Radiation-induced thrombocytopenia(RIT)faces a perplexing challenge in the clinical treatment of cancer patients,and current therapeutic approaches are inadequate in the clinical settings.In this research,oxy-matrine,a new molecule capable of healing RIT was screened out,and the underlying regulatory mecha-nism associated with magakaryocyte(MK)differentiation and thrombopoiesis was demonstrated.The capacity of oxymatrine to induce MK differentiation was verified in K-562 and Meg-01 cells in vitro.The ability to induce thrombopoiesis was subsequently demonstrated in Tg(cd41:enhanced green fluorescent protein(eGFP))zebrafish and RIT model mice.In addition,we carried out network pharmacological pre-diction,drug affinity responsive target stability assay(DARTS)and cellular thermal shift assay(CETSA)analyses to explore the potential targets of oxymatrine.Moreover,the pathway underlying the effects of oxymatrine was determined by Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses,Western blot(WB),and immunofluorescence.Oxymatrine markedly promoted MK differentiation and maturation in vitro.Moreover,oxymatrine induced thrombopoiesis in Tg(cd41:eGFP)zebrafish and accelerated thrombopoiesis and platelet function recovery in RIT model mice.Mechanistically,oxymatrine directly binds to toll-like receptor 2(TLR2)and further regulates the downstream pathway stimulator of interferon genes(STING)/nuclear factor-kappaB(NF-κB),which can be blocked by C29 and C-176,which are specific inhibitors of TLR2 and STING,respectively.Taken together,we demonstrated that oxymatrine,a novel TLR2 agonist,plays a critical role in accelerating MK differentiation and thrombopoiesis via the STING/NF-κB axis,suggesting that oxymatrine is a promising candidate for RIT therapy.

Turning to critical illness is a common stage of various diseases and injuries before death. Patients usually have complex health conditions, while the treatment process involves a wide range of content, along with high requirements for doctor′s professionalism and multi-specialty teamwork, as well as a great demand for time-sensitive treatments. However, this is not matched with critical care professionals and the current state of medical care in China. Telemedicine, which shortens the distance of medical professionals and the gap of disease diagnosis and treatments in various regions through electronic information, can effectively solve the current problem. Therefore, there is an urgent need to develop a standardized, high-quality visualization telemedicine round system .Therefore, experts have been organized to search domestic and foreign literature on telemedicine round for critically ill patients and to form this consensus based on clinical experiences so as to further improve the level of critical care treatments in regions.

Radiation-induced thrombocytopenia (RIT) faces a perplexing challenge in the clinical treatment of cancer patients, and current therapeutic approaches are inadequate in the clinical settings. In this research, oxymatrine, a new molecule capable of healing RIT was screened out, and the underlying regulatory mechanism associated with magakaryocyte (MK) differentiation and thrombopoiesis was demonstrated. The capacity of oxymatrine to induce MK differentiation was verified in K-562 and Meg-01 cells in vitro. The ability to induce thrombopoiesis was subsequently demonstrated in Tg (cd41:enhanced green fluorescent protein (eGFP)) zebrafish and RIT model mice. In addition, we carried out network pharmacological prediction, drug affinity responsive target stability assay (DARTS) and cellular thermal shift assay (CETSA) analyses to explore the potential targets of oxymatrine. Moreover, the pathway underlying the effects of oxymatrine was determined by Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, Western blot (WB), and immunofluorescence. Oxymatrine markedly promoted MK differentiation and maturation in vitro. Moreover, oxymatrine induced thrombopoiesis in Tg (cd41:eGFP) zebrafish and accelerated thrombopoiesis and platelet function recovery in RIT model mice. Mechanistically, oxymatrine directly binds to toll-like receptor 2 (TLR2) and further regulates the downstream pathway stimulator of interferon genes (STING)/nuclear factor-kappaB (NF-κB), which can be blocked by C29 and C-176, which are specific inhibitors of TLR2 and STING, respectively. Taken together, we demonstrated that oxymatrine, a novel TLR2 agonist, plays a critical role in accelerating MK differentiation and thrombopoiesis via the STING/NF-κB axis, suggesting that oxymatrine is a promising candidate for RIT therapy.

Turning to critical illness is a common stage of various diseases and injuries before death. Patients usually have complex health conditions, while the treatment process involves a wide range of content, along with high requirements for doctor′s professionalism and multi-specialty teamwork, as well as a great demand for time-sensitive treatments. However, this is not matched with critical care professionals and the current state of medical care in China. Telemedicine, which shortens the distance of medical professionals and the gap of disease diagnosis and treatments in various regions through electronic information, can effectively solve the current problem. Therefore, there is an urgent need to develop a standardized, high-quality visualization telemedicine round system .Therefore, experts have been organized to search domestic and foreign literature on telemedicine round for critically ill patients and to form this consensus based on clinical experiences so as to further improve the level of critical care treatments in regions.

Traumatic supraorbital fissure syndrome (TSOFS) is a symptom complex caused by nerve entrapment in the supraorbital fissure after skull base trauma. If the compressed cranial nerve in the supraorbital fissure is not decompressed surgically, ptosis, diplopia and eye movement disorder may exist for a long time and seriously affect the patients′ quality of life. Since its overall incidence is not high, it is not familiarized with the majority of neurosurgeons and some TSOFS may be complicated with skull base vascular injury. If the supraorbital fissure surgery is performed without treatment of vascular injury, it may cause massive hemorrhage, and disability and even life-threatening in severe cases. At present, there is no consensus or guideline on the diagnosis and treatment of TSOFS that can be referred to both domestically and internationally. To improve the understanding of TSOFS among clinical physicians and establish standardized diagnosis and treatment plans, the Skull Base Trauma Group of the Neurorepair Professional Committee of the Chinese Medical Doctor Association, Neurotrauma Group of the Neurosurgery Branch of the Chinese Medical Association, Neurotrauma Group of the Traumatology Branch of the Chinese Medical Association, and Editorial Committee of Chinese Journal of Trauma organized relevant experts to formulate Chinese expert consensus on the diagnosis and treatment of traumatic supraorbital fissure syndrome ( version 2024) based on evidence of evidence-based medicine and clinical experience of diagnosis and treatment. This consensus puts forward 12 recommendations on the diagnosis, classification, treatment, efficacy evaluation and follow-up of TSOFS, aiming to provide references for neurosurgeons from hospitals of all levels to standardize the diagnosis and treatment of TSOFS.

To establish the experts consensus on the management of delirium in critically ill patients.A special committee was set up by 15 experts from the Chinese Critical Hypothermia-Sedation Therapy Study Group.Each statement was assessed based on the GRADE (Grading of Recommendations Assessment,Development,and Evaluation) principle.Then the Delphi method was adopted by 36 experts to reassess all the statements.(1) Delirium is not only a mental change,but also a clinical syndrome with multiple pathophysiological changes.(2) Delirium is a form of disturbance of consciousness and a manifestation of abnormal brain function.(3) Pain is a common cause of delirium in critically ill patients.Analgesia can reduce the occurrence and development of delirium.(4) Anxiety or depression are important factors for delirium in critically ill patients.(5) The correlation between sedative and analgesic drugs and delirium is uncertain.(6) Pay attention to the relationship between delirium and withdrawal reactions.(7) Pay attention to the relationship between delirium and drug dependence/ withdrawal reactions.(8) Sleep disruption can induce delirium.(9) We should be vigilant against potential risk factors for persistent or recurrent delirium.(10) Critically illness related delirium can affect the diagnosis and treatment of primary diseases,and can also be alleviated with the improvement of primary diseases.(11) Acute change of consciousness and attention deficit are necessary for delirium diagnosis.(12) The combined assessment of confusion assessment method for the intensive care unit and intensive care delirium screening checklist can improve the sensitivity of delirium,especially subclinical delirium.(13) Early identification and intervention of subclinical delirium can reduce its risk of clinical delirium.(14) Daily assessment is helpful for early detection of delirium.(15) Hopoactive delirium and mixed delirium are common and should be emphasized.(16) Delirium may be accompanied by changes in electroencephalogram.Bedside electroencephalogram monitoring should be used in the ICU if conditions warrant.(17) Pay attention to differential diagnosis of delirium and dementia/depression.(18) Pay attention to the role of rapid delirium screening method in delirium management.(19) Assessment of the severity of delirium is an essential part of the diagnosis of delirium.(20) The key to the management of delirium is etiological treatment.(21) Improving environmental factors and making patient comfort can help reduce delirium.(22) Early exercise can reduce the incidence of delirium and shorten the duration of delirium.(23) Communication with patients should be emphasized and strengthened.Family members participation can help reduce the incidence of delirium and promote the recovery of delirium.(24) Pay attention to the role of sleep management in the prevention and treatment of delirium.(25) Dexmedetomidine can shorten the duration of hyperactive delirium or prevent delirium.(26) When using antipsychotics to treat delirium,we should be alert to its effect on the heart rhythm.(27) Delirium management should pay attention to brain functional exercise.(28) Compared with non-critically illness related delirium,the relief of critically illness related delirium will not accomplished at one stroke.(29) Multiple management strategies such as ABCDEF,eCASH and ESCAPE are helpful to prevent and treat delirium and improve the prognosis of critically ill patients.(30) Shortening the duration of delirium can reduce the occurrence of long-term cognitive impairment.(31) Multidisciplinary cooperation and continuous quality improvement can improve delirium management.Consensus can promote delirium management in critically ill patients,optimize analgesia and sedation therapy,and even affect prognosis.

Objective To investigate the clinical features of IgG4 related autoimmune pancreatitis (AIP). Methods Clinical data of 12 patients pathologically diagnosed as IgG4 related AIP in Department of Hepatopancreatobiliary Surgery, Sun Yat-sen Memorial Hospital of Sun Yat-sen University from January 2003 to December 2012 were retrospectively analyzed. The informed consents of all patients were obtained and the ethical committee approval was received. All the patients were males with a mean age of (54±13) years old. All were misdiagnosed as pancreatic head carcinoma and received pancreatoduodenectomy. Data of the clinical manifestations, laboratory, imaging and pathological examinations were collected. The patients were followed up after operations, the treatment and outcome were studied. Results The clinical manifestations of the 12 patients were abdominal pain (n=7), jaundice(n=7), emaciation(n=6) and no obvious symptom (n=1). Three cases were combined with diabetes, 1 case with chronic sialadenitis of submandibular gland. The patient's blood and urine amylase were normal. Blood gamma-glutamyl transpeptidase (GGT) increase was observed in 12 cases. Mild increase of carbohydrate antigen 19-9 (CA19-9) was observed in 9 cases. Cancer antigen (CA) 125 increase was observed in 3 cases, and carcinoembryonic antigen (CEA) increase in 2 cases. Through contrast-enhanced CT, partial pancreatic head enlargement was observed in 11 cases, in which 3 cases were observed combining with mild expansion of pancreatic duct. Through magnetic resonance imaging (MRI), sausage-like change of pancreas body was observed in 4 cases, peripancreatic sheath-like change in 5 cases. Through magnetic resonance cholangiopancreatography (MRCP), stenoses in the pancreatic duct of pancreatic head segment and distal common bile duct were observed including 4 cases of mild expansion in the distal pancreatic duct. Local invasion was not observed by imaging examinations. Lymphoplasmacytic sclerosing pancreatitis was determined by pathological examination. Positive expression of IgG4 was observed by immunohistochemistry. Twelve cases suffered from discontinuous abdominal pain after operations, in which 7 cases needed acesodyne. One case relieved after using prednisone. Conclusions Clinical manifestations of IgG4 related AIP are similar to pancreatic carcinoma and can be misdiagnosed as pancreatic carcinoma easily. The main clinical features are mild increase of blood CA19-9. Partial pancreatic head enlargement, pancreas body sausage-like change, peripancreatic sheath-like change, and no local invasion are observed by imaging examinations. Lymphoplasmacytic sclerosing pancreatitis is determined by pathological examination. Positive expression of IgG4 is observed by immunohistochemistry. Adrenocortical hormone treatment is effective.

To investigate the effects of dendritic cells (DCs) transfected with full length wild type p53 and modified by gastric cancer lysates on immune response, the wild type P53 was transducted to DCs with adenovirus, and the DCs were modified by gastric cancer lysates (Lywt-P53DC). The concentration of the surface molecules (B7-1, B7-2, MHC-I , MHC-II) of all DCs was determined by FACS, and the ability of the DCs to induce efficient and specific immunological response in anti-51Cr-labeled target cells studied. BALB/c mice model infected with DCs and Mk28 was established. CTL response in mice immunized with Lywt-p53DC and the effectiveness of Lywt-p53DC in the treatment of tumor-bearing mice was assayed. FACS revealed that the surface molecules of Ly-wt-P53 DC had a high expression: for B7-1 86.70% +/- 0.07%, B7-2 18.77% +/- 0.08%, MHC-I 87.20% +/- 0.05%, MHC-II 56.70%+/-0.07%; The T lymphocytes had a specific CTL lysing ability induced by Lywt-P53DC with the CTL lysis rate being 81%. The immune protective effect of Lywt-p53DC group was more obvious than any other groups (P<0.05). The tumor diameter in Lywt-p53DC group was 3.10+/-0.31 mm, 2.73+/-0.23 mm, 3.70+/-0.07 mm on the day 13, 16 and 19, smaller than DC, wtp53DC and LyDC groups (P<0.05). On the other hand, the growth rate of tumor in Lywt-p53DC group was slower than any other groups (P<0.05). It was suggested that DCs transfected with wild type P53 and modified by gastric cancer lysates had specific CTL killing capability.
Adenoviridae ; genetics ; metabolism ; Animals ; Cell Line, Tumor ; Dendritic Cells ; immunology ; metabolism ; Female ; Genetic Vectors ; Mice ; Mice, Inbred BALB C ; Recombinant Proteins ; biosynthesis ; genetics ; Stomach Neoplasms ; immunology ; pathology ; T-Lymphocytes, Cytotoxic ; immunology ; Transfection ; Tumor Suppressor Protein p53 ; biosynthesis ; genetics