Objective:To investigate alterations in the immune lineage of T-cell large granular lymphocytic leukemia (T-LGLL) at the single-cell transcriptome level and to elucidate its pathogenic mechanisms.Methods:Peripheral blood samples were collected from 5 T-LGLL patients before and after treatment (from June 2019 to December 2020) and 3 healthy controls at the Institute of Hematology & Blood Diseases Hospital, CAMS & PUMC. Single-cell transcriptome sequencing libraries were prepared and sequenced using 10× Genomics technology. Differentially expressed genes in immune cells were compared between patients and healthy donors, followed by pathway enrichment analyses.Results:Profiling 67,237 immune cells revealed that, in T-LGLL: 1) Effector CD8+ T cells exhibited increased numbers, enhanced cytotoxicity, and greater proliferative capacity. Following effective immunosuppressive therapy, both the proliferative capacity and effector functions of these cells significantly decreased ( P<0.05). 2) The proportion of regulatory T (Treg) cells was reduced, accompanied by increased apoptosis. After effective immunosuppressive therapy leading to remission, Treg cell proportions increased, and apoptotic pathways were downregulated ( P<0.05). 3) Antigen-presenting cells (APCs) showed enhanced functionality. Monocytes and dendritic cells were enriched in antigen synthesis and presentation pathways, while B cells displayed increased antigen-binding capacity and were enriched in pathways related to T-cell activation ( P<0.05). 4) Natural killer (NK) cells exhibited attenuated cytotoxic function but demonstrated an enhanced regulatory capacity over T cells ( P<0.05) . Conclusions:T-LGLL patients present a characteristic immunological profile marked by an imbalance in immune homeostasis. This profile includes abnormal activation and expansion of effector CD8 + T cells, and a reduction in Treg cell numbers accompanied by functional impairment. Furthermore, APCs and NK cells were found to positively regulate T-lymphocyte activation, differentiation, and proliferation.

Objective:To investigate the inhibitory effect of tripartite motif-containing 25 (TRIM25) on the replication of Japanese encephalitis virus (JEV) in cells and its molecular mechanism.Methods:Human glioma cells (U251 cells) and Kunming mice were infected with JEV, and then the cells and brain tissue samples were collected. The transcription levels of six TRIM genes were detected by real-time PCR, and the expression of TRIM25 in cells was detected by Western blot. U251 and A549 cells overexpressed with TRIM25 and U251 cells knocked out with TRIM25 gene were constructed. Cells were infected with JEV, and the replication of JEV was detected by viral plaque assay, real-time PCR and Western blot. The interaction of TRIM25 with viral proteins was investigated by co-immunoprecipitation (Co-IP) and indirect immunofluorescence assay. The expression of IFN-β in overexpressed TRIM25 cells was detected by real-time PCR and ELISA.Results:JEV infection promoted the expression of TRIM25 in cells and mouse brain tissues. TRIM25 overexpression restricted JEV replication in U251 and A549 cells, while TRIM25 knockout enhanced JEV replication. TRIM25 overexpression upregulated the level of IFN-β in cells. TRIM25 interacted with JEV capsid protein and promoted the degradation of capsid protein.Conclusion:TRIM25 can inhibit the replication of JEV in cells by upregulating IFN-β and promoting the degradation of JEV C protein.

Small cell lung cancer (SCLC) is the thoracic malignant tumor and accounts for about 15% of lung malignancies and transfer often occurs by the time of diagnosis. Extensive stage-small cell lung cancer (ES-SCLC) accounts for about 2/3 of all SCLC. For many years, radiotherapy has occupied an important position in the treatment of SCLC, especially in the treatment of ES-SCLC, because SCLC is more sensitive to radiotherapy. However, in recent years, immune checkpoint inhibitor has shown more excellent antitumor activity in the treatment of ES-SCLC and become the mainstream argument for the treatment of ES-SCLC. However, will radiotherapy be buried by the times among the therapeutic approaches for ES-SCLC? In this article, we will review the clinical progress of radiotherapy, immunotherapy and combination therapy for ES-SCLC.
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Humans ; Small Cell Lung Carcinoma/therapy* ; Lung Neoplasms/therapy* ; Immunotherapy ; Neoplasm Staging ; Radiotherapy/methods* ; Combined Modality Therapy

Objective:To construct a risk prediction model for non-suicidal self-injury (NSSI) in adolescents with mood disorders, providing a basis for identifying and intervening in high-risk patients.Methods:A convenience sampling method was used to retrospectively analyze 724 adolescent patients with mood disorders admitted to the open ward of Qingdao Mental Health Center from January 2019 to July 2023. Patients admitted from January 2019 to December 2022 (641 cases) were randomly divided into a modeling group and an internal validation group in a 7∶3 ratio, while patients admitted from January to July 2023 (83 cases) were used as an external validation group. A binary multivariate logistic regression analysis was used to construct a nomogram prediction model for NSSI risk in adolescents with mood disorders. The predictive performance of the model was evaluated using the area under the curve (AUC), sensitivity, and specificity.Results:There were 179 males and 545 females, aged 15 (14, 17) years old. Among the 724 patients, 449 were in the modeling group, 192 in the internal validation group, and 83 in the external validation group. The incidence of NSSI in the modeling group was 32.96% (148/449). Reduced food intake ( OR=10.980, 95% CI 4.462-27.017), passive contact ( OR=4.681, 95% CI 1.986-11.031), Hamilton Depression Rating Scale-17 score >17 ( OR=12.235, 95% CI 4.657-32.141), Hamilton Anxiety Rating Scale score>15 ( OR=27.888, 95% CI 8.700-124.630), Insomnia Severity Index score >15 ( OR=6.357, 95% CI 2.257-17.899), and higher levels of past self-injury ( OR=1.663, 95% CI 1.428-1.935) were independent risk factors for NSSI in adolescents with mood disorders (all P<0.05). The AUC of the nomogram model based on these six factors was 0.973, with a sensitivity of 0.94 and a specificity of 0.89. Conclusions:The risk prediction model for NSSI in adolescents with mood disorders has good discrimination, accuracy, and practicality, and can help identify high-risk NSSI populations among adolescents with mood disorders.

Objective:To construct a risk prediction model for non-suicidal self-injury (NSSI) in adolescents with mood disorders, providing a basis for identifying and intervening in high-risk patients.Methods:A convenience sampling method was used to retrospectively analyze 724 adolescent patients with mood disorders admitted to the open ward of Qingdao Mental Health Center from January 2019 to July 2023. Patients admitted from January 2019 to December 2022 (641 cases) were randomly divided into a modeling group and an internal validation group in a 7∶3 ratio, while patients admitted from January to July 2023 (83 cases) were used as an external validation group. A binary multivariate logistic regression analysis was used to construct a nomogram prediction model for NSSI risk in adolescents with mood disorders. The predictive performance of the model was evaluated using the area under the curve (AUC), sensitivity, and specificity.Results:There were 179 males and 545 females, aged 15 (14, 17) years old. Among the 724 patients, 449 were in the modeling group, 192 in the internal validation group, and 83 in the external validation group. The incidence of NSSI in the modeling group was 32.96% (148/449). Reduced food intake ( OR=10.980, 95% CI 4.462-27.017), passive contact ( OR=4.681, 95% CI 1.986-11.031), Hamilton Depression Rating Scale-17 score >17 ( OR=12.235, 95% CI 4.657-32.141), Hamilton Anxiety Rating Scale score>15 ( OR=27.888, 95% CI 8.700-124.630), Insomnia Severity Index score >15 ( OR=6.357, 95% CI 2.257-17.899), and higher levels of past self-injury ( OR=1.663, 95% CI 1.428-1.935) were independent risk factors for NSSI in adolescents with mood disorders (all P<0.05). The AUC of the nomogram model based on these six factors was 0.973, with a sensitivity of 0.94 and a specificity of 0.89. Conclusions:The risk prediction model for NSSI in adolescents with mood disorders has good discrimination, accuracy, and practicality, and can help identify high-risk NSSI populations among adolescents with mood disorders.

Objective:To investigate alterations in the immune lineage of T-cell large granular lymphocytic leukemia (T-LGLL) at the single-cell transcriptome level and to elucidate its pathogenic mechanisms.Methods:Peripheral blood samples were collected from 5 T-LGLL patients before and after treatment (from June 2019 to December 2020) and 3 healthy controls at the Institute of Hematology & Blood Diseases Hospital, CAMS & PUMC. Single-cell transcriptome sequencing libraries were prepared and sequenced using 10× Genomics technology. Differentially expressed genes in immune cells were compared between patients and healthy donors, followed by pathway enrichment analyses.Results:Profiling 67,237 immune cells revealed that, in T-LGLL: 1) Effector CD8+ T cells exhibited increased numbers, enhanced cytotoxicity, and greater proliferative capacity. Following effective immunosuppressive therapy, both the proliferative capacity and effector functions of these cells significantly decreased ( P<0.05). 2) The proportion of regulatory T (Treg) cells was reduced, accompanied by increased apoptosis. After effective immunosuppressive therapy leading to remission, Treg cell proportions increased, and apoptotic pathways were downregulated ( P<0.05). 3) Antigen-presenting cells (APCs) showed enhanced functionality. Monocytes and dendritic cells were enriched in antigen synthesis and presentation pathways, while B cells displayed increased antigen-binding capacity and were enriched in pathways related to T-cell activation ( P<0.05). 4) Natural killer (NK) cells exhibited attenuated cytotoxic function but demonstrated an enhanced regulatory capacity over T cells ( P<0.05) . Conclusions:T-LGLL patients present a characteristic immunological profile marked by an imbalance in immune homeostasis. This profile includes abnormal activation and expansion of effector CD8 + T cells, and a reduction in Treg cell numbers accompanied by functional impairment. Furthermore, APCs and NK cells were found to positively regulate T-lymphocyte activation, differentiation, and proliferation.

Objective:To investigate the inhibitory effect of tripartite motif-containing 25 (TRIM25) on the replication of Japanese encephalitis virus (JEV) in cells and its molecular mechanism.Methods:Human glioma cells (U251 cells) and Kunming mice were infected with JEV, and then the cells and brain tissue samples were collected. The transcription levels of six TRIM genes were detected by real-time PCR, and the expression of TRIM25 in cells was detected by Western blot. U251 and A549 cells overexpressed with TRIM25 and U251 cells knocked out with TRIM25 gene were constructed. Cells were infected with JEV, and the replication of JEV was detected by viral plaque assay, real-time PCR and Western blot. The interaction of TRIM25 with viral proteins was investigated by co-immunoprecipitation (Co-IP) and indirect immunofluorescence assay. The expression of IFN-β in overexpressed TRIM25 cells was detected by real-time PCR and ELISA.Results:JEV infection promoted the expression of TRIM25 in cells and mouse brain tissues. TRIM25 overexpression restricted JEV replication in U251 and A549 cells, while TRIM25 knockout enhanced JEV replication. TRIM25 overexpression upregulated the level of IFN-β in cells. TRIM25 interacted with JEV capsid protein and promoted the degradation of capsid protein.Conclusion:TRIM25 can inhibit the replication of JEV in cells by upregulating IFN-β and promoting the degradation of JEV C protein.

Objective:To evaluate the effect of ultrasound-guided internal branch of superior laryngeal nerve(ibSLN) block on the quality of anesthesia recovery in the patients undergoing intracranial tumor surgery.Methods:The data from patients of either gender, aged 18-65 yr, with a body mass index of 18-28 kg/m 2, who underwent intracranial tumor surgery from December 2022 to October 2023, were retrospectively collected. Patients were divided into control group (group C) and ultrasound-guided ibSLN block group (group U). Bilateral ibSLN block was performed with 0.375% ropivacaine hydrochloride 2 ml.The tracheal extubation time, emergence time, development of cardiovascular events within 15 min after extubation, emergence agitation, Ramsay sedation score, Steward recovery score, visual analogue scale scores at 10 min after extubation and development of postoperative sore throat and hoarseness in postanesthesia care unit were recorded. Results:Compared with group C, the incidence of emergence agitation, Ramsay sedation score, visual analogue scale scores and sore throat were significantly decreased, the incidence of hoarseness was increased ( P<0.05), and no significant change was found in the extubation time, emergence time and Steward recovery score in group U( P>0.05). No hypertension, hypotension, tachachycardia and bradycardia were found in two groups. Conclusions:Ultrasound-guided ibSLN block can improve the quality of anesthesia recovery in the patients undergoing intracranial tumor surgery.

OBJECTIVE To optimize the processing technology of wine steamed Cnidii Fructus. METHODS The content of xanthotoxol, xanthotoxin, bergapten, isobergapten, imperatorin and osthole was used as the evaluation index. The response surface methodology combined with entropy weight method was used to investigate the adding amount of rice wine, the soaking time and the steaming time with aim to find the best processing technology. RESULTS The best processing technology for Cnidii Fructus with wine steaming was: adding 30 g of rice wine 4 mL for infiltrating 18.5 h, and steaming for 10 h. CONCLUSION The optimized wine steaming process is stable and feasible. The establishment of an HPLC analytical method for the determination of 6 components in wine steamed Cnidii Fructus is accurate and reliable, which can be used for the quality control of wine steamed Cnidii Fructus decoction pieces.

Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.