Background::Adamantinomatous craniopharyngioma (ACP) is the commonest pediatric sellar tumor. No effective drug is available and interpatient heterogeneity is prominent. This study aimed to identify distinct molecular subgroups of ACP based on the multi-omics profiles, imaging findings, and histological features, in order to predict the response to anti-inflammatory treatment and immunotherapies.Methods::Totally 142 Chinese cases diagnosed with craniopharyngiomas were profiled, including 119 ACPs and 23 papillary craniopharyngiomas. Whole-exome sequencing (151 tumors, including recurrent ones), RNA sequencing (84 tumors), and DNA methylome profiling (95 tumors) were performed. Consensus clustering and non-negative matrix factorization were used for subgrouping, and Cox regression were utilized for prognostic evaluation, respectively.Results::Three distinct molecular subgroups were identified: WNT, ImA, and ImB. The WNT subgroup showed higher Wnt/β-catenin pathway activity, with a greater number of epithelial cells and more predominantly solid tumors. The ImA and ImB subgroups had activated inflammatory and interferon response pathways, with enhanced immune cell infiltration and more predominantly cystic tumors. Mitogen-activated protein kinases (MEK/MAPK) signaling was activated only in ImA samples, while IL-6 and epithelial-mesenchymal transition biomarkers were highly expressed in the ImB group, mostly consisting of children. The degree of astrogliosis was significantly elevated in the ImA group, with severe finger-like protrusions at the invasive front of the tumor. The molecular subgrouping was an independent prognostic factor, with the WNT group having longer event-free survival than ImB (Cox, P = 0.04). ImA/ImB cases were more likely to respond to immune checkpoint blockade (ICB) therapy than the WNT group ( P <0.01). In the preliminary screening of subtyping markers, CD38 was significantly downregulated in WNT compared with ImA and ImB ( P = 0.01). Conclusions::ACP comprises three molecular subtypes with distinct imaging and histological features. The prognosis of the WNT type is better than that of the ImB group, which is more likely to benefit from the ICB treatment.

Traumatic cerebrospinal fluid leakage commonly presents in traumatic brain injury patients, and it may lead to complications such as meningitis, ventriculitis, brain abscess, subdural hematoma or tension pneumocephalus. When misdiagnosed or inappropriately treated, traumatic cerebrospinal fluid leakage may result in severe complications and may be life-threatening. Some traumatic cerebrospinal fluid leakage has concealed manifestations and is prone to misdiagnosis. Due to different sites and mechanisms of trauma and degree of cerebrospinal fluid leak, treatments for traumatic cerebrospinal fluid leakage varies greatly. Hence, the Craniocerebral Trauma Professional Group of Neurosurgery Branch of Chinese Medical Association and the Neurological Injury Professional Group of Trauma Branch of Chinese Medical Association organized relevant experts to formulate the " Chinese expert consensus on the diagnosis and treatment of traumatic cerebrospinal fluid leakage in adults ( version 2023)" based on existing clinical evidence and experience. The consensus consisted of 16 recommendations, covering the leakage diagnosis, localization, treatments, and intracranial infection prevention, so as to standardize the diagnosis and treatment of traumatic cerebrospinal fluid leakage and improve the overall prognosis of the patients.

Objective:To verify that hypoxia induces epithelial mesenchymal transition in HaCaT cells, and to observe the effect of LncRNA HOTAIR on epithelial mesenchymal transition in HaCaT cells.Methods:From Jan. 2018 to Dec. 2018 in Chinese Academy of Medical Science, HaCaT cells were divided into four groups: group A cultured under normoxia, group B cultured under hypoxia, group C transfected with sh-control cultured under hypoxia, and group D transfected with sh-LncRNA HOTAIR cultured under hypoxia. After 36 hours of culturing, the expression of E-cadherin and vimentin were detected using qPCR and Western blot. The migration of HaCaT cells was evaluated by Transwell assay.Results:The relative quantity of E-cadherin mRNA in the four groups were 3.076±0.271, 1.000±0.089, 1.024±0.222, and 2.595±0.085, while vimentin mRNAs were 1.002±0.183, 4.170±0.279, 4.111±0.477, and 2.412±0.134, respectively. In addition, the Transwll invasion assay showed that numbers of cell migration in the four groups were 32.70±3.93, 125.40±6.26, 120.10±6.79, and 58.24±7.06, respectively.Conclusions:The study suggests that hypoxia promotes epithelial mesenchymal transition in keratinocytes. Furthermore, downregulation of HOTAIR is noted to inhibit epithelial mesenchymal transition of keratinocytes under hypoxia condition.

C-fos is a transcription factor that plays an important role in cell proliferation, differentiation and tumor formation. The aim of this study was to clone the goat c-fos gene, clarify its biological characteristics, and further reveal its regulatory role in the differentiation of goat subcutaneous adipocytes. We cloned the c-fos gene from subcutaneous adipose tissue of Jianzhou big-eared goats by reverse transcription-polymerase chain reaction (RT-PCR) and analyzed its biological characteristics. Using real-time quantitative PCR (qPCR), we detected the expression of c-fos gene in the heart, liver, spleen, lung, kidney, subcutaneous fat, longissimus dorsi and subcutaneous adipocytes of goat upon induced differentiation for 0 h to 120 h. The goat overexpression vector pEGFP-c-fos was constructed and transfected into the subcutaneous preadipocytes for induced differentiation. The morphological changes of lipid droplet accumulation were observed by oil red O staining and bodipy staining. Furthermore, qPCR was used to test the relative mRNA level of the c-fos overexpression on adipogenic differentiation marker genes. The results showed that the cloned goat c-fos gene was 1 477 bp in length, in which the coding sequence was 1 143 bp, encoding a protein of 380 amino acids. Protein structure analysis showed that goat FOS protein has a basic leucine zipper structure, and subcellular localization prediction suggested that it was mainly distributed in the nucleus. The relative expression level of c-fos was higher in the subcutaneous adipose tissue of goats (P < 0.05), and the expression level of c-fos was significantly increased upon induced differentiation of subcutaneous preadipocyte for 48 h (P < 0.01). Overexpression of c-fos significantly inhibited the lipid droplets formation in goat subcutaneous adipocytes, significantly decreased the relative expression levels of the AP2 and C/EBPβ lipogenic marker genes (P < 0.01). Moreover, AP2 and C/EBPβ promoter are predicted to have multiple binding sites. In conclusion, the results indicated that c-fos gene was a negative regulatory factor of subcutaneous adipocyte differentiation in goats, and it might regulate the expression of AP2 and C/EBPβ gene expression.
Animals ; Goats/genetics* ; Cell Differentiation/genetics* ; Adipogenesis/genetics* ; Gene Expression Regulation ; Proteins/genetics* ; Cloning, Molecular

Objective:To observe the effect of LncRNA HOTAIR on the expression of HIF-1α in HaCat cell under low oxygen condition, and to explore the role of LncRNA HOTAIR in the pathogenesis and development of keloid.Methods:From Jan. 2018 to Dec. 2018 in Chinese Academy of Medical Science, recombinant plasmids were designed and constructed by specific shRNA-HOTAIR. After transfected HaCat cells with sh-LncRNA HOTAIR, RT-PCR was used to detect the expression level of HOTAIR. HaCat cells were cultured in different conditions and divided into four groups: group A cultured under normoxia condition, the other three groups cultured under hypoxia condition. Group C was transfected with sh-control before hypoxic culture, while group D were transfected with sh-LncRNA HOTAIR. After 24 hours′ culture, dual luciferase reporter gene assay was used to verify the relationship of LncRNA HOTAIR and HIF-1α. Expression of HIF-1α in four groups of HaCat cells were determined by Western blot analysis.Results:Recombinant plasmids of shRNA-HOTAIR were successfully constructed, and the HOTAIR expression was significantly decreased. The relative luciferase activity was 0.94±0.30 in group A, 20.39±1.15 in group B, 18.09±0.80 in group C and 3.04±1.15 in group D. The relative luciferase activity of group B was higher than those of group A ( t=29.03, P<0.05), and the difference was statistically significant ( P<0.05). According to the results of Western blotting, group B (1.19±0.07) and group D (1.15±0.06) had higher expression of HIF-1α than group A (0.56±0.29) and group C (0.37±0.38). Down-regulation of HOTAIR significantly inhibited the protein level of HIF-1α. Conclusions:LncRNA HOTAIR plays a positive role in upregulation of HIF-1α in HaCat cells under hypoxia condition. Thus LncRNA HOTAIR may take part in the pathogenesis and development of keloid through HIF-1α pathway.

Objective:To compare and analyze the clinical features of patients with severe coronavirus disease 2019 (sCOVID-19) and severe community acquired pneumonia (sCAP) who meet the diagnostic criteria for severe pneumonia of the Infectious Diseases Society of America/American Thoracic Society (IDSA/ATS).Methods:A retrospective comparative analysis of the clinical records of 116 patients with sCOVID-19 admitted to the department of critical care medicine of Wuhan Third Hospital from January 1, 2020 to March 31, 2020 and 135 patients with sCAP admitted to the department of critical care medicine of Shanghai First People's Hospital from January 1, 2010 to December 31, 2017 was conducted. The basic information, diagnosis and comorbidities, laboratory data, etiology and imaging results, treatment, prognosis and outcome of the patients were collected. The differences in clinical data between sCOVID-19 and sCAP patients were compared, and the risk factors of death were analyzed.Results:The 28-day mortality of sCOVID-19 and sCAP patients were 50.9% (59/116) and 37.0% (50/135), respectively. The proportion of arterial partial pressure of oxygen/fraction of inspired oxygen (PaO 2/FiO 2)≤250 mmHg (1 mmHg ≈ 0.133 kPa) in sCOVID-19 patients was significantly higher than that of sCAP [62.1% (72/116) vs. 34.8% (47/135), P < 0.01]. The possible reason was that the proportion of multiple lung lobe infiltration in sCOVID-19 was significantly higher than that caused by sCAP [94.0% (109/116) vs. 40.0% (54/135), P < 0.01], but the proportion of sCOVID-19 patients requiring mechanical ventilation was significantly lower than that of sCAP [45.7% (53/116) vs. 60.0% (81/135), P < 0.05]. Further analysis of clinical indicators related to patient death found that for sCOVID-19 patients PaO 2/FiO 2, white blood cell count (WBC), neutrophils (NEU), neutrophil percentage (NEU%), neutrophil/lymphocyte ratio (NLR), total bilirubin (TBil), blood urea nitrogen (BUN), albumin (ALB), Ca 2+, prothrombin time (PT), D-dimer, C-reactive protein (CRP) and other indicators were significantly different between the death group and the survival group, in addition, the proportion of receiving mechanical ventilation, gamma globulin, steroid hormones and fluid resuscitation in death group were higher than survival group. Logistic regression analysis showed that the need for mechanical ventilation, NLR > 10, TBil > 10 μmol/L, lactate dehydrogenase (LDH) > 250 U/L were risk factors for death at 28 days. For sCAP patients, there were significant differences in age, BUN, ALB, blood glucose (GLU), Ca 2+ and D-dimer between the death group and the survival group, but there was no significant difference in treatment. Logistic regression analysis showed that BUN > 7.14 mmol/L and ALB < 30 g/L were risk factors for 28-day death of sCAP patients. Conclusions:The sCOVID-19 patients in this cohort have worse oxygen condition and symptoms than sCAP patients, which may be due to the high proportion of lesions involving the lungs. The indicators of the difference between the death group and the survival group were similar in sCOVID-19 and sCAP patients. It is suggested that the two diseases have similar effects on renal function, nutritional status and coagulation function. But there were still differences in risk factors affecting survival. It may be that sCOVID-19 has a greater impact on lung oxygenation function, inflammatory cascade response, and liver function, while sCAP has a greater impact on renal function and nutritional status.

The global coronavirus disease 2019 epidemic is still in a pandemic state. Aging population with underlying diseases is prone to become severe, and have a higher mortality. The treatment capacity of the critical care department directly determines the treatment success rate of critical illness. At present, there is still a certain gap between domestic and foreign countries in intensive care unit (ICU), which is not only in the allocation of medical staff, but also in the beds and settings. The current medical model cannot fully meet the needs of development. The experience and lessons of many major public health emergencies suggested that " dual track of peace and war" approach in discipline construction of critical care is the best medical model. Following the concept of "combination of peace and war", strengthening the discipline construction of critical care department in municipal and district designated hospitals, allocating reasonable standard ICU, step-down ICU and combat readiness ICU, establishing rapid response team, and strengthening regular training and scientific management may be the key measures to deal with the epidemic.

ABSTRACT: Meningiomas are the most common primary intracranial neoplasm with diverse pathological types and complicated clinical manifestations. The fifth edition of the WHO Classification of Tumors of the Central Nervous System (WHO CNS5), published in 2021, introduces major changes that advance the role of molecular diagnostics in meningiomas. To follow the revision of WHO CNS5, this expert consensus statement was formed jointly by the Group of Neuro-Oncology, Society of Neurosurgery, Chinese Medical Association together with neuropathologists and evidence-based experts. The consensus provides reference points to integrate key biomarkers into stratification and clinical decision making for meningioma patients. REGISTRATION Practice guideline REgistration for transPAREncy (PREPARE), IPGRP-2022CN234.
Humans ; Meningioma/pathology* ; Consensus ; Neurosurgical Procedures ; Meningeal Neoplasms/pathology*

Objective:To respond to the national requirements on the construction of research integrity, and improve the capacity building of research integrity at hospitals.Methods:Dealing with research integrity problems identified at hospital before 2018, measurements that include " policy and procedures development, standardization of the management of scientific research activities, and optimizing the scientific and technological evaluation system" were adopted to promote the construction of research integrity. Such corrective activities were monitored to summarize experiences and lessons for the continuing improvement of research integrity construction.Results:Both " heteronomy" and " self-discipline" of research integrity have been sublimated simultaneously, at the same time, a tailored research integrity management system with the characteristics of local hospitals has been established.Conclusions:Updating institutional policy and procedures, taking paper management as a priority, as well as research integrity training, these measurements played important roles in promoting the research integrity capacity building at hospitals.

Objective: To investigate the effect of three-dimensional conformal radiotherapy (3D-CRT) combined with PC chemotherapy (paclitaxel + carboplatin) on non-small cell lung cancer (NSCLC) patients and the serum levels of CA125, tissue inhibitor of metalloproteinase-1 (TIMP-1), serum amyloid A (SAA) and T-lymphocyte subsets. Methods: A total of 100 patients with NSCLC treated in Affiliated Hospital of Guangdong Medical University from May 2015 to December 2017 were selected as the study subjects. They were divided into control group and observation group according to random number table method, with 50 cases in each group. The observation group was treated with 3D-CRT combined with PC chemotherapy, while the control group was treated with PC chemotherapy. The two groups were treated for 4 cycles. The therapeutic effect, serum CA125, TIMP-1, SAA, T-lymphocyte subsets and adverse reactions were compared between the two groups. Results: Four cases were lost to follow-up both in the two groups. The overall response rate in the observation group (43.48%, 20/46) was higher than that in the control group (23.91%, 11/46; χ²=3.941, P=0.047). The serum levels of CA125, TIMP-1 and SAA of the two groups had no significant difference before treatment, and the levels of these indexes decreased after treatment. The serum levels of CA125, TIMP-1 and SAA in the observation group after treatment were (12.31±1.13) U/ml, (275.31±13.69) pg/ml and (47.21±7.21) mg/L, which were lower than those in the control group [(30.36±1.98) U/ml, (320.36±17.23) pg/ml, (65.92±8.36) mg/L], with significant differences (t=53.699, P<0.001; t=13.884, P<0.001; t=11.495, P<0.001). The levels of CD3⁺ , CD4⁺ , CD8⁺ and CD4⁺ /CD8⁺ of the two groups had no significant difference before treatment, and the levels of these indexes decreased after treatment. The levels of CD3⁺ , CD4⁺ , CD8⁺ and CD4⁺ /CD8⁺ in the observation group were (35.27±10.31)%, (20.27±6.72)%, (15.89±3.37)% and 0.91±0.37, which were higher than those in the control group [(30.77±9.27)%, (15.27±5.73)%, (12.02±2.69)% and 0.75±0.39], with significant differences (t=2.201, P=0.030; t=3.840, P<0.001; t=6.087, P<0.001; t=2.019, P=0.047). There were no significant differences in the adverse reactions such as nausea and vomiting [63.04% (29/46) vs. 43.48% (20/46); χ²=3.537, P=0.060], phlebitis [6.52% (3/46) vs. 4.35% (2/46); χ²=0.000, P>0.999], abnormal liver function [6.52% (3/46) vs. 2.17% (1/46); χ²=0.261, P=0.609] and myelosuppression [8.70% (4/46) vs. 6.52% (3/46); χ²=0.000, P>0.999] between the observation group and the control group. Conclusion For patients with NSCLC, 3D-CRT combined with PC chemotherapy can improve the overall response rate, decrease the levels of serum CA125, TIMP-1 and SAA, and improve the immune function of patients. The therapeutic effect is remarkable and the safety is good. The therapeutic scheme is suitable for the treatment of NSCLC.