During the global efforts to prevent and control the COVID-19 pandemic, extensive research and development of SARS-CoV-2 vaccines using various technical approaches have taken place. Among these, vaccines based on adenovirus vector have gained substantial knowledge and experience in effectively combating potential emerging infectious diseases, while also providing novel ideas and methodologies for vaccine research and development (R&D). This comprehensive review focuses on the adenovirus vector technology platform in vaccine R&D, emphasizing the importance of mucosal immunity induced by adenoviral vector-based vaccine for COVID-19 prevention. Furthermore, it analyzes the key technical challenges and obstacles encountered in the development of vaccines based on the adenovirus vector technology platform, with the aim of providing valuable insights and references for researchers and professionals in related fields.
Humans ; COVID-19 Vaccines ; Pandemics/prevention & control* ; COVID-19/prevention & control* ; SARS-CoV-2/genetics* ; Viral Vaccines/genetics* ; Adenoviridae/genetics* ; Technology

We wished to establish an expert consensus on late stage of critical care (CC) management. The panel comprised 13 experts in CC medicine. Each statement was assessed based on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) principle. Then, the Delphi method was adopted by 17 experts to reassess the following 28 statements. (1) ESCAPE has evolved from a strategy of delirium management to a strategy of late stage of CC management. (2) The new version of ESCAPE is a strategy for optimizing treatment and comprehensive care of critically ill patients (CIPs) after the rescue period, including early mobilization, early rehabilitation, nutritional support, sleep management, mental assessment, cognitive-function training, emotional support, and optimizing sedation and analgesia. (3) Disease assessment to determine the starting point of early mobilization, early rehabilitation, and early enteral nutrition. (4) Early mobilization has synergistic effects upon the recovery of organ function. (5) Early functional exercise and rehabilitation are important means to promote CIP recovery, and gives them a sense of future prospects. (6) Timely start of enteral nutrition is conducive to early mobilization and early rehabilitation. (7) The spontaneous breathing test should be started as soon as possible, and a weaning plan should be selected step-by-step. (8) The waking process of CIPs should be realized in a planned and purposeful way. (9) Establishment of a sleep-wake rhythm is the key to sleep management in post-CC management. (10) The spontaneous awakening trial, spontaneous breathing trial, and sleep management should be carried out together. (11) The depth of sedation should be adjusted dynamically in the late stage of CC period. (12) Standardized sedation assessment is the premise of rational sedation. (13) Appropriate sedative drugs should be selected according to the objectives of sedation and drug characteristics. (14) A goal-directed minimization strategy for sedation should be implemented. (15) The principle of analgesia must be mastered first. (16) Subjective assessment is preferred for analgesia assessment. (17) Opioid-based analgesic strategies should be selected step-by-step according to the characteristics of different drugs. (18) There must be rational use of non-opioid analgesics and non-drug-based analgesic measures. (19) Pay attention to evaluation of the psychological status of CIPs. (20) Cognitive function in CIPs cannot be ignored. (21) Delirium management should be based on non-drug-based measures and rational use of drugs. (22) Reset treatment can be considered for severe delirium. (23) Psychological assessment should be conducted as early as possible to screen-out high-risk groups with post-traumatic stress disorder. (24) Emotional support, flexible visiting, and environment management are important components of humanistic management in the intensive care unit (ICU). (25) Emotional support from medical teams and families should be promoted through"ICU diaries"and other forms. (26) Environmental management should be carried out by enriching environmental content, limiting environmental interference, and optimizing the environmental atmosphere. (27) Reasonable promotion of flexible visitation should be done on the basis of prevention of nosocomial infection. (28) ESCAPE is an excellent project for late stage of CC management.
Humans ; Consensus ; Critical Care/methods* ; Intensive Care Units ; Pain/drug therapy* ; Analgesics/therapeutic use* ; Delirium/therapy* ; Critical Illness

The global pandemic of coronavirus disease 2019 (COVID-19) has brought great challenges to the traditional medical model. During the outbreak of COVID-19 in Shanghai, China, from March to May, 2022, there was a significant increase in the number of pediatric cases due to high transmissibility, immune escape, and vaccine breakthrough capacity of Omicron variants. The designated hospitals for children with COVID-19 served as a connecting link between children's specialized hospitals and mobile cabin hospitals. From April 7 to June 2, 2022, a total of 871 children with COVID-19 were admitted to Renji Hospital, Shanghai Jiao Tong University School of Medicine (South Branch), a designated hospital for children with COVID-19. Among these patients, 568 (65.2%) were children under 3 years old, 870 (99.9%) were mild or moderate, and 1 was severe. This article reports the experience in the management of pediatric cases in this designated hospital, which included the following aspects: establishing an optimal case-admission process; strengthening multidisciplinary standardized diagnosis and treatment; optimizing the management, warning, and rescue system for severe COVID-19; implementing family-centered nursing care; formulating an individualized traditional Chinese medicine treatment regimen; optimizing the discharge process and strengthening bed turnover; implementing strict whole-process control to reduce the risk of nosocomial infection; constructing a structured medical record system and using information platforms to adapt to the work mode of large-volume cases; conducting scientific research and sharing the experience in diagnosis and treatment.
COVID-19 ; Child ; Child, Preschool ; China ; Hospitals, Pediatric ; Humans ; SARS-CoV-2

Objective: To investigate the distribution of HIV-1 genetic subtypes and pretreatment drug resistance (PDR) among men who have sex with men (MSM) from 19 cities of 6 provinces in China. Methods: From April to November 2019, 574 plasma samples of ART-naive HIV-1 infected MSM were collected from 19 cities in Hebei, Shandong, Jiangsu, Zhejiang, Fujian, and Guangdong provinces, total ribonucleic acid (RNA) was extracted and amplified the HIV-1 pol gene region by nested polymerase chain reaction (PCR) after reverse transcription. Then sequences were used to construct a phylogenetic tree to determine genetic subtypes and submitted to the Stanford drug resistance database for drug resistance analysis. Results: A total of 479 samples were successfully amplified by PCR. The HIV-1 genetic subtypes included CRF01_AE, CRF07_BC, B, CRF55_01B, CRF59_01B, CRF65_cpx, CRF103_01B, CRF67_01B, CRF68_01B and unrecognized subtype, which accounted for 43.4%, 36.3%, 6.3%, 5.9%, 0.8%, 0.8%, 0.4%, 0.4%, 0.2% and 5.5%, respectively. The distribution of genetic subtypes among provinces is statistically different (χ²=44.141, P<0.001). The overall PDR rate was 4.6% (22/479), the drug resistance rate of non-nucleoside reverse transcriptase inhibitors, nucleoside reverse transcriptase inhibitors, and protease inhibitors were 3.5% (17/479), 0.8% (4/479) and 0.2% (1/479), respectively. The PDR rate of recent infections was significantly higher than that of long-term infections (χ²=4.634, P=0.031). Conclusions: The HIV-1 genetic subtypes among MSM infected with HIV-1 from 19 cities of 6 provinces in China are diverse, and the distribution of subtypes is different among provinces. The overall PDR rate is low, while the PDR rate of recent infections was significantly higher than that of long-term infections, suggesting the surveillance of PDR in recent infections should be strengthened.
China/epidemiology* ; Cities ; Drug Resistance ; Drug Resistance, Viral/genetics* ; Female ; Genotype ; HIV Infections/epidemiology* ; HIV Seropositivity/drug therapy* ; HIV-1/genetics* ; Homosexuality, Male ; Humans ; Male ; Phylogeny ; Reverse Transcriptase Inhibitors/therapeutic use* ; Sexual and Gender Minorities

Objective: To explore the role and related mechanism of mammalian sterile 20-like kinase 1(Mst-1)in regulating hypoxia reoxygenation (HR) induced myocardial cell autophagy and apoptosis. Methods: Enzyme digestion method combined with differential adherent method was used to culture neonatal mouse myocardial cells. HR model was established by hypoxia for 24 hours and reoxygenation for 6 hours. The experimental groups including control group (normal cultured cardiomyocytes), Mst-1 empty virus group (cardiomyocytes transfected with recombinant lentiviral empty vector for 48 hours), Mst-1 knockdown group (recombinant lentivirus carrying Mst-1small interfering RNA (siRNA) was transfected into cardiomyocytes for 48 hours), Mst-1 overexpression group (cardiomyocytes were transfected with recombinant lentivirus carrying Mst-1 gene for 48 hours), HR group (cardiomyocytes exposed to HR), Mst-1 knockdown+HR group (HR model of cardiomyocyte was established 48 hours after transfection with recombinant lentivirus carrying Mst-1siRNA) and Mst-1 overexpression+HR group (HR model of cardiomyocyte was established 48 hours after transfection with recombinant lentivirus carrying Mst-1 gene). Real-time fluorescence quantitative RCR (qPCR) and Western blot were used to detect the relative expression of Mst-1 mRNA and protein in the cells, immunofluorescence staining was used to detect cardiomyocyte troponin T (cTnT), and autophagosomes and autophagy enzyme changes. TUNEL method was used to detect myocardial cell apoptosis, Western blot was adopted to detect autophagy-related protein microtubule-related protein 1 light chain 3 (LC3) Ⅱ/LC3 Ⅰ, P62 and apoptosis-related protein cleaved-caspase 9, pro-caspase 9, cleaved-caspase-3, pro-caspase-3, and myeloid leukemia 1 (MCL-1) expression. MCL-1 inhibitor A1210477 was used to validate the signaling pathway of Mst-1 on regulating cardiomyocyte apoptosis and autophagy. Results: Immunofluorescence detection revealed that the cultured cells expressed cardiomyocyte-specific marker cTnT. The expression of Mst-1 in cardiomyocytes increased in HR model. Lentiviral transfection could effectively inhibit or overexpress Mst-1 in treated cells. The levels of autophagosomes and autophagolysosomes in cardiomyocytes undergoing HR and in Mst-1 overexpression+HR group were lower than those of control group, while autophagosomes and autophagolysosomes in cardiomyocytes of Mst-1 knockdown+HR group was significantly higher than in the HR group (all P<0.05). The TUNEL results showed that the proportion of TUNEL positive cells was significantly increased in the HR group and Mst-1 overexpression+HR group than in the control group, while the proportion of TUNEL positive cells was significantly decreased in the Mst-1 knockdown group+HR group as compared to the HR group (all P<0.05). Western blot results showed that the LC3 Ⅱ/LC3 Ⅰ levels were significantly lower, while the expression levels of P62, cleaved-caspase-9 and cleaved-caspase-3 were significantly higher in the HR group and Mst-1 overexpression+HR group than in control group (all P<0.05). The LC3 Ⅱ/LC3 Ⅰ value was significantly higher, and the expression levels of P62, cleaved-caspase-9 and cleaved-caspase-3 were significantly lower in the Mst-1 knockdown+HR group than in the HR group (P both<0.05). The expression level of P-MCL-1 protein was significantly lower in cardiomyocytes of HR and Mst-1 overexpression+HR group than in control group, and the expression level of P-MCL-1 protein was higher in Mst-1 knockdown+HR group than in HR group (P both<0.05). The recovery experiment showed that inhibiting MCL-1 in cells can block the regulatory effect of Mst-1 siRNA on cell autophagy and apoptosis. Conclusion: Inhibiting Mst-1 expression in cardiomyocytes can promote the autophagy of cardiomyocytes induced by hypoxic reoxygenation and reduce the apoptosis of cardiomyocytes via activating McL-1.
Animals ; Apoptosis ; Autophagy ; Hypoxia ; Mice ; Myocytes, Cardiac ; Signal Transduction

BACKGROUND: Resting-state functional magnetic resonance imaging (rs-fMRI) is a promising method for the study of brain function. Typically, rs-fMRI is performed on anesthetized animals. Although different functional connectivity (FC) in various anesthetics on whole brain have been studied, few studies have focused on different FC in the aged brain. Here, we measured FC under three commonly used anesthesia methods and analyzed data to determine if the FC in whole brain analysis were similar among groups. METHODS: Twenty-four male aged Wistar rats were randomly divided into three groups (n = 8 in each group). Anesthesia was performed under either isoflurane (ISO), combined ISO + dexmedetomidine (DEX) or α-chloralose (AC) according to the groups. Data of rs-fMRI was analyzed by FC in a voxel-wise way. Differences in the FC maps between the groups were analyzed by one-way analysis of variance and post hoc two-sample t tests. RESULTS: Compared with ISO + DEX anesthesia, ISO anesthesia caused increased FC in posterior brain and decreased FC in the middle brain of the aged rat. AC anesthesia caused global suppression as no increase in FC was observed. CONCLUSION ISO could be used as a substitute for ISO + DEX in rat default mode network studies if the left temporal association cortex is not considered important.
Anesthesia ; Animals ; Brain/diagnostic imaging* ; Brain Mapping ; Isoflurane ; Magnetic Resonance Imaging ; Male ; Rats ; Rats, Wistar

Antineoplastic Agents ; Dasatinib ; Humans ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Protein Kinase Inhibitors ; Pyrimidines/therapeutic use*

OBJECTIVE: To evaluate the satisfaction and performance of water colonoscopy and gas colonoscopy. METHODS: 240 continuous cases were randomly divided into two groups(gas colonoscopy group, water colonoscopy group). Record the general condition, success rate, period of performance and abdominal pain score. Investigate the degree of abdominal pain, distension and the will of receiving anesthetic colonoscopy next time in the follow-up. RESULTS: There were no significant difference between two groups in the general condition, success rate, depth of insertion, abdominal pain after examination or the will of receiving anesthetic colonoscopy next time(P>0.05). The period of insertion, period of withdrawal and period of performance in water colonoscopy group was longer than those in the gas colonoscopy group(P<0.001, P=0.013, P<0.001). The degree of abdominal distension at 1 hour after colonoscopy in water colonoscopy group was higher than those in the gas colonoscopy group(P<0.001), but no significant difference was found at6 hours after examination. CONCLUSION: Patients undergoing water colonoscopy have better outcomes with less abdominal pain and abdominal distension except for longer time of performance.

OBJECTIVE: To analyze the clinical and imaging characteristics of the neurological damage caused by nitrous oxide (N₂O). METHODS: In the study, 10 patients in the Department of Neurology of China-Japan Friendship Hospital from October 2015 to February 2018 were retrospectively analyzed for the demographic data, the history of inhaled N₂O, clinical features, blood examination, electrophysiological examination, spinal magnetic resonance imaging and therapeutic efficacy profiles. RESULTS: The male-to-female ratio was 4:6 and it presented with an age-of-onset 17-26 years [the average age: (20.80±3.12) years]. The time from inhaled N₂O to onset was 1 month to 1 year [the average time: (6.95±4.19) months]. Paralysis in all the patients and numbness in 9 patients were the main clinical features, while positive Lhermitte's sign in 3 patients, urinary and defecation disturbance in 4 patients were also found. Blood examination indicated anemia in 2 patients, giant cell anemia in 1 case and small cell hypochromic anemia in 1 case. 3 cases had been treated with vitamin B12 in an external hospital, and the other 7 cases had abnormal increase in homocysteine levels. Electrophysiological examinations showed sensory and motor nerve involvement in 9 patients, and motor nerve involvement in 1 patient. The severity of lower extremity lesion was significantly heavier than that of upper extremity. Spinal magnetic resonance imagings showed that long segmental lesions were present in the cervical spinal cord of all the patients, 3 cases with long segmental lesions of the thoracic cord and 2 cases with spinal cord swelling. In 6 cases, the horizontal axis had an "inverted V-type" T2 high signal, 1 case was classified as "crescent", and 3 cases were "eight-shaped". The symptoms in these 10 cases were alleviated in varying degrees after stopping the inhalation of nitrous oxide, actively supplementing high doses of vitamin B12 and doing early rehabilitation exercises. CONCLUSION Myelopathy with nitrous oxide presents as paralysis and numbness in limb extremities. In imaging, cervical spinal cord damage is common, accompanied by thoracic spinal cord damage. The horizontal axis is more common in the "inverted V-type". Treatment with high doses of vitamin B12 is effective.
Adolescent ; China ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Nitrous Oxide ; Retrospective Studies ; Spinal Cord Diseases ; Young Adult