OBJECTIVE: To analyze the clinical characteristics of patients with 11q23 rearrangement acute lymphoblastic leukemia (ALL) with non-KMT2A::AFF1 fusion genes. METHODS: The clinical data of 10 patients with KMT2A fusion gene positive and partner gene non-AFF1 ALL admitted to Henan Cancer Hospital from December 2016 to December 2024 were retrospectively summarized. The immunophenotype, molecular genetic characteristics, clinical manifestations and disease prognosis of these patients were analyzed. This research has been approved by the Medical Ethics Committee of Henan Cancer Hospital (Ethics No.: 2019342). RESULTS: Among the 10 patients, the fusion genes were KMT2A::MLLT1 in 7 cases, KMT2A::MLLT4, KMT2A::MLLT3 and KMT2A::MLLT10 in 1 case each. The European Group for the Immunological Classification of Leukemias (EGIL) classification included 6 cases of T-ALL, 2 cases of pro-B-ALL, 1 case of Common-B-ALL and 1 case of pre-B-ALL. 4 cases of B-ALL all expressed CD19, cCD79a, CD38 and HLA-DR, and some expressed CD34 and CD22, without expression or weak expression of CD10, without expression of CD20. One case was accompanied by myeloid marker CD15 expression. 6 cases of T-ALL all expressed CD34, CD7, most expressed CD38, and some expressed CD3, CD5, CD2, CD4 and CD8, and 1 case expressed CD4 and CD8 together. Chromosomal abnormalities were detected in 3 cases, 5 cases were positive for WT1 fusion gene, and 6 cases had gene alterations. 9 patients achieved the first complete remission (CR1) during chemotherapy, and 1 patient relapsed within 6 months after CR1. At the last follow up, 1 patient (the fusion gene was KMT2A::MLLT4) remained unrelieved. There were 2 cases of KMT2A rearrangement (KMT2A-r) persistent positive (+/+) and 8 cases of KMT2A-r negative (+/-). The overall survival (OS) rate and leukemia-free survival (LFS) rate of patients with KMT2A-r persistent positive were significantly lower than those of patients with negative change, and the differences were statistically significant (P values were all < 0.05). Among the 3 patients who received chemotherapy+allogeneic hematopoietic stem cell transplantation (allo-HSCT), no relapse was observed until the follow up day. The OS rate and LFS rate of patients with KMT2A::MLLT1 and chemotherapy+allo-HSCT were higher than those of non-KMT2A::MLLT1 and single chemotherapy patients, and the differences were not statistically significant (P values were all ≥ 0.05). There was no significant difference in OS rate and LFS rate between T-ALL and B-ALL patients (P values were all ≥ 0.05). The median LFS time of the 10 patients was 32 (0 ~ 100) months, and the median OS time was 36 (1 ~ 101) months. CONCLUSION The 11q23 rearrangement ALL with non-KMT2A::AFF1 transcript is mainly KMT2A::MLLT1, T-ALL is more common, and the rate of chromosomal karyotype detection is relatively low. Persistent positive KMT2A-r is unfavorable for patient survival, and allo-HSCT during the CR1 period may improve patient survival.
Humans ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics* ; Female ; Male ; Myeloid-Lymphoid Leukemia Protein/genetics* ; Histone-Lysine N-Methyltransferase/genetics* ; Adult ; Adolescent ; Chromosomes, Human, Pair 11/genetics* ; Child ; Transcriptional Elongation Factors/genetics* ; Gene Rearrangement ; Oncogene Proteins, Fusion/genetics* ; Retrospective Studies ; Young Adult ; Middle Aged ; Prognosis ; Child, Preschool ; DNA-Binding Proteins/genetics*

Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder primarily caused by pathogenic variants in the TSC1 or TSC2 genes. It is characterized by multisystem hamartomatous lesions and neuropsychiatric manifestations. Here we report a young male patient with TSC involving multiple organs, caused by a heterozygous frameshift mutation in TSC2 (c.2071delC, p.Arg691Alafs^*7). The patient initially presented with classic facial angiofibromas and hypomelanotic macules, and subsequently developed psychiatric and behavioral disturbances with auditory hallucinations. Neuroimaging revealed an intracranial mass lesion, which was confirmed as a subependymal giant cell astrocytoma on postoperative histopathology following surgery performed at an outside institution. After admission, the patient underwent a comprehensive diagnostic workup, and multidisciplinary treatment evaluation revealed extensive multisystem involve-ment, including the nervous system, skin, kidneys, lungs, heart, eyes, pancreas, liver and bones. Combined with relevant literature, this article discusses the molecular mechanisms, clinical phenotypes, and comprehensive management of TSC, in order to provide a reference for the standardized and individualized management of this disease.

Digital and intelligent technologies serve as the core engine driving the inheritance of the essence and the innovation while upholding the fundamentals of traditional Chinese medicine（TCM）. Currently， the digital and intelligent transformation of TCM has undergone four developmental stages， exhibiting inherent characteristics such as long-term inevitability， objective standardization， and ecological evolution. By introducing quantitative metrics， digital and intelligent technologies have achieved breakthroughs in TCM knowledge inheritance and innovation， clinical diagnosis and treatment， and herbal medicine supply. The practical applicability of methodological innovations has been empirically validated， though significant disparities exist in technological adaptability and application depth across different fields. Overall， the digital and intelligent transformation of TCM remains in its nascent stage， grappling with multiple structural challenges：weak data foundations， inadequate technological adaptability， incomplete institutional frameworks， shortages of multidisciplinary talent， lagging policies and regulations， and urban-rural digital divide. In order to foster sustainable development and modernization of TCM， this paper establishes a six-dimensional collaborative governance framework of encompassing data， technology， organization， institutions， environment and ethics， which is rooted in data governance and digital governance theories. Future efforts should center on standardization， integration， and ecosystem development to build a data and technology foundation. Focus should be placed on deepening innovation and application of key TCM-specific technologies， while simultaneously strengthening interdisciplinary talent cultivation， improving institutional mechanisms and policy frameworks， and increasing support for rural areas. By adopting a people-centered and technology-empowered approach， we can overcome developmental constraints and unleash the powerful driving force of digital and intelligent technologies for the inheritance of TCM.

This article reports a rare case of autoinflammatory disease presenting initially with skin induration and swelling after trauma as the initial manifestation, followed by progressive limb weakness. The patient was a middle-aged female who developed skin induration and swelling after trauma, which gradually progressed to limb weakness, dysarthria and bilateral facial paralysis, accompanied by livedo reticularis of the lower extremities, diffuse skin induration of the limbs, and beaded subcutaneous nodules in the right upper limb. The patient had a susceptibility to infection since childhood and a history of chronic livedo reticularis. Skin pathological examination revealed panniculitis. A comprehensive etiological screening for special infections and autoimmune diseases was completed with an unremarkable results, and whole-exome sequencing showed no abnormal findings. Following a multidisciplinary discussion combined with RNA sequencing results, the patient was diagnosed with an autoinflammatory disease, with a suspected type Ⅰ interferonopathy. Treatment with tofacitinib resulted in gradual improvement of clinical symptoms. This case highlights the importance of detailed medical history collection, systematic physical examination and multidisciplinary collaborative diagnosis and treatment, and underscores the pivotal role of molecular diagnosis in the confirmation of rare diseases. It can provide a reference for the clinical diagnosis and management of similar rare cases.

ObjectiveTo evaluate the effect of action observation therapy (AOT) combined with low-frequency repetitive transcranial magnetic stimulation (rTMS) on post-stroke unilateral spatial neglect. MethodsA total of 108 patients with post-stroke unilateral spatial neglect admitted to Suqian Integrated Traditional Chinese and Western Medicine Hospital from January, 2023 to March, 2024 were enrolled. The patients were randomly allocated to AOT group, rTMS group and combined group with 36 patients in each group. All the groups received conventional treatment. The AOT group additionally received AOT, the rTMS group additionally received rTMS, and the combined group received both AOT and rTMS, for four weeks. Before and after treatment, the patients were assessed using the Montreal Cognitive Assessment (MoCA), Fugl-Meyer Assessment (FMA), modified Barthel Index (MBI), Chinese Behavioural Inattention Test-conventional test (CBIT-C) and CBIT-behavioural test (CBIT-B). The latency and amplitude of the N20 potential on the affected side were also measured. ResultsThree patients dropped out from each group. After intervention, significant main effects of time (F > 77.096, P < 0.001) and group (F > 5.119, P < 0.01) and significant time-by-group interaction effects (F > 3.320, P < 0.05)were observed in the MoCA, FMA, MBI, and CBIT-C scores. For the CBIT-B score, the main effects of time (F = 367.430, P < 0.001) and group (F = 4.995, P = 0.008) were significant. After intervention, MoCA, FMA, MBI, CBIT-C and CBIT-B scores, and N20 amplitude and latency were better in the combined group than in the AOT and rTMS groups (P < 0.05). ConclusionThe combination of AOT and rTMS may further ameliorate cognitive function, motor function, activities of daily living, and the degree of spatial neglect in post-stroke patients with unilateral spatial neglect, potentially attributable to improved nerve conduction function.

ObjectiveTo analyze the trend of lung cancer incidence in Fenghua District, Ningbo City of Zhejiang Province from 2009 to 2023, and to estimate the age-period- cohort effects of incidence rate, so as to provide scientific basis for the formulation of lung cancer prevention and control measures in Fenghua District. MethodsJoinpoint software was utilized to analyze the trends and calculate the average annual percentage change (AAPC) of lung cancer incidence based on the tumor incidence surveillance data from Fenghua District, 2009‒2023. The age-period-cohort (APC) model for lung cancer incidence was analyzed using STATA 17.0 software, and net drift and local drift of lung cancer incidence rates were analyzed using online analytical tools. ResultsThe incidence of lung cancer in Fenghua District showed an overall upward trend from 2009 to 2023, with the standardized incidence rate increasing from 45.05/100 000 in 2009 to 108.20/100 000 in 2023(AAPC=7.05%, P<0.05). The increase in the standardized incidence rate for females (AAPC=12.72%, P<0.05) was higher than that for males (AAPC=2.97%, P<0.05). The overall net drift in lung cancer incidence for residents of Fenghua District was 11.71%, with the net drift for females (16.54%) being higher than that for males (6.64%). The local drift in lung cancer incidence among different age groups ranged from -3.37% to 35.18%. The results of APC model showed that the risk of lung cancer incidence increased and then decreased with age, with the highest age effect coefficient observed in the 65‒69 years age group at 1.08. The period effect showed a gradually increasing trend in lung cancer incidence risk with the progression of time, and the period effect coefficient in 2019‒2023 (0.46) was higher than that in 2009‒2013 (-0.39), increasing by 217.95%. The cohort effect coefficient showed a trend of first decreasing and then increasing with the expansion of the birth cohort, in which the lowest cohort effect coefficient was -1.07 observed in the birth cohort of 1964‒1968 and the highest cohort effect coefficient was 1.77 in the birth cohort of 1924‒1928. ConclusionThe incidence of lung cancer in Fenghua District shows an upward trend from 2009 to 2023, with a higher increase in incidence rates among females than that in males. The risk of lung cancer incidence exists a trend of increasing and then decreasing with age growth. With the progression of time, the risk of lung cancer incidence shows a gradually increasing trend. However, with the expansion the birth cohort, the risk of lung cancer incidence demonstrates a trend of first decreasing and then increasing.

This paper summarizes Professor WANG Xiuxia's clinical experience in treating hyperprolactinemia using the liver soothing therapy. Professor WANG identifies liver qi stagnation and rebellious chong qi （冲气） as the core pathomechanisms of hyperprolactinemia. Furthermore， liver qi stagnation may transform into fire or lead to pathological changes such as spleen deficiency with phlegm obstruction or kidney deficiency with essence depletion. The treatment strategy centers on soothing the liver， with a modified version of Qinggan Jieyu Decoction （清肝解郁汤） as the base formula. Depending on different syndrome patterns such as liver stagnation transforming into fire， liver stagnation with spleen deficiency， or liver stagnation with kidney deficiency， heat clearing， spleen strengthening， or kidney tonifying herbs are added accordingly. In addition， three paired herb combinations are commonly used for symptom specific treatment， Danggui （Angelica sinensis） with Chuanxiong （Ligusticum chuanxiong）， Zelan （Lycopus lucidus） with Yimucao （Leonurus japonicus） ， and Jiegeng （Platycodon grandiflorus） with Zisu （Perilla frutescens）.

Objective　A predictive model should be established during the early stages of dengue progression to evaluate the likelihood of severe dengue and dengue with warning signs, thereby preventing delayed clinical management and reducing dengue-related mortality. Methods　Clinical and laboratory examination data of 831 patients admitted to Ruili People's Hospital of Yunnan Province during 2019-2023 were retrospectively collected. The dataset was divided into a training set and a validation set in a 7∶3 ratio. Statistical description and univariate analysis were performed on the training set, with LASSO regression employed to screen variables, followed by logistic regression to develop a risk prediction model for severe dengue. Model performance was validated using ROC curves on both the training set and validation set. Results　A total of 831 dengue patients were included in the study, with a mean age of (44.20±15.02) years. Among them, 52.59% were male and 5.42% were Myanmar nationality. In total, 122 cases (14.68%) exhibited severe dengue or dengue with warning signs, predominantly female (58.20%). LASSO regression was used in the training set to screen 11 variables related to the risk of severe dengue and dengue with warning signs: Age, dizziness, vomiting, prothrombin time, partial activated thromboplastin time, hematocrit, platelet, monocyte percentage, absolute value of monocytes, hemoglobin, C-reactive protein (λmin= 0.011 59); Logistic regression identified statistically significant variables for the risk model of severe dengue and dengue with warning signs as follows: age [OR=1.034 (95%CI: 1.016-1.053)], red blood cells deposited [OR=1.258 (95%CI: 1.143-1.519)], platelet [OR=0.991 (95%CI: 0.985-0.997)], hemoglobin (OR=0.919 (95%CI: 0.873-0.950)], C-reactive protein [OR=1.019 (95%CI:1.004-1.034)]. The model achieved an AUC of 0.894 (95%CI: 0.796-0.867) in the training set and 0.862 (95%CI: 0.709-0.827) in the validation set. At a cut-off threshold of 0.197, sensitivity and specificity were 0.850 and 0.743, respectively. Conclusion　This study established a LASSO-logistic regression model, which can predict the risk of severe dengue and dengue with warning signs. The model enhances the capability of hospitals to prevent and manage severe dengue and provides valuable guidance for clinical decision-making.

Objective To explore the mechanism by which Wandai Decoction prevents and treats vulvovaginal candidiasis(VVC)of the spleen deficiency and excessive dampness type and restores the vaginal flora structure,and to identify the potential metabolic pathways involved using metagenomics and metabolomics.Methods Twenty VVC patients who met the inclusion criteria were randomly assigned to a Wandai Decoction group and a fluconazole group(n=10 in each group).Subjects in the fluconazole group were given a single oral dose of 150 mg fluconazole,while those in the Wandai Decoction group took the Wandai Decoction orally for 14 days.The vulvovaginal signs and symptoms(VSS)scores of both patient groups were evaluated before and after treatment.Vaginal secretions were collected before and after treatment.The Illumina sequencing and the liquid chromatography with tandem mass spectrometry(LC-MS/MS)platform were used to conduct metagenomic and metabolomics analyses of the vaginal secretions,respectively.Results The VSS score results showed that the VSS scores of both groups decreased after treatment compared with those before treatment(P＜0.01),and there was no statistically significant difference in the VSS scores between the two groups after treatment.Metagenomics results showed that,after treatment,the vaginal microbial communities in the Wandai Decoction group were of CST Ⅱ and Ⅴ types(predominated by Lactobacillus gasseri and Lactobacillus jensenii),while those in the fluconazole group were Lactobacillus_intestinalis and Streptococcus_sp._oral_taxon_431.KEGG functional enrichment analysis results showed that,in terms of the cell cycle and meiosis functions of Candida albicans,statistically significant differences between the Wandai Decoction and fluconazole groups were observed(P＜0.05).Metabolomic analysis identified 120 differential metabolites between the two groups after treatment.The results of KEGG metabolic pathway enrichment analysis of differential metabolites showed that the Wandai Decoction might be significantly superior to fluconazole in improving local vaginal metabolic pathways of α-linolenic acid,glycerophospholipid metabolism,pentose and glucuronic acid interconversion,and arachidonic acid.Conclusion The Wandai Decoction can improve the vaginal flora of VVC patients.It may be superior to fluconazole in the signaling pathways of the cell cycle and meiosis.The improvement of the vaginal flora by the Wandai Decoction may be associated with its effect on metabolic pathways of glycerophospholipid metabolism,pentose and glucuronic acid interconversion,and others in the vagina.

Objective To investigate the effect of Gd-hydroxyapatite(Gd-HA)stents with adipose mesenchymal cells(ADSCs)on the repair of knee articular cartilage defects.Methods To isolate,culture,and identify rabbit ADSCs by establishing a rabbit knee joint full-thickness cartilage defect model,a total of 18 rabbits were randomly divided into blank control group,Gd-HA scaffold group,and ADSCs+Gd-HA scaffold group.At week 12 and 24 after surgery,International Curtilage Repair Society(ICRS)score,HE,toluidine blue,modified red O bright green and ColⅡ were detected by immunohistochemical staining,then ColⅡand GAG mRNA expression levels were detected by O'Driscoll and Real-time PCR.ColⅡ protein expression was detected by Western blotting,GAG content was detected by DMMB,biomechanical strength was detected by indentation test,and PKH26 labeled ADSCs was used to trace the tissue engineering scaffold with Gd-HA composite ADSCs to evaluate the repair effect of rabbit knee cartilage defects.Results The ADSCs isolated and cultured in vitro showed good growth,stable phenotype and good directional differentiation through macroscopic observation and histological staining,it could be seen that the repair degree and effect of the knee joint full-thickness cartilage defect model implanted with Gd-HA scaffold group were better than those of the blank control group,while the cartilage repair situation of the ADSCs+Gd-HA scaffold group was better than that of the Gd-HA scaffold group(P＜0.05);The ICRS and improved O'Driscoll scores were higher than the other two groups(P＜0.05).Compared with the Gd-HA group,the ADSCs+Gd-HA group could produce ColⅡ and GAG during the process of cartilage repair,with stronger mechanical strength of the repaired tissue(P＜0.05);PKH26 labeled ADSCs were found in the repaired tissues of the ADSCs+Gd-HA group,and they were involved in the composition of newly formed tissues.Conclusion Gd-HA scaffold material combined with ADSCs has a good repair effect on full-thickness cartilage defects in the knee joint as a new type of biological material for repairing joint cartilage defects.