It is believed that the occurrence and development of squamous cell carcinoma （SCC） is closely associated with inflammatory responses. The theory of fire and heat， advocated by LIU Wansu， provides significant clinical guidance for understanding the pathogenesis and treatment of SCC. Based on this theory， the pathological mechanisms and clinical characteristics of SCC at different stages were analyzed. In the precancerous and early stages， the primary pathogenesis is qi stagnation leading to internal generation of constrained heat； in post-surgery， the condition shifts to qi deficiency with latent yin fire； during the treatment phase， the pathogenesis involves accumulation of pathogenic factors， excess toxins， and severe heat toxicity； in the late stage， the main pathology is yin deficiency with toxic heat， and phlegm-stasis obstruction of the internal organs. Corresponding stage-based treatment strategies are proposed. In the early stage， regulating qi movement to dissipate constrained heat； for post-surgery， tonifying qi and raising yang to dispel latent fire； during treatment stage， clearing heat and detoxifying to eliminate cancerous toxins； and in the late stage， nourishing yin and unblocking the bowels to clear deficiency heat.

OBJECTIVE To systematically investigate the current status and effectiveness of the standardized on-the-job training program for community clinical pharmacists in Shanghai， and to provide a scientific basis for optimizing the training scheme. METHODS A questionnaire survey was conducted to collect the data from trainees and mentor pharmacists who participated in the program between 2016 and 2024. The survey examined their basic information， evaluations of the training scheme， satisfaction with training outcomes， and suggestions for improvement. Statistical analyses were also conducted. RESULTS A total of 420 valid responses were collected， including 340 from trainees and 80 from mentor pharmacists. Before training， only 30.29% of trainees were engaged in clinical pharmacy-related work， whereas this proportion increased to 73.24% after training. Most mentor pharmacists had extensive experience in clinical pharmacy （76.25% with ≥5 years of experience） and mentoring （78.75% with ≥3 teaching sessions）. Totally 65.59% of trainees and 55.00% of mentor pharmacists believed that blended training yielded the best learning outcomes. Over 80.00% of both trainees and mentor pharmacists considered the overall training duration， theoretical study time， and practical training time to be reasonable. More than 95.00% of trainees and mentor pharmacists agreed that the homework and assessment schemes were appropriate. Trainees rated the relevance of training content to their actual work highly （with an average relevance score ＞4.5）， though they perceived the chronic disease medication therapy management module as significantly more challenging than the prescription review and evaluation module and the home-based pharmaceutical care module. The average satisfaction score of trainees and mentor pharmacists with the training effectiveness of each project was above 4 points， indicating a high overall satisfaction. Inadequate provision of teaching resources was unanimously recognized by trainees and mentor pharmacists as the key area requiring improvement. CONCLUSIONS The standardized on-the-job training program for community clinical pharmacists in Shanghai has contributed to improving pharmaceutical services in community healthcare settings. However， ongoing improvements must concentrate on content design， resource development， and faculty cultivation.

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.

OBJECTIVES: To explore the expression profile of circular RNAs (circRNAs) and their potential roles in prognosis and progression of Wilms' tumor (WT). METHODS: Four pairs of WT and adjacent tissues were collected for high-throughput circRNA sequencing to identify the differentially expressed circular RNAs. RT-qPCR was used to verify the expression levels of the top 6 candidate circRNAs in the clinical samples. hsa_circ_0001900 was selected for analysis of its correlation with clinicopathological features and prognosis in 34 patients with WT. Sanger sequencing and RNase R digestion experiments were used to verify the cycling site and structural stability of hsa_circ_0001900 molecule. RESULTS: A total of 23 978 circular RNA molecules were identified in WT tissues by high-throughput circular RNA sequencing, and among them 614 were differentially expressed in WT. hsa_circ_0001900 showed the highest expression level among the differentially expressed circRNAs, which was consistent with the findings in clinical tumor samples and the sequencing results. Correlation analysis showed that hsa_circ_0001900 expression level was positively correlated with WT volume, and the children with high hsa_circ_0001900 expression had a lowered recurrence-free survival rate. The results of Sanger sequencing verified the circular splice site sequence of the molecule, and Rnase R digestion assay confirmed its stable covalent structure. CONCLUSIONS This study presents a comprehensive expression profile of circular RNAs in WT, and the expression level of hsa_circ_0001900 is related to the size of WT and the patients' prognosis, suggesting its possible role as a key driving gene in WT progression.
Humans ; RNA, Circular ; Wilms Tumor/pathology* ; Prognosis ; High-Throughput Nucleotide Sequencing ; Kidney Neoplasms/genetics* ; Sequence Analysis, RNA ; Male ; Female

Stromal interaction molecules (STIM)s are Ca²⁺ sensors in internal Ca²⁺ stores of the endoplasmic reticulum. They activate the store-operated Ca²⁺ channels, which are the main source of Ca²⁺ entry in non-excitable cells. Moreover, STIM proteins interact with other Ca²⁺ channel subunits and active transporters, making STIMs an important intermediate molecule in orchestrating a wide variety of Ca²⁺ influxes into excitable cells. Nevertheless, little is known about the role of STIM proteins in brain functioning. Being involved in many signaling pathways, STIMs replenish internal Ca²⁺ stores in neurons and mediate synaptic transmission and neuronal excitability. Ca²⁺ dyshomeostasis is a signature of many pathological conditions of the brain, including neurodegenerative diseases, injuries, stroke, and epilepsy. STIMs play a role in these disturbances not only by supporting abnormal store-operated Ca²⁺ entry but also by regulating Ca²⁺ influx through other channels. Here, we review the present knowledge of STIMs in neurons and their involvement in brain pathology.
Neurons/metabolism* ; Animals ; Humans ; Calcium/metabolism* ; Stromal Interaction Molecules/metabolism* ; Calcium Signaling/physiology* ; Calcium Channels/metabolism* ; Brain/metabolism*

Objective:To analyze the correlation between MRI indicators and clinical features of multifidus degeneration in patients with unilateral lumbar disc hemiation. Method:Eighty-six eligible patients with unilateral lumbar disc hemiation admitted to our hospital from Janu-ary 2018 to December 2021 with complete clinical data were retrospectively analyzed and divided into three groups according to the level and number of lumbar disc hemiation:27 patients in group A were treated with L4/5 disc hemiation only,30 patients in group B were treated with L5/S1 disc hemiation only,and 29 pa-tients with multi-level lumbar disc hemiation in group C.All patients underwent lumbar MRI scans,and the measurements included the ratio of the total cross-sectional area of the unaffected and affected sides of the multifidus muscle at L4/5 and L5/S1 levels,the degree of bilateral multifidus muscle atrophy,and the propor-tion of fatty infiltration.The lumbar visual analogue scale(VAS),Oswestry disability index(ODI)and other clinical features of patients with lumbar disc herniation were obtained from the medical records,and Spearman correlation was used to analyze the correlation between the ratio of the total cross-sectional area of the unaffect-ed and affected sides of the multifidus muscle at L4/5 and L5/S1 levels and the proportion of fatty infiltration. Result:There was no significant difference in age,gender and body mass index(BMI)between the groups(P＞0.05);the total cross-sectional area ratio of the unaffected and affected sides of the multifidus muscle in the three groups was positively correlated with the VAS score(P＜0.05)and not correlated with the ODI score(P＞0.05);the degree of bilateral multifidus muscle atrophy and the proportion of fatty infiltration were posi-tively correlated with the ODI score(P＜0.05)and not correlated with the VAS score(P＞0.05). Conclusion:In patients with unilateral lumbar disc herniation,the degree of asymmetry in the left and right cross-sectional areas of the multifidus muscle was associated with lumbar pain,whereas the degree of bilateral multifidus muscle atrophy and the proportion of fatty infiltration were associated with ODI scores.

Immunotherapy drugs are a class of medications that treat diseases by modulating the function of immune system.As frontline therapies in clinical practice,they play a particularly crucial role in alleviating disease symptoms and improving adverse prognoses caused by severe inflammation.In recent years,with the rapid development of internet technology and the continuous innova-tion in the technology industry,various national directives have been issued,urging schools to strengthen online teaching and promote the development of"Internet+education".Online teaching,unaffected by time or geographical constraints,has facilitated resource sharing and stimulated student interest.However,in practice,both singular online or offline teaching models have their drawbacks.This article takes the severe inflammation immunotherapy drugs as an example,integrating the concept of intersubjectivity in teaching to explore a"two-line"teaching mode in immunotherapy drugs.This study views students as the main body of learning,emphasizes the importance of individual learning,and solves the drawbacks of"one-line"teaching mode.Exploration and application of intersubjective"two-line"teaching mode has guiding significance for educational reform in the internet era.

Purpose To predict the 2015 American thyroid association(ATA)recurrence risk stratification based on ultrasonographic features and Hashimoto's thyroiditis(HT)-specific antibody status of papillary thyroid carcinoma(PTC)in the context of HT.Materials and Methods A retrospective analysis was conducted on the ultrasonographic and clinical data of 479 patients with coexisting PTC and HT,who underwent their first thyroid surgery at the First Medical Center of Chinese PLA General Hospital from January 2017 to December 2019.All patients were divided in chronological order into a training group(n=327)and a validation group(n=152).Multivariate Logistic regression analysis was utilized to identify independent factors associated with high recurrence risk stratification according to the ATA guidelines.Predictive models were constructed and screened,and the efficacy of these models was evaluated using the area under the curve,calibration curves and Brier scores.Results Multivariate Logistic regression analysis identified the following as independent predictive factors for high recurrence risk stratification:multifocal malignancy of nodules(OR=3.812,95％CI 1.275-11.397,P=0.017),nodule contact with the capsule(OR=8.012,95％CI 1.647-38.972,P=0.010),microcalcifications(OR=4.220,95％CI 1.302-13.678,P=0.016),an aspect ratio＞1(OR=4.017,95％CI 1.286-12.548,P=0.017),abundant nodule vascularity(OR=6.120,95％CI 2.225-16.832,P＜0.001),maximum nodule diameter ≥1 cm(OR=4.784,95％CI 1.360-16.833,P=0.015),a glandular echo characteristic of typical HT(OR=0.114,95％CI 0.039-0.330,P＜0.001),and anti-thyroid peroxidase antibody monopositivity(OR=0.088,95％CI 0.006-1.299,P=0.077).The predictive model demonstrated strong performance,as evidenced by the area under the curve of 0.942(95％CI 0.911-0.972)in the training set and 0.933(95％CI 0.878-0.990)in the validation set.Both groups exhibited well-fitting calibration curves.The Brier scores were 0.054 and 0.058 for the training and validation sets,respectively,indicating excellent predictive efficacy of the model.Conclusion The preoperative prediction model,based on ultrasonographic features combined with antibody status,demonstrates good efficacy in assessing ATA recurrence risk stratification for coexisting PTC and HT patients,which can assist clinicians in formulating treatment plans.

Objective:To evaluate clinical efficacy of local treatment for prostate cancer patients with bone metastases at the initial diagnosis.Methods:Clinical data of 211 prostate cancer patients with bone metastases at the initial diagnosis admitted to the First Affiliated Hospital of Soochow University from January 2014 to December 2021 were retrospectively analyzed. All patients were divided into the systemic and combined local treatment groups according to whether they received local treatment or not. Patients in the combined local treatment group were further divided into the prostatectomy and radical radiotherapy groups. According to whether they received radiotherapy, they were divided into the radiotherapy and non-radiotherapy groups. Statistical analysis was performed by SPSS 26.0 statistical software. The differences in the survival of patients among different groups were analyzed and compared by Kaplan-Meier method and log-rank test. The comparison was repeatedly conducted after the propensity score matching. Clinical characteristics and treatment factors of patients were included in Cox's proportional hazard regression model, and their relationship with survival was analyzed.Results:Compared with systemic treatment, local treatment significantly improved the 5-year clinical progression-free survival (CPFS) and 5-year overall survival (OS) ( P=0.049, 0.010). After propensity score matching was performed, patients in the local treatment group outperformed those in the systemic treatment in 5-year biochemical progression-free survival (BPFS) and 5-year OS ( P=0.036, 0.029). There were no statistically significant differences in 5-year BPFS, CPFS and OS between the prostatectomy and radical radiotherapy groups. Radiotherapy improved 5-year BPFS and 5-year OS compared with non-radiotherapy ( P=0.030, 0.020). After propensity score matching was performed, 5-year BPFS and 5-year OS in the radiotherapy group remained significantly higher than those in the non-radiotherapy group ( P=0.046, 0.047). Overall, patients who received radiotherapy were well tolerated and did not experience serious radiation-related adverse events. Radiotherapy improved 5-year OS for patients who were older than 65 years, had bone metastases confined to the pelvis and had a Gleason score of ≤ 8 ( P=0.039, 0.024, 0.036). Conclusions:Local treatment, especially radiotherapy, prolongs BPFS and OS rates in prostate cancer patients with bone metastases at first diagnosis. Radiotherapy appears to be more effective in patients of advanced age, with bone metastases confined to the pelvis and with relatively low Gleason scores.

Background::T-cell-mediated immunity is crucial for the effective clearance of viral infection, but the T-cell-mediated immune responses that are induced by booster doses of inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in people living with human immunodeficiency virus (PLWH) remain unclear.Methods::Forty-five PLWH who had received antiretroviral therapy (ART) for more than two years and 29 healthy controls (HCs) at Beijing Youan Hospital were enrolled to assess the dynamic changes in T-cell responses between the day before the third vaccine dose (week 0) and 4 or 12 weeks (week 4 or week 12) after receiving the third dose of inactivated SARS-CoV-2 vaccine. Flow cytometry, enzyme-linked immunospot (ELISpot), and multiplex cytokines profiling were used to assess T-cell responses at the three timepoints in this study.Results::The results of the ELISpot and activation-induced marker (AIM) assays showed that SARS-CoV-2-specific T-cell responses were increased in both PLWH and HCs after the third dose of the inactivated SARS-CoV-2 vaccine, and a similar magnitude of immune response was induced against the Omicron (B.1.1.529) variant compared to the wild-type strain. In detail, spike-specific T-cell responses (measured by the ELISpot assay for interferon γ [IFN-γ] release) in both PLWH and HCs significantly increased in week 4, and the spike-specific T-cell responses in HCs were significantly stronger than those in PLWH 4 weeks after the third vaccination. In the AIM assay, spike-specific CD4 + T-cell responses peaked in both PLWH and HCs in week 12. Additionally, significantly higher spike-specific CD8 + T-cell responses were induced in PLWH than in HCs in week 12. In PLWH, the release of the cytokines interleukin-2 (IL-2), tumour necrosis factor-alpha (TNF-α), and IL-22 by peripheral blood mononuclear cells (PBMCs) that were stimulated with spike peptides increased in week 12. In addition, the levels of IL-4 and IL-5 were higher in PLWH than in HCs in week 12. Interestingly, the magnitude of SARS-CoV-2-specific T-cell responses in PLWH was negatively associated with the extent of CD8 + T-cell activation and exhaustion. In addition, positive correlations were observed between the magnitude of spike-specific T-cell responses (determined by measuring IFN-γ release by ELISpot) and the amounts of IL-4, IL-5, IL-2 and IL-17F. Conclusions::Our findings suggested that SARS-CoV-2-specific T-cell responses could be enhanced by the booster dose of inactivated COVID-19 vaccines and further illustrate the importance of additional vaccination for PLWH.