Demyelination of the central nervous system often occurs in neurodegenerative diseases， such as multiple sclerosis （MS）. The myelin sheath， a layer of myelin membrane wrapping the axon， plays a role in the rapid conduction and metabolic coupling of impulses for neurons. The exposure of the axon will lead to axonal degeneratio， and further neuronal degeneration， which is the main cause of dysfunction and even disability in patients with demyelinating neurodegenerative diseases. In addition to the demyelination of mature myelin sheath， remyelination disorder is also one of the major reasons leading to the development of the diseases. The myelin sheath is composed of oligodendrocytes （OLs） derived from oligodendrocyte progenitor cells （OPCs） which are differentiated from neural stem cells （NSCs）. The process of myelin regeneration， i.e.， remyelination， is the differentiation of NSCs into OLs. Recent studies have shown that this process is regulated by a variety of genes. MicroRNAs， as important regulators of neurodegenerative diseases， form a complex regulatory network in the process of myelin regeneration. This review summarizes the main molecular pathways of myelin regeneration and microRNAs involved in this process and classifies the mechanisms and targets. This review is expected to provide a theoretical reference for the future research on the treatment of demyelinating diseases by targeting the regulation of microRNAs.

Objective: To compare the effectiveness of qualitative and quantitative fecal immunochemical tests (FIT) in identifying colorectal cancer, so as to provide insights into perfecting screening strategies for colorectal cancer. Methods: Participants in the Colorectal Cancer Screening Program for Key Populations in Zhejiang Province from May 2020 to December 2021 were recruited, and their demographic information, lifestyle and disease history were collected through a questionnaire survey. Qualitative or quantitative FIT along with a questionnaire-based risk assessment were employed as the initial screening tests. Individuals who were positive in any FIT or had high-risk assessment results were required to attend a subsequent colonoscopy examination. The positive rate, detection rate of colorectal cancer, positive predictive value and number of colonoscopies required were compared between qualitative and quantitative FITs, and stratified analyses by gender and age were conducted. Results: Totally 4 099 769 participants were included. The qualitative FIT group included 3 574 917 individuals, yielding a positive rate of 11.35%, a detection rate of 1.19%, a positive predictive value of 0.48% and 83.84 colonoscopies required to detect one cancer case. The quantitative FIT group involved 524 852 individuals, yielding a positive rate of 6.70%, a detection rate of 2.31%, a positive predictive value of 1.01% and 43.23 colonoscopies required to detect one cancer case. The quantitative FIT group showed significantly higher detection rate of colorectal cancer, higher positive predictive value and less number of colonoscopies required compared to the qualitative FIT group (all P<0.05). The same results were obtained after stratification by gender and age. Conclusion Compared to qualitative FIT, quantitative FIT improves the detection of colorectal cancer and reduces the workload of colonoscopy examinations, making it more suitable for colorectal cancer screening in large-scale populations.

ObjectiveTo investigate the effects of Jiaohong pills （JHP） and its prescription， Pericarpium Zanthoxyli （PZ） and Rehmanniae Radix （RR） cognitive dysfunction in scopolamine-induced Alzheimer's disease （AD） mice and its mechanism through pharmacodynamic and metabolomics study. MethodThe animal model of AD induced by scopolamine was established and treated with PZ， RG and JHP， respectively. The effects of JHP and its formulations were investigated by open field test， water maze test， object recognition test， avoidance test， cholinergic system and oxidative stress related biochemical test. Untargeted metabolomics analysis of cerebral cortex was performed by ultra-performance liquid chromatography-Quadrupole/Orbitrap high resolution mass spectrometry （UPLC Q-Exactive Orbitrap MS）. ResultThe behavioral data showed that， compared with the model group， the discrimination indexes of the high dose of JHP， PZ and RR groups was significantly increased （P<0.05）. The staging rate of Morris water maze test in the PZ， RR， high and low dose groups of JHP was significantly increased （P<0.05， P<0.01）， the crossing numbers in the PZ， JHP high and low dose groups were significantly increased （P<0.05， P<0.01）； the number of errors in the avoidance test were significantly reduced in the PZ and high-dose JHP groups （P<0.01）， and the error latencies were significantly increased in the JHP and its prescription drug groups （P<0.01）. Compared with the model group， the activities of acetylcholinesterase in the cerebral cortex of the two doses of JHP group and the PZ group were significantly increased （P<0.05， P<0.01）， and the activity of acetylcholinesterase in the high-dose JHP group was significantly decreased （P<0.05）， and the level of acetylcholine was significantly increased （P<0.01）. At the same time， the contents of malondialdehyde in the serum of the two dose groups of JHP decreased significantly （P<0.05， P<0.01）. The results of metabolomics study of cerebral cortex showed that 149 differential metabolites were identified between the JHP group and the model group， which were involved in neurotransmitter metabolism， energy metabolism， oxidative stress and amino acid metabolism. ConclusionJHP and its prescription can antagonize scopolamine-induced cognitive dysfunction， regulate cholinergic system， and reduce oxidative stress damage. The mechanism of its therapeutic effect on AD is related to the regulation of neurotransmitter， energy， amino acid metabolism， and improvement of oxidative stress.

Dementia in traditional Chinese medicine （TCM） mainly presents amnesia and dullness. Alzheimer's disease and vascular dementia belong to the category of dementia in TCM. These progressive neurological diseases have a complex etiology and a long course， and the drugs that can reverse the disease course remain to be developed. Therefore， early intervention plays a vital role in delaying the disease progression. Apathy refers to a lack of motivation that leads to the attenuation or disappearance of goal-directed behaviors， cognitive functions， and emotional responses. Clinical studies have suggested that apathy exists in the early stage of a variety of neurodegenerative diseases， being one of the key symptoms to the early diagnosis of dementia. The severity of apathy is related to the severity of dementia. Therefore， early diagnosis and treatment of apathy are of great significance to the prevention and treatment of dementia. The preclinical research on apathy in dementia is still in its infancy， and the systematic evaluation method has not been prescribed. The clinical diagnosis and treatment are also in the exploratory stage， and the complex pathophysiological mechanisms of apathy and dementia development have not been fully elucidated. This article reviews the research progress of apathy in dementia， the apathetic behaviors of dementia animal models， the behaviors of patients with apathy， and the treatment methods in recent years and summarizes the research status of apathy in dementia. This review aims to provide a theoretical basis for exploring the behavior of apathy in dementia and conducting preclinical research and evaluation of the pathogenesis and to lay a foundation for the treatment of apathy in dementia.

Traditional Chinese medicine （TCM） has a long history of application in China and has consistently played a vital role in treating diseases and saving lives. TCM prescriptions （compounds） constitute the primary form of clinical TCM treatment and significantly differ from western medicine （chemicals） due to the diverse composition and chemical constituents of TCM （compounds）. Nevertheless， the potential multi-component， multi-target， and multi-pathway action characteristics of TCM prescriptions also demonstrate their possible （complementary） therapeutic advantages when compared with single-component chemical drugs. Therefore， driven by the development of modern science and technology and the demands of the modernization and internationalization of TCM， modern theories regarding the complexity of TCM prescription effects have been continuously proposed： Different from the abstract language of traditional prescription theory， the modern TCM prescription theory is more inclined to illustrate the connotation of prescription compatibility concretely and vividly from an experimental and scientific perspective. In this paper， new theories on the complexity of TCM prescriptions proposed in recent years are summarized to provide research references and ideas for the greater role of TCM prescriptions and a better scientific understanding.

This study reports on three patients with Shwachman-Diamond syndrome (SDS) who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) at the First Affiliated Hospital of Zhejiang University School of Medicine. Based on relevant literature, the clinical manifestations and genetic mutation characteristics of SDS were summarized, and the efficacy and timing of allo HSCT for such patients were explored. Three SDS patients were all male, with transplant ages of 32, 33, and 32 years old, respectively. All three patients were diagnosed in childhood. Case 1 presented with anemia as the initial clinical manifestation, which gradually progressed to a decrease in whole blood cells; Case 2 and 3 both present with a decrease in whole blood cells as the initial clinical manifestation. Case 1 and 3 have intellectual disabilities, while case 3 presents with pancreatic steatosis and chronic pancreatitis. All three patients have short stature. Three patients all detected heterozygous mutations in the SBDS: c.258+2T>C splice site. The family members of the three patients have no clinical manifestations of SDS. All three patients were treated with a reduced dose pre-treatment regimen (Fludarabine+Busulfan+Me-CCNU+Rabbit Anti-human Thymocyte Globulin). Case 1 and case 2 underwent haploid hematopoietic stem cell transplantation, while case 3 underwent unrelated donor hematopoietic stem cell transplantation. Case 1 was diagnosed with myelodysplastic syndrome transforming into acute myeloid leukemia before transplantation, but experienced early recurrence and death after transplantation; Case 2 is secondary implantation failure, dependent on platelet transfusion; Case 3 was removed from medication maintenance treatment after transplantation, and blood routine monitoring was normal.

Objective:To explore the clinical application value of a deep learning algorithm-based ultrasound biomicroscopy (UBM) image analysis system for primary angles-closure glaucoma (PACG) anterior located ciliary body.Methods:A diagnostic test study was conducted.A total of 2 132 UBM images from 726 eyes of 378 PACG patients who underwent UBM examination were collected at Renmin Hospital of Wuhan University from August 2022 to December 2023.The dataset was divided into a training set of 1 599 images and a test set of 533 images, and a deep learning algorithm was employed to construct a model.An additional 334 UBM images from 101 eyes of 69 PACG patients treated at Huangshi Aier Eye Hospital were selected to conduct external testing.A separate set of another 110 UBM images were selected for a human-machine competition to compare the accuracy and speed between anterior located ciliary body evaluation system and three senior ophthalmologists.Furthermore, eight junior ophthalmologists assessed the 110 UBM images independently without and with the assistance of the model, and the differences between the two evaluations were analyzed to assess the assisstance effect of the model.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Renmin Hospital of Wuhan University (No.WDRY-2022-K109).Results:The model achieved an accuracy of 93.43% for anterior located ciliary body identification in the internal test set, with a sensitivity of 84.30% and a specificity of 97.78%.The model also performed well on the external test set with an accuracy of 92.81%.In the human-machine competition, the model's accuracy was comparable to that of the senior ophthalmologists and outperformed two of the three senior ophthalmologists.The average total time of the three senior ophthalmologists was 726.73 seconds, approximately 12.47 times longer than the model's 58.30 seconds.With model assistance, the diagnostic accuracy of the eight junior ophthalmologists was 86.71%, which was significantly higher than 76.25% without model assistance ( χ2=-7.550, P<0.001).And the image evaluation time was (714.91±213.82)seconds, which was significantly lower than (987.90±238.56)seconds without model assistance ( t=2.774, P<0.05). Conclusions:The UBM image analysis system based on a deep learning algorithm demonstrates high accuracy in diagnosing anterior located ciliary body in PACG and provides a strong support for the UBM image recognition training of junior ophthalmologists.

[Purpose]To analyze the compliance rates and influencing factors for gastroscopy and colonoscopy in gastrointestinal cancer screening,and to provide evidence and management recom-mendations for gastrointestinal cancer screening programs.[Methods]The study was based on the joint gastrointestinal cancer screening program conducted in Fenghua District of Ningbo City in 2023.The target population underwent risk assessments,following which high-risk individuals were mobilized for gastroscopy and colonoscopy screenings.The x2 test was used to compare the positive rates of gastrointestinal cancer risk assessments and the compliance rates of clinical screenings among populations with different characteristics.Multivariable Logistic regression models were applied to analyze the factors associated with compliance rates of clinical gastroscopy and colonoscopy screenings among high-risk individuals.[Results]A total of 48 587 individuals were included in the analysis,with an average age of(63.95±7.48)years old.Among them,39.45％(19 166 individuals)were male.The positive rates of risk assessment for upper gastrointestinal cancer and colorectal cancer were 39.00％(18 949 individuals)and 16.02％(7 782 individuals),respectively.The compliance rates for gastroscopy and colonoscopy were 59.51％(11 227/18 949)and 50.85％(3 957/7 782),respectively.Multivariable Logistic regression analysis revealed that unmarried in-dividuals and those with an assessment interval of more than 14 d had lower compliance with gas-troscopy(both P＜0.05).High-risk individuals for upper gastrointestinal cancer with BMI≥24 kg/m2,gastrointestinal symptoms,history of upper gastrointestinal diseases,family history of cancers,history of gastroscopy,lower intake of fresh vegetables and fruits,and higher intake of processed meats had higher compliance with gastroscopy(all P＜0.05).High educational levels and an assess-ment interval of more than 14 d were associated with lower compliance with colonoscopy(both P＜0.05).Among individuals at high risk for colorectal cancer,those with gastrointestinal symptoms,history of upper gastrointestinal diseases,higher intake of processed meats and fried or grilled foods,and a positive risk assessment for upper gastrointestinal cancer had higher compliance with colonoscopy(all P＜0.05).[Conclusion]Participants in the joint gastrointestinal cancer screening program exhibit high compliance with both gastroscopy and colonoscopy.Compliance with gas-troscopy and colonoscopy is associated with individual lifestyle,health conditions,disease history,medical history,and family history of cancers.

Objective: To examine the effects of air pollution on overall mortality, mortality of respiratory diseases, and mortality of circulatory diseases among residents in Hangzhou City. Methods: Residents' mortality data in Hangzhou City from 2014 to 2016 were captured from Zhejiang Provincial Chronic Disease Surveillance Information Management System, and the ambient air quality in Hangzhou City from 2014 to 2016 were collected from Hangzhou Environmental Monitoring Center, while the meteorological monitoring data during the study period were collected from Hangzhou Meteorological Bureau. The effects of PM2.5, PM10, NO2 and SO2 on overall mortality, morality of respiratory diseases and mortality of circulatory diseases were evaluated a generalized additive model (GAM) based on Poisson distribution, and the risk of mortality was described with excess risk (ER) and its 95%CI. Results: The daily M (QR) overall deaths, deaths from respiratory diseases and deaths from circulatory diseases were 111 (30), 16 (9) and 37 (14) persons in Hangzhou City from 2014 to 2016, respectively. A 10 μg/m3 increase in PM2.5, PM10, NO2 and SO2 resulted in 0.47% (95%CI: 0.23%-0.70%), 0.37% (95%CI: 0.21%-0.53%), 1.06% (95%CI: 0.50%-1.61%) and 3.08% (95%CI: 2.18%-3.99%) rises in the risk of overall mortality, 0.60% (95%CI: 0.04%-1.16%), 0.45% (95%CI: 0.06%-0.83%), 2.01% (95%CI: 0.84%-3.20%) and 6.06% (95%CI: 3.80%-8.37%) rises in the risk of mortality of respiratory diseases, and 0.45% (95%CI: 0.08%-0.83%), 0.44% (95%CI: 0.17%-0.71%), 1.43% (95%CI: 0.49%-2.37%) and 3.66% (95%CI: 2.13%-5.22%) rises in the risk of mortality of circulatory diseases, and the greatest effect was observed at a 2-day lag. Multi-pollutant model analysis showed that, after adjustment for PM2.5, NO2 and PM2.5+NO2+SO2, a 10 μg/m3 increase in SO2 resulted in an elevated risk of mortality of respiratory diseases than a single-pollutant model. Conclusions The air pollutants PM10, PM2.5, NO2, and SO2 correlated positively with the risk of overall mortality, mortality of respiratory diseases and mortality of circulatory diseases in Hangzhou City from 2014 to 2016, and the co-existence of multiple pollutants enhanced the effect of SO2 on mortality of respiratory diseases.

Objective:To investigate the effects and regulation mechanism of lipid-associated membrane proteins (LAMPs) derived from Mycoplasma pneumoniae( Mp) on the expression of quinine oxidoreductase 1 (NQO-1) in human monocyte cell line THP-1 cells, and to know the effect of NQO-1 to interleukin 8 secretion in LAMPs stimulated cells, so as to better understand the regulation mechanism upon Mp infection. Methods:Mp were cultivated and the precipitate was collected to extract LAMPs. The cytotoxicity of LAMPs to THP-1 cells was analyzed by using CCK8 test. THP-1 cells were cultured in vitro with different concentrations of LAMPs for different times, and the expression of NQO-1 protein was detected by Western blot. Nrf2 siRNA was used to investigate the role of Nrf2 in NQO-1 expression in LAMPs induced cells, and NQO-1 inhibitor Diminutol was performed to test whether they blocked interleukin 8 (IL-8) secretion when treated with LAMPs in THP-1 cells. Results:LAMPs extracted from Mp had no cytotoxicity to THP-1 cells. The expression of NQO-1 protein in LAMPs-stimulated THP-1 cells showed a dose-dependent and time-dependent manner. The production of NQO-1 protein reached peaks when treated with 5.0 μg/ml or 7.5 μg/ml of LAMPs for 12 h. Silencing of Nrf2 by siRNA significantly decreased NQO-1 production, and blocking NQO-1 by Dim increased the level of IL-8 in LAMPs-stimulated cells. Conclusions:LAMPs derived from Mp induced the expression of NQO-1 protein in THP-1 cells via Nrf2, and NQO-1 can inhibit IL-8 secretion in LAMPs stimulated monocytes.