A rare case of Langerhans cell histiocytosis (LCH) combined with Erdheim-Chester disease (ECD) in the tibia is presented. A 55-year-old female patient experienced a six-month history of left lower leg pain of unknown origin, which progressively worsened over the past month and was accompanied by restricted mobility. Radiographic imaging revealed patchy, mixed-density shadows within the medullary cavities of the middle and lower segments of both tibiae and fibulae. Magnetic resonance imaging (MRI) showed extensive abnormal signal areas in the lower segments of the left tibia and fibula, as well as in the left talus and calcaneus. Positron emission tomography-computed tomography (PET-CT) demonstrated significantly increased diffuse radioactive uptake in the middle and lower segments of both femora, the upper and lower segments of the tibiae, the bilateral talus, the distal radius, and symmetrical uptake in the bilateral elbow joints. Additionally, mild radionuclide uptake was observed in the bilateral clavicles and the upper segment of the right femur. The initial diagnosis suggested a space-occupying lesion in the tibia with a suspicion of ECD. Histopathological examination of a biopsy from the left tibial lesion indicated a histiocytic proliferative disorder. After a multidisciplinary consultation, a definitive diagnosis of LCH with fibrous hyperplasia and extensive infiltration of foam cells, along with scattered multinucleated giant cells, was established. The presence of the BRAFV600E mutation further supported the concurrent diagnosis of ECD. Subcutaneous interferon-α therapy was initiated. Two years later, pulmonary lesions were identified. Computed tomography (CT) revealed multiple round nodules in both lungs, chronic inflammatory changes, and fibrous cord-like lesions. Consequently, interferon treatment was discontinued, and oral vemurafenib was administered. After three years of follow-up, chest CT demonstrated a significant reduction in chronic inflammatory lesions and fibrous cords, along with a decrease in nodule size. Currently, after four years of continuous follow-up, the patient remains in stable condition, experiences no significant discomfort, and continues to receive vemurafenib maintenance therapy. A review of the literature suggests that the co-occurrence of LCH and ECD is rare, often leading to misdiagnosis or delayed diagnosis. While no standardized treatment protocol exists, patients harboring the BRAFV600E mutation may benefit from BRAF inhibitors such as vemurafenib.

Objective To investigate the association of neutrophil-to-lymphocyte ratio(NLR)with all-cause and cause-specific mortality in elderly hypertensive patients.Methods In this cohort study,9939 elderly hypertensive patients were enrolled from the National Health and Nutrition Examination Survey between 1999 and 2018.According to the quartile of NLR,the participants were divided into Q1(n=2461),Q2(n=2460),Q3(n=2522)and Q4(n=2496)groups.Their survival status was determined based on National Death Index records.Cox proportional risk regression model,restricted cubic spline curve,Kaplan-Meier survival analysis and ROC analysis were performed.Results After adjusting for confounding factors,Cox proportional risk regression analysis showed a progressive increase in all-cause and cause-specific mortality across quartiles of NLR in elderly hypertensive patients.Compared with the Q1 group,the Q4 group had higher risks for all-cause mortality(HR=1.52,95％CI:1.32-1.74,P=0.000),cardiovascular mortality(HR=2.04,95％CI:1.63-2.56,P=0.000),and non-cardiovascular mortality(HR=1.30,95％CI:1.11-1.53,P=0.000)after adjustment.Restricted cubic spline curve analysis indicated that NLR was positively correlated with all-cause mortality,cardiovacular mortality and non-cardio-vascular mortality.More pronounced association between NLR and cardiovascular death was observed in patients not taking statins(P=0.035).ROC analysis revealed that the AUC value of NLR in predicting all-cause mortality,cardiovascular mortality and non-cardiovascular mortality was 0.612,0.597 and 0.581,respectively,showing better performance than high-sensitivity C-reac-tive protein and neutrophils.Conclusion Elevated NLR level is independently associated with increased risks of all-cause and cause-specific mortality in elderly hypertensive patients.In the patients not taking statins,a stronger association is observed between NLR and cardiovascular mortality.

A rare case of Langerhans cell histiocytosis (LCH) combined with Erdheim-Chester disease (ECD) in the tibia is presented. A 55-year-old female patient experienced a six-month history of left lower leg pain of unknown origin, which progressively worsened over the past month and was accompanied by restricted mobility. Radiographic imaging revealed patchy, mixed-density shadows within the medullary cavities of the middle and lower segments of both tibiae and fibulae. Magnetic resonance imaging (MRI) showed extensive abnormal signal areas in the lower segments of the left tibia and fibula, as well as in the left talus and calcaneus. Positron emission tomography-computed tomography (PET-CT) demonstrated significantly increased diffuse radioactive uptake in the middle and lower segments of both femora, the upper and lower segments of the tibiae, the bilateral talus, the distal radius, and symmetrical uptake in the bilateral elbow joints. Additionally, mild radionuclide uptake was observed in the bilateral clavicles and the upper segment of the right femur. The initial diagnosis suggested a space-occupying lesion in the tibia with a suspicion of ECD. Histopathological examination of a biopsy from the left tibial lesion indicated a histiocytic proliferative disorder. After a multidisciplinary consultation, a definitive diagnosis of LCH with fibrous hyperplasia and extensive infiltration of foam cells, along with scattered multinucleated giant cells, was established. The presence of the BRAFV600E mutation further supported the concurrent diagnosis of ECD. Subcutaneous interferon-α therapy was initiated. Two years later, pulmonary lesions were identified. Computed tomography (CT) revealed multiple round nodules in both lungs, chronic inflammatory changes, and fibrous cord-like lesions. Consequently, interferon treatment was discontinued, and oral vemurafenib was administered. After three years of follow-up, chest CT demonstrated a significant reduction in chronic inflammatory lesions and fibrous cords, along with a decrease in nodule size. Currently, after four years of continuous follow-up, the patient remains in stable condition, experiences no significant discomfort, and continues to receive vemurafenib maintenance therapy. A review of the literature suggests that the co-occurrence of LCH and ECD is rare, often leading to misdiagnosis or delayed diagnosis. While no standardized treatment protocol exists, patients harboring the BRAFV600E mutation may benefit from BRAF inhibitors such as vemurafenib.

Objective To investigate the association between cystatin C level and 6-month mortali-ty as well as re-hospitalization in elderly patients with heart failure(HF).Methods The clinical data in this study were from a retrospective cohort study,Zigong Heart Failure Study.A total of 1786 elderly HF patients admitted in Zigong Fourth People's Hospital from December 2016 to June 2019 were selected.According to the tertiles of cystatin C level,the subjected patients were divided into three groups,with the cystatin C level of 1.10±0.17(587 cases),1.60±0.17(599 ca-ses),and 2.91±0.90 mg/L(600 cases),respectively.The primary endpoint was a composite end-point of death at 6 months after discharge and readmission due to HF.Multivariate Cox propor-tional hazards regression analysis was employed to analyze the relationship of the cystatin C level with the composite endpoint of 6-month mortality and readmission due to HF.Restricted cubic spline was used to model the relationship between the cystatin C level and the composite end-point,Kaplan-Meier survival curve was plotted to analyze the differences in 6-month event free survival rates among the three groups,and ROC curve was drawn to analyze the predictive value of cystatin C level for the composite endpoint.Results Multivariate Cox proportional hazards re-gression analysis showed that the middle and upper tertiles of cystatin C level were risk factors for the composite endpoint of 6-month mortality and readmission due to HF(HR=1.170,95％CI:0.970-1.390,P=0.111;HR=1.452,95％CI:1.190-1.756,P=0.000).When taking cystatin C level as a continuous variable,the results remained consistent:for every one standard deviation increase in cystatin C level,HR=1.141,95％CI:1.060-1.226 in Model 3;For every 1 mg/L in-crease,HR=1.152,95％CI:1.057-1.250 in Model 3.Restricted cubic spline displayed a non-linear inverse J-shaped relationship between cystatin C level and the composite endpoint of 6-month mortality and readmission due to HF,with a risk inflection point of cystatin C level at 2.13 mg/L.ROC curve analysis showed that the AUC value of cystatin C level in predicting the composite endpoint,6-month death and re-admission due to HF was 0.572,0.667 and 0.554,respectively.Conclusion Elevated cystatin C level is independently associated with an increased risk of the composite endpoint of 6-month death and re-admission in elderly HF patients.

Objective To investigate the association between cystatin C level and 6-month mortali-ty as well as re-hospitalization in elderly patients with heart failure(HF).Methods The clinical data in this study were from a retrospective cohort study,Zigong Heart Failure Study.A total of 1786 elderly HF patients admitted in Zigong Fourth People's Hospital from December 2016 to June 2019 were selected.According to the tertiles of cystatin C level,the subjected patients were divided into three groups,with the cystatin C level of 1.10±0.17(587 cases),1.60±0.17(599 ca-ses),and 2.91±0.90 mg/L(600 cases),respectively.The primary endpoint was a composite end-point of death at 6 months after discharge and readmission due to HF.Multivariate Cox propor-tional hazards regression analysis was employed to analyze the relationship of the cystatin C level with the composite endpoint of 6-month mortality and readmission due to HF.Restricted cubic spline was used to model the relationship between the cystatin C level and the composite end-point,Kaplan-Meier survival curve was plotted to analyze the differences in 6-month event free survival rates among the three groups,and ROC curve was drawn to analyze the predictive value of cystatin C level for the composite endpoint.Results Multivariate Cox proportional hazards re-gression analysis showed that the middle and upper tertiles of cystatin C level were risk factors for the composite endpoint of 6-month mortality and readmission due to HF(HR=1.170,95％CI:0.970-1.390,P=0.111;HR=1.452,95％CI:1.190-1.756,P=0.000).When taking cystatin C level as a continuous variable,the results remained consistent:for every one standard deviation increase in cystatin C level,HR=1.141,95％CI:1.060-1.226 in Model 3;For every 1 mg/L in-crease,HR=1.152,95％CI:1.057-1.250 in Model 3.Restricted cubic spline displayed a non-linear inverse J-shaped relationship between cystatin C level and the composite endpoint of 6-month mortality and readmission due to HF,with a risk inflection point of cystatin C level at 2.13 mg/L.ROC curve analysis showed that the AUC value of cystatin C level in predicting the composite endpoint,6-month death and re-admission due to HF was 0.572,0.667 and 0.554,respectively.Conclusion Elevated cystatin C level is independently associated with an increased risk of the composite endpoint of 6-month death and re-admission in elderly HF patients.

Objective To investigate the association of neutrophil-to-lymphocyte ratio(NLR)with all-cause and cause-specific mortality in elderly hypertensive patients.Methods In this cohort study,9939 elderly hypertensive patients were enrolled from the National Health and Nutrition Examination Survey between 1999 and 2018.According to the quartile of NLR,the participants were divided into Q1(n=2461),Q2(n=2460),Q3(n=2522)and Q4(n=2496)groups.Their survival status was determined based on National Death Index records.Cox proportional risk regression model,restricted cubic spline curve,Kaplan-Meier survival analysis and ROC analysis were performed.Results After adjusting for confounding factors,Cox proportional risk regression analysis showed a progressive increase in all-cause and cause-specific mortality across quartiles of NLR in elderly hypertensive patients.Compared with the Q1 group,the Q4 group had higher risks for all-cause mortality(HR=1.52,95％CI:1.32-1.74,P=0.000),cardiovascular mortality(HR=2.04,95％CI:1.63-2.56,P=0.000),and non-cardiovascular mortality(HR=1.30,95％CI:1.11-1.53,P=0.000)after adjustment.Restricted cubic spline curve analysis indicated that NLR was positively correlated with all-cause mortality,cardiovacular mortality and non-cardio-vascular mortality.More pronounced association between NLR and cardiovascular death was observed in patients not taking statins(P=0.035).ROC analysis revealed that the AUC value of NLR in predicting all-cause mortality,cardiovascular mortality and non-cardiovascular mortality was 0.612,0.597 and 0.581,respectively,showing better performance than high-sensitivity C-reac-tive protein and neutrophils.Conclusion Elevated NLR level is independently associated with increased risks of all-cause and cause-specific mortality in elderly hypertensive patients.In the patients not taking statins,a stronger association is observed between NLR and cardiovascular mortality.

Objective To explore the efficacy and safety of evolocumab in elderly patients with high-risk cardiovascular diseases.Methods A total of 153 patients with poor lipid control after conventional statin therapy who were hospitalized in the cardiologic departments in the First,Sec-ond,Sixth and Eighth Medical Centers of Chinese PLA General Hospital from November 2019 to November 2022 were included,and divided into non-elderly group(＜60 years old,46 cases),eld-erly group(60-74 years old,66 case)and very elderly group(≥75 years old,41 cases).They were all given evolocumab treatment according to guidelines.Another 50 over-75-year-old patients with high-risk cardiovascular diseases and poor lipid control who were hospitalized in the above cardiologic departments during the same period were treated with a statin drug combined with ezetimibe,and served as conventional treatment group(control group).The baseline clinical data and the blood indicators at 4th and 12th week after drug administration,and the occurrence of ad-verse drug reactions and major adverse cardiovascular events(MACE)within 12 weeks were com-pared among the groups.Results The levels of LDL-C and TC were significantly decreased in the three evolocumab treatment groups at 4 and 12 weeks after medication when compared with the baseline values(P＜0.05,P＜0.01),but there were no obvious differences in the 2 levels among the 3 groups at 12 weeks(P＞0.05).At the time point,no statistical difference was observed in the incidence of adverse events in the three groups(2.2％vs 3.0％vs 2.4％,P＞0.05).The levels of LDL-C and TC were decreased significantly in the very elderly group and the conventional treatment group at the 12th week when compared with the baseline levels(P＜0.05,P＜0.01),and the LDL-C level at the week was notably lower in the very elderly group than the convention-al treatment group(1.36±0.44 mmol/L vs 1.87±0.56 mmol/L,P＜0.01).But no difference was seen in the incidence of MACE between the 2 groups(12.2％vs 16.0％,P＞0.05),either in sur-vival rate between them(P=0.576).Conclusion For patients of all ages,evolocumab has good short-term efficacy in lipid control,and for those over 75 years old,the drug also shows good effi-cacy and sound safety.

Biomolecular condensates formed by phase separation are widespread and play critical roles in many physiological and pathological processes. cGAS-STING signaling functions to detect aberrant DNA signals to initiate anti-infection defense and antitumor immunity. At the same time, cGAS-STING signaling must be carefully regulated to maintain immune homeostasis. Interestingly, exciting recent studies have reported that biomolecular phase separation exists and plays important roles in different steps of cGAS-STING signaling, including cGAS condensates, STING condensates, and IRF3 condensates. In addition, several intracellular and extracellular factors have been proposed to modulate the condensates in cGAS-STING signaling. These studies reveal novel activation and regulation mechanisms of cGAS-STING signaling and provide new opportunities for drug discovery. Here, we summarize recent advances in the phase separation of cGAS-STING signaling and the development of potential drugs targeting these innate immune condensates.
Humans ; Nucleotidyltransferases/chemistry* ; Signal Transduction/physiology* ; Membrane Proteins/chemistry* ; Phase Separation

Objective     To investigate short-term outcomes of robot-assisted Heller-Dor myotomy (RAHM-Dor) for achalasia of cardia and our learning curve experience. Methods     The clinical data and recent follow-up results of 42 patients who received RAHM-Dor from November 2015 to January 2020 in the Department of Thoracic Surgery of the First Affiliated Hospital of Nanchang University were retrospectively analyzed, including 20 males and 22 females with a mean age of 40.8±18.4 years. Results    Dysphagia was the most common symptom, followed by heartburn and regurgitation. The mean operation time was 122.8±23.9 min. The mean blood loss was 47.5±32.7 mL. Two patients suffered mucosal injury, and successfully repaired by suturing during surgery. There was no esophageal fistula, conversion to an open operation or perioperative death in this series. The median length of hospital stay was 8 (6, 9) d. In all patients, the Stooler and Eckardt scores of postoperative 1, 6 and 12 months decreased compared to those of pre-operation (P<0.001). Conclusion     RAHM-Dor is a safe and feasible avenue for the treatment of achalasia of cardia, and can achieve a satisfying short-term results. The learning curve shows a transition to the standard stage from the learning stage after 16-18 operations.

Objective To evaluate the preliminary clinical effect of anterior anatomical reduction plate fixation on the treatment of atlantoaxial dislocation. Methods A retrospective case series study was conducted to analyze the 13 patients with atlantoaxial dislocation admitted to the second affiliated hospital of Xi'an Jiaotong University from January 2016 to December 2017. There were eight males and five females, aged 20-57 years, with an average age of 42 years. All patients received transoropharyngeal reconstruction and atlantoaxial anterior anatomical reduction plate fixation, 12 of which underwent the surgery for the first time but one had the revision surgery. The operation time and intraoperative bleeding were recorded. The angle of the clivus axis was measured, and the reduction of the atlantoaxial spine and the fusion of bone graft were observed. The neurological function was evaluated by Japanese Orthopedic Association ( JOA ) score and the improvement rate of spinal cord function was calculated. The complications were also recorded. Results All patients were followed up for 10-30 months [(14. 2 ± 5. 0)months]. The operation time was 150-285 minutes [(216. 8 ± 36. 7)minutes]. The intraoperative blood loss was 50-130 ml [(80. 5 ± 19. 7)ml]. The slope axis angle was (113. 2 ± 9. 1)° before operation and (145. 8 ± 6. 7)° after operation, with an average increase of 32. 6° (P<0. 01). Anatomical reduction was obtained in nine patients, and partial reduction in four patients. At the last follow-up, the atlantoaxial fusion was obtained in all patients, and the healing time was ( 4. 6 ± 1. 1 ) months. Postoperative neurological symptoms were improved compared with those before operation. The JOA score was improved from preoperative (8. 7 ± 1. 7) points to postoperative (14. 3 ± 1. 2) points, with an average increase of 5. 6 points (P<0. 01). The average improvement rate of spinal cord function was 69％. Except for one patient with cerebrospinal fluid leakage, there were no complications such as spinal cord, nerve, blood vessel injury or wound infection after operation. Conclusions Anterior atlantoaxial anatomical reduction plate fixation can effectively restore the dislocated atlantoaxial joint, restore slope axis angle, improve bone fusion rate, and improve nerve function. It can be used as an alternative or supplement to posterior fixation.