The dysfunction of the lysosome and autophagy-lysosome system serves as a driving force for neurodegenerative diseases, metabolic disorders, inflammatory conditions, and other related diseases, closely influencing their onset and progression. Therefore, restoring the function of the lysosome or autophagy-lysosome system has become an increasingly crucial therapeutic strategy in disease management. In this review, we will introduce the lysosomal biogenesis, structure, and function, as well as the biological process of the autophagy-lysosome system. Various diseases closely associated with lysosomal/autophagic dysfunction are also reviewed, emphasizing the significance of targeting the function of the lysosome or autophagy-lysosome system in disease treatment. Finally, we focus on engineered nanomaterials that have the capabilities to restore the function of the lysosome or autophagy-lysosome system, and summarize different strategies and methods for achieving this goal. This review aims to elucidate the latest progress in the field of nanomedicine for lysosomal/autophagic defect-related diseases and inspire the development of innovative and clinically valuable nanomedicines.
Humans ; Lysosomes/physiology* ; Autophagy/physiology* ; Nanomedicine/methods* ; Neurodegenerative Diseases/therapy* ; Animals ; Nanostructures ; Lysosomal Storage Diseases/therapy*

Objective To explore the efficacy of endoscopic therapy for esophageal and gastric variceal bleeding(EGVB),investigate the risk factors for rebleeding within 1 year,and establish a predictive model accordingly.Methods A retrospective study was conducted using the clinical and follow-up data of 120 EGVB patients who underwent endoscopy at our hospital between January 2021 and December 2022.The efficacy of endoscopic therapy was analyzed,and the patients were divided into a bleeding group and a non-bleeding group based on whether rebleeding occurred within 1 year after treatment.The factors influencing rebleeding within 1 year after treatment were analyzed,and a predictive model was established using logistic regression analysis.The model's goodness of fit was evaluated using the Hosmer-Lemeshow test,and its clinical value was analyzed using the receiver operating characteristic(ROC)curve.Results The hemostasis success rate within 72 hours after endoscopic therapy was 100％in all 120 patients.Four weeks after endoscopic treatment,endoscopic reexamination showed that the complete and partial disappearance rate of varices was 75.83％(91/120),with rebleeding occurring in 10 cases(8.33％).There were 34 cases(28.33％)of cumulative rebleeding at 6 months and 63 cases(52.50％)at 1 year after endoscopic therapy.Nine patients(7.50％)died within 1 year after endoscopic therapy,all of whom were rebleeding cases.A total of 63 patients with rebleeding were included in the bleeding group,and 57 patients without rebleeding were included in the non-bleeding group.Serum sodium＜135 mmol/L(odds ratio[OR]=3.837,95％confidence interval[CI]:1.095-13.445),Child-Pugh grade C(OR=3.835,95％CI:1.137-12.935),esophageal varices degree G3(OR=5.113,95％CI:1.565-16.707),and main portal vein diameter＞12 mm(OR=5.964,95％CI:2.295-15.497)were identified as risk factors of rebleeding within 1 year after endoscopic therapy in EGVB patients(P＜0.05).The risk prediction model for rebleeding within 1 year after endoscopic therapy in EGVB patients was shown as P=1/{1+e[-(-3.815+1.345×serum sodium+1.344×Child-Pugh grade+1.786×main portal vein diameter+1.632×esophageal varices degree)]}.The Hosmer-Lemeshow x2 was 3.158(P=0.856).The area under the curve(AUC)for predicting rebleeding within 1 year after endoscopic therapy in EGVB patients was 0.815,indicating good predictive performance.Clinical validation showed that the model had an accuracy of 82.30％,with sensitivity and specificity being 81.03％and 83.63％,respectively.Conclusion Endoscopic therapy for EGVB achieves a high rate of acute bleeding control,but patients remain at risk of rebleeding.Rebleeding is associated with serum sodium＜135 mmol/L,Child-Pugh grade C,main portal vein diameter＞12 mm,and esophageal varices degree G3.The logistic regression model can effectively predict the probability of rebleeding within 1 year after endoscopic therapy.

Objective This study analyzes the risk points in the quality control of bioink and the main processes of bioprinting,clarifies and explores the quality control and supervision model for bioprinting medical devices,and provides theoretical and practical guidance to ensure the safety and effectiveness of bioprinting medical devices.Methods The quality control risk points throughout the bioprinting process were comprehensively analyzed,with a particular focus on bioprinting materials and key processes.The regulatory model and methods for bioprinting medical devices were examined.This research concentrated on critical technologies such as extrusion,laser-assisted,and in situ bioprinting,assessing their potential for clinical applications and regulatory challenges.Results Bioink from different sources should meet regulatory requirements.It is essential to ensure aseptic handling of raw materials and to validate sterilization under"worst-case"conditions.Conclusion As bioprinting technology advances rapidly,corresponding research into materials,processes,and quality risk control should be conducted to ensure the concurrent development of the regulatory system.This will continuously contribute to the orderly progression of the entire industry and human health.

Objective:To explore whether Corona Virus Disease 2019 (COVID-19) has any impact on human centrifuge training of flying cadets and to provide references to the human centrifuge training for the recovered flying personnel by comparing the changes of flying cadets′ G-tolerance and physiological indicators in human centrifuge training.Methods:Twelve flying cadets who underwent the current batch of human centrifuge training in 2022 were selected and divided into rehabilitation group and control group according to whether they had been infected with COVID-19, with 6 in each group. The rapid G onset rate (ROR) and gradual G onset rate (GOR) were respectively chosen for human centrifuge test. At the same time, the changes of their heart rate and respiratory rate during the tests were recorded, and the G-tolerance situations of the subjects were collected.Results:The average relaxed G-tolerance under GOR (GOR tolerance 1) was (4.2±0.8) G in rehabilitation group, and their average anti-G straining maneuver aided G-tolerance under GOR (GOR tolerance 2) was (5.7±0.6) G. Compared with that of the control group, there was no significant difference in GOR tolerance 1 and GOR tolerance 2 (both P>0.05). There was no significant changes in heart rate and respiratory rate in ROR and GOR human centrifuge tests between 2 groups (all P>0.05). Conclusions:COVID-19 didn't impact the recovered flying cadets' performance in human centrifuge training, as well as the anti-G straining maneuver effect and cardiovascular regulation.

Cervical cancer is one of the most common gynecological malignant tumors,the five-year survival rate decreased significantly in the case of lymph node metastasis and distant metasta-sis,so the development of new anti-cervical cancer drugs is of great significance for the treatment of cervical cancer.Molecular docking technology is one of the most commonly used research methods in computer aided drug design,which is widely used in screening the effective components of drugs,finding the targets of drugs acting on tumors and exploring the mechanism of antineoplastic drugs.This paper reviews the molecular docking technology in the screening of anti-cervical cancer drugs,the determination of anti-tumor targets and the mechanism of anti-cervical cancer,in order to provide more sufficient theoretical basis for the screening of anti-cervical cancer drugs and new drug research and development.

Objective To investigate the geographical distribution and seasonal fluctuations of visceral leishmaniasis vectors sandflies in Henan Province in 2023, so as to provide insights into the prevention and control of visceral leishmaniasis vectors. Methods A total of 23 counties (districts) were sampled from 18 cities of Henan Province from May to September, 2023 as sandfly surveillance sites, and sandflies were captured using human capture and light trapping methods. Following morphological identification, the changes in the sandfly density were calculated at different months and in different breeding habitats. Results A total of 406 light traps were set at sandfly surveillance sites in Henan Province from May to September, 2023, and a total of 3 137 female sandlies were captured, with an average density of 7.73 sandlies/(light·night). A total of 1 494 Phlebotomus chinensis sandflies were captured, including 1 222 female sandflies, with an average density of 3.01 sandflies/(light·night), and the highest density of P. chinensis was found in Gongyi City [17.00 sandflies/(light·night)]. A total of 5 544 sandflies were captured using the human capture method, including 230 P. chinensis, and the density of P. chinensis appeared a unimodal distribution, with a peak in early July [5.81 sandflies/(light·night)]. Among different breeding habitats, the highest P. chinensis density was detected in pigpens [4.50 sandflies/(light·night)]. Conclusions P. chinensis was predominantly distributed in hilly areas of northern and central-western Henan Province in 2023, and the sandfly density appeared a unimodal distribution. Intensified monitoring of visceral leishmaniasis vectors is recommended.

Objective To characterize the species of common sandflies in Henan Province using DNA barcoding with cytochrome c oxidase subunit I (COI) gene as the molecular marker, and to analyze the genetic polymorphisms of sandflies, so as to provide insights into visceral leishmaniasis prevention and control in Henan Province. Methods Sandfly specimens were sampled from 13 sandflies surveillance sites from 2021 to 2023 in Anyang City, Zhengzhou, Luoyang and Xuchang cities (Zhengzhou-Luoyang-Xuchang areas) where visceral leishmaniasis cases were reported and in Jiaozuo and Xinxiang cities (Jiaozuo-Xinxiang areas) without visceral leishmaniasis cases reported. Genomic DNA was extracted from a single sandfly, and COI gene was amplified. The amplification product was subjected to bidirectional sequencing. Following sequence assembly, the species of sandflies was characterized through sequence alignment using the BLAST tool. The intra-specific and inter-specific genetic distances of sandflies were estimated among different areas using the software Mega 11, and phylogenetic trees were created. The polymorphisms of nucleotide sequences in the sandflies COI gene were estimated using the software DnaSP. The fixation index (F_ST) of different geographical isolates of sandflies was calculated using the Arlequin software, and the gene flow value (Nm) was used to measure the gene flow in the sandflies populations. In addition, the population genetic structure of different geographical populations of Phlebotomus chinensis was analyzed using the STRUCTURE software. Results A total of 978 sandflies were collected from 13 sandflies surveillance sites in Zhengzhou-Luoyang-Xuchang areas, Jiaozuo-Xinxiang areas and Anyang City of Henan Province from 2021 to 2023, and 475 sandflies were randomly sampled for subsequent detections. A total of 304 Ph. chinensis, 162 Se. squamirostris and 9 Se. bailyi were identified based on molecular biological detection of the COI gene, and Se. bailyi was reported for the first time in Henan Province. The intraspecific genetic distances of sandflies were 0.000 to 0.040, and the inter-specific genetic distances ranged from 0.133 to 0.161. Phylogenetic analysis revealed that each of the three sandfly species was clustered into a clade. The genetic polymorphisms of Ph. chinensis populations varied among different areas, with the highest haplotype diversity (0.966 ± 0.007) and the greatest nucleotide diversity (0.011) in Zhengzhou-Luoyang-Xuchang areas, and the lowest haplotype diversity (0.720 ± 0.091) and nucleotide diversity (0.004) in Anyang City. The dominant haplotype of Ph. chinensis populations was Pch_Hap_2 in Anyang City and Jiaozuo-Xinxiang areas, with moderate genetic differentiation (0.05 < F_ST < 0.15) and frequent gene exchange (Nm value > 1) between Ph. chinensis populations sampled from Anyang City, and Jiaozuo-Xinxiang areas. Population genetic structure analysis showed that the dominant component of Ph. chinensis populations was K5 in Anyang City and Jiaozuo-Xinxiang areas. No obvious dominant haplotype was observed in Ph. chinensis populations sampled from Zhengzhou-Luoyang-Xuchang areas, which had very high genetic differentiation (F_ST > 0.25) and little gene exchange (Nm value < 1) with Ph. chinensis populations from Anyang City, and Jiaozuo-Xinxiang areas, with K3 as the dominant component. In addition, there was no significant difference in the genetic polymorphism level among Se. squamirostris populations from the three areas. Conclusions There are Ph. chinensis, Se. squamirostris and Se. bailyi in Henan Province, and S. bailyi is recorded for the first time in Henan Province by molecular biological assays. There are different levels of genetic differentiation and gene exchange among P. chinensis populations in different areas of Henan Province.

Objective To analyze the characteristics of visceral leishmaniasis cases in Henan Province, so as to provide insights into formulation of the visceral leishmaniasis control srtrategy. Methods All epidemiological data of reported visceral leishmaniasis cases in Henan Province from 2021 to 2023 were retrieved from the National Notifiable Disease Report Information Management System of Chinese Center for Disease Control and Prevention, and the epidemiological features and diagnosis of visceral leishmaniasis cases were descriptively analyzed. Results A total of 93 visceral leishmaniasis cases were reported in Henan Province from 2021 to 2023, with a male to female ratio of 2.58∶1, and including 2 imported cases from other provinces and 91 local cases. The number of visceral leishmaniasis cases peaked during the period between March and May, and between July and October. The reported visceral leishmaniasis cases had ages of 7 months to 74 years, with the largest number of cases found at ages of 0 to 9 years (26 cases, 27.96%), followed by at ages of 60 to 70 years (24 cases, 25.81%). Farmer (47 cases, 50.54%) and diaspora children (19 cases, 20.43%) were predominant occupations, and 91 local visceral leishmaniasis cases were found in 6 cities of Zhengzhou, Luoyang, Anyang, Hebi, Sanmenxia and Xuchang. The median duration from onset of visceral leishmaniasis to diagnosis was 20 days, and there were 25.81% (24/93) cases with 10 days and less duration from onset to diagnosis, 38.71% (36/93) cases receiving diagnosis at 11 to 30 days following onset, and 35.48% (33/93) cases receiving diagnosis for more than 30 days following onset. All cases were predominantly diagnosed in province- (60.00%) and city-level (28.89%) medical institutions. Conclusions The number of visceral leishmaniasis is on the rise in Henan Province, with a gradually expanding coverage. Intensified monitoring of visceral leishmaniasis cases, dogs, and vectors, dog management, sandflies control and improved individual protection are recommended to prevent the spread of visceral leishmaniasis.

Objective: To investigate the characteristics of HIV-1 molecular transmission network among HIV/AIDS patients in Zhoushan City, Zhejing Province. Methods: The newly reported HIV/AIDS cases in Zhoushan City from 2020 to 2022 were selected. Basic information was collected and whole blood samples were obtained at the initial follow-up. The pol gene sequences of HIV-1 were amplified by RT-PCR and nested-PCR. HIV-1 subtypes were identified by Neighbor-Joining phylogenetic trees. The HIV-1 molecular transmission network was built and analyzed using Cytoscape 3.6.1 software. Results: A total of 222 HIV/AIDS cases were reported in Zhoushan City from 2020 to 2022, 200 whole blood samples were collected, and 152 sequences were obtained successfully, including 122 males (80.26%), 75 cases aged 50 years and above (49.34%), 109 cases with a junior high school education or below (71.71%), and 63 cases with commercial heterosexual contact (41.45%). The main subtypes were CRF07_BC and CRF01_AE, accounting for 45.39% and 21.05%, respectively. When the threshold of genetic distance was set to 1%, 20 molecular clusters were formed in 69 cases, with a clustering rate of 45.39%. Using the molecular network constituted by reported HIV/AIDS cases in 2020 as the baseline network, there were 2 active molecular clusters with ≥5 new cases in 2022, each with 9 cases, characterized mainly by individuals aged 50 or above, with a junior high school education or below, and transmission through commercial heterosexual sex. Conclusions The predominant HIV-1 subtypes among HIV/AIDS cases in Zhoushan City are CRF07_BC and CRF01_AE. Transmission through commercial heterosexual contact among middle-aged and elderly people is a main mode of HIV transmission.

BACKGROUND:Traditional scoliosis orthosis has some disadvantages,such as complex manufacturing process,long processing cycle,poor fit and so on.Three-dimensional printed scoliosis orthosis has the advantages of high manufacturing precision and personalization. OBJECTIVE:To evaluate the efficacy of three-dimensional printed scoliosis orthosis for scoliosis based on multi-criteria decision model. METHODS:Clinical data of 72 patients with scoliosis admitted to Chen Xinghai Hospital of Integrated Traditional Chinese and Western Medicine from January 2019 to October 2022 were retrospectively collected and divided into two groups according to the treatment of orthosis.Study group(n=23)received three-dimensional printed scoliosis orthosis.Traditional group(n=49)received the traditional polypropylene spine brace treatment.The clinical efficacy and complications were compared between the two groups.A multi-criteria decision model for the treatment of scoliosis with three-dimensional printed scoliosis orthosis was established,and the stability of the benefit value,risk value and decision model of the two groups were evaluated. RESULTS AND CONCLUSION:(1)Compared with the traditional group,there were significant differences in the top vertebral offset distance,Cobb angle,top vertebral rotation,Functional Movement Screen score,visual analog scale score and total effective rate in the study group at 6 months after surgery(P<0.05).(2)Among the benefit indexes,Cobb angle had the greatest impact on the condition of patients,while the risk indexes had the greatest impact on dyspnea.(3)The benefit values of the study group and the traditional group for scoliosis were 79 and 64,and the risk values were 74 and 57,respectively.The combined benefit and risk values found that the benefit-risk value of the study group was 16 higher than that of the traditional group.(4)In the range of 0-100%relative risk weight,the benefit-risk value of the study group was always higher than that of the traditional group,which proved that the multi-criteria decision-making model had good stability.(5)It is indicated that three-dimensional printed scoliosis orthosis can better restore the physiological curvature of scoliosis and improve the efficiency of treatment.