Cholangiocarcinoma (CCA) is a fatal malignancy with steadily increasing incidence and poor prognosis. Since most CCA cases are diagnosed at an advanced stage, systemic therapies, including chemotherapy, radiotherapy, targeted therapy, and immunotherapy, play a crucial role in the management of unresectable CCA. The recent advances in targeted therapies and immunotherapies brought more options in the clinical management of unresectable CCA. This review depicts the advances of targeted therapies and immunotherapies for unresectable CCA, summarizes crucial clinical trials, and describes the efficacy and safety of different drugs, which may help further develop precision and individualization in the clinical treatment of unresectable CCA.
Humans ; Cholangiocarcinoma/drug therapy* ; Immunotherapy/methods* ; Bile Duct Neoplasms/drug therapy* ; Molecular Targeted Therapy/methods*

Objective:To conduct a multi-center cross-sectional study of elderly patients with cognitive impairment based on real-world data; To analyze the clinical characteristics and core medication law of the disease population.Methods:The medical records of elderly patients diagnosed with cognitive impairment from January 1, 2016 to December 31, 2024 were retrieved from Chinese Evidence-based TCM Database. Excel 2010 software was used to collect general information, TCM syndrome elements and syndrome types, use frequency of Chinese materia medica, property, taste, meridian tropism, efficacy classification and other information, using PivotTable to establish Chinese materia medica matrix. IBM SPSS Modeler 18.0 software was used to display the frequency of co-occurrence among high-frequency Chinese materia medica, and the association rules were analyzed based on the Apriori algorithm. R language 4.4.1 was used for clustering analysis on Chinese materia medica and the cluster pedigree and correlation heat map were drawn.Results:A total of 1 194 elderly patients with cognitive impairment were enrolled, with a mean age of (79.51±7.65) years, and the highest frequency of comorbidities was hypertension (891 cases, 74.62%); AD was the most frequent diagnosis of cognitive impairment (367 times, 30.74%). The proportion of mild cognitive impairment in the low value group of Systemic Immune Inflammation Index (SII) was relatively high, and the high value group of SII was mainly vascular dementia and AD. Wind-phlegm blocking syndrome (106 times, 13.73%) topped the list; phlegm was the most frequent element of pathogenicity (353 times, 45.73%), and meridians and collaterals (194 times, 25.13%). Totally 328 prescriptions were included, involving 308 kinds of Chinese materia medica. The total recorded frequency of Chinese materia medica was 5 665, with tonifying herbs constituting the most frequently used category, accounting for 1 633 times; the medicinal property of drugs for treating elderly patients with cognitive disorders was mostly warm (103 times, 33.44%), the taste was mostly bitter (141 times, 45.78%), and attributed to the liver meridian (145 times, 47.08%); among the two and three association rules, the drug pairs with the highest confidence were Gastrodiae Rhizoma→Uncariae Ramulus cum Uncis (97.22%) and Hyperici Perforati Herba→Acanthopanacis Senticosi Radix et Rhizoma seu Caulis+Alpiniae Oxyphyllae Fructus (97.06%); five medicinal combinations were obtained by high frequency drug clustering analysis.Conclusions:Elderly patients with cognitive impairment are mainly diagnosed with AD. There may be a potential correlation between SII level and the progression of cognitive impairment. The drugs are used to tonify the kidney and replenish essence, detoxify and unblock collaterals, replenish qi and activate blood circulation, and awaken the brain and open the orifices. Shengmai Decoction, Renshen Yangrong Decoction and other TCM classic prescriptions can be used in clinic.

Objective The aim of this study was to explore the role and mechanism of ferroptosis in SiO2-induced cardiac injury using a mouse model. Methods Male C57BL/6 mice were intratracheally instilled with SiO2 to create a silicosis model.Ferrostatin-1(Fer-1)and deferoxamine(DFO)were used to suppress ferroptosis.Serum biomarkers,oxidative stress markers,histopathology,iron content,and the expression of ferroptosis-related proteins were assessed. Results SiO2 altered serum cardiac injury biomarkers,oxidative stress,iron accumulation,and ferroptosis markers in myocardial tissue.Fer-1 and DFO reduced lipid peroxidation and iron overload,and alleviated SiO2-induced mitochondrial damage and myocardial injury.SiO2 inhibited Nuclear factor erythroid 2-related factor 2(Nrf2)and its downstream antioxidant genes,while Fer-1 more potently reactivated Nrf2 compared to DFO. Conclusion Iron overload-induced ferroptosis contributes to SiO2-induced cardiac injury.Targeting ferroptosis by reducing iron accumulation or inhibiting lipid peroxidation protects against SiO2 cardiotoxicity,potentially via modulation of the Nrf2 pathway.

Objective To evaluate the perioperative safety of lung surgery for patients with corona virus disease 2019 (COVID-19). Methods We retrospectively analyzed the clinical data of the patients recovered from COVID-19 infection and received lung surgery from December 2022 to February 2023 in the Department of Thoracic Surgery at Beijing Hospital. Patients who received lung surgery and without COVID-19 at the same time were selected as a control group. Perioperative data between the two groups were compared. Results A total of 103 patients were included with 44 males and 49 females at an average age of (62.2±12.1) years. All surgeries were performed by uniportal video-assisted thoracoscopic surgery (VATS). Among patients who recovered from COVID-19, 53 (51.5%) received lobectomy, 30 (29.1%) received segmentectomy, and 20 (19.4%) received wedge resection. The interval between diagnosis of infection and lung surgery was ≤1 month in 32 (31.1%) patients, and >1 month in 71 (68.9%) patients. The results of virus nucleic acid test for all patients before surgery were negative. A total of 13 (12.6%) patients had positive IgM, and 100 (97.1%) patients had positive IgG. A total of 20 patients experienced perioperative complications (13 patients with pulmonary air leakage, 3 patients with chylothorax, 2 patients with atrial fibrillation, and 2 patients with severe pulmonary complications). There was one perioperative death. Comparing the patients who recovered from COVID-19 with those without COVID-19, we found no statistical difference in perioperative outcomes including surgical duration, postoperative drainage, duration of thoracic tube, and duration of postoperative stay (P>0.05). There was no significant difference in perioperative complications between the two groups (P>0.05). Multivariable logistical regression analysis demonstrated that positive IgM before surgery (OR=7.319, 95%CI 1.669 to 32.103, P=0.008), and longer duration of surgery (OR=1.016, 95%CI 1.003 to 1.028, P=0.013) were independent risk factors of perioperative complications for patients who recovered from COVID-19. Conclusion It is safe for patients recover from COVID-19 to receive lung surgery when symptoms disappear and the nucleic acid test turn negative. However, positive COVID-19 IgM is an independent risk factor for perioperative complications. We suggest that lung surgery could be performed when the nucleic acid test and COVID-19 IgM are both negative for patients recover from COVID-19 infection.

Objective:To evaluate the safety of thymic surgery in patients aged 65 years and over.Methods:A total of 696 patients who underwent thymectomy/thymoma resection in the Department of Thoracic Surgery of Beijing Hospital from November 2011 to March 2022 were collected and divided into two groups according to the age of 65 years old.The preoperative course of disease, MG stage, dosage of pyridostigmine bromide, American College of Anesthesiologists(ASA)score, surgical method, intraoperative bleeding, postoperative drainage, postoperative complications, Clavien-dindo score(CDC), and myasthenic crisis were recorded and statistically analyzed.Results:A total of 696 patients were enrolled, including 364 males and 332 females, aged 15~86 years, with an average age of 49.1 years.There were 309 patients with thymoma, 565 patients with MG, and 178 patients with both.There were 124 cases in the elderly group(≥65 years old)and 572 cases in the non-elderly group(<65 years old). The incidence of thymoma was higher in the elderly group(54.8 % versus 42.1 %, χ2=6.664, P=0.010), while the incidence of MG was lower(67.7 % versus 84.1 %, χ2=17.827, P<0.001). The ASA score of the elderly group was higher than that of the non-elderly group( χ2=52.372, P=0.000), and the preoperative ventilation function FEV1 and FEV1/FVC were also significantly lower than those of the non-elderly group( z=8.187, 4.580, P=0.000 for all). The drainage volume in the first 3 days after operation and postoperative drainage tube time in the elderly group were significantly higher than those in the non-elderly group( P=0.018, P=0.003). The incidence of postoperative myasthenia crisis in the elderly group was higher than that in the non-elderly group( P=0.034). There was no significant difference in the incidence of postoperative complications between the two groups, but after Clavien-dindo classification, the score of the elderly group was higher than that of the non-elderly group( P=0.003). Although the ASA score and Clavien-dindo score of the elderly group were both higher than those of the non-elderly group, there was no correlation between the two. Conclusions:Although the preoperative ASA score and pulmonary function of elderly patients were poorer than those in the non-elderly group, while the incidence of postoperative myasthenia crisis was higher, and the incidence of postoperative complications was not higher, the Clavien-dindo classification, however, was higher in elderly patients than that of the non-elderly group.After careful preoperative evaluation and strengthening perioperative management, most elderly patients can receive thymus surgery safely with acceptable risks.

ObjectiveTo investigate the distribution of vascular cognitive impairment （VCI） with kidney Yang deficiency syndrome and explore the biological nature of VCI with kidney Yang deficiency syndrome from the perspective of DNA methylation under the combination of disease and syndrome， so as to provide an epigenetic target for traditional Chinese medicine （TCM） treatment of this disease with this syndrome in the future. MethodCommunity residents in Beijing were screened out for cognitive impairment from September 2020 to November 2022 through the scale， and VCI patients were analyzed for the syndrome. VCI patients with kidney Yang deficiency syndrome and healthy people were enrolled in this study. Peripheral venous blood was collected and subjected to genome-wide DNA methylation detection by Illumina Human Methylation 850K BeadChip. Then， differentially methylated genes （DMGs） were screened out for bioinformatics analysis. ResultA total of 1 902 people were investigated in this study， and 201 of them had VCI， accounting for 10.57%， including 72.14% with kidney Yang deficiency syndrome. The methylation results showed that compared with the normal group， the VCI group had 386 differential methylation sites， and 136 DMGs were annotated. The Kyoto Encyclopedia of Gene and Genomes（KEGG） signaling pathway enrichment analysis showed that the DMGs between the two groups were mainly involved in mammalian target of rapamycin（mTOR） signaling pathway， Estrogen signaling pathway， cyclic adenosine monophosphate（cAMP） signaling pathway， etc. Protein-protein interaction （PPI） analysis showed that DMGs， such as epidermal growth factor receptor（EGFR）， epidermal growth factor （EGF）， and signal transducer and activator of transcription 3（STAT3）， played important roles in the network. ConclusionKidney Yang deficiency is the main syndrome in VCI patients. DMGs including EGFR， EGF， and STAT3 and the related pathways such as mTOR signaling pathway， Estrogen signaling pathway， and cAMP signaling pathway may play a vital role in the occurrence and development of VCI with kidney Yang deficiency syndrome.

Ultra-rapid cooling and rewarming rate is a critical technical approach to achieve ice-free cells during the freezing and melting process. A set of ultra-rapid solid surface freeze-thaw visualization system was developed based on a sapphire flim, and experiments on droplet freeze-thaw were carried out under different cryoprotectant components, volumes and laser energies. The results showed that the cooling rate of 1 μL mixed cryoprotectant [1.5 mol/L propylene glycol (PG) + 1.5 mol/L ethylene glycol (EG) + 0.5 mol/L trehalose (TRE)] could be 9.2×10 ³ °C/min. The volume range of 1-8 μL droplets could be vitrified. After comparing the proportions of multiple cryoprotectants, the combination of equal proportion mixed permeability protectant and trehalose had the best vitrification freezing effect and more uniform crystallization characteristics. During the rewarming operation, the heating curve of glassy droplets containing gold nanoparticles was measured for the first time under the action of 400-1 200 W laser power, and the rewarming rate was up to the order of 10 ⁶ °C/min. According to the droplet images of different power rewarming processes, the laser power range for ice-free rewarming with micron-level resolution was clarified to be 1 400-1 600 W. The work of this paper simultaneously realizes the ultra-high-speed temperature ramp-up, transient visual observation and temperature measurement of droplets, providing technical means for judging the ice free droplets during the freeze-thaw process. It is conducive to promoting the development of ultra-rapid freeze-thaw technology for biological cells and tissues.
Freezing ; Vitrification ; Cryopreservation/methods* ; Trehalose ; Gold ; Rewarming ; Metal Nanoparticles ; Cryoprotective Agents ; Lasers

Objective:To proceed a comparative study of characteristics and safety of video-assisted thoracoscopic thymectomy between artificial pneumothorax combining subxiphoid-costal margin approach versus right thoracic cavity approach.Methods:From January 2018 to December 2021, 251 patients(including myasthenia gravis with thymic hyperplasia or thymoma, thymic cysts and anterior mediastinal occupying lesions)undergoing thoracoscopic extended thymectomy in our department were retrospectively studied, and their clinical data were collected.The surgical methods were divided into artificial pneumothorax combining xiphoid costal margin approach(artificial pneumothorax group, n=165)and via right thoracic approach(right thoracic group, n=86). Clinical data such as preoperative information, operative duration, blood loss, postoperative drainage, drainage duration, and surgical complication were compared between two groups.Results:There were no statistical differences in age, gender and pathology between two groups(all P>0.05). Compared with the right thoracic group, operative duration[(108.6±45.2)min vs.(127.6±42.1)min, t=-3.628, P=0.000], intraoperative blood loss[(37.9±131.7)ml vs.(107.4±284.8)ml, t=-8.215, P=0.000], postoperative drainage volume[(379.0±285.5)ml vs.(646.6±373.3 ml), t=-6.277, P=0.000]and drainage duration[(2.2±1.0)d vs.(3.1±1.0)d, t=-7.275, P=0.000]were statistically significantly decreased in the artificial pneumothorax group.No significant difference was found(all P>0.05)in phrenic nerve injury(1/165 vs.0/86, P=1.000), myasthenia crisis(3/89 vs.2/66, χ2=0.014, P=0.906), and the conversion to thoracotomy(3/165 vs.2/86, P=1.000). Conclusions:VATS thymectomy by artificial pneumothorax combining subxiphoid-costal margin approach is a safer method, having a less trauma, less bleeding and less incidence rate of complication.Especially, it is more suitable for elderly female patients who cannot be intubated in double lumen, cannot tolerate one-lung ventilation, and have pulmonary insufficiency.

Objective:To evaluate the clinical characteristics and the surgical safety in patients aged 65 years and over with thymic epithelial tumor, and analyze the prognosis of 3-10 years postoperative tumor and myasthenia gravy.Methods:A total of 228 patients diagnosed as thymic tumor and undergoing surgical surgery to remove the tumor in Beijing Hospital from Jan.2011 to Dec.2018 were retrospectively enrolled.Patients were divided into a young(≤ 65 yrs)and old(>65 yrs)groups.The operation time, intra-operative bleeding, drainage volume in the first 3 days after operation, days with drainage tube after operation, postoperative days of hospital stays, the diameter of the tumors, pathological classification, Tumor-Node-Metastasis(TNM)staging, Masaoka-Koga staging, whether or not complicated with myasthenia gravis and complications were compared between two groups.The patients were followed up by outpatient or telephone, and recurrence of thymoma, survival status and improvement of myasthenia gravis were tracked.Results:There were significant differences in pathological classification between the two groups( P=0.002). The postoperative days with drainage tube were longer in patients≥65 years old than in patients<65 years old[4(2-17)days and 3(1-9), Z=2.316, P=0.021]. Thymic atrophy was more common in patients ≥ 65 years old than in patients <65 years old(10.2% and 1.7%, χ2=5.937, P=0.015). Incidence of thymoma plus myasthenia gravis were higher in patients aged <65 years than those aged ≥65years(68.2% vs.40.8%, χ2=12.240, P<0.001), and incidence of thymic hyperplasia were higher in patients aged <65 years than those aged ≥65years(58.1% and 38.8%, χ2=2.316, P=0.016). The recurrence of thymoma was a poor prognostic factor affecting the survival of patients.Meanwhile, Masaoka-Koga stage Ⅲ and Ⅳ and TNM stage Ⅲ and Ⅳ were independent risk factors for postoperative recurrence of thymoma. Conclusions:Thymectomy is safe and effective in the patients aged 65 and over, and may have a better long-term prognosis.

The record speed at which Chinese scientists identified severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) and shared its genomic sequence with the world, has greatly facilitated the development of coronavirus disease (COVID-19) diagnostics, drugs, and vaccines. It is unprecedented in pandemic control history to develop a dozen successful vaccines in the first year and to immunize over half of the global population in the second year, due to the efforts of the scientific community, biopharmaceutical industry, and regulatory agencies worldwide. The challenges are both great and multidimensional due to the rapid emergence of virus variants and waning of vaccine immunity. Vaccination strategies need to adapt to these challenges to keep population immunity above the herd immunity threshold, by increasing vaccine coverage, especially for older adults and young people, and providing timely booster doses with homologous or heterologous vaccine boosts. Further research should be undertaken to develop more effective vaccines against SARS-CoV-2 variants and to understand the best prime-boost vaccine combinations and immunization strategies to provide sufficient and sustainable immune protection against COVID-19.
Adolescent ; Aged ; COVID-19/prevention & control* ; COVID-19 Vaccines ; Humans ; Pandemics/prevention & control* ; SARS-CoV-2 ; Vaccination