Objective:To analyze the changes of pathogen spectrum of pulmonary infection in human immunodeficiency virus (HIV) infection/acquired immunodeficiency syndrome (AIDS) patients before and during coronavirus disease 2019 (COVID-19) epidemic.Methods:The clinical data of hospitalized HIV infection/AIDS patients with pulmonary infection confirmed by etiology and/or imaging examinations in the Department of Infection and Immunity, Shanghai Public Health Clinical Center, Fudan University from January 2017 to December 2022 were collected, including the types of pathogens, the peripheral blood CD4 + T lymphocyte counts at admission due to pulmonary infection, and the treatment outcome of the patients at discharge. The changes of pathogen spectrum of pulmonary infection before COVID-19 epidemic (2017 to 2019) and during the epidemic (2020 to 2022) were analyzed, and their effects on adverse treatment outcomes (death during hospitalization or automatic discharge) were analyzed. Statistical analysis was performed using the chi-square test, trend chi-square test or Kruskal-Wallis test. Results:The proportion of patients with pulmonary infection during the epidemic was lower than that before the epidemic, the difference was statistically significant (23.01%(1 061/4 612) vs 28.68%(1 463/5 102), χ2=40.76, P<0.001). From 2017 to 2022, the proportion of hospitalized HIV infection/AIDS patients with pulmonary infection showed a downward trend ( χ2trend=8.81, P<0.001). Among the pathogens causing pulmonary infection from 2017 to 2022, bacteria, mycobacteria, and fungi were the three main pathogenic pathogens, accounting for 48.77%(1 231/2 524), 32.13%(811/2 524), and 14.34%(362/2 524), respectively. The proportion of bacterial infection decreased from 55.02%(805/1 463) before the epidemic to 40.15%(426/1 061) during the epidemic, and the proportion of fungal infection increased from 9.23%(135/1 463) to 21.39%(227/1 061), the differences were both statistically significant ( χ2=54.45 and 74.11, respectively, both P<0.001). There was no significant difference in the proportion of mycobacteria between before and during the epidemic ( P=0.169), but the proportion of Mycobacterium tuberculosis (MTB) infection decreased from 22.01%(322/1 463) before the epidemic to 15.08%(160/1 061) during the epidemic, while the proportion of nontuberculous mycobacterium (NTM) infection increased from 7.11%(104/463) to 11.78%(125/1 061), the differences were both statistically significant ( χ2=19.11 and 16.28, respectively, both P<0.001). There was a significant difference in the pathogen spectrum of pulmonary infection before and during the epidemic ( χ2=128.91, P<0.001). There was a significant difference in the peripheral blood CD4 + T lymphocyte counts of patients with MTB, NTM, Pnenmocystis, Talaromycosis marneffei and Cryptococcus infection ( H=71.92, P<0.001). There were 63.74%(109/171) of Pneumocystis infection and 67.65%(69/102) of Talaromycosis marneffei infection occurred in patients with CD4 + T lymphocyte count<50/μL. Among the patients with pulmonary infection, the proportion of patients with adverse treatment outcomes during the epidemic was higher than that before the epidemic, and the difference was statistically significant (13.29%(141/1 061) vs 10.39%(152/1 463), χ2=5.04, P=0.025). Among the patients with pulmonary infection who developed adverse treatment outcomes, the top three pathogens (from high to low) were bacteria (63.48%(186/293)), mycobacteria (27.65%(81/293)), and fungi (6.83%(20/293)). The proportion of adverse treatment outcomes caused by bacterial infection decreased during the epidemic compared with that of before the epidemic (71.71%(109/152) vs 54.61%(77/141), χ2=9.23, P=0.002), while the proportion of adverse treatment outcomes caused by fungal infection increased (2.63%(4/152) vs 11.35%(16/141), χ2=8.74, P=0.003), and the differences were both statistically significant. The proportion of adverse treatment outcomes caused by mycobacterial infection increased, but without statistically significant (23.03%(35/152) vs 32.62%(46/141), χ2=3.37, P=0.066), among which there was no difference in the proportion of adverse treatment outcomes caused by MTB infection (13.82%(21/152) vs 14.89%(21/141), χ2=0.07, P=0.793), while the proportion of adverse treatment outcomes caused by NTM infection increased (5.92%(9/152) vs 14.89%(21/141), χ2=6.41, P=0.011). There was a significant difference in the pathogen spectrum of pulmonary infection patients with adverse treatment outcomes before and during the epidemic ( χ2=12.22, P=0.007). Conclusions:Among the spectrum of pathogens causing pulmonary infection and adverse treatment outcomes of HIV infection/AIDS patients during the epidemic, compared with that before the epidemic, the proportion of bacterial decreases, while the proportion of fungi increases, and the proportion of mycobacteria remains stable with the proportion of NTM increasing. The proportion of MTB causing pulmonary infection decreases, while the proportion of MTB causing adverse treatment outcomes remains stable.

Blood brain barrier (BBB) injury is the main pathological manifestation of many neurological diseases. Glycocalyx is the gel layer covering the lumen side of vascular endothelial cells, which plays an important role in regulating BBB function. However, glycocalyx is very fragile and easily damaged in various neurological diseases, leading to BBB destruction. This article focuses on the potential role of glycocalyx in cerebrovascular disease, the possible mechanisms related to glycocalyx and BBB injury, and explores the potential therapeutic strategies for protecting and restoring endothelial glycocalyx.

Objective:To investigate the protective effect and related mechanisms of Huatuo Zaizao pills (HT) on white matter injury and cognitive impairment induced by chronic cerebral hypoperfusion in mice. Methods:Forty adult male C57BL/6J mice were randomly divided into sham-operation group, bilateral carotid artery stenosis (BCAS) model group, and HT group. An animal model of BCAS was constructed using the spring loop into the bilateral common carotid arteries. After continuous treatment with 5 g/kg HT (or an equal amount of purified water) for 4 weeks, cognitive function was evaluated using the novel object recognition test. Morphological and structural changes in myelin sheath were evaluated by LFB myelin staining. White matter damage and glial cell expression were detected by myelin associated glycoprotein (MAG) in the corpus callosum, ionized calcium-binding adapter molecule 1 (IBA-1), and glial fibrillar acidic protein (GFAP) in corpus callosum and hippocampus through immunofluorescence staining. Real time quantitative polymerase chain reaction (qPCR) was used to detect mRNA expressions of myelin-associated proteins, Janus kinase 2 (JAK2), signal transducer and activator of the transcription 3 (STAT3) in corpus callosum, as well as brain-derived neurotrophic factor (BDNF), glutathione peroxidase 1 (GPx-1), and various inflammatory factors in hippocampus.Results:The novel object recognition test showed that mice had significant working memory impairment at 4 weeks after BCAS ( P<0.01), while the HT group showed significant improvement in working memory impairment compared to the BCAS group ( P<0.01). LFB myelin staining showed significant myelin damage in the BCAS group ( P<0.001), while the degree of myelin damage in the HT group was significantly improved compared to the BCAS group. Immunofluorescence staining showed that both the BCAS and HT groups had proliferation of microglia in the corpus callosum and hippocampus, and there was no significant difference between the two groups. In contrast, the activation of astrocytes in the corpus callosum was significantly improved in the HT group compared to the BCAS group ( P<0.05). qPCR showed upregulation of myelin-associated proteins as well as JAK2 and STAT3 mRNA expression in the BCAS group. Compared with the BCAS group, the expressions of JAK2 and STAT3 mRNA were decreased in the HT group (all P<0.05), while the expression of myelin-associated proteins were upregulated (all P<0.05). There were no significant difference in the expressions of inflammatory factors, BDNF, and GPX1 mRNA in the hippocampal tissue between the BCAS group and the HT group. Conclusion:HT may improve cognitive impairment and white matter damage in mice with chronic cerebral hypoperfusion, and the JAK2-STAT3 pathway may be one of its effect pathways.

O'Sullivan-Mcleod syndrome is a very rare variant of MND with a good prognosis. Its clinical feature is distal lower motor neuron syndrome of both upper limbs, and there is no effective treatment at present. We reported a case of O'Sullivan-Mcleod syndrome in this paper.The patient exhibited with middle-aged progressive distal muscle weakness and atrophy of both upper limbs, without sensory, cognitive or behavioral impairment and without pyramidal tract sign. Laboratory examination, imaging and genetic tests showed no obvious abnormalities. EMG revealed neurogenic damage to the small muscles of both hands. Now we retrospectively analyzed the clinical features of a patient with O'Sullivan-McLeod syndrome, and data from 18 cases for comparative analysis, in order to improve its understanding by clinicians.

Although endovascular therapy improves the recanalization rate of acute large vessel occlusive ischemic stroke, about half of the patients still have poor functional outcome at 90 d, which is called " futile recanalization" . This article reviews and summarizes the predictive factors of futile recanalization after endovascular therapy in acute anterior circulation ischemic stroke, in order to provide help for clinical work and scientific research in the future.

Objective To investigate the expression of S100A16 in pancreatic cancer and its clinical significance. Methods Immunohistochemical experiment was used to detect the expression of S100A16 protein in pancreatic cancer tissues and adjacent tissues, and we analyzed the relation between S100A16 positive expression and clinicopathological parameters, prognosis of pancreatic cancer patients. PPI was used to predict a protein relationship network that directly interacted with S100A16. Results The positive rate of S100A16 expression in cancer tissues was significantly higher than that in adjacent tissues (P=0.001). S100A16 expression was higher in patients with vascular infiltration and lymph node metastasis. The overall survival time of patients with pancreatic cancer was related to tumor size, TNM stage and S100A16 expression level. Multivariate analysis showed that the expression level of S100A16 was an independent risk factor for the prognosis of pancreatic cancer patients, and the risk of death in patients with high S100A16 expression increased by 1.5 times. PPI predicted that S100A16 and S100A14, IL36G, PITX1, PERP played an important role in the interaction network. Conclusion Pancreatic cancer patients with high S100A16 expression have poor prognosis. The positive expression of S100A16 is an independent prognostic indicator.

OBJECTIVETo investigate the value of the junction fragments between the breakpoints of introns in identifying deletional Duchenne muscular dystrophy (DMD) carriers.

METHODSA DMD family (including the index patient III2 and the suspected carrier II3) and a sporadic DMD case (including the patient II1 and his mother I2) were studied. The patient III2 of the DMD family was identified as having exons 31-43 deletion of the DMD gene, and the sporadic patient II1 had exons 45-54 deletion. A PCR-based genome-walking method was used to locate the breakpoints in the corresponding introns. The junction fragments of the patients and their female relatives waiting for a diagnosis were amplified by PCR with primers adjacent to the deletion junctions.

RESULTSPCR amplification yielded identical positive results for the female suspected carrier II3 of and the index patient of the DMD family, and the former was thus diagnosed as a carrier of DMD. PCR amplification of the sporadic patient's mother I2 showed a negative result, but the patient II1 had a positive result, so that the patient's mother was excluded as being a carrier of DMD.

CONCLUSIONRoutine PCR technique for detecting the junction fragments allows identification of carriers among female relatives of patients with deletional DMD.

DNA Primers ; Exons ; Female ; Genetic Carrier Screening ; Heterozygote ; Humans ; Introns ; Male ; Muscular Dystrophy, Duchenne ; genetics ; Polymerase Chain Reaction ; Sequence Analysis, DNA ; Sequence Deletion

Neurology is one of the most difficult subjects in clinical medical education.How to improve the teaching model of neurology is a crucial problem.The systematic instructional design and problem-based learning (PBL) emerge as mature teaching techniques,and having a broad application prospect.However,simple PBL teaching model has not achieved the desired results,because PBL teaching method pays excessive attention to the subjective initiative of students,but ignores the supervision and assessment mechanisms,such as assessment,feedback,adjustment,which are the major concerns of systematic instructional design.This research tries to combine systematic instructional design with PBL teaching model,and explore the position in neurology teaching.By determining the teaching target,analysis of PBL teaching,writing teaching plans,organization of PBL teaching,feedback to adjust teaching design method,the final summative evaluation is done and the teaching,was completed.After practice tips may bring progress on neurology teaching mode.

Objective To investigate the relationship between apolipoprotein B (ApoB),apolipoprotein A Ⅰ (ApoA Ⅰ) and their ratios and intracranial cerebral atherosclerotic stenosis (ICAS) in patients with acute ischemic stroke.Methods The patients with large artery atherosclerotic stroke were enrolled retrospectively.The patients were divided into either an ICAS group or a non-ICAS group based on their vascular imaging data.The blood pressure,blood lipids,blood glucose,ApoB,ApoA Ⅰ,and ApoB/ApoA Ⅰ ratios and demographic data were collected.The differences of the above indicators were compared between the two groups.Results A total of 360 patients with large artery atherosclerotic stroke were enrolled.There were 177 patients in the ICAS group (49.2％) and 183 in the non-ICAS group (50.8％).There were significant differences in the constituent ratios of the patients with hypertension,diabetes and coronary heart disease,as well as the levels of low-density lipoprotein cholesterol,ApoB and ApoA Ⅰ and ApoB/ApoA Ⅰ ratios between the 2 groups (all P ＜0.05).Multivariable logistic regression analysis showed that hypertension (odds ratio [OR] 1.75,95％ confidence interval [CI] 1.04-2.93; P =0.035),diabetes mellitus (OR 2.09,95％ CI 1.31-3.32; P =0.002),coronary heart disease (OR 2.68,95％ CI 1.09-6.57; P =0.031),ApoB ≥ 0.84 g/L (0.84-1.00 g/L:OR 2.68,95％ CI 1.30-5.56; 1.00-1.16 g/L:OR 3.95,95％ CI 1.87-8.40; ＞ 1.00 g/L:OR 6.41,95％ CI 2.82-14.49) and ApoB/ApoA Ⅰ ratio ≥0.60 (0.60-0.73:OR 1.92,95％ CI 1.14-3.24; 0.74-0.91:OR 1.79,95％ CI 1.06-3.02; ＞0.91:OR 3.30,95％ CI 1.92-5.67) were the independent risk factors for ICAS,while ApoA Ⅰ ＞ 1.28 g/L was an independent protective factor for ICAS (OR 0.39,95％ CI 0.16-0.98; P=0.044).Conclusions The increased ApoB level and ApoB/ApoA Ⅰ ratio are the independent risk factors for ICAS,and the increased ApoA Ⅰ level is an independent protective factor for ICAS in patients with acute ischemic stroke.The ApoB/ApoA Ⅰ ratio can be used as a biomarker of ICAS in patients with ischemic stroke in Chinese population.

Objective To investigate the value of the junction fragments between the breakpoints of introns in identifying deletional Duchenne muscular dystrophy (DMD) carriers. Methods A DMD family (including the index patient III2 and the suspected carrier II3) and a sporadic DMD case (including the patient II1 and his mother I2) were studied. The patient III2 of the DMD family was identified as having exons 31-43 deletion of the DMD gene, and the sporadic patient II1 had exons 45-54 deletion. A PCR-based genome-walking method was used to locate the breakpoints in the corresponding introns. The junction fragments of the patients and their female relatives waiting for a diagnosis were amplified by PCR with primers adjacent to the deletion junctions. Results PCR amplification yielded identical positive results for the female suspected carrier II3 of and the index patient of the DMD family, and the former was thus diagnosed as a carrier of DMD. PCR amplification of the sporadic patient’s mother I2 showed a negative result, but the patient II1 had a positive result, so that the patient's mother was excluded as being a carrier of DMD. Conclusion Routine PCR technique for detecting the junction fragments allows identification of carriers among female relatives of patients with deletional DMD.