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 systematically integrate the disease experience of patients with systemic lupus erythematosus, and to provide evidence-based evidence for the formulation of health management programs based on the psychological experience of patients with systemic lupus erythematosus.Methods:Qualitative studies on psychological experience of patients with systemic lupus erythematosus were searched by computer in PubMed, Cochrane Library, CINAHL, Embase, Web of Science, ProQuest, CNKI, Wanfang Database, VIP and China Biology Medicine disc. The search period was from the establishment of the databases to July 2023. The quality of literature was evaluated using the Quality Evaluation Criteria (2020) of Evidence-Based Health Care Center of Joanna Briggs Institute, Australia, and the results of literature studies were integrated by Meta integration method.Results:A total of 13 articles were included, 48 research results were extracted and eight categories were summarized, ultimately forming three integrated results including "negative psychological experience", "increased disease demand" and "active regulation strategies".Conclusions:Medical staff should pay attention to the physical and mental feelings of patients with systemic lupus erythematosus during the disease process and provide targeted and effective intervention strategies in clinical practice to alleviate their negative emotions and improve their quality of life.

Objective:To evaluate the relationship between serum folate and the prognosis of cervical intraepithelial neoplasia grade I (CIN1) and the interaction between folate and high risk human papillomavirus (HR-HPV) infection.Methods:From a community-based married women cohort established in Jiexiu and Yangqu County of Shanxi Province from June to December 2014, a total of 564 eligible women with CIN1 by pathologically diagnosed were recruited. The pathological examination was performed again 12 months later. According to the prognosis of CIN1, participants were divided into CIN1 regression group, persistence and progression group, respectively. Nested case-control study was used to explore the relationship between serum folate and CIN1 prognosis, and additive model was used to analyze the interaction between serum folate and HR-HPV infection.Results:Among 564 CIN1 patients, 479 cases underwent pathological examination again, 331 were divided in CIN1 regression group and other 148 in persistence and progression group. The levels of serum folate in CIN1 regression group and persistence and progression group were (18.890±8.360) and (15.640±5.550) nmol/L, respectively, and the difference was statistically significant ( Z=-6.937, P<0.001). HPV infection was detected in 154 patients, including 148 cases of HR-HPV infection and 6 cases of low risk human papillomavirus (LR-HPV) infection. Univariate analysis showed that there were significant differences in the age, passive smoking, frequency of pudendal cleaning, frequency of cleaning after sex, frequency of changing underwear, serum folate and HR-HPV infection between regression group and persistence and progression group ( P<0.05). Multivariate logistic regression analysis showed that the frequency of pudendal cleaning ( OR=0.422, 95% CI: 0.238-0.750), frequency of changing underwear ( OR=0.574, 95% CI: 0.355-0.928), serum folate (13.06-16.78nmol/L: OR=4.806, 95% CI: 2.355-9.810; ≤13.05nmol/L: OR=8.378, 95% CI: 4.024-17.445), HR-HPV infection ( OR=1.852, 95% CI: 1.170-2.933) were the independent influencing factors of CIN1 prognosis. Interaction analysis showed that the relative excess risk of low serum folate level and HR-HPV infection for the CIN1 persistence and progression was 4.992 (95% CI: 0.189-9.796), attributable proportion due to interaction was 0.552 (95% CI: 0.279-0.824), synergy index was 2.632 (95% CI: 1.239-5.588), a OR of serum folate≤16.78 nmol/L and HR-HPV infection positive was 9.055 (95% CI: 4.878-16.807). Conclusion:Low serum folate level could increase the risk of CIN1 persistence and progression, and might enhance the risk when combined with HR-HPV infection.

Objective:To explore the effect of dietary water-soluble vitamins on the poor prognosis of low-grade cervical intraepithelial neoplasia (CINⅠ).Methods:A total of 564 participants with CINⅠ were selected from a community-based married women cohort established in 2014. The general baseline information was collected, and HPV genotyping was detected. A food frequency questionnaire was used to investigate dietary water-soluble vitamins' consumption and determine their exposure levels. The follow-up program was carried out for 12 months, and the regression, persistence, and progression of CINⅠ was determined according to histopathological results at 12-month.Results:The low-levels of dietary water-soluble vitamins could promote CINⅠ's persistence and progression, showing the increasing tendency of CINⅠ poor prognosis with the decrease of water-soluble vitamin levels. Especially folate, VB1, VB2, VB6, niacin, biotin, and VC ( RR values were 15.22, 1.86, 1.92, 2.11, 2.98, 2.14, 2.19, respectively) played an important role. Considering the status of high-risk human papillomavirus (HR-HPV) infection, our results showed that the low levels of folate, niacin, biotin could promote the poor prognosis of CINⅠ. Conclusions:The low-level of dietary water-soluble vitamins could facilitate the poor prognosis of CINⅠ. In addition, folate, niacin, biotin were more effective on HR-HPV positive women.

Objective:To describe the characteristics of high-risk human papillomavirus (HR-HPV) infection and its influences by vaginal micro-environmental factors.Methods:A total of 421 women with HR-HPV infection and normal cervix diagnosed by pathology were selected from a community cohort established earlier by our research group for a 24-month follow-up. The baseline data were collected at enrollment. The vaginal micro-environmental factors were detected by using the combined detection kit of aerobic vaginitis and bacterial vaginosis. And the HPV was detected by using the flow-through hybridization technology. According to the HR-HPV infection status in baseline and 24 months of follow-up, with the prognosis characteristics of HR-HPV infection described, the impact of vaginal micro-environmental factors on the prognosis of HR-HPV infection was explored as well.Results:Among 390 HR-HPV infected women who completed 24 months of follow-up, the top five types of persistent HR-HPV infection rate appeared as HPV16 (24.1%), HPV58 (22.2%), HPV53 (21.7%), HPV52 (20.0%), and HPV39 (11.8%), respectively. The results showed that women with abnormal vaginal pH (a OR=1.74, 95% CI: 1.08-2.80), abnormal neuraminidase (a OR=2.70, 95% CI: 1.52-4.83), or abnormal leucocyte esterase (a OR=3.41, 95% CI: 2.13-5.44), the risk of HR-HPV persistent infection increased. The abnormalities of neuraminidase and leukocyte esterase could increase the risk of persistent infection of homotype and heterotypic HR-HPV. Conclusions:HPV16 was prone to persistent infection. Abnormalities of vaginal pH, neuraminidase, and leukocyte esterase might increase the risk of HR-HPV persistent infection. Both the abnormalities of neuraminidase and leukocyte esterase play an essential role in the HR-HPV persistent infection.

Objective:To investigate the diagnostic value of different vaginal micro-environmental factors in low-grade cervical intraepithelial neoplasia (CIN Ⅰ) and determine the optimal model in high-risk human papillomavirus (HR-HPV) infection.Methods:A total of 926 women, including 623 with normal cervical (NC) condition and 303 CINⅠ patients, had undergone pathological examinations, and were enrolled in the study. All the women were from a community previously established cohort. Vaginal cleanliness, pH, H 2O 2, β-glucuronidase, coagulase, sialidase, and leukocyte esterase (LE) were detected by the combined detection method aerobic vaginitis/bacterial vaginosis in vaginal secretions. HPV genotyping was performed by using the flow-through hybridization technology. The data were analyzed by SAS 9.2 and SPSS 23.0. Results:The vaginal cleanliness, pH, sialidase, and LE were determined as the representative vaginal micro-environment factors by principal component analysis. Based on logistic regression theory to analyze the ROC curve, the results showed that the highest sensitivity was with pH value (76.2%), and the highest specificity was with sialidase (90.9%). The area under ROC curve were higher in combination detection modes of sialidase+LE (0.714), pH+sialidase+LE (0.719), vaginal cleanness+sialidase+LE (0.713) and pH+vaginal cleanness+sialidase+LE (0.709). According to HR-HPV infection status, the TOPSIS method was used to analyze the combined detection optimal model. Specifically, we found that the best diagnostic model was pH+sialidase +LE ( C i=0.585) in the HR-HPV positive group and vaginal cleanness+sialidase+LE ( C i=0.641) in the negative group. Conclusions:The combined detection of vaginal microenvironment factors could be used for auxiliary diagnosis for CINⅠ. It would be more effective when detecting pH, sialidase, and LE in HR-HPV positive women while vaginal cleanness, sialidase, and LE in HR-HPV negative women at the same time.

Objective:To investigate the effects of polycyclic aromatic hydrocarbons (PAHs) exposure on the prognosis of high risk human papillomavirus (HR-HPV) infection.Methods:In this prospective study, 564 patients with low-grade cervical intraepithelial neoplasia confirmed by pathology were selected from the natural cohort population established by our research group in Shanxi province in 2014. Based on the baseline data of demographic characteristics and factors related to HPV infection, the concentrations of 1-hydroxypyrene in urine samples of the patients were determined by high performance liquid chromatography to define the exposure level of PAHs. At baseline survey and follow-up after 24 months, flow-through hybridization was used to detect HPV infection types, and to evaluate the prognosis of HR-HPV (persistent infection, negative conversion, positive conversion and persistent negative status).Results:Of the 564 subjects, 483 completed the follow-up, with a follow-up rate of 85.6% (483/564). Among them, the persistent infection rate was 52.4% (75/143), the persistent homotype infection rate was 35.7% (51/143), the negative conversion rate was 47.6% (68/143), the positive conversion rate was 19.7% (67/340), and the persistent negative rate was 80.3% (273/340). The follow-up results showed that the persistent infection rate (a RR=3.22, 95% CI: 1.85-5.62) and positive conversion rate (a RR=2.84, 95% CI: 1.64-4.94) of HR-HPV in high PAHs exposure group were higher than those in low PAHs exposure group, while the persistent negative rate (a RR=0.55, 95% CI: 0.43-0.70) of HR-HPV in high PAHs exposure group were lower than those in low PAHs exposure group. Based on restrictive cubic spline analysis, the results showed that the effects of PAHs exposure on persistent HR-HPV infection and persistent homotype infection showed an ascending linear dose-response relationship, while on HR-HPV positive conversion and persistent negative status showed an ascending and declining nonlinear dose-response relationship respectively ( P<0.01). Conclusions:High PAHs exposure could promote persistent HR-HPV infection and persistent homotypic infection. Reducing PAHs exposure might conducive to HR-HPV continuous negative maintenance. Active prevention and control of PAHs exposure is of great significance to prevent HR-HPV infection and persistent infection.

Objective:To investigate the effect of red blood cell folate on the prognosis of high-risk human papillomavirus (HR-HPV) infection .Methods:A total of 564 participants with low-grade cervical intraepithelial neoplasias (CINⅠ) were selected from the community-based married women cohort established in 2014. The general baseline information and factors related to HPV infection were collected. Meanwhile, HPV genotyping and levels of folate were measured. The subjects were divided into different levels of exposure group according to the folate levels and followed up for 24 months to observe the changes of HR-HPV infection status. There were four changes, including persistent infection, infection turned negative, from negative to positive and constant negative by comparing HR-HPV infection status at baseline and follow-up to 24 months.Results:483 participators completed 24 months of follow-up observation, with a follow-up rate of 85.64% (483/564). The rates of persistent infection, infection turned negative, from negative to positive, and the constant negative were 52.45% (75/143), 47.55% (68/143), 19.71% (67/340), 80.29% (273/340), respectively. Our results demonstrated that the risk of persistent infection (a RR=2.50, 95% CI: 1.55-4.02) and from negative to positive (a RR=4.55, 95% CI: 2.52-8.23) in the low level of folate were significantly higher than that in the high level of folate, especially the risk of homotype persistent infection (a RR=2.72, 95% CI: 1.51-4.90). The risk of persistent infection (trend χ2=20.62, P<0.001), from negative to positive (trend χ2=31.76, P<0.001), persistent homotypic infection (trend χ2=20.09, P<0.001) increased with the decrease of red blood cell folate level. On the contrary, no similar results were found in persistent heterotypic infection. Conclusions:A low level of red blood cell folate could increase the risk of HR-HPV persistent infection and from negative to positive. In women with HR-HPV infection, the risk of persistent homotypic infection is higher.

Objective:To evaluate the relationship between serum folate and the prognosis of cervical intraepithelial neoplasia grade I (CIN1) and the interaction between folate and high risk human papillomavirus (HR-HPV) infection.Methods:From a community-based married women cohort established in Jiexiu and Yangqu County of Shanxi Province from June to December 2014, a total of 564 eligible women with CIN1 by pathologically diagnosed were recruited. The pathological examination was performed again 12 months later. According to the prognosis of CIN1, participants were divided into CIN1 regression group, persistence and progression group, respectively. Nested case-control study was used to explore the relationship between serum folate and CIN1 prognosis, and additive model was used to analyze the interaction between serum folate and HR-HPV infection.Results:Among 564 CIN1 patients, 479 cases underwent pathological examination again, 331 were divided in CIN1 regression group and other 148 in persistence and progression group. The levels of serum folate in CIN1 regression group and persistence and progression group were (18.890±8.360) and (15.640±5.550) nmol/L, respectively, and the difference was statistically significant ( Z=-6.937, P<0.001). HPV infection was detected in 154 patients, including 148 cases of HR-HPV infection and 6 cases of low risk human papillomavirus (LR-HPV) infection. Univariate analysis showed that there were significant differences in the age, passive smoking, frequency of pudendal cleaning, frequency of cleaning after sex, frequency of changing underwear, serum folate and HR-HPV infection between regression group and persistence and progression group ( P<0.05). Multivariate logistic regression analysis showed that the frequency of pudendal cleaning ( OR=0.422, 95% CI: 0.238-0.750), frequency of changing underwear ( OR=0.574, 95% CI: 0.355-0.928), serum folate (13.06-16.78nmol/L: OR=4.806, 95% CI: 2.355-9.810; ≤13.05nmol/L: OR=8.378, 95% CI: 4.024-17.445), HR-HPV infection ( OR=1.852, 95% CI: 1.170-2.933) were the independent influencing factors of CIN1 prognosis. Interaction analysis showed that the relative excess risk of low serum folate level and HR-HPV infection for the CIN1 persistence and progression was 4.992 (95% CI: 0.189-9.796), attributable proportion due to interaction was 0.552 (95% CI: 0.279-0.824), synergy index was 2.632 (95% CI: 1.239-5.588), a OR of serum folate≤16.78 nmol/L and HR-HPV infection positive was 9.055 (95% CI: 4.878-16.807). Conclusion:Low serum folate level could increase the risk of CIN1 persistence and progression, and might enhance the risk when combined with HR-HPV infection.

Objective:To study the relations of human papillomavirus (HPV) infection, vaginal micro-environmental disorder with cervical lesion.Methods:A total of 1 019 women including 623 with normal cervical (NC), 303 with low-grade cervical lesion (CIN Ⅰ) and 93 with high-grade cervical lesion (CIN Ⅱ/Ⅲ) were enrolled in this study from the communities in Shanxi province, China. Case-control method was adopted, with NC as the control group and CIN as the case group. Related information was collected including demographic characteristics and relevant factors related to cervical lesions. HPV genotypes were detected by flow-through hybridization technology. Vaginal pH was detected by the pH test paper. Vaginal H 2O 2 was detected by the combined detection kit of aerobic vaginitis and bacterial vaginosis. Vaginal cleanliness was detected by smear method. Results:Data from the unconditional logistic regression analysis showed that HPV infection (CINⅠ: a OR=1.39, 95 %CI: 1.01-1.90; CINⅡ/Ⅲ: a OR=11.74, 95 %CI: 6.96-19.80), H 2O 2 (CINⅠ: a OR=2.09, 95 %CI: 1.47-2.98; CINⅡ/Ⅲ: a OR=4.12, 95 %CI: 2.01-8.43), cleanliness (CIN Ⅱ/Ⅲ: a OR=2.62, 95 %CI: 1.65-4.14), and composite indicators (CINⅠ: a OR=1.67, 95 %CI: 1.24-2.25; CINⅡ/Ⅲ: a OR=4.24, 95 %CI: 2.30-7.81) all had increased the risk of cervical lesion and the trend on the severity ( P<0.001) of cervical lesions. Additionally, we observed a synergic effect between HPV infection and vaginal micro-environmental composite indicator in CINⅡ/Ⅲ. With or without HPV infection, the ORs value of CINⅠ caused by vaginal micro-environment disorder remained close. Conclusions:Results from our study revealed that vaginal micro-environmental composite indicator could increase the risk for cervical lesion, in particular with the high-grade ones which all posed stronger risks when combined with HPV infection. However, the role of vaginal micro-environment disorder in the occurrence of CIN Ⅰ should not be ignored.