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

Pre-admission is a critical initiative to optimize medical service processes and alleviate the challenge of "difficult access to healthcare. "However, there is currently a lack of standardized protocols for pre-admission procedures. This study aims to systematically analyze key nodes and risk factors in pre-admission process design and propose optimization strategies, providing a foundation for policy formulation and hospital practices. By constructing a "forward-reverse" dual-process model of pre-admission and identifying risk points based on stakeholder theory (patients, hospitals, healthcare administration, and insurance), the study reveals that while pre-admission can reduce the average length of stay, improve bed turnover rates, and enhance patient satisfaction, it also presents risks such as cross-period financial settlement, challenges in insurance policy adaptability, demands for information system integration, and the need for defining medical safety boundaries. To optimize the pre-admission process and mitigate these risks, this study explores framework improvements in areas including eligibility criteria, mode selection, cost settlement, transition between pre-admission and inpatient status, and cancellation of pre-admission, offering practical guidance for public hospitals. The authors argue that pre-admission requires tripartite collaboration among hospitals, insurers, and healthcare administrations: hospitals should establish top-level design, continuously refine processes, and implement dynamic risk assessment mechanisms; insurance providers should support cross-period settlement policies; and healthcare administrations should issue guiding policies or standardized protocols. Through multi-department coordination and collaborative efforts, the optimization and innovation of pre-admission processes can be advanced, ultimately delivering more efficient and convenient healthcare experiences for patients.

Objective To summarize the best evidence of early rehabilitation management of hand function in patients with hand burn,and provide basis for medical personnel to carry out early rehabilitation management of hand burn.Methods According to the 5S model,all evidence on early rehabilitation management of hand function in patients with hand burns was retrieved from databases and websites including UpToDate,BMJ Best Practice,NICE,RNAO,GIN,and so on.The retrieved evidence included clinical decisions,guidelines,evidence summaries,expert consensuses,systematic reviews,Meta analysis.The search period of the summary of best evidence,expert concensus and guidelines are from the establishment of the database to December 20,2024,and the search period of the systematic reviews is from January 1,2019 to December 20,2024.Quality evaluation of literature,evidence extraction and summary were conducted.The evidence was graded according to JBI evidence pre-grading system 2014.Results Totally 17 pieces of the literature were included,including 1 clinical decision,4 guidelines,6 evidence summaries,3 expert consensus articles,and 3 systematic reviews.Totally pieces of best evidence were summarized,including 7 aspects of assessment,hand positioning,treatment of edema,dressing,use of orthotics,joint mobility training,and health education.Conclusion This study summarized the best evidence of early rehabilitation management of hand function in patients with hand burn,and provided evidence-based evidence for clinical rehabilitation management plan.According to the clinical situation,the medical staff can apply the evidence to clinical practice,so as to improve the hand function and quality of life of patients.

Objective To investigate the role and mechanism of RNA-Specific adenosine deaminase 3 (Adar3) in regulating macrophage polarization during Coxsackievirus B3(CVB3)-induced viral myocarditis (VM). Methods Bone marrow-derived macrophages (BMDM) from mice were cultured in vitro and induced into M1/M2 macrophages using interferon-gamma (IFN-γ)/lipopolysaccharide (LPS) or interleukin 4 (IL-4), respectively. The mRNA expression levels of Adar1, Adar2, and Adar3 in each group of cells were assessed by real-time quantitative PCR (qRT-PCR). Specific siRNAs targeting the Adar3 gene were designed, synthesized, and transiently transfected into M2 macrophages. The mRNA levels of M2 polarization-related marker genes-including arginase 1 (Arg1), chitinase 3-like molecule 3 (YM1/Chi3l3), and resistin-like molecule alpha (RELMα/FIZZ1)-were detected by qRT-PCR. RNA sequencing was performed to analyze the signaling pathways affected by Adar3. The expression levels of Wnt/β-catenin signaling pathway were further validated using qRT-PCR and Western blot. The adeno-associated virus overexpressing Adar3 was designed, synthesized, and injected into mice via tail vein. Three weeks later, a myocarditis mouse model was established. After an additional week, the phenotype and function of cardiac macrophages, as well as multiple indicators of VM (including echocardiography, body weight, histopathology and serology) were examined. Additionally, the protein levels of the Wnt/β-catenin signaling pathway were assessed. Results Compared to M0-type macrophages, the expression level of Adar3 was significantly increased in M2-type macrophages. After transfection of Adar3 siRNA, the mRNA levels of Arg1, YM1 and FIZZ1 in M2 macrophages were downregulated. RNA sequencing revealed 149 upregulated genes and 349 downregulated genes. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and subsequent validation experiments indicated that Adar3 modulated the Wnt/β-catenin signaling pathway. In vivo experiments demonstrated that Adar3 overexpression alleviated the cardiac dysfunction of VM mice. The proportion of M1 macrophages in the heart decreased, while the proportion of M2 macrophages increased. At the same time, the Adar3 overexpression activated the Wnt/β-catenin signaling pathway. Conclusion Adar3 promotes macrophage polarization toward the M2 phenotype by activating the Wnt/β-catenin signaling pathway, thereby alleviating VM.
Animals ; Adenosine Deaminase/metabolism* ; Macrophages/immunology* ; Wnt Signaling Pathway/genetics* ; Myocarditis/immunology* ; Mice ; Coxsackievirus Infections/metabolism* ; Male ; Mice, Inbred BALB C ; Enterovirus B, Human/physiology* ; beta Catenin/genetics*

Objective:To investigate the current status of implementing medical insurance performance evaluation in the hospitals of China under the background of China Healthcare Security Diagnosis Related Groups (CHS-DRG) and Diagnosis-Intervention Packet (DIP) payment reform, explore the perspectives and recommendations of key department leaders (e.g., health insurance, medical affairs, pricing, and performance evaluation departments) regarding health insurance performance evaluation, analyze the influencing factors in its implementation, so as to provide references for hospitals to develop and refine health insurance performance evaluation strategies.Methods:A questionnaire was designed and distributed to hospitals across 31 provincial-level administrative regions in China from December 1 to 31, 2023. The survey targeted secondary and tertiary general or specialized hospitals. The main responsible persons from four functional departments, including medical insurance, healthcare, pricing, and performance, were invited to participate in the survey. Descriptive analysis was conducted on the questionnaire data, and the chi-square test was used for differential analysis of unordered categorical variables, while the Wilcoxon rank sum test was used for differential analysis of ordered categorical variables.Results:A total of 761 valid questionnaires were collected. Most respondents were health insurance department leaders (420, 55.19%). Among them, 741 respondents reported that their hospitals used CHS-DRG or DIP payment, with 258 indicating that their hospitals had already developed and implemented health insurance performance evaluation plans. A majority (685, 90.01%) expressed support for such initiatives. Influencing factor analysis revealed that hospital type, level, scope of health insurance management departments, and payment methods might impact the implementation of health insurance performance evaluation ( P<0.05). Conclusions:Few hospitals have currently adopted health insurance performance evaluation, underscoring the urgency to establish a scientific and reasonable evaluation plan as a robust tool for internal hospital management.

Objective:To analyze the cost and structural impact of the new technology"transhysteroscopic mechanical rotary excision of abnormal uterine tissues"on the DRG group of"surgery for intrauterine lesions"under the DRG payment method,and to provide clinical data for supporting the development of the exclusion policy for the new technology and new items.Methods:Cases in which transhysteroscopic mechanical rotary excision of abnormal uterine tissues was used in the gynecology day unit of the Peking Union Medcial College Hospital from March 2022 to November 2023,which were paid for under the DRG group of"surgery for intrauterine pathology",were retrospectively analyzed for the impact of the new technology on the cost and structure of the cases.Results:The price of"transhysteroscopic mechanical rotary excision of abnormal uterine tissues"in the Beijing Medical Service Price Item Specification is 8 000 yuan(Class C out-of-pocket expenses),which is higher than the payment standard of 6 866 yuan for the NE19 group,and the use of this new technology significantly increased the total hospitalization medical cost,the out-of-pocket ratio of the patients and the surgical cost,which led to an increase in the burden of the patients and the loss of the hospitals.Conclusion:"Transhysteroscopic mechanical rotary excision of abnormal uterine tissue"has the advantages of improving patients'prognosis and accelerating recovery,shortening operation time,avoiding intraoperative thermal injuries,and shortening the learning curve of doctors,etc.Policy makers should take into account cost control,patients'prognosis and the development of medical technology,scientifically and prudently formulate the exclusion policy of the new technology,reasonably determine the payment standard,and make good use of the exclusion policy and the payment standard.

L-citrulline is a nonprotein amino acid that plays an important role in human health and has great market demand. Although microbial cell factories have been widely used for biosynthesis, there are still challenges such as genetic instability and low efficiency in the biosynthesis of L-citrulline. In this study, an efficient, plasmid-free, non-inducible L-citrulline-producing strain of Escherichia coli BL21(DE3) was engineered by combined strategies. Firstly, a chassis strain capable of synthesizing L-citrulline was constructed by block of L-citrulline degradation and removal of feedback inhibition, with the L-citrulline titer of 0.43 g/L. Secondly, a push-pull-restrain strategy was employed to enhance the L-citrulline biosynthesis, which realized the L-citrulline titer of 6.0 g/L. Thirdly, the NADPH synthesis and L-citrulline transport were strengthened to promote the synthesis efficiency, which achieved the L-citrulline titer of 11.6 g/L. Finally, fed-batch fermentation was performed with the engineered strain in a 3 L fermenter, in which the L-citrulline titer reached 44.9 g/L. This study lays the foundation for the industrial production of L-citrulline and provides insights for the modification of other amino acid metabolic networks.
Citrulline/biosynthesis* ; Escherichia coli/genetics* ; Metabolic Engineering/methods* ; Fermentation ; NADP/biosynthesis*

Objective:To comparatively evaluate the efficacy of anti-tumor necrosis factor (TNF)-α and anti-interleukin (IL)-12/23 biologics as the first-line treatment in Crohn′s disease (CD).Methods:From January 1, 2016 to December 31, 2024, at the Department of Gastroenterology of the First Affiliated Hospital of Soochow University, the clinical data of patients with CD treated with anti-TNF-α (infliximab or adalimumab) or anti-IL-12/23 biologics (ustekinumab) as first-line treatment were retrospectively collected. All the patients were followed up for 1 year since the initiation of first-line biologic treatment, with the follow-up concluding on December 31, 2024. The primary outcomes were the clinical efficacy (including clinical response rate and clinical remission rate) of anti-TNF-α or anti-IL-12/23 treatment at week 24 and week 48, and the endoscopic efficacy(including endoscopic response rate and endoscopic remission rate) at week 48. The clinical efficacy was assessed based on Crohn′s disease activity index(CDAI). The clinical response was defined as a reduction in CDAI by ≥ 70 from baseline (week 0), and clinical remission was defined as CDAI < 150. The endoscopic efficacy was assessed based on simple endoscopic score for Crohn′s disease (SES-CD), the endoscopic response was defined as a reduction in SES-CD by ≥50% from baseline (week 0), and endoscopic remission was defined as SES-CD ≤2. Chi-square test or Fisher′s exact test was used for statistical analysis.Results:A total of 215 CD patients were enrolled, including 160 males and 55 females, with the age of (31.88±11.55) years old. Among them, 179 patients completed the clinical efficacy evaluation, 110 cases were treated with anti-TNF-α, 69 cases were treated with anti-IL-12/23. The clinical response rates of patients treated with anti-TNF-α and anti-IL-12/23 at week 24 were 95.5%(105/110) and 95.7%(66/69), respectively, and the clinical remission rates at week 24 were 86.4%(95/110) and 85.5%(59/69), respectively; the clinical response rates at week 48 were 95.5%(105/110) and 97.1%(67/69), respectively, and the clinical remission rates at week 48 were 89.1%(98/110) and 88.4%(61/69), respectively; and the differences were not statistically significant(Fisher′s exact test, χ2=0.03, Fisher′s exact test, χ2=0.02; P=1.000, 0.708, 0.872, and 0.887). A total of 76 patients completed endoscopic efficacy evaluation, among which 55 cases were treated with anti-TNF-α, and 21 cases were treated with anti-IL-12/23. The endoscopic response rates of patients treated with anti-TNF-α and anti-IL-12/23 were 74.5%(41/55) and 66.7%(14/21), respectively, and the endoscopic remission rates at week 48 were 49.1%(27/55) and 28.6%(6/21), respectively; and the differences were not statistically significant( χ2=0.47 and 2.60, P=0.492 and 0.107). Conclusion:Both anti-TNF-α and anti-IL-12/23 are effective as first-line biological therapies for CD, and there are no significant differences in both clinical and endoscopic efficacy between these 2 biologics.

Objective:To compare the role of double-balloon enteroscopy (DBE) and dual-energy CT enterography (DCTE) in evaluating the clinical characteristics of Crohn′s disease (CD).Methods:From July 1, 2016 to November 1, 2023, 72 patients with CD who underwent both DBE and DCTE (with an interval of less than 3 months) in the First Affiliated Hospital of Soochow University were enrolled in this retropective study. Among them, 4 patients underwent both DBE and DCTE twice (a total of 76 cases). The data of DBE and DCTE in the diagnosis of 76 CD cases were analyzed, including the diagnostic rate of CD, the consistency of the 2 methods in detecting the lesion location (ileocecal, colonic, ileocolonic, and upper gastrointestinal tract involvement), and the detection rates of stenosis, ulcer and the location, long ulcer (long-diameter≥2 cm), and fistula. Kappa test was performed for the consistency analysis, and Chi-square test was used for statistical analysis.Results:The diagnostic rate of CD by DBE was higher than that by DCTE (80.3% (61/76) vs. 65.8% (50/76)), and the diagnostic rate of combination of the 2 methods (89.5% (68/76)) was higher than that by DCTE alone, and the differences were statistically significant ( χ2=4.04 and 12.28, P=0.044 and <0.001). The result of Kappa consistency test showed that the consistency of CD lesion location detected by DBE and DCTE was poor (Kappa value=0.29, t=3.17, P=0.002). The detection rate of stenosis by DBE was higher than that by DCTE (46.1% (35/76) vs. 13.2% (10/76)), the detection rate of stenosis by combination of the 2 methods (52.6% (40/76)) was higher than that by DCTE alone, and the differences were statistically significant ( χ2=19.73 and 26.82, both P<0.001). There were no statistically significant differences in the detection rates of fistula among DBE, DCTE, and the combination of the 2 methods (3.9%(3/76), 2.6% (2/76), 5.3% (4/76); all P>0.05). The detection rate of ulcer by DBE was higher than that by DCTE(73.7% (56/76) vs. 7.9% (6/76)), the detection rate of ulcer by combination of the 2 methods (76.3%(58/56)) was higher than that by DCTE alone, and the differences were statistically significant ( χ2=68.10 and 72.98, both P<0.001). The detection rates of long ulcer and non-terminal ileum ulcer by DBE were both 17.9% (10/56). All the 6 cases with ulcer detected by DCTE were located in the terminal ileum, and no long ulcers were observed. Conclusions:In the diagnosis of CD, as well as in the detection of stenosis and ulcer, DBE and the combination of DBE and DCTE have more advantages over DCTE alone. The consistency between DBE and DCTE in identifying the location of lesion is poor. DBE has advantages in detecting long ulcer and non-terminal ileum ulcer.

Sj?gren's syndrome(SS)is one of the common rheumatic diseases in clinical practice.Modern medicine commonly uses drugs such as artificial tears,saliva,glucocorticoids,immunosuppressants,and biologics to control the condition.Clinical practice has shown that in addition to modern medical basic treatment,the use of traditional Chinese medicine(TCM)can help improve the clinical efficacy of SS.According to the symptoms and signs of Sj?gren's syndrome in TCM,it is classified as"dryness and obstruction",and the core pathogenesis of the disease is spleen deficiency and deficiency of body fluids.Subsequently,toxic and pathogenic factors gather,leading to the decline of internal organs.The initial causes are spleen damage,unstable barrier,and invasion of pathogenic factors.The core link is spleen dysfunction,insufficient body fluid,and dryness arising from it.Spleen deficiency generates evil,obstruction of qi,and lack of body fluids are the root causes of illness.The main treatment method is the"spleen strengthening method",which treats spleen deficiency,dampness and stagnation,and the body fluid is not distributed.The treatment focuses on strengthening the spleen and qi,supplementing the lungs and generating fluids.Spleen deficiency leads to loss of vitality,blood stasis obstructs blood vessels,and the treatment is to strengthen the spleen,soothe the liver,remove blood stasis,and unblock the orifices.The spleen yang is not vigorous,and qi transformation is impaired.The treatment is to invigorate the spleen and warm the stomach,promote yang circulation,and promote diuresis.