Based on spleen deficiency-phlegm dampness as the core pathogenesis of obesity， and integrating recent advances in modern medicine regarding the key role of immune inflammation in obesity， this paper proposes a multidimensional pathogenic network of "obesity-spleen deficiency-phlegm dampness-immune imbalance". Various traditional Chinese medicine （TCM） herbs that strengthen the spleen， regulate qi， and resolve phlegm and dampness can treat obesity by improving spleen-stomach transport and transformation， promoting water-damp metabolism， and regulating immune homeostasis. This highlights immune inflammation as an important entry point to elucidate the TCM concepts of "spleen deficiency-phlegm dampness" and the therapeutic principle of "strengthening the spleen and eliminating dampness to treat obesity". By systematically analyzing the intrinsic connection between "spleen deficiency generating dampness， internal accumulation of phlegm dampness" and immune dysregulation in obesity， this paper aims to provide theoretical support for TCM treatment of obesity based on dampness.

Objective To investigate the effect of tritiated water on the immune system of zebrafish and its potential molecular mechanism. Methods Zebrafish embryos (2.5 to 3 hours post-fertilization [hpf]) were exposed to 3.7 × 10⁴ Bq/mL tritiated water (tritiated water group), and those exposed to E3 culture medium were used as the control group. The mortality rate, hatching rate, deformity rate, heart rate, body length, yolk sac area, neutrophil count in the tail, immune-related gene expression, and immune-related protein expression of zebrafish in the two groups were determined. Then transcriptome technology was used to further analyze the possible mechanism of tritiated water affecting the immune system of zebrafish. Results Compared with the control group, zebrafish at 72 hpf in the tritiated water group had no significant changes in the mortality rate, hatching rate, deformity rate, body length, and yolk sac area((t = 0.9045, 0.5000, 1.0000, 0.7238, 0.0337, P = 0.4169, 0.6433, 0.3739, 0.4785, 0.9735), but had significantly increased heart rate(t = 4.575，P = 0.002). At 4 days post-fertilization (dpf), the neutrophil count in the tail of zebrafish in the tritiated water group was significantly increased(t = 2.563，P = 0.0196), the mRNA expression of TNF-α was significantly decreased(t = 2.891, P = 0.045), the protein expression of nuclear factor-kappa B (NF-κB) was significantly increased(t = 3.848, P = 0.018), and the protein expression of NLRP3 was significantly decreased(t = 14.98, P = 0.001). At 7 dpf, the neutrophil count in the tail and the protein expression levels of NF-κB, NLRP3, and interleukin-1β were significantly decreased(t = 3.772, 7.048, 15.620, 4.423, P = 0.014, 0.002, 0.0001, 0.012). Transcriptome sequencing revealed that differentially expressed genes were mainly enriched in the “neutrophil activation” and “platelet activation pathways” at 4 dpf and in the “neutrophil apoptosis”, “ferroptosis”, and “necroptosis” pathways at 7 dpf. Conclusion Tritiated water exposure induces a temporally dynamic immune response in zebrafish, potentially affecting immune homeostasis by regulating neutrophil activation and apoptosis, as well as the expression of NF-κB and NLRP3.

Objective: To comprehensively evaluate the current alanine aminotransferase (ALT) screening strategies and provide a basis for their optimization. Methods: ALT test results of 21 345 blood samples were collected from 33 blood collection institutions. Multiple probability distribution functions were employed to fit the data, and the akaike information criterion (AIC) was used to determine the optimal fitting model. Based on this model, 1 million random samplings were conducted to simulate the final ALT test results of blood donors under different ALT screening strategies, eligibility criteria, and pre-donation ALT detection deviations. A decision tree was subsequently constructed for health economic analysis. Results: The log-normal distribution with a mean of 2.96 and a variance of 0.65 provided the best fit for the data. When the eligibility criteria was 50 U/L and the pre-donation detection deviation was ±20%, not conducting pre-donation testing increased blood donation by 1.14%. When the pre-donation detection deviation was ±20% and the eligibility criteria was raised from 50 U/L to 100 U/L, conducting and not conducting pre-donation testing increased blood donation by 7.59% and 6.60%, respectively. With a eligibility criteria of 50 U/L and a pre-donation detection deviation of ±20%, 1.14% of eligible blood donors would be disqualified from donating blood. Health economic analysis showed that when the eligibility criteria was adjusted to 56 U/L or higher, not conducting pre-donation ALT testing was the dominant strategy; under other conditions, conducting pre-donation testing was the dominant strategy. Conclusion: The selection of ALT testing strategies is a complex process influenced by multiple factors, and it is necessary to adopt an appropriate ALT screening strategy based on specific testing circumstances.

OBJECTIVE: To observe the effects of "olfactory three needles" on cognition, learning and memory abilities, as well as hippocampal microglia (MG) phagocytic activity in vascular dementia (VD) rats, and explore the mechanisms of acupuncture in regulating MG activation and improving remyelination, so as to ameliorate VD. METHODS: Among 38 SD rats meeting experimental requirements, 9 rats were randomly assigned to a sham-operation group, and the remaining rats underwent permanent bilateral common carotid artery ligation to establish VD model. Eighteen successfully modeled rats were randomly divided into a model group and an electroacupuncture (EA) group, with 9 rats in each one. In the EA group, EA was performed at "olfactory three needles" ("Yintang" [GV24⁺] and bilateral "Yingxiang" [LI20]), at disperse-dense wave, the frequency of 2 Hz/15 Hz and the current intensity of 1 mA, for 15 min per intervention, once daily. One course was composed of 7 days, and 2 courses were required, with the interval of 2 days. The novel object recognition test was employed to assess the cognition of rats, and the Morris water maze was adopted to observe learning and memory abilities. Luxol fast blue (LFB) staining was performed to evaluate myelin sheath loss in the hippocampus, the Western blot was used to detect the protein expression of triggering receptor expressed on myeloid cells-2 (TREM2) and proteolipid protein (PLP) in the hippocampus; and the immunofluorescence staining was used to detect the positive expression of PLP, sex determining region Y-box 10 (SOX10), ionized calcium binding adaptor molecule 1 (Iba1)⁺ TREM2⁺ and Iba1⁺ lysosome-associated membrane protein 1 (LAMP1)⁺ in the hippocampus. RESULTS: Compared with the sham-operation group, the rats in the model group exhibited the prolonged escape latency on day 3 and 4 (P<0.05, P<0.01), the increase of the total distance traveling (P<0.01) and the decrease of the recognition index (RI) and platform crossing frequency (P<0.01). Compared with the model group, the rats in the EA group showed the shortened escape latency on day 3 and 4 (P<0.05), the decrease of total distance traveling (P<0.01) and the increase of RI and platform crossing frequency (P<0.05, P<0.01). When compared with the sham-operation group, the rats of the model group presented uneven staining, sparse arrangement of myelin sheath fibers, unclear contours, and prominent vacuole-like changes in the hippocampal CA1 region. When compared with the model group, the EA group showed more dense staining, the increase of myelin sheath fibers with more orderly alignment, and fewer vacuolar changes in the hippocampal CA1 region. Compared with the sham-operation group, the model group exhibited the increase of TREM2 protein expression and the decrease of PLP protein expression in the hippocampus (P<0.01), whereas the EA group showed the up-regulation of TREM2 and PLP protein expression when compared with the model group (P<0.01, P<0.05). The positive expression of the hippocampal PLP, SOX10, and Iba1⁺LAMP1⁺ in the model group was reduced in comparison with the sham-operation group (P<0.05, P<0.01), and the positive expression of Iba1⁺ TREM2⁺ was elevated (P<0.05). In the EA group, the positive expression of PLP, SOX10, Iba1⁺TREM2⁺, and Iba1⁺ LAMP1⁺ was higher compared with that in the model group (P<0.05, P<0.01). CONCLUSION "Olfactory three needles" can improve the learning and memory, and cognitive functions of VD rats, and its mechanism may be associated with the up-regulation of TREM2 and LAMP1 to adjust MG phagocytic activity and intracellular degradation, and promote remyelination.
Animals ; Dementia, Vascular/metabolism* ; Rats ; Rats, Sprague-Dawley ; Microglia/metabolism* ; Male ; Acupuncture Therapy/instrumentation* ; Acupuncture Points ; Humans ; Remyelination ; Memory ; Hippocampus/cytology* ; Cognition ; Electroacupuncture ; Needles

OBJECTIVE: To explore the clinical characteristics and prognosis of children with SIL-TAL1-positive T-cell acute lymphoblastic leukemia ( SIL-TAL1⁺ T-ALL). METHODS: The clinical data of 110 children with newly diagnosed T-ALL admitted to the pediatric department of our hospital from January 2010 to December 2018 were reviewed to compare the clinical characteristics, treatment response and prognosis between SIL-TAL1⁺ group and SIL-TAL1^-group. RESULTS: Among the 110 children with T-ALL, 25 cases (22.7%) were in the SIL-TAL1⁺ group and 85 cases (77.3%) in the SIL-TAL1^- group. The white blood cell (WBC) count in the SIL-TAL1⁺ group was significantly higher than that in the SIL-TAL1^- group (P < 0.05), while the other clinical characteristics and treatment response were not significantly different between the two groups. The 5-year overall survival (OS) rates of SIL-TAL1⁺ group and SIL-TAL1^- group were 80.0% and 75.5%, and 5-year disease-free survival (DFS) rates were 76.0% and 72.9%, respectively. There were no significant differences in OS rate and DFS rate between the two groups ( P >0.05). In children aged < 10 years, the 5-year OS rate of SIL-TAL1⁺ group and SIL-TAL1^- group was 100% and 75.1%, respectively, and the difference between the two groups was statistically significant (P < 0.05). CONCLUSION Although the WBC level is significantly higher in children with SIL-TAL1⁺ T-ALL than that in those with SIL-TAL1^- T-ALL, the treatment efficacy is similar between the two groups. In children aged < 10 years, the longterm survival rate is superior in the SIL-TAL1⁺ group.
Humans ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/diagnosis* ; Prognosis ; Child ; Male ; Female ; Survival Rate ; T-Cell Acute Lymphocytic Leukemia Protein 1 ; Child, Preschool ; Oncogene Proteins, Fusion ; Leukocyte Count

Objective:To summarize the clinical characteristics and first aid measures of children with drowning，and to provide scientific basis for the treatment and prevention of drowning in children.Methods:The clinical data of drowning children admitted to the Children's Medical Center of the First Affiliated Hospital of Hunan Normal University（Hunan Provincial People's Hospital）from January 2011 to December 2021 were retrospectively summarized. Baseline characteristics，prehospital emergency care and prognosis of the included children were analyzed.According to the time span, drowning children were divided into two stages, the first stage (2011-2016) and the second stage (2017-2021). According to cerebral performance category assessment scale,drowning children with cardiac arrest were divided into two groups: a group with good neurological prognosis and a group with poor neurological prognosis. The baseline characteristics,pre-hospital emergency care, and prognosis of drowning children during different periods and with different prognosis were analyzed.Results:A total of 53 children were enrolled during the study period，with 24 cases in the first phase（2011-2016）and 29 cases in the second phase（2017-2021）.Boys accounted for 73.6%（39/53）of the cases, the age ranged from 1 month and 24 days to 14 years old，with 1-4 years old being the most common，accounting for 58.5%（31/53）, and the season in which drowning occurred was more common in the summer（39.6%, 21/53）.Six cases (11.3%) had significant neurological sequelae, and the mortality rate was 3.8%（2/53）.There was a decrease in the proportion of drowning with water control in the second stage compared to the first stage（37.5% vs. 13.79%, P=0.046）.Thirty-two（60.4%）children experienced on-site cardiopulmonary resuscitation(CPR) after drowning，with 24 cases in the group with good neurological prognosis and 8 cases in the group with poor neurological prognosis.Children in the poor neurological prognosis group required CPR for a long duration [10.00（1.50, 25.00）min]，had lower body temperature，Glasgow Coma Score，pH and higher blood glucose levels on admission（all P < 0.05）. Conclusion:Drowning is most common in preschool children，common in boys，and drowning prevention measures for young children deserve focused attention. Children found to be in cardiac arrest at the time of drowning have a long duration of drowning and CPR，which predicts a poor neurological prognosis，and timely and effective on-site CPR is the key to reducing the drowning rate.

Objective:To explore the risk factors for malnutrition after a tracheotomy and to construct a predictive model useful for its prevention through early intervention.Methods:Clinical data describing 440 tracheotomy patients were subjected to a retrospective analysis. The variables examined were age, sex, etiology, Glasgow Coma Score (GCS), activities of daily living (ADL) score, age-corrected Charlson comorbidity index (aCCI), food intake, swallowing function, incidence of infections, as well as any history of diabetes mellitus, hypertension, smoking or alcohol consumption. Patients identified as being at risk of malnutrition (NRS-2002≥3) were screened using the Nutritional Risk Screening tool (NRS-2002) and the European Society of Clinical Nutrition and Metabolism′s ESPEN2015 criteria. The subjects were thus categorized into a malnutrition group of 343 and a control group of 97. Unifactorial and multifactorial logistic regression analyses were performed, and stepwise regression was applied to include the factors found significant in the unifactorial analysis into the multifactorial logistic regression analysis, and to construct a column-line graph prediction model. The clinical utility of the model was assessed by applying the receiver operator characteristics (ROC) curves, calibration plots and decision curve analysis (DCA).Results:Of the 440 persons studied, 343 (78%) were malnourished. The multivariate logistic regression analysis showed that pulmonary infection, dysphagia, low GCS score and high aCCI score were significant risk factors for malnutrition after a tracheotomy. A prediction nomograph was constructed. After fitting and correcting, the area under the curve (AUC) of the prediction model′s ROC curve was 0.911, the specificity was 80.4%, and the sensitivity was 91.3%. That was significantly higher than the AUCs for pulmonary infection (0.809), dysphagia (0.697), aCCI (0.721) and GCS (0.802). Bootstrap self-sampling was used to verify the model internally. After 1000 samples the average absolute error between the predicted risk and the actual risk was 0.013, indicating good prediction ability. The DCA results demonstrated that the model has substantial clinical applicability across a range of nutritional interventions, particularly for threshold probability values ranging from 0 to 0.96.Conclusion:Pulmonary infection, dysphagia, low GCS score, and high aCCI score are risk factors for malnutrition among tracheotomy patients. The nomogram model constructed in this study has good predictive value for the occurrence of malnutrition among such patients.

Regulated cell death (RCD) is a critical physiological process essential in maintaining skin homeostasis. Among the various forms of RCD, ferroptosis stands out due to its distinct features of iron accumulation, lipid peroxidation, and involvement of various inhibitory antioxidant systems. In recent years, an expanding body of research has solidly linked ferroptosis to the emergence of skin disorders. Therefore, understanding the mechanisms underlying ferroptosis in skin diseases is crucial for advancing therapy and prevention strategies. This review commences with a succinct elucidation of the mechanisms that underpin ferroptosis, embarks on a thorough exploration of ferroptosis’s role across a spectrum of skin conditions, encompassing melanoma, psoriasis, systemic lupus erythematosus (SLE), vitiligo, and dermatological ailments precipitated by ultraviolet (UV) exposure, and scrutinizes the potential therapeutic benefits of pharmacological interventions aimed at modulating ferroptosis for the amelioration of skin diseases.

Cells not only contain membrane-bound organelles (MBOs), but also membraneless organelles (MLOs) formed by condensation of many biomacromolecules. Examples include RNA-protein granules such as nucleoli and PML nuclear bodies (PML-NBs) in the nucleus, as well as stress granules and P-bodies in the cytoplasm. Phase separation is the basic organizing principle of the form of the condensates or membraneless organelles (MLOs) of biomacromolecules including proteins and nucleic acids. In particular, liquid-liquid phase separation (LLPS) compartmentalises and concentrates biological macromolecules into liquid condensates. It has been found that phase separation of biomacromolecules requires some typical intrinsic characteristics, such as intrinsically disordered regions, modular domains and multivalent interactions. The phase separation of biomacromolecules plays a key role in many important cell activities. In recent years, the phase separation of biomacromolecules phase has become a focus of research in gene transcriptional regulation. Transcriptional regulatory elements such as RNA polymerases, transcription factors (TFs), and super enhancers (SEs) all play important roles through phase separation. Our group has previously reported for the first time that long-term inactivation or absence of assembly factors leads to the formation of condensates of RNA polymerase II (RNAPII) subunits in the cytoplasm, and this process is reversible, suggesting a novel regulatory model of eukaryotic transcription machinery. The phase separation of biomacromolecules provides a biophysical understanding for the rapid transmission of transcriptional signals by a large number of TFs. Moreover, phase separation during transcriptional regulation is closely related to the occurrence of cancer. For example, the activation of oncogenes is usually associated with the formation of phase separation condensates at the SEs. In this review, the intrinsic characteristics of the formation of biomacromolecules phase separation and the important role of phase separation in transcriptional regulation are reviewed, which will provide reference for understanding basic cell activities and gene regulation in cancer.

Objective:To investigate the clinicopathological and genetic features of epithelioid and spindle cell rhabdomysarcoma with EWSR1-TFCP2 or FUS-TFCP2 fusion.Methods:The clinical, morphological and immunohistochemical features of 14 cases of epithelioid and spindle cell rhabdomysarcoma with EWSR1-TFCP2 or FUS-TFCP2 fusion diagnosed from January 2019 to December 2022 in the Department of Pathology, Foshan Traditional Chinese Medicine Hospital, Foshan, China were retrospectively analyzed. The cases were all subject to FISH or next generation sequencing for analysis of molecular genetic features. The literature was reviewed.Results:There were 5 males and 9 females, with the age at presentation ranging from 6 to 36 years (mean, 22 years). Tumors occurred in the head and neck (9 cases), pelvic region (2 cases), bladder (one case), right humerus (one case), and the abdominal wall, humerus and pubic at the same time (one case). Presenting symptoms varied by location but often included pain or discomfort. Most of the patients showed aggressive radiographic features with soft tissue extension. The tumors had a median size of 6.6 cm (range, 2-23 cm). The tumors were poorly defined and irregularly shaped. Microscopic examination showed diffuse proliferation of spindle or epithelioid cells. While morphologically high-grade tumors displayed obvious cytological atypia, a high mitotic count and tumor necrosis, low-grade tumors grew in sheets and fascicles composed of spindle, epithelioid cells with moderate or abundant amounts of eosinophilic cytoplasm, without pronounced cytological atypia. The tumor cells expressed Desmin, MyoD1, and Myogenin, as well as ALK, EMA, and CKpan. EWSR1/FUS-TFCP2 gene fusion was detected in 14 cases with next generation sequencing and confirmed by FISH. Six cases had EWSR1-TFCP2 fusions and 8 cases showed FUS-TFCP2 fusions. Follow-up information was available in 13 patients, ranged from 5 to 37 months. At the end of follow-up period, 7 patients died of the disease. Six patients were alive:two cases had local recurrences and metastases, two cases of recurrences, one case of metastasis and one case without recurrences and metastasis.Conclusions:Epithelioid and spindle cell rhabdomysarcomas with EWSR1-TFCP2 or FUS-TFCP2 fusion show a very aggressive clinical course, and more commonly occur in the head and neck. Their genetic hallmark is the presence of EWSR1/FUS-TFCP2 fusions. Familiarity with its clinicopathological characteristics is helpful in avoiding misdiagnoses.