Purpose: Leptin interacts not only with leptin receptor (LEPR) but also engages with other receptors. While the pro-oncogenic effects of the adrenergic receptor β2 (ADRB2) are well-established, the role of leptin in activating ADRB2 in triple-negative breast cancer (TNBC) remains unclear. Materials and Methods: The pro-carcinogenic effects of LEPR were investigated using murine TNBC cell lines, 4T1 and EMT6, and a tumor-bearing mouse model. Expression levels of LEPR, NADPH oxidase 4 (NOX4), and ADRB2 in TNBC cells and tumor tissues were analyzed via western blot and quantitative real-time polymerase chain reaction. Changes in reactive oxygen species (ROS) levels were assessed using flow cytometry and MitoSox staining, while immunofluorescence double-staining confirmed the co-localization of LEPR and ADRB2. Results: LEPR activation promoted NOX4-derived ROS and mitochondrial ROS production, facilitating TNBC cell proliferation and migration, effects which were mitigated by the LEPR inhibitor Allo-aca. Co-expression of LEPR and ADRB2 was observed on cell membranes, and bioinformatics data revealed a positive correlation between the two receptors. Leptin activated both LEPR and ADRB2, enhancing intracellular ROS generation and promoting tumor progression, which was effectively countered by a specific ADRB2 inhibitor ICI118551. In vivo, leptin injection accelerated tumor growth and lung metastases without affecting appetite, while treatments with Allo-aca or ICI118551 mitigated these effects. Conclusion This study demonstrates that leptin stimulates the growth and metastasis of TNBC through the activation of both LEPR and ADRB2, resulting in increased ROS production. These findings highlight LEPR and ADRB2 as potential biomarkers and therapeutic targets in TNBC.

ObjectiveTo investigate the clinical features of patients with acute-on-chronic liver failure （ACLF）， and to construct a risk scoring table that can accurately predict the prognosis of patients in the early stage. MethodsA retrospective analysis was performed for the clinical data of 502 patients with ACLF who were admitted to Tangdu Hospital， Air Force Medical University， from January 1， 2010 to December 31， 2020 （training set）， and the influencing factors for 28-day mortality rate were identified. The 69 ACLF patients who were admitted to Tangdu Hospital， Air Force Medical University， from January 1 to December 31， 2021 were enrolled as the validation set. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups， and the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. A univariate Cox regression analysis was used to obtain the early warning indicators associated with the 28-day prognosis of ACLF patients， and variance inflation factors were used to assess multicollinearity among predictors； a multivariate Cox regression analysis was used to construct a risk model for ACLF prognosis （mortality）. A risk scoring table for ACLF prognosis （mortality） was developed based on regression coefficients （β） from the model equation and weight assignments in the nomogram. Internal validation and comparison were performed for the risk model for ACLF prognosis （mortality）， the scoring table for ACLF prognosis （mortality）， and other scoring models （Child-Turcotte-Pugh ［CTP］ score， Model for End-Stage Liver Disease ［MELD］ score， MELD combined with serum sodium concentration ［MELD-Na］ score， and integrated MELD ［iMELD］ score） in the training set， while external validation and comprehensive evaluation of the scoring table and the other scoring models were performed in the validation set. The Nagelkerke’s R² test and the Hosmer-Lemeshow test were used to assess the degree of fitting of the risk model for ACLF prognosis （mortality）， the scoring table for ACLF prognosis （mortality）， and other scoring models， and fitting curves were plotted. C-index was used to assess the discriminatory ability of the scoring table for ACLF prognosis （mortality） and the other scoring models， and the Z-test was used for comparison of C-index between different models. The decision curve analysis was used to compare the clinical benefits of the scoring table for ACLF prognosis （mortality） and the other scoring models. ResultsThe multivariate Cox regression analysis showed that age （hazard ratio ［HR］=1.027， 95% confidence interval ［CI］： 1.015 — 1.039， P<0.001）， hepatic encephalopathy grade （grade 1： HR=2.928， 95%CI： 1.463 — 5.858， P=0.002； grade 2： HR=3.811， 95%CI： 2.078 — 6.988， P<0.001； grade 3： HR=3.916， 95%CI： 1.917 — 8.001， P<0.001； grade 4： HR=6.966， 95%CI： 4.559 — 10.644， P<0.001）， an increase in total bilirubin （TBil） by ≥17.1 μmol/L per day （HR=1.771， 95%CI： 1.248 — 2.513， P=0.001）， creatinine （HR=1.005， 95%CI： 1.004 — 1.006， P<0.001）， neutrophil count （HR=1.092， 95%CI： 1.060 — 1.126， P<0.001）， and international normalized ratio （HR=1.298， 95%CI： 1.187 — 1.418， P<0.001） were independent risk factors associated with the 28-day mortality rate of ACLF patients， and a risk scoring table was constructed for ACLF prognosis （mortality）. The Nagelkerke’s R² test showed that the risk scoring table for ACLF prognosis （mortality） had an R² value of 0.599 in the training set and 0.722 in the validation set， which were higher than the R² values of CTP， MELD， MELD-Na， and iMELD scores. The Hosmer-Lemeshow test showed that the risk scoring table for ACLF prognosis （mortality） had a P value of 0.280 in the training set and 0.788 in the validation set. The C-index analysis showed that the scoring table had a higher C-index than the other scoring models in the validation set （all P<0.001）， as well as a higher C-index than CTP score in the training set （P<0.001）. The decision curve analysis showed that the risk scoring table for ACLF prognosis （mortality） had higher clinical net benefits than the other scoring models. ConclusionCompared with other scoring models currently used in clinical practice， the novel risk scoring table for ACLF prognosis （mortality） constructed based on the six predictive factors of age， hepatic encephalopathy grade， an increase in TBil by ≥17.1 μmol/L per day， creatinine， neutrophil count， and international normalized ratio has a relatively high value in predicting the 28-day prognosis of ACLF patients.

Purpose: Leptin interacts not only with leptin receptor (LEPR) but also engages with other receptors. While the pro-oncogenic effects of the adrenergic receptor β2 (ADRB2) are well-established, the role of leptin in activating ADRB2 in triple-negative breast cancer (TNBC) remains unclear. Materials and Methods: The pro-carcinogenic effects of LEPR were investigated using murine TNBC cell lines, 4T1 and EMT6, and a tumor-bearing mouse model. Expression levels of LEPR, NADPH oxidase 4 (NOX4), and ADRB2 in TNBC cells and tumor tissues were analyzed via western blot and quantitative real-time polymerase chain reaction. Changes in reactive oxygen species (ROS) levels were assessed using flow cytometry and MitoSox staining, while immunofluorescence double-staining confirmed the co-localization of LEPR and ADRB2. Results: LEPR activation promoted NOX4-derived ROS and mitochondrial ROS production, facilitating TNBC cell proliferation and migration, effects which were mitigated by the LEPR inhibitor Allo-aca. Co-expression of LEPR and ADRB2 was observed on cell membranes, and bioinformatics data revealed a positive correlation between the two receptors. Leptin activated both LEPR and ADRB2, enhancing intracellular ROS generation and promoting tumor progression, which was effectively countered by a specific ADRB2 inhibitor ICI118551. In vivo, leptin injection accelerated tumor growth and lung metastases without affecting appetite, while treatments with Allo-aca or ICI118551 mitigated these effects. Conclusion This study demonstrates that leptin stimulates the growth and metastasis of TNBC through the activation of both LEPR and ADRB2, resulting in increased ROS production. These findings highlight LEPR and ADRB2 as potential biomarkers and therapeutic targets in TNBC.

Objective:To investigate the clinical efficacy of haploidentical high-dose in vitro non-T-cell-depleted peripheral blood hematopoietic stem cell transplantation (haplo-HDPSCT) in treating adult patients with Ph + acute lymphoblastic leukemia (Ph + ALL) . Method:This retrospective analysis was conducted on the clinical efficacy of 25 adult patients with Ph + ALL who underwent haplo-HDPSCT from July 2011 to June 2022 at our hospital. Results:This study included 25 patients with a median age of 27 (16-61) years, consisting of 12 males and 13 females. CR1 and ≥CR2 before transplantation were found in 23 and 2 cases, positive and negative minimal residual lesions were observed in 8 and 17 cases, and myeloablative conditioning and reduced-intensity conditioning were reported in 21 and 4 cases, respectively. Hematopoietic function was restored in all 25 patients after stem cell infusion. Of the 25 patients who underwent transplantation, 16 developed acute graft-versus-host disease (aGVHD). The cumulative incidence rates of Ⅱ-Ⅳ and Ⅲ-Ⅳ aGVHD were (40.4±11.3) % and (4.8±4.6) %, respectively. Four patients experienced relapse after transplantation, the cumulative relapse rates at 1 and 2 years after transplantation were (4.0±3.9) % and (14.5±7.9) %, respectively. The 2-year overall survival rate after transplantation was (81.3±8.5) % and the disease-free survival rate was (77.1±9.1) %.Conclusion:This study reveals that the unique haplo-HDPSCT protocol achieves good clinical efficacy in Ph + ALL treatment.

Purpose: Leptin interacts not only with leptin receptor (LEPR) but also engages with other receptors. While the pro-oncogenic effects of the adrenergic receptor β2 (ADRB2) are well-established, the role of leptin in activating ADRB2 in triple-negative breast cancer (TNBC) remains unclear. Materials and Methods: The pro-carcinogenic effects of LEPR were investigated using murine TNBC cell lines, 4T1 and EMT6, and a tumor-bearing mouse model. Expression levels of LEPR, NADPH oxidase 4 (NOX4), and ADRB2 in TNBC cells and tumor tissues were analyzed via western blot and quantitative real-time polymerase chain reaction. Changes in reactive oxygen species (ROS) levels were assessed using flow cytometry and MitoSox staining, while immunofluorescence double-staining confirmed the co-localization of LEPR and ADRB2. Results: LEPR activation promoted NOX4-derived ROS and mitochondrial ROS production, facilitating TNBC cell proliferation and migration, effects which were mitigated by the LEPR inhibitor Allo-aca. Co-expression of LEPR and ADRB2 was observed on cell membranes, and bioinformatics data revealed a positive correlation between the two receptors. Leptin activated both LEPR and ADRB2, enhancing intracellular ROS generation and promoting tumor progression, which was effectively countered by a specific ADRB2 inhibitor ICI118551. In vivo, leptin injection accelerated tumor growth and lung metastases without affecting appetite, while treatments with Allo-aca or ICI118551 mitigated these effects. Conclusion This study demonstrates that leptin stimulates the growth and metastasis of TNBC through the activation of both LEPR and ADRB2, resulting in increased ROS production. These findings highlight LEPR and ADRB2 as potential biomarkers and therapeutic targets in TNBC.

[Purpose]To analyze the incidence and mortality of colorectal cancer in Zhejiang can-cer registration areas in 2021 and its temporal trends from 2000 to 2021.[Methods]Data from 22 cancer registries in Zhejiang Province in 2021 that met the quality standards were included.The crude incidence/mortality rate,age-standardized incidence/mortality rates by Chinese standard population(ASIRC/ASMRC)and by world standard population(ASIRW/ASMRW),and cumulative incidence(mortality)rate for 0～74 years old were calculated.Trends from 2000 to 2021 were ana-lyzed using the Joinpoint regression model by calculating the annual percentage change(APC)and average annual percentage change(AAPC).[Results]In 2021,the number of new colorectal cancer cases in Zhejiang cancer registration areas was 12 265,with 4 323 deaths.ASIRC and ASMRC were significantly higher in men(32.74/105 and 10.11/105)than those in women(20.78/105 and 5.99/105).Urban areas showed higher ASIRC and ASMRC(28.27/105 and 8.06/105)than rural areas(24.12/105 and 7.85/105).The age-specific incidence and mortality rates of colorectal cancer in Zhejiang Province showed an increasing trend with age,with a peak of 219.63/105 in the age group of 80～84 years old.The age-specific mortality rate peaked in the age group of 85 years old and above,with a peak of 199.65/105.From 2000 to 2021,ASIRC in Zhejiang Province showed an upward trend(AAPC=2.23％,P＜0.001),ASMRC showed a marginal increase(AAPC=0.78％,P=0.067).[Conclusion]The incidence of colorectal cancer in Zhejiang Province had been on a continuous rise in the past 22 years,and health education and early screening should be empha-sized.

Objective:To analyze the epidemiological and clinical features of infectious diseases of the central nervous system (CNS).Methods:A cross-sectional study and analysis were conducted to summarize the epidemiological and clinical characteristics of 9 918 patients with CNS infectious diseases, who were diagnosed and treated at 29 hospitals across China from January 1, 2001 to December 31, 2020. Data collected included demographic data, clinical manifestations, health economic indicators, and prognostic outcomes.Results:Among the 9 918 collected cases of CNS infectious diseases, 5 559 were male (56.0%) and 4 359 were female (44.0%), with an onset age of 38 (25, 53) years. Education level: slightly more junior high school education (2 651 cases, 26.7%), and less elementary school education and below (2 181 cases, 22.0%) were found. Occupational distribution: farmers were found predominant (3 215 cases, 32.4%), followed by workers (1 826 cases, 18.4%) and students (1 633 cases, 16.5%). Clinical manifestations: headache (6 074 cases, 61.2%), fever (5 869 cases, 59.2%) and positive meningeal irritation signs (2 273 cases, 22.9%) were the 3 most common clinical manifestations, followed by nausea and (or) vomiting (2 095 cases, 21.1%), impaired consciousness (2 077 cases, 20.9%), psychiatric symptom (1 866 cases, 18.8%) and epilepsy (1 627 cases, 16.4%), etc., and cranial nerve involvement was found in 669 cases (6.7%). Major pathogens included viruses in 6 814 cases (68.7%), Mycobacterium tuberculosis in 1 677 cases (16.9%), common bacteria in 864 cases (8.7%), fungi in 254 cases (2.6%), spirochetes of syphilis in 183 cases (1.8%), parasites in 121 cases (1.2%), and rickettsiae in 5 cases (0.1%). Urban-rural distribution: slightly more cases were found in the countryside (5 418 cases, 54.6%) than in the towns (4 500 cases, 45.4%). Distribution of onset by season: 2 412 cases (24.3%) fell ill in spring, 2 835 cases (28.6%) in summer, 2 187 cases (22.1%) in fall, and 2 484 cases (25.0%) in winter. Health economics: the duration of hospitalization was 15 (8, 27) days, and the cost of hospitalization was 1.53 (0.91, 3.02)×10 000 yuan. Prognosis: 9 531 cases (96.1%) were cured or improved, and 92 cases (0.9%) died. Conclusions:The pathogens responsible for CNS infectious diseases are predominantly viruses. Although the incidence is slightly higher during the summer months, the overall seasonal pattern is not particularly pronounced. These infections are more commonly observed in young and middle-aged males and present with a diverse range of clinical manifestations, contributing to a significant disease burden.

Objective:To investigate and analyze the predictive value of inhibin A (INHA), galectin-13 (Gal-13), leucine rich alpha-2-glycoprotein 1 (LRG1) in serum for adverse pregnancy outcomes in pregnant women with gestational diabetes mellitus (GDM) .Methods:From Jan. 2022 to Dec. 2023, 87 GDM pregnant women admitted to Obstetrics Department of Shanxi Children’s Hospital were included as the study group, and were assigned into a good outcome group ( n=54) and an adverse outcome group ( n=33) based on pregnancy outcomes. Meantime, another 87 healthy pregnant women who underwent normal prenatal examinations at our hospital and had no complications were selected as the control group. ELISA method was applied to detect serum levels of INHA, LRG1, and Gal-13. Multiple factor Logistic regression model was constructed to analyze the factors affecting adverse pregnancy outcomes in GDM pregnant women. Receiver operating characteristic (ROC) curves were applied to evaluate the efficacy of the three methods in predicting adverse pregnancy outcomes in GDM pregnant women. Results:Compared with the control group, the levels of INHA and LRG1 in the serum of pregnant women in the study group were obviously higher, and the level of Gal-13 in the serum was obviously lower ( P<0.05). Compared with the good outcome group, the adverse outcome group showed an increase in serum INHA and LRG1 levels and a decrease in serum Gal-13 level ( P<0.05). Elevated levels of serum INHA and LRG1 were risk factors for adverse pregnancy outcomes in GDM pregnant women, while elevated level of serum Gal-13 was a protective factor ( P<0.05). The AUC values for predicting adverse pregnancy outcomes in GDM pregnant women based solely on serum INHA, Gal-13, and LRG1 levels were 0.859, 0.850, and 0.841, respectively. The AUC predicted by the combination of the three factors was 0.978, which was better than the individual predictions of serum INHA, Gal-13, and LRG1 ( Zcombination-HA=2.378, Z combination-Gal-13=3.193, Zcombination-LRG1=3.050, P=0.017, 0.001, 0.002) . Conclusions:Serum levels of INHA and LRG1 are elevated in GDM pregnant women, while serum level of Gal-13 is decreased. All three are potential factors that affect the pregnancy outcomes of GDM pregnant women, and the combination of the three shows higher efficacy in predicting adverse pregnancy outcomes in GDM pregnant women.

Objective:To investigate the clinical efficacy of haploidentical high-dose in vitro non-T-cell-depleted peripheral blood hematopoietic stem cell transplantation (haplo-HDPSCT) in treating adult patients with Ph + acute lymphoblastic leukemia (Ph + ALL) . Method:This retrospective analysis was conducted on the clinical efficacy of 25 adult patients with Ph + ALL who underwent haplo-HDPSCT from July 2011 to June 2022 at our hospital. Results:This study included 25 patients with a median age of 27 (16-61) years, consisting of 12 males and 13 females. CR1 and ≥CR2 before transplantation were found in 23 and 2 cases, positive and negative minimal residual lesions were observed in 8 and 17 cases, and myeloablative conditioning and reduced-intensity conditioning were reported in 21 and 4 cases, respectively. Hematopoietic function was restored in all 25 patients after stem cell infusion. Of the 25 patients who underwent transplantation, 16 developed acute graft-versus-host disease (aGVHD). The cumulative incidence rates of Ⅱ-Ⅳ and Ⅲ-Ⅳ aGVHD were (40.4±11.3) % and (4.8±4.6) %, respectively. Four patients experienced relapse after transplantation, the cumulative relapse rates at 1 and 2 years after transplantation were (4.0±3.9) % and (14.5±7.9) %, respectively. The 2-year overall survival rate after transplantation was (81.3±8.5) % and the disease-free survival rate was (77.1±9.1) %.Conclusion:This study reveals that the unique haplo-HDPSCT protocol achieves good clinical efficacy in Ph + ALL treatment.

Objective:To analyze the epidemiological and clinical features of infectious diseases of the central nervous system (CNS).Methods:A cross-sectional study and analysis were conducted to summarize the epidemiological and clinical characteristics of 9 918 patients with CNS infectious diseases, who were diagnosed and treated at 29 hospitals across China from January 1, 2001 to December 31, 2020. Data collected included demographic data, clinical manifestations, health economic indicators, and prognostic outcomes.Results:Among the 9 918 collected cases of CNS infectious diseases, 5 559 were male (56.0%) and 4 359 were female (44.0%), with an onset age of 38 (25, 53) years. Education level: slightly more junior high school education (2 651 cases, 26.7%), and less elementary school education and below (2 181 cases, 22.0%) were found. Occupational distribution: farmers were found predominant (3 215 cases, 32.4%), followed by workers (1 826 cases, 18.4%) and students (1 633 cases, 16.5%). Clinical manifestations: headache (6 074 cases, 61.2%), fever (5 869 cases, 59.2%) and positive meningeal irritation signs (2 273 cases, 22.9%) were the 3 most common clinical manifestations, followed by nausea and (or) vomiting (2 095 cases, 21.1%), impaired consciousness (2 077 cases, 20.9%), psychiatric symptom (1 866 cases, 18.8%) and epilepsy (1 627 cases, 16.4%), etc., and cranial nerve involvement was found in 669 cases (6.7%). Major pathogens included viruses in 6 814 cases (68.7%), Mycobacterium tuberculosis in 1 677 cases (16.9%), common bacteria in 864 cases (8.7%), fungi in 254 cases (2.6%), spirochetes of syphilis in 183 cases (1.8%), parasites in 121 cases (1.2%), and rickettsiae in 5 cases (0.1%). Urban-rural distribution: slightly more cases were found in the countryside (5 418 cases, 54.6%) than in the towns (4 500 cases, 45.4%). Distribution of onset by season: 2 412 cases (24.3%) fell ill in spring, 2 835 cases (28.6%) in summer, 2 187 cases (22.1%) in fall, and 2 484 cases (25.0%) in winter. Health economics: the duration of hospitalization was 15 (8, 27) days, and the cost of hospitalization was 1.53 (0.91, 3.02)×10 000 yuan. Prognosis: 9 531 cases (96.1%) were cured or improved, and 92 cases (0.9%) died. Conclusions:The pathogens responsible for CNS infectious diseases are predominantly viruses. Although the incidence is slightly higher during the summer months, the overall seasonal pattern is not particularly pronounced. These infections are more commonly observed in young and middle-aged males and present with a diverse range of clinical manifestations, contributing to a significant disease burden.