation analysis showed that ILC2 level was positively correlated with GATA3 mRNA,IL-33,IL-4 and IL-13 levels,while negatively correlated with ST2 level.ROC curve suggested that ILC2,GATA3,IL-33 and ST2 had good predictive ability for severity of brucellosis patients(AUC>0.7).Conclusion:Increase of ILC2 and its related factors are closely related to chronic brucella infection,which may play an important immune role in pathogenesis of brucella infection.

Objective:To explore the effects of hydroxychloroquine(HCQ)on immune mediators dysregulation in severe infection after chemotherapy in acute myeloid leukemia(AML)and its molecular mechanism.Methods:Bone marrow or peripheral blood samples of 36 AML patients with severe infection(AML-SI)and 29 AML patients without infection(AML-NI)after chemotherapy were collected from the First Affiliated Hospital of Gannan Medical University from August 2022 to June 2023.In addition,the peripheral blood of 21 healthy subjects from the same period in our hospital was selected as the control group.The mRNA expressions of CXCL12,CXCR4 and CXCR7 were detected by RT-qPCR technology,and the levels of IL-6,IL-8 and TNF-α were detected by ELISA.Leukemia-derived THP-1 cells were selected and constructed as AML disease model.At the same time,bone marrow mesenchymal stem cells(BM-MSCs)from AML-SI patients were co-cultured with THP-1 cells and divided into Mono group and Co-culture group.THP-1 cells were treated with different concentration gradients of HCQ.The cell proliferation activity was subsequently detected by CCK-8 method and apoptosis was detected by Annexin V/PI double staining flow cytometry.ELISA was used to detect the changes of IL-6,IL-8 and TNF-α levels in the supernatant of the cell co-culture system,RT-qPCR was used to detect the mRNA expression changes of the core members of the CXCL12-CXCR4/7 regulatory axis,and Western blot was used to detect the expressions of apoptosis regulatory molecules and related signaling pathway proteins.Results:CXCL12,CXCR4,CXCR7,as well as IL-6,IL-8,and TNF-α were all abnormally increased in AML patients,and the increases were more significant in AML-SI patients(P＜0.01).Furthermore,there were statistically significant differences between AML-NI patients and AML-SI patients(all P＜0.05).HCQ could inhibit the proliferation and induce the apoptosis of THP-1 cells,but the low concentration of HCQ had no significant effect on the killing of THP-1 cells.When THP-1 cells were co-cultured with BM-MSCs of AML patients,the levels of IL-6,IL-8 and TNF-α in the supernatance of Co-culture group were significantly higher than those of Mono group(all P＜0.01).After HCQ intervention,the levels of IL-6,IL-8 and TNF-α in cell culture supernatant of Mono group were significantly decreased compared with those before intervention(all P＜0.01).Similarly,those of Co-culture group were also significantly decreased(all P＜0.001).However,the expression of the core members of the CXCL12-CXCR4/7 regulatory axis was weakly affected by HCQ.HCQ could up-regulate the expression of pro-apoptotic protein Bax,down-regulate the expression of anti-apoptotic protein Bcl-2,as well as simultaneously promote the hydrolytic activation of Caspase-3 when inhibiting the activation level of TLR4/NF-κ B pathway,then induce the programmed death of THP-1 cells after intervention.Conclusion:The core members of CXCL12-CXCR4/7 axis and related cytokines may be important mediators of severe infectious immune disorders in AML patients.HCQ can inhibit cytokine levels to reverse immune mediators dysregulation and suppress malignant biological characteristics of leukemia cells.The mechanisms may be related to regulating the expression of Bcl-2 family proteins,hydrolytically activating Caspase-3 and inhibiting the activation of TLR4/NF-κ B signaling pathway.

Thoracolumbar spine fracture often leads to severe pain, functional impairments, and neurological deficits, for which open reduction and internal fixation can effectively restore the spinal structural stability. Open decompression and reduction with internal fixation can help relieve spinal cord compression and improve spinal function in cases of concomitant cord injury. Although spinal stability can be restored through surgery, patients often face chronic pain and functional impairments postoperatively. A postoperative rehabilitation program is critical in optimizing therapeutic outcomes, reducing complications, and minimizing the risk of secondary injuries. However, current rehabilitation methods, such as physical therapy, functional training, and pain management, are confronted with problems in clinical practice, including significant variation in efficacy, poor patient adherence, and prolonged rehabilitation period. There is an urgent need for a unified rehabilitation strategy to address these problems. To this end, the Spinal Trauma Group of the Orthopedic Physicians Branch of the Chinese Medical Association and the Spine Health Professional Committee of the Chinese Human Health Technology Promotion Association organized experts from relevant fields to formulate Evidence-based guidelines for rehabilitation treatment after internal fixation of thoracolumbar spine fracture in adults ( version 2025) by integrating evidences from clinical researches and advanced rehabilitation concepts at home and abroad. A total number of 14 recommendations concerning the rehabilitation treatment with multimodal analgesia, psychological intervention, deep vein thrombosis prevention, core muscle and extremity exercise, appropriate use of braces, early weight-bearing, device-aided rehabilitation exercise, neuroregulatory therapy, rehabilitation team were put forward, aiming to standardize the post-operative rehabilitation process following internal fixation, promote the functional recovery, and enhance patients′ quality of life.