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

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease with high global prevalence and long course, which affects more than 30% of the population and seriously endangers human health. Lipid metabolism plays an important role in the occurrence and development of MASLD. An increasing number of studies have shown that active ingredients in traditional Chinese medicine can regulate lipid metabolism to improve MASLD. Due to the obvious advantages of multi-target regulation and fewer side effects, the active ingredients have shown great potential and value for application. However, the pathological mechanism of MASLD is intricate and the active ingredients of traditional Chinese medicine can improve MASLD from multiple aspects, there is currently a lack of systematic discussion on lipid metabolism. Therefore, this review focuses on lipid metabolism and reviews the latest research progress of active ingredients from traditional Chinese medicine in ameliorating MASLD from the aspects of lipid uptake, lipid synthesis, lipid oxidation, lipid secretion, etc., in order to provide more theoretical references for active ingredients of traditional Chinese medicine in regulating lipid metabolism to improve MASLD.

Objective To evaluate the clinical efficacy of"Tongdu Tiaoshen"acupuncture combined with hand function rehabilitation training in patients with hand dysfunction following cerebral infarction.Methods A total of 104 patients were randomly assigned to either the observation group(receiving"Tongdu Tiaoshen"acupunc-ture combined with hand function rehabilitation training)or the control group(undergoing hand function rehabilita-tion training alone),with 52 patients in each group.Both groups underwent a 4-week treatment regimen.The following outcome measures were assessed pre-and post-treatment:Modified Ashworth Scale(MAS),Modified Lindmark Scale(MLS),Brunnstrom Motor Function Score(BMS)for upper limbs,Fugl-Meyer Assessment(FMA)of upper limb motor function,Modified Barthel Index(MBI),and grip strength(GS).Adverse events were docu-mented,and the clinical efficacy in each group was evaluated by calculating the effective rate.Results After excluding dropouts,a total of 94 cases were included in the final statistical analysis,with 48 cases assigned to the observation group and 46 to the control group.Both groups demonstrated significant improvements in MLS,MAS,BMS,FMA,MBI,and GS scores compared to pre-treatment levels,with all differences being statistically significant(P<0.05).Following treatment,intergroup comparisons also revealed statistically significant differences in all mea-sured indicators(P<0.05).The total effective rate was higher in the observation group(91.7%)than in the control group(82.6%),and the difference in efficacy grades between the two groups was statistically significant(P<0.05).Conclusions"Tongdu Tiaoshen"acupuncture,when combined with hand function training,demonstrates signifi-cantly greater efficacy than hand function rehabilitation training alone in improving post-cerebral infarction hand dysfunction.It enhances grip strength and fine motor coordination of the affected limb,alleviates hand muscle spasticity and joint stiffness,and promotes recovery of upper limb motor function,thereby improving patients'activities of daily living.This integrated therapeutic approach warrants further clinical validation and in-depth research for broader implementation.

Objective To analyze the reasons for the failure of subject screening in clinical trials of antineoplastic drugs and the impact of natriuretic criteria on the entry of subjects into clinical trials,to explore the strategies to improve the suc-cessful enrolment of screened subjects,and to provide reference bases for research institutes and sponsors in the formulation of na-triuretic criteria.Methods This study selected data from 40 drug clinical trials conducted at the Drug Clinical Trial Research Center of the Cancer Hospital of the Chinese Academy of Medical Sciences from January 1,2016,to June 30,2022.It statistically described the collected data on the frequency and percentage composition of screening failures among participants and the inclu-sion and exclusion criteria in the protocols.Results A total of 425 subjects were screened out of 40 clinical trial programmers covering 8 tumor types,with the majority being＜65 years of age(333,78.4％),of which the most important reasons included vol-untary withdrawal(71,16.7％),tumor metastasis(52,12.2％),failure to recover from treatment of pre-existing disease(38,8.9％),failure of bone marrow function(19,4.5％),and non-compliant liver function(15,3.5％).Among the nadir indicators,the age of the subjects(100％),ECOG score(97.5％),bone marrow function(ANC:95.0％,PLT:97.5％,HB:97.5％),liver function(T-BiL:95.0％,ALT:87.5％,AST:95.0％),renal function(CR:80.0％),and viral screening(HIV:80.0％,HBV:70.0％,HCV:62.5％)were relatively stringent.Conclusion The main reasons for subject screening failure in clinical trials in oncology in our hospital are voluntary withdrawal,brain metastasis,and failure of their biochemical test standards,which are close-ly related to the setting of clinical trial nadir criteria.Therefore,an in-depth understanding of subjects'characteristics,accurate set-ting of appropriate nadir criteria,continuous improvement of trial design,and strengthening of communication with subjects to pro-vide more relevant information will help to improve the screening success rate of clinical trials.

Objective To screen and analyze the differentially expressed genes (DEGs) related to oxidative stress in a silicosis mouse model using transcriptome sequencing technology. Methods i) A total of 30 workers without occupational dust-exposed history were selected as the control group and 17 patients with silicosis were selected as the silicosis group using a judgment sampling method. The levels of glutathione and malondialdehyde in the plasma of workers in the two groups were determined by enzyme-linked immunosorbent assay. ii) RAW264.7 cells in the logarithmic growth phase were randomly divided into the control group and the silica group, treated with 0 and 50 mg/L silica suspensions for 24 hours. Protein expression of superoxide dismutase 2 (SOD2), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in the cells was determined by Western blotting. iii) The specific pathogen free male C57BL/6 mice were randomly divided into the control group and the silicosis model group, with 10 mice in each group. Mice were exposed to 50 μL of 0.9% sodium chloride solution and silica suspension at a mass concentration of 100 g/L, respectively, using a single tracheal exposure method. After 28 days of exposure, the pathological changes of mouse lung tissues were observed. Transcriptome sequencing was used to screen DEGs in the lung tissues of the silicosis mouse model, and gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed. The expression of DEGs was verified using quantitative real-time polymerase chain reaction (qPCR). Results i) The level of malondialdehyde in the patients′ plasma was higher (P<0.01), while the level of glutathione was lower (P<0.01) in the silicosis group than that of the control group. ii) The relative expression of SOD2 protein decreased (P<0.05), while the relative expression of IL-6 and TNF-α proteins increased (all P<0.05) in the silica group of RAW264.7 cells compared with the control group. iii) The pathological results of lung tissues showed that the alveolar structure of mice was destroyed and silicotic nodules were formed in the silicosis model group. Transcriptome sequencing identified 3 703 DEGs, of which 3 199 were significantly down-regulated and 504 were significantly up-regulated. The GO enrichment analysis results showed that the DEGs were significantly enriched in biological processes such as oxidative stress, inflammation, immunity and hypoxia, with cellular components mainly located in membranes, cytoplasm, and nucleus. Molecular functions were enriched in oxidoreductase activity, protein binding, and adenosine triphosphate binding. The KEGG enrichment analysis results showed that the DEGs were mainly involved in the phosphatidylinositol 3-kinase-protein kinase B signaling pathway, cyclic adenosine monophosphate signaling pathway, chemokine signaling pathway, and apoptosis signaling pathway. A total of 28 DEGs involved in the "oxidative stress response" pathway were screened by GO enrichment analysis. The qPCR verification results showed that the relative expression of DEGs carbonic anhydrase 3 (Car3), matrix metalloproteinase 9 (Mmp9), and MutY DNA glycosylase (Mutyh) involved in the "oxidative stress response" of lung tissues in the silicosis model group were lower than those of the control group (all P<0.05). Conclusion Oxidative stress response exists in silicosis patients. The oxidative stress-related genes Car3, Mmp9, and Mutyh are altered in the mouse lung tissues of the silicosis model through the oxidative stress pathway, suggesting that they could be new targets for the treatment of silicosis.

This paper summarizes Professor SHI Zaixiang's clinical experience in treating high fever caused by sepsis using Chaihu Guizhi Ganjiang Decoction （柴胡桂枝干姜汤）. He holds that the key pathogenesis of sepsis involves constrained heat in the shaoyang and internal accumulation of water and fluids. The clinical manifestations such as high fever， chills， and alternating sensations of cold and heat are attributed to pathogenic heat constrained in the shaoyang. Meanwhile， soft tissue edema and serous cavity effusions are due to shaoyang dysfunction and internal water retention. In clinical practice， treating sepsis-related high fever requires addressing both the shaoyang-constrained heat and the associated edema and effusions. The therapeutic approach focuses on harmonizing the shaoyang and resolving internal fluids， using Chaihu Guizhi Ganjiang Decoction as the base formula with flexible modifications. Professor SHI emphasizes that this formula shows a rapid antipyretic effect， particularly in cases where multiple anti-infective treatments have failed.

Objective To evaluate the clinical efficacy of"Tongdu Tiaoshen"acupuncture combined with hand function rehabilitation training in patients with hand dysfunction following cerebral infarction.Methods A total of 104 patients were randomly assigned to either the observation group(receiving"Tongdu Tiaoshen"acupunc-ture combined with hand function rehabilitation training)or the control group(undergoing hand function rehabilita-tion training alone),with 52 patients in each group.Both groups underwent a 4-week treatment regimen.The following outcome measures were assessed pre-and post-treatment:Modified Ashworth Scale(MAS),Modified Lindmark Scale(MLS),Brunnstrom Motor Function Score(BMS)for upper limbs,Fugl-Meyer Assessment(FMA)of upper limb motor function,Modified Barthel Index(MBI),and grip strength(GS).Adverse events were docu-mented,and the clinical efficacy in each group was evaluated by calculating the effective rate.Results After excluding dropouts,a total of 94 cases were included in the final statistical analysis,with 48 cases assigned to the observation group and 46 to the control group.Both groups demonstrated significant improvements in MLS,MAS,BMS,FMA,MBI,and GS scores compared to pre-treatment levels,with all differences being statistically significant(P<0.05).Following treatment,intergroup comparisons also revealed statistically significant differences in all mea-sured indicators(P<0.05).The total effective rate was higher in the observation group(91.7%)than in the control group(82.6%),and the difference in efficacy grades between the two groups was statistically significant(P<0.05).Conclusions"Tongdu Tiaoshen"acupuncture,when combined with hand function training,demonstrates signifi-cantly greater efficacy than hand function rehabilitation training alone in improving post-cerebral infarction hand dysfunction.It enhances grip strength and fine motor coordination of the affected limb,alleviates hand muscle spasticity and joint stiffness,and promotes recovery of upper limb motor function,thereby improving patients'activities of daily living.This integrated therapeutic approach warrants further clinical validation and in-depth research for broader implementation.

Objective To analyze the reasons for the failure of subject screening in clinical trials of antineoplastic drugs and the impact of natriuretic criteria on the entry of subjects into clinical trials,to explore the strategies to improve the suc-cessful enrolment of screened subjects,and to provide reference bases for research institutes and sponsors in the formulation of na-triuretic criteria.Methods This study selected data from 40 drug clinical trials conducted at the Drug Clinical Trial Research Center of the Cancer Hospital of the Chinese Academy of Medical Sciences from January 1,2016,to June 30,2022.It statistically described the collected data on the frequency and percentage composition of screening failures among participants and the inclu-sion and exclusion criteria in the protocols.Results A total of 425 subjects were screened out of 40 clinical trial programmers covering 8 tumor types,with the majority being＜65 years of age(333,78.4％),of which the most important reasons included vol-untary withdrawal(71,16.7％),tumor metastasis(52,12.2％),failure to recover from treatment of pre-existing disease(38,8.9％),failure of bone marrow function(19,4.5％),and non-compliant liver function(15,3.5％).Among the nadir indicators,the age of the subjects(100％),ECOG score(97.5％),bone marrow function(ANC:95.0％,PLT:97.5％,HB:97.5％),liver function(T-BiL:95.0％,ALT:87.5％,AST:95.0％),renal function(CR:80.0％),and viral screening(HIV:80.0％,HBV:70.0％,HCV:62.5％)were relatively stringent.Conclusion The main reasons for subject screening failure in clinical trials in oncology in our hospital are voluntary withdrawal,brain metastasis,and failure of their biochemical test standards,which are close-ly related to the setting of clinical trial nadir criteria.Therefore,an in-depth understanding of subjects'characteristics,accurate set-ting of appropriate nadir criteria,continuous improvement of trial design,and strengthening of communication with subjects to pro-vide more relevant information will help to improve the screening success rate of clinical trials.

Objective:To evaluate the efficacy and safety of θ short burst rapid pulse stimulation(TBS)in treating schizophrenia by meta-analysis.Methods:Randomized controlled trials(RCTS)on TBS in the treatment of schizophrenia were searched from CNKI,Wanfang,VIP,China Biomedicine,Web of science,PubMed,Embase and Cochrane Library databases to December 2022.The main study indicator was the Positive and Negative Symptoms Scale(PANSS).Risk quality assessment of the included literatures was performed by two reviewers and statistical analysis was performed using RevMan5.3.Results:A total of 13 RCTS with 641 patients were included.Meta-anal-ysis showed that TBS targeting the left dorsolateral prefrontal cortex(DLPFC)with intervention duration longer than 2 weeks decreased the PANSS total scores(WMD=-4.63,95％CI:-5.75--3.51,P＜0.001),positive symptom scores(WMD=-1.13,95％CI:-2.00--0.26,P＜0.05),negative symptom scores(WMD=-2.51,95％CI:-2.77--1.53,P＜0.001)and general psychopathological symptom scores(WMD=-1.20,95％CI:-1.80--0.60,P＜0.001).The adverse reactions of TBS included dizziness,and no serious adverse e-vents were reported.Conclusion:TBS has high safety,and stimulation of left dorsolateral prefrontal cortex targets for more than 2 weeks could effectively improve psychiatric symptoms in patients with schizophrenia.

Objective:To investigate the proportion of helper T lymphocytes 22(Th22) and levels of interleukin(IL)-22 in peripheral blood of children with juvenile idiopathic arthritis (JIA), and analyze their relevance with JIA-related inflammatory cytokines.Methods:A total of 30 children with JIA who received treatment at the Department of Rheumatology, the Affiliated Children′s of Capital Institute of Pediatrics from November 2018 to December 2019 were enrolled as JIA group, and 12 healthy children at the same age were selected as healthy control group.The percen-tage of Th22 cells in peripheral blood was detected using flow cytometry.Concentrations of IL-22, IL-6, tumor necrosis factor(TNF-α), IL-17 and IL-10 were measured by enzyme-linked immunosorbent assay.Statistical analysis of the relevance of Th22 cells, IL-22 levels and inflammatory cytokines levels of IL-6, TNF-α, IL-17 and IL-10 in JIA were performed by Pearson test. Results:The proportion of Th22 cells in peripheral blood of patients in JIA group[(0.94±0.26)%] was higher than that of the healthy control group [(0.46±0.29)%], and the difference was statistically significant ( t=2.227, P<0.05). Plasma level of IL-22 of patients in JIA group[(185.2±11.93) ng/L] was significantly higher than that of healthy control group[(114.7±6.29) ng/L], and the difference was statistically significant ( t=3.632, P<0.001). The proportion of Th22 cells and the levels of plasma IL-22 in JIA patients were positively correlated with plasma levels of IL-6 (Th22: r=0.501, IL-22: r=0.573, all P<0.01), IL-17 (Th22: r=0.686, P<0.001; IL-22: r=0.445, P<0.01) and IL-10 (Th22: r=0.609, IL-22: r=0.284, all P<0.001). There was no relationship for Th22 cells and plasma levels of IL-22 with TNF-α. Conclusions:The proportion of Th22 cells and plasma levels of IL-22 significantly increase in peripheral blood of JIA patients and correlated with JIA-related inflammatory cytokines, which may play a potential role in the pathogenesis of JIA disease.