With the advent of an aging society,Alzheimer's disease(AD)has gradually become a major ailment affecting the elderly.AD is a neurodegenerative disorder associated with cognitive impairments.In AD patients,brain network connections are disrupted,and their topological properties are also affected,leading to the disintegration of anatomical and functional connections.Anatomical connections can be tracked and evaluated using structural magnetic imaging(MRI)and diffusion tensor imaging(DTI),while functional connections are detected through functional MRI to assess their connectivity status.This review incorporates the findings of previous scholars and summarizes the current research of AD.It mainly discusses the imaging characteristics of large-scale brain network changes in AD patients,so as to provide researchers with scientific and objective imaging markers for AD prediction and early diagnosis,as well as future research.

Rare diseases still lack effective treatments, and the development of drugs for rare diseases (known as orphan drugs) is an urgent medical problem. As natural active ingredients in living organisms, some biomacromolecule drugs have good biocompatibility, low immunogenicity, and high targeting. They have become one of the most promising fields in drug research and development in the 21st century. However, there are still many obstacles in terms of in vivo delivery. In view of the unique advantages of nanocarriers prepared from polymers, lipids, organic biomimetic and inorganic materials in drug delivery, researchers are committed to building an efficient delivery system with versatility and synergy to solve the bottleneck issues in treating rare diseases with biomacromolecule drugs. Therefore, this article reviews the research progress of nanocarrier delivering proteins, peptides and nucleic acids in the field of rare disease treatment in the past ten years, which provides ideas for researches on biomacromolecule drug nanosystems in the field of treatment of rare diseases.

With the increasing proportion of human papilloma virus(HPV)infection in the pathogenic factors of oro-pharyngeal cancer,a series of changes have occurred in the surgical treatment.While the treatment mode has been im-proved,there are still many problems,including the inconsistency between diagnosis and treatment modes,the lack of popularization of reconstruction technology,the imperfect post-treatment rehabilitation system,and the lack of effective preventive measures.Especially in terms of treatment mode for early oropharyngeal cancer,there is no unified conclu-sion whether it is surgery alone or radiotherapy alone,and whether robotic minimally invasive surgery has better func-tional protection than radiotherapy.For advanced oropharyngeal cancer,there is greater controversy over the treatment mode.It is still unclear whether to adopt a non-surgical treatment mode of synchronous chemoradiotherapy or induction chemotherapy combined with synchronous chemoradiotherapy,or a treatment mode of surgery combined with postopera-tive chemoradiotherapy.In order to standardize the surgical treatment of oropharyngeal cancer in China and clarify the indications for surgical treatment of oropharyngeal cancer,this expert consensus,based on the characteristics and treat-ment status of oropharyngeal cancer in China and combined with the international latest theories and practices,forms consensus opinions in multiple aspects of preoperative evaluation,surgical indication determination,primary tumor re-section,neck lymph node dissection,postoperative defect repair,postoperative complication management prognosis and follow-up of oropharyngeal cancer patients.The key points include:① Before the treatment of oropharyngeal cancer,the expression of P16 protein should be detected to clarify HPV status;② Perform enhanced magnetic resonance imaging of the maxillofacial region before surgery to evaluate the invasion of oropharyngeal cancer and guide precise surgical resec-tion of oropharyngeal cancer.Evaluating mouth opening and airway status is crucial for surgical approach decisions and postoperative risk prediction;③ For oropharyngeal cancer patients who have to undergo major surgery and cannot eat for one to two months,it is recommended to undergo percutaneous endoscopic gastrostomy before surgery to effectively improve their nutritional intake during treatment;④ Early-stage oropharyngeal cancer patients may opt for either sur-gery alone or radiation therapy alone.For intermediate and advanced stages,HPV-related oropharyngeal cancer general-ly prioritizes radiation therapy,with concurrent chemotherapy considered based on tumor staging.Surgical treatment is recommended as the first choice for HPV unrelated oropharyngeal squamous cell carcinoma(including primary and re-current)and recurrent HPV related oropharyngeal squamous cell carcinoma after radiotherapy and chemotherapy;⑤ For primary exogenous T1-2 oropharyngeal cancer,direct surgery through the oral approach or da Vinci robotic sur-gery is preferred.For T3-4 patients with advanced oropharyngeal cancer,it is recommended to use temporary mandibu-lectomy approach and lateral pharyngotomy approach for surgery as appropriate;⑥ For cT1-2N0 oropharyngeal cancer patients with tumor invasion depth＞3 mm and cT3-4N0 HPV unrelated oropharyngeal cancer patients,selective neck dissection of levels ⅠB to Ⅳ is recommended.For cN+HPV unrelated oropharyngeal cancer patients,therapeutic neck dissection in regions Ⅰ-Ⅴ is advised;⑦ If PET-CT scan at 12 or more weeks after completion of radiation shows intense FDG uptake in any node,or imaging suggests continuous enlargement of lymph nodes,the patient should undergo neck dissection;⑧ For patients with suspected extracapsular invasion preoperatively,lymph node dissection should include removal of surrounding muscle and adipose connective tissue;⑨ The reconstruction of oropharyngeal cancer defects should follow the principle of reconstruction steps,with priority given to adjacent flaps,followed by distal pedicled flaps,and finally free flaps.The anterolateral thigh flap with abundant tissue can be used as the preferred flap for large-scale postoperative defects.

Objective To discuss the teaching method of staged target teaching(STT)combined with problem-based learning(PBL)in improving the effectiveness of cerebrovascular intervention training.Methods A total of 44 refresher doctors,who received cerebrovascular interventional training at the Department of Interventional Radiology of the First Affiliated Hospital of Zhengzhou University of China between March 2021 and March 2023,were enrolled in this study.Traditional teaching method was adopted for 20 refresher doctors(control group)and STT+PBL teaching method was adopted for the remaining 24 refresher doctors(study group).Before and after the training,the basic theoretical knowledge,operation skill,comprehensive interventional knowledge and the satisfaction survey were compared between the two groups.Results Before training the differences in the basic theoretical knowledge score and learning motivation between the two groups were not statistically significant(P＞0.05).After 6 months training the completion examination score of the study group was significantly better than that of the control group(P＜0.05).Through independently working in clinical practice for one year after training completion,the operation skill,basic theoretical knowledge and comprehensive ability of the study group were remarkably better than those of the control group(P＜0.05).Moreover,the scores of understanding ability,teacher-student interaction,communication skill,clinical thinking ability,self-learning ability,teamwork skill,knowledge mastery degree in the study group were strikingly higher than those in the control group,and the differences were statistically significant(P＜0.05).Conclusion The combination teaching method of STT and PBL can significantly improve the quality and effectiveness of the training on the interventional treatment of cerebrovascular diseases.

Objective To explore the influencing factors of gastric cancer and construct the clinical prediction model.Methods From December 2020 to October 2023,the clinical data of 1000 patients with stomach neoplasm admitted to Putuo Hospital,Shanghai U-niversity of Traditional Chinese Medicine and Shuguang Hospital,Shanghai University of Traditional Chinese Medicine were collected.Af-ter data cleaning and eliminating abnormal values,the patients were divided into gastric polyps group(n=487)and gastric cancer group(n=479).Non-parametric test was used to screen out meaningful indicators,Lasso regression to screen out the characteristic factors re-lated to gastric cancer with non-zero coefficient,and stepwise Logistic regression analysis to screen out the factors with significant correla-tion,and Lasso-Logistic regression model was constructed.The receiver operator characteristic(ROC)curve was plotted to calculate the area under the curve(AUC)and the confusion matrix to evaluate the model efficiency.Results The results of multivariate Logistic re-gression analysis showed that age,white blood cell(WBC)count,monocyte(M)count,alanine amiontransferase(ALT),cancer anti-gen 724(CA724),cancer antigen 242(CA242),cancer antigen 50(CA50)and carcinoembryonic antigen(CEA)were independent factors affecting gastric cancer.Based on the results of multivariate Logistic regression analysis,the risk prediction nomogram model of gas-tric cancer was constructed.The AUC of test set was 0.91,the accuracy rate was 100％,and the recall rate was 100％;the AUC of valida-tion set was 0.93,the accuracy rate was 93.63％,and the recall rate was 74.1％.The model has good prediction efficiency.Conclusion In this study,8 common predictors of gastric cancer were constructed,and the Lasso-logistic regression prediction model had good differen-tiation,which could be used to complete the early screening of gastric cancer based on the physical examination reports of patients.

Objective:To explore the effects of 10Hz repetitive transcranial magnetic stimulation(rTMS)on verbal and spatial working memory with different loads in patients with stroke. Method:Twenty-nine patients with working memory impairments after the left hemisphere stroke were random-ly assigned into the rTMS group(n=14)and control group(n=15).The patients in the rTMS group were treated with 10Hz rTMS while the patients in the control group received sham stimulation.Before and after the intervention,digital/spatial N-back tasks and digit span forward(DSF)and digit span backward(DSB)tests were used to assess work memory.Montreal Cognitive Assessment(MoCA)and the Functional Indepen-dence Measure(FIM)was used to assess cognitive function. Result:There were statistically significant differences before and after the intervention in the scores of DSF,the accuracy rates of 1-back and 2-back tasks of digit and space,the scores of MoCA,attention,memory,executive function,and FIM for the rTMS and control groups,and the scores of DSB in the rTMS group(P＜0.05).Post-intervention differences in DSB,digit 1 and 2-back,spatial 2-back,FIM,MoCA total score,and subtests of memory and executive function were significant between the groups(P＜0.05).The linear mixed-ef-fect analysis showed that improvements in the accuracy rates of digital N-back tasks in the rTMS group were more affected by load compared to the control group(P＜0.05).Controlling for the confounding factors such as age and effects of different content working memory tasks,improvements in the accuracy rates of digital 1-back and 2-back tasks were positively correlated with the improvements in the score on FIM(P＜0.05),and the improvements of the digital 2-back task was positively correlated with the improvement of MoCA scores and executive function(P＜0.05). Conclusions:rTMS can significantly improve verbal and spatial working memory manipulation in stroke pa-tients,with more significant improvement in high cognitive demand working memory(2-back).In addition,the improvement in higher-load verbal working memory brought by rTMS is associated with the improvement in cognition,self-care,and survival ability of patients with stroke.

BACKGROUND: Studies have shown that the incidence and severity of corona virus disease 2019 (COVID-19) in patients with lung cancer are higher than those in healthy people. At present, the main anti-tumor treatments for lung cancer include surgery, immunotherapy, chemotherapy, radiotherapy, targeted therapy and anti-angiogenesis therapy. While the effects of different anti-tumor treatments on the occurrence and severity of COVID-19 pneumonia are not uniform. Therefore, we aimed to describe clinical characteristics and antitumor therapy of patients with lung cancer and COVID-19 pneumonia, and examined risk factors for severity in this population. METHODS: From December 1, 2022 to February 15, 2023, a retrospective study was conducted in 217 patients diagnosed with COVID-19 and pathologically confirmed lung cancer in the Jinling Hospital. We collected data about patients' clinical features, antitumor treatment regimen within 6 months, and the diagnosis and treatment of COVID-19. Risk factors for occurrence and severity of COVID-19 pneumonia were identified by univariable and multivariable Logistic regression models. RESULTS: (1) Among the 217 patients included, 51 (23.5%) developed COVID-19 pneumonia, of which 42 (82.4%) were classified as medium and 9 (17.6%) were classified as severe; (2) Univariate and multivariate analysis revealed overweight (OR=2.405, 95%CI: 1.095-5.286) and intrapulmonary focal radiotherapy (OR=2.977, 95%CI: 1.071-8.274) are risk factors for increasing occurrence of COVID-19 pneumonia, while other therapies are not; (3) Chronic obstructive pulmonary disease (COPD) history (OR=7.600, 95%CI: 1.430-40.387) was more likely to develop severe pneumonia and anti-tumor therapies such as intrapulmonary focal radiotherapy, chemotherapy, targeted therapy and immunotherapy did not increase severity. CONCLUSIONS Intrapulmonary focal radiation therapy within 6 months increased the incidence of COVID-19 pneumonia, but did not increase the severity. However, there was no safety concern for chemotherapy, targeted therapy, surgery and immunotherapy.
Humans ; COVID-19 ; Retrospective Studies ; Lung Neoplasms/drug therapy* ; Incidence ; Pneumonia/etiology*

OBJECTIVE: To investigate the molecular mechanism underlying inherent fosfomycin resistance of Klebsiella pneumoniae (K. pneumoniae). METHODS: The draft genomic sequences of 14 clinical hypervirulent/hypermucoviscous K. pneumoniae (HvKP/ HmKP) isolates were obtained using the next-generation sequencing technology. The genomic sequences were analyzed using the Resistance Gene Identifier (RGI) software for predicting the resistome based on homology and SNP models in the Comprehensive Antibiotic Resistance Database (CARD) and for identification of the presence of phosphomycin resistancerelated genes uhpt and fosA and their mutations in the bacterial genomes. The results were verified by analyzing a total of 521 full-length genomic sequences of K. pneumonia strains obtained from GenBank. RESULTS: All the 14 clinical isolates of HvKP/ HmKP carried hexose phosphate transporter (UhpT) gene mutation, in which the glutamic acid was mutated to glutamine at 350aa (UhpT^E350Q mutation); the presence of fosA6 gene was detected in 12 (85.71%) of the isolates and fosA5 gene was detected in the other 2 (14.29%) isolates. Analysis of the genomic sequences of 521 K. pneumonia strains from GenBank showed that 508 (97.50%) strains carried UhpT^E350Q mutation, 439 (84.26%) strains harbored fosA6, and 80 (15.36%) strains harbored fosA5; 507 (97.31%) strains were found to have both UhpT^E350Q mutation and fosA6/5 genes in the genome. Only 12 (2.30%) strains carried fosA6/5 genes without UhpT^E350Q mutation; 1 (0.19%) strain had only UhpT^E350Q mutation without fosA6/5 genes, and another strain contained neither UhpT^E350Q mutation nor fosA6/5 genes. CONCLUSION UhpT^E350Q mutation with the presence of fosA6/5 genes are ubiquitous in K. pneumonia genomes, indicating a possible intrinsic mechanism of fosfomycin resistance in the bacterium to limit the use of fosfomycin against infections caused by K. pneumoniae, especially the multi-resistant HvKP/HmKP strains.
Fosfomycin ; Klebsiella pneumoniae ; Mutation ; Databases, Factual ; High-Throughput Nucleotide Sequencing

Purinergic P2Y Receptor Antagonists ; Consensus ; Cardiovascular System ; Cardiology ; Asia

To summarize and analyze the clinical application characteristics of Qugu (CV 2) in ancient and modern literature based on data mining technology. The Chinese Medical Code (the 5th edition) was taken as the retrieval source of ancient literature, while the CNKI, Wanfang, and VIP databases were taken as the retrieval source of modern literature. The indications of Qugu (CV 2) used alone or with compatible acupoints, compatible acupoints, acupuncture-moxibustion manipulation, etc., were systematically sorted out. As a result, a total of 140 articles of ancient literature were included. The common indications of Qugu (CV 2) used alone were urinary retention, profuse vaginal discharge and hernia. The common indications of Qugu (CV 2) used with compatible acupoints were profuse vaginal discharge, stranguria and hernia. Sixty-four acupoints were concurrently used with Qugu (CV 2), Qugu (CV 2) was mainly compatible with acupoints of conception vessel, bladder meridian and liver meridian, and the high-frequency acupoints included Zhongji (CV 3), Guanyuan (CV 4) and Sanyinjiao (SP 6); five-shu points were the most used special acupoints, and moxibustion therapy was often used. A total of 73 modern articles were included. The common indications of Qugu (CV 2) used alone were urinary retention, erectile dysfunction and chronic prostatitis; the common indications of Qugu (CV 2) used with compatible scupoints were urinary retention, erectile dysfunction and prostatic hyperplasia. Thirty-six acupoints were concurrently used with Qugu (CV 2), Qugu (CV 2) was mainly compatible with acupoints of conception vessel, kidney meridian and spleen meridian, and the high-frequency acupoints included Zhongji (CV 3), Guanyuan (CV 4) and Zusanli (ST 36); front-mu points were the most used special acupoints, and acupuncture therapy was often used. Qugu (CV 2) treats a wide range of diseases in ancient times, the distant treatment effectiveness of acupoints is emphasized; and it mainly treats local diseases in modern times, the nearby treatment effectiveness of acupoints is emphasized.
Female ; Male ; Humans ; Literature, Modern ; Erectile Dysfunction ; Urinary Retention ; Meridians ; Acupuncture Therapy ; Acupuncture Points ; Moxibustion ; Vaginal Discharge