Objective:To analyze the association between the number and type of comorbidities—specifically high-risk(HR)and at-risk(AR)—and the risk of in-hospital mortality among elderly patients aged 65 years and older with community-acquired pneumonia(CAP).Methods:A retrospective study was conducted to gather basic information, along with diagnostic and treatment data, for elderly CAP patients hospitalized at the Third Hospital of Peking University from January 1, 2010, to December 31, 2019.Binary logistic regression was employed to examine the relationships between both the number and type of coexisting chronic diseases and in-hospital mortality in this patient population.Results:This study included a total of 2 466 elderly patients aged ≥65 years with CAP, of whom 428(17.36%)died during hospitalization.The presence of HR comorbidities was associated with an increased likelihood of in-hospital mortality ( OR=1.81, 95% CI: 1.44-2.28, P<0.001).Similarly, the presence of AR comorbidities was significantly linked to higher in-hospital mortality ( OR=15.72, 95% CI: 7.39-33.42, P<0.001).The risk of mortality escalated with the accumulation of AR comorbidities, with risk ratios ranging from 5.46 to 44.72.Notably, elderly CAP patients with 4 to 5 AR comorbidities in conjunction with HR comorbidities exhibited the highest mortality risk ( OR=85.56, 95% CI: 19.86-368.67, P<0.001).Among the comorbidities assessed, chronic liver disease emerged as the most significant factor associated with mortality in elderly CAP patients, with an importance coefficient of 0.258. Conclusions:In addition to specific comorbidities, the total number of combined comorbidities and the interplay between AR and HR comorbidities may significantly influence the outcomes of hospitalized CAP patients aged 65 years and older.Therefore, it is essential to carefully consider the diagnosis and management of comorbidities in elderly CAP patients to mitigate their risk of mortality.

Objective:To investigate the clinical significance of serum galectin-9 (Gal-9) in patients with dermatomyositis (DM) or clinically amyopathic dermatomyositis (CADM) .Methods:This cross-sectional study included 105 newly diagnosed patients with DM or CADM who were admitted to the Department of Dermatology in Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, from January 2015 to October 2024, among whom 53 had cancer-associated DM/CADM (CRDM). Additionally, an age-matched control group was included, consisting of 30 newly diagnosed cancer patients without autoimmune diseases, 27 systemic lupus erythematosus (SLE) patients, and 31 healthy controls. Serum levels of Gal-9 and transcriptional intermediary factor 1-gamma (TIF1-γ) were measured using enzyme-linked immunosorbent assay. The relationship between Gal-9 levels and laboratory indicators of DM disease activity was analyzed. Comparisons between different groups were performed using the t-test, Mann-Whitney U test, and chi-square test. Spearman correlation analysis was used to assess the association between Gal-9 levels and laboratory indicators. The diagnostic efficacy of Gal-9 and TIF1-γ for CRDM was evaluated using receiver operating characteristic (ROC) curve analysis. Results:Among the 105 DM/CADM patients, 35 were male (33.3%) and 70 were female (66.7%), with a mean age of 53.2 ± 15.1 years. In the 53 CRDM patients, the incidence rates of V-neck sign, dyschromia, and dysphagia were higher than those in non-CRDM patients (all P > 0.05). Serum Gal-9 levels in DM/CADM patients (21.2 [12.2, 32.3] ng/ml) were significantly higher than those in healthy controls (6.8 [5.4, 7.9] ng/ml, P < 0.001), SLE patients (12.3 [8.1, 15.5] ng/ml, P = 0.011), and cancer patients without autoimmune diseases (7.5 [4.9, 8.5] ng/ml, P < 0.001). Gal-9 levels were positively correlated with serum TIF1-γ antibody levels ( rs = 0.21, P = 0.029), serum ferritin ( rs = 0.29, P = 0.003), lactate dehydrogenase ( rs = 0.44, P < 0.001), creatine kinase ( rs = 0.28, P = 0.004), aspartate aminotransferase ( rs = 0.42, P < 0.001), C-reactive protein ( rs = 0.34, P < 0.001), and erythrocyte sedimentation rate ( rs = 0.46, P < 0.001). Among CRDM patients, those who had not received cancer treatment had higher Gal-9 levels (30.1 [23.3, 38.3] ng/ml) than those in stable condition after cancer treatment (13.5 [10.5, 27.9] ng/ml, P = 0.007). The area under the ROC curve (AUC) for serum TIF1-γ in diagnosing CRDM was 0.718, with an optimal cutoff value of 23.02 U/ml. The AUC for serum Gal-9 was 0.719, with an optimal cutoff value of 55.02 ng/ml. When combining both markers, the AUC increased to 0.783, with a sensitivity of 0.85 and specificity of 0.74. Conclusions:Gal-9 was highly expressed in serum of DM/CADM patients, particularly in CRDM patients. Dynamic monitoring of Gal-9 in CRDM patients may be helpful to monitor the therapeutic effect of malignancies.

Objective:To investigate the clinical significance of serum galectin-9 (Gal-9) in patients with dermatomyositis (DM) or clinically amyopathic dermatomyositis (CADM) .Methods:This cross-sectional study included 105 newly diagnosed patients with DM or CADM who were admitted to the Department of Dermatology in Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, from January 2015 to October 2024, among whom 53 had cancer-associated DM/CADM (CRDM). Additionally, an age-matched control group was included, consisting of 30 newly diagnosed cancer patients without autoimmune diseases, 27 systemic lupus erythematosus (SLE) patients, and 31 healthy controls. Serum levels of Gal-9 and transcriptional intermediary factor 1-gamma (TIF1-γ) were measured using enzyme-linked immunosorbent assay. The relationship between Gal-9 levels and laboratory indicators of DM disease activity was analyzed. Comparisons between different groups were performed using the t-test, Mann-Whitney U test, and chi-square test. Spearman correlation analysis was used to assess the association between Gal-9 levels and laboratory indicators. The diagnostic efficacy of Gal-9 and TIF1-γ for CRDM was evaluated using receiver operating characteristic (ROC) curve analysis. Results:Among the 105 DM/CADM patients, 35 were male (33.3%) and 70 were female (66.7%), with a mean age of 53.2 ± 15.1 years. In the 53 CRDM patients, the incidence rates of V-neck sign, dyschromia, and dysphagia were higher than those in non-CRDM patients (all P > 0.05). Serum Gal-9 levels in DM/CADM patients (21.2 [12.2, 32.3] ng/ml) were significantly higher than those in healthy controls (6.8 [5.4, 7.9] ng/ml, P < 0.001), SLE patients (12.3 [8.1, 15.5] ng/ml, P = 0.011), and cancer patients without autoimmune diseases (7.5 [4.9, 8.5] ng/ml, P < 0.001). Gal-9 levels were positively correlated with serum TIF1-γ antibody levels ( rs = 0.21, P = 0.029), serum ferritin ( rs = 0.29, P = 0.003), lactate dehydrogenase ( rs = 0.44, P < 0.001), creatine kinase ( rs = 0.28, P = 0.004), aspartate aminotransferase ( rs = 0.42, P < 0.001), C-reactive protein ( rs = 0.34, P < 0.001), and erythrocyte sedimentation rate ( rs = 0.46, P < 0.001). Among CRDM patients, those who had not received cancer treatment had higher Gal-9 levels (30.1 [23.3, 38.3] ng/ml) than those in stable condition after cancer treatment (13.5 [10.5, 27.9] ng/ml, P = 0.007). The area under the ROC curve (AUC) for serum TIF1-γ in diagnosing CRDM was 0.718, with an optimal cutoff value of 23.02 U/ml. The AUC for serum Gal-9 was 0.719, with an optimal cutoff value of 55.02 ng/ml. When combining both markers, the AUC increased to 0.783, with a sensitivity of 0.85 and specificity of 0.74. Conclusions:Gal-9 was highly expressed in serum of DM/CADM patients, particularly in CRDM patients. Dynamic monitoring of Gal-9 in CRDM patients may be helpful to monitor the therapeutic effect of malignancies.

Objective:To analyze the association between the number and type of comorbidities—specifically high-risk(HR)and at-risk(AR)—and the risk of in-hospital mortality among elderly patients aged 65 years and older with community-acquired pneumonia(CAP).Methods:A retrospective study was conducted to gather basic information, along with diagnostic and treatment data, for elderly CAP patients hospitalized at the Third Hospital of Peking University from January 1, 2010, to December 31, 2019.Binary logistic regression was employed to examine the relationships between both the number and type of coexisting chronic diseases and in-hospital mortality in this patient population.Results:This study included a total of 2 466 elderly patients aged ≥65 years with CAP, of whom 428(17.36%)died during hospitalization.The presence of HR comorbidities was associated with an increased likelihood of in-hospital mortality ( OR=1.81, 95% CI: 1.44-2.28, P<0.001).Similarly, the presence of AR comorbidities was significantly linked to higher in-hospital mortality ( OR=15.72, 95% CI: 7.39-33.42, P<0.001).The risk of mortality escalated with the accumulation of AR comorbidities, with risk ratios ranging from 5.46 to 44.72.Notably, elderly CAP patients with 4 to 5 AR comorbidities in conjunction with HR comorbidities exhibited the highest mortality risk ( OR=85.56, 95% CI: 19.86-368.67, P<0.001).Among the comorbidities assessed, chronic liver disease emerged as the most significant factor associated with mortality in elderly CAP patients, with an importance coefficient of 0.258. Conclusions:In addition to specific comorbidities, the total number of combined comorbidities and the interplay between AR and HR comorbidities may significantly influence the outcomes of hospitalized CAP patients aged 65 years and older.Therefore, it is essential to carefully consider the diagnosis and management of comorbidities in elderly CAP patients to mitigate their risk of mortality.

ObjectiveTo explore the effect of grain-sized moxibustion at "Zhongwan （RN12）" "Tianshu （ST25）" and "Shangjuxu （ST37）" on the colon tissue of mice with ulcerative colitis （UC）， and to analyze the potential mechanism. MethodsForty C57BL/6 male mice were randomly divided into blank group， model group， moxibustion group and mesalazine group， with 10 mice in each group. In all the groups except for the blank group， UC mouse model was prepared by freely drinking 3% sodium dextran sulfate solution. After successful modeling， the moxibustion group was treated with grain-sized moxibustion at Zhongwan， Tianshu and Shangjuxu ， 3 cones per acupoint， 30 s of each cone. The mesalazine group was given 300 mg/kg of mesalazine enteric-coated tablet solution by gavage. The blank group and the model group were only fixed by grasping without any intervention. Each group was intervened once a day for 7 consecutive days. The general condition of mice in each group was observed， and the disease activity index （DAI） score was evaluated. The colon length， intestinal weight and colon mucosal injury score were detected. The contents of serum intercellular adhesion molecule-1 （ICAM-1）， interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α） were detected by ELISA. The pathological changes of colon tissue were observed by HE staining. The mRNA and protein expressions of non-receptor tyrosine protein kinase 2 （JAK2）， signal transducer and activator of transcription 3 （STAT3） and suppressor of cytokine signaling 3 （SOCS3） in colon tissue of mice were detected by real-time fluorescence quantitative PCR and immunohistochemistry， respectively. The mean fluorescence intensity of JAK2 and SOCS3 in colon tissue of mice was detected by immunofluorescence double staining. ResultsCompared to the blank group， the mice in the model group had unclean perianal area， unformed stool， destroyed colonic mucosal morphology， shortened body weight and colon length， increased DAI score， intestinal weight index， colonic mucosal injury and pathological score， serum ICAM-1， IL-6 and TNF-α levels， increased mRNA and protein expression of JAK2 and STAT3 in colon tissue， and decreased mRNA and protein expression of SOCS3 （P＜0.01）. Compared to those in the model group， the perianal area of mice in the moxibustion group and the mesalazine group was improved， and the colonic mucosal morphology was more complete； body weight and colon length increased， while DAI score， intestinal weight index， colonic mucosal injury and pathological score， serum ICAM-1， IL-6 and TNF-α levels decreased， with decreased mRNA and protein expression of JAK2 and STAT3 in colon tissue， and increased SOCS3 mRNA and protein expression （ P＜0.01 or P＜0.05 ）. There was no significant difference in any index between the moxibustion group and the mesalazine group. ConclusionGrain-sized moxibustion at "Zhongwan"， "Tianshu" and "Shangjuxu" can improve the damage of colon mucosa in UC model mice， and the mechanism may be related to the key factors regulating JAK2 / STAT3 signaling pathway based on SOCS3.

Objective:To investigate the relationship between the age-adjusted Charlson comorbidity index(aCCI)and the risk of in-hospital death for people aged ≥ 90 years with community-acquired pneumonia(CAP), and to construct a novel scoring model for predicting in-hospital mortality.Methods:Basic personal and medical data about sex, age, hospitalization days, hospitalization expenses, in-hospital outcomes and discharge/admitting diagnosis of CAP patients aged ≥ 90 years hospitalized in Peking University Third Hospital between 2010 and 2019 were collected retrospectively.Multivariate Logistic regression analysis was conducted to examine the association between aCCI or other complications and in-hospital death.The receiver operating characteristic curve(ROC)was used to assess the value of aCCI and a new scoring model in predicting in-hospital death of CAP in people aged ≥ 90 years.Results:A total of 274 CAP patients aged ≥ 90 years were included in this study, of whom 85 died in hospital.Multivariate Logistic regression analysis showed that malnutrition( OR=2.21, 95% CI: 1.05-4.67, P<0.05), respiratory failure( OR=18.91, 95% CI: 9.34-38.25, P<0.001)and aCCI( OR=1.51, 95% CI: 1.23-1.85, P<0.001)were prognostic factors for in-hospital death in CAP patients aged ≥ 90 years.Based on the above results, a novel scoring model, MRC(malnutrition, respiratory failure, aCCI)was established.The area under the ROC curve of the aCCI score for predicting the risk of in-hospital death in CAP patients aged ≥ 90 years was 0.743(95% CI: 0.684-0.802). The area under the ROC curve of the MRC score was 0.891(95% CI: 0.848-0.933), indicating a higher predictive value than that of the aCCI score alone( Z=6.337, P<0.001). Conclusions:The MRC score model can be used to evaluate and predict the risk of in-hospital death in long-living CAP patients.

We retrospectively analyzed a child with early-onset globoid cell leukodystrophy(Krabbe's disease)caused by complex heterozygous variations in the GALC gene.The girl was admitted to the hospital at the age of 4 month with main complaints of"No obvious cause of milk refusal,poor mental state,drowsiness,convulsions,fever."Brain MRI showed abnormal symmetric signals changes in bilateral cerebellar hemispheres,bilateral internal capsule hind limbs and bilateral ventricles,thin corpus callosum,myelination process lags behind the level of children of the same age.High-throughput sequencing analysis identified compound heterozygous mutations in GALC gene(NM 000153.4):c.[908+1G>A];[194G>A and the two heterozygous mutations were correspondingly inherited from his father and mother,respectively.The application of high-throughput sequencing technology can diagnose Krabbe disease efficiently and accurately,which assists in clinical identification and diagnosis.

Objective:To explore the feasibility of mismatch of amide proton transfer weighted (APTw) imaging with diffusion weighted imaging (DWI) in evaluating ischemic penumbra (IP) in patients with wake-up stroke.Methods:A prospective study was performed; 96 patients with wake-up stroke and unilateral middle cerebral artery territory infarction admitted to Emergency Stroke Department, Affiliated Hospital of Jining Medical University from September 2020 to January 2023 were chosen. All patients underwent routine MRI, DWI, APTw imaging and 3D arterial spin labeling (3D-ASL) before treatment and 90 d after treatment. IP presence was defined as changes of abnormal signal on T2-fluid-attenuated inversion recovery (FLAIR) 90 d after treatment greater than 20% of high signal range on DWI before treatment, and it was used as the gold standard to compare the efficacy in evaluating whether the patients had IP based on mismatch of 3D-ASLwith DWI and mismatch of APTw imaging with DWI before treatment. The infarct core (IC) region, mismatch region of APTw imaging with DWI, mismatch region of 3D-ASL with APTw imaging were delineated on the fusion images in patients with IP based on mismatch of 3D-ASLwith DWI and mismatch of APTw with DWI, and the differences of APTw values in different regions were compared.Results:According to the 90-d follow-up results, 50 patients had IP and 46 patients did not have IP. Specificity, accuracy and sensitivity evaluating whether the patients had IP based on mismatch of 3D-ASL with DWI were 86.9%, 93.7% and 100.0%, respectively; specificity, accuracy and sensitivity evaluating whether the patients had IP based on mismatch of APTw imaging with DWI were 100.0%, 95.8% and 92.0%, respectively. The APTw max, APTw min and APTw ave values of the IC region were significantly lower than those of mismatch region of APTw with DWI, and the APTw max-min values of mismatch region of APTw imaging with DWI were significantly higher than those of mismatch region of 3D-ASL with APTw imaging ( P<0.05). Conclusion:APTw imaging can reflect the acidosis status of different brain regions in patients with wake-up stroke; specificity and accuracy evaluating whether the patients have IP based on mismatch of APTw imaging with DWI are higher than those based on mismatch of 3D-ASL with DWI.

After the specific binding of programmed death-1 (PD-1) to programmed death ligand 1 (PD-L1) , the PD-1/PD-L1 complex can exert a co-suppressive/co-stimulatory immunoregulatory effect, which can inhibit the activation and proliferation of T cells and their cytokine secretion, and play a key role in tumor immunity, autoimmunity and immune tolerance. This review summarizes structures and regulatory mechanisms of the PD-1/PD-L1 signaling pathway, aimming to facilitate the understanding of immune pathogenesis of idiopathic inflammatory myopathies complicated by malignant tumors, and to seek potential therapeutic targets and diagnostic strategies.

Objective To evaluate the role of programmed cell death ligand-1 (PD-L1) in a mouse model of bone cancer pain.Methods Ninety-six male C3H/HeN mice (20-25 g,4-6 weeks old),which inoculated with osteolytic NCTC 2472 cells,were used to build the model of bone cancer pain.Part one:sixtyfour male C3H/HeJ mice were randomly divided into sham group (group Sham,n =32) and tumor group (group Tumor,n=32).Part two:Twenty-four male C3H/HeJ mice which were inoculated with osteolytic NCTC 2472 cells were randomly divided into group T (tumor,n=8),group PD-L1 (intrathecal injection with PLX3397,1 μg/5μl,n=8) and group NS (intrathecal injection with normal saline,n=8).Also,there were eight male C3H/HeJ mice in group S which were intra-femur inoculated with α-MEM.The pain behaviors of Sham group and Tumor group were observed and the expression of PD-L1 was detected before inoculation and on 4,7,10,14 and 21 days after inoculation,including paw withdrawal mechanical threshold (PWMT) and the number of spontaneous flinches (NSF).On 14 d after inoculation,the mice of group PD-L1 and group NS were intrathecal injected with drugs respectively.Pain behaviors were observed before injection and 2,4,6,24h after injection.Results Compared with group Sham,PWMT was significantly decreased and NSF was increased on 7～ 21 d after inoculation in group Tumor (P＜0.05).Compared with baseline and group S (baseline (0.38±0.06),group Sham (0.35±0.08),(0.38±0.08),(0.36±0.07)),the expression of PDL1 was up-regulated on 10-21 d after inoculation in group Tumor ((0.77±0.06),(1.21±0.04),(1.18±0.06)) (P＜0.05).Compared with group NS,PWMT was significantly increased (group NS (0.25t0.12),(0.25±0.12),(0.31±0.12),group PD-L1 (1.43±0.49),(1.35±0.44),(0.95±0.26)),and NSF was decreased on 2-6 h after injection in group PD-L1 (group NS(11.74± 1.31),(13.78±0.0.91),(13.63±1.06),group P D-L1 (4.90± 0.82),(4.15± 0.71),(7.65±0.56)) (P＜0.05).Conclusion Expression of PD-L1 in spinal cord was up-regulated in the mouse model of bone cancer pain.Intrathecal injection of recombinant PD-L1 has an analgesic effect on mice with bone cancer.