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.

BACKGROUND:Patients with degenerative cervical spondylosis often suffer from changed varicosity of the cervical spine,unbalanced neck-shoulder muscular strength,and descending power. OBJECTIVE:To probe into the correlation between sagittal curvature parameters and pain threshold for neck-shoulder muscles in degenerative cervical spondylosis. METHODS:Totally 50 patients with degenerative cervical spondylosis received treatment at the 3D Printed Outpatient Center of Shanghai Ninth People's Hospital,Shanghai Jiao Tong University School of Medicine from January 2022 to March 2023 were included in the study.After excluding the 10 patients of cervical lateral projection that failed to meet the measurement conditions,the cervical lateral projections were shot to measure the following iconography parameters:Borden value and C2-7 Cobb angle as well as pain thresholds on the midpoint of the superior trapezius muscle in bilateral bundles and at 1 cm beside the C5-6 interspike.The correlation between sagittal curvature parameters and pain threshold of neck-shoulder muscles in degenerative cervical spondylosis was analyzed. RESULTS AND CONCLUSION:(1)The Borden value of sagittal curvature showed a moderately positive correlation with the bundle pain threshold in the left upper trapezius muscle,the bundle pain threshold in the right upper trapezius muscle,and the pain threshold at the 1 cm of the left side beside the C5-6 interspike(r=0.498,P<0.01;r=0.448,P<0.05;r=0.405,P<0.05)and a weak positive correlation with the pain threshold at the 1 cm of the right side beside the C5-6 interspike(r=0.322,P<0.05).(2)The C2-7 Cobb angle showed a weak positive correlation with the left squared myalgia threshold(r=0.355,P<0.05),and there was no correlation with the pain threshold of the left trapezius muscle and the pain threshold at the 1 cm of both sides beside the C5-6 interspike.(3)There was a correlation between the pain threshold of the neck-shoulder muscles,and a high correlation between the pain threshold of the left and right muscles and the pain threshold within the left and right side muscles,indicating that the neck-shoulder muscles are consistent and may be related to the coordination of the neck-shoulder movements.

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.

Objective:To investigate the diagnostic performance of different thyroid imaging reporting and data systems (TI-RADS) in the diagnosis of medullary thyroid carcinoma (MTC) .Methods:A total of 160 thyroid nodules diagnosed as MTC by postoperative pathology from Aug. 2011 to Aug. 2022 at the First Affiliated Hospital of Zhengzhou University were included. Additionally, 160 papillary thyroid carcinomas (PTC) and 160 benign nodules were randomly selected as controls during the same period. Differences in gender, age, nodule diameter and various ultrasound features were observed. The nodules were classified according to American College of Radiology (ACR) TI-RADS, artificial intelligence (AI) TI-RADS and Chinese (C TI-RADS). Then, receiver operating characteristic curve (ROC) were plotted to calculate the diagnostic value. The Kendall concordance coefficient was used to evaluate the interobserver consistency of each TI-RADS system.Results:There was no statistically significant difference in gender among the three groups ( χ2=1.17, P=0.558). However, significant differences were observed in age and nodule diameter ( F=12.08,40.12, P<0.001 for both). The area under ROC (AUC) for diagnosing MTC and benign nodules using ACR, AI, and C-TIRADS were 0.762, 0.773, and 0.761, respectively, with no statistically significant differences ( Z=1.33, 0.01, 0.87, P=0.183, 0.994, 0.386). However, the sensitivity of C TI-RADS (87.5%) was lower than that of ACR and AI TI-RADS (both 95.0%) ( P=0.018). After combining the biopsy threshold, the false negative rate of C-TIRADS was lower than that of ACR (30.6% vs. 41.3%) ( P=0.048) and AI TIRADS (30.6% vs. 43.1%) ( P=0.020). The inter-observer diagnostic consistency of C-TIRADS was superior to ACR (0.884 vs. 0.819, P<0.001) and AI TIRADS (0.884 vs. 0.839) ( P<0.001) . Conclusions:AI and ACR TI-RADS have higher sensitivity in diagnosing MTC, while C TI-RADS has a lower puncture missed diagnosis rate. AI has similar diagnostic performance to ACR TI-RADS and can replace ACR TI-RADS.

In clinical surgery,various anesthetic drugs produce different effects on the blood circulation of patients.For example,propofol and inhaled anesthetics may lead to dose-related cardiovascular depression,meanwhile which is accompanied by sympathetic nerve tensile decline,vascular resistance decrease and is easy to induce postoperative hypotension.Ketamine can activate the sympathetic nervous system leading to release catecholamines and inhibit the vagus nerve,thus which is clinically manifested as increased blood pressure,in-creased heart rate and other cardiovascular excitation characteristics.As the dextroisomer-isomer of ketamine,esketamine(S-ketamine)not only retains the properties of ketamine,but also has relatively few side effects.Currently,it has been used in clinical anesthesia induction and maintenance,analgesia and treatment of refrac-tory depression.This paper provides a comprehensive overview of the effects of ketamine and S-ketamine on the hemodynamics of general anesthesia.

Objective:To summarize the ultrasound features of medullary thyroid cancer (MTC) and analyze its diagnosis value for MTC.Methods:91 patients with medullary thyroid carcinoma (103 nodules) in Department of Thyroid Surgery of the First Affiliated Hospital of Zhengzhou University from Apr. 2013 to Nov. 2018 were retrospectively analyzed, including 36 males and 55 females. Preoperative ultrasound features and serum calcitonin levels were recorded. SPSS 22.0 was used and the measurement data of normal distribution was expressed as ± s, and the enumeration data was described by ratio or rate. The comparison between groups was performed by single factor ANOVA and rank sum test. Results:83.5% (86/103) of the MTC nodules were located in the middle and upper thyroid gland. Hypoechoic accounted for 78.6% (80/103) . 81.6% (84/103) of them had calcification and 74.8% (77/103) of these nodules had abundant blood flow signals (color Doppler flow imaging, CDFI Ⅱ-Ⅲ) . 91.3% (94/103) of them had aspect ratio less than 1, 87.4% (90/103) were solid and 35.0% (36/103) had comet tail sign. The positive rate of preoperative serum calcitonin was 86.8% (79/91) . There were significant differences in shape ( P=0.001) , margin ( P=0.012) , cystic ( P=0.004) , comet-tail ( P<0.001) , lymph node ( P<0.001) and color Doppler flow imaging ( P=0.001) through comparing MTC nodules in different TI-RADS grades. Conclusions:MTC can behave as single, solid, hypoechoic, large round nodule located in the middle or upper thyroid gland, with thick calcification and abundant blood flow signals in ultrasound. The surrounding area may be accompanied with comet tail sign, and the probability of lymph node metastasis is high. The suspicious nodules screened by ultrasound can be further diagnosed by serum calcitonin.

Objective:To investigate the clinical and pathological characteristics of acquired immunodeficiency syndrome (AIDS) patients with intestinal Talaromycosis marneffei (TM) infection. Methods:A total of 64 AIDS patients who underwent colonoscopy in Guangzhou Eighth People′s Hospital from January, 2010 to December, 2018 were retrospectively collected. Among them, 32 patients were co-infected with TM (AIDS with intestinal TM infection group) and 32 patients were not (AIDS without intestinal TM infection group) according to the colonic mucosa pathology. The clinical manifestations and pathological differences were compared between the two groups. Nonparametric rank sum test and Fisher exact probability method were used for statistical analysis.Results:The proportions of patients presented with fever, cough, retroperitoneal lymph nodes tume faction, nausea and vomiting, abdominal muscle tension, abdominal tenderness and rebound pain in AIDS with intestinal TM infection group were 28 (87.5%), 16 (50.0%), 13 (40.6%), 9 (28.1%), 8 (25.0%), 20 (62.5%) and 12 (37.5%), respectively, which were all significantly higher than those in AIDS without intestinal TM infection group 11 (34.4%), 6 (18.8%), 3 (9.4%), 2 (6.2%), 1 (3.1%), 8 (25.0%) and 1 (3.1%), respectively, the differences were statistically significant (Fisher exact test, all P<0.05). The median counts of peripheral blood CD4 + T lymphocyte, lymphocytes, monocytes, hemoglobin, platelet and albumin in AIDS with intestinal TM infection group were 13.5/μL, 0.30×10 9/L, 0.16×10 9/L, 88 g/L, 122×10 9/L and 23.5 g/L, respectively, which were all significantly lower than those in AIDS without intestinal TM infection group 207.0/ μL, 1.35×10 9/L, 0.35×10 9/L, 128 g/L, 201×10 9/L and 37.5 g/L, respectively, the differences were all statistically significant ( Z=-6.111, -6.191, -4.273, -5.353, -2.974 and-6.666, respectively, all P<0.05). Multivariate logistic regression analysis showed that CD4 + T lymphocytes <50/μL, hemoglobin <90 g/L and fecal occult blood positive were independent risk factors for AIDS with intestinal TM infection. The main manifestations of colonoscopy in AIDS with intestinal TM infection group were discontinuous ulcers (31.2%(10/32)), erosion (31.2%(10/32)) or co-exitance of ulcer and erosion (21.9%(7/32)), while suspected tumor-like eminence lesions were less common (15.6%(5/32)). The pathological features of colon mucosa were ulcer and/or erosion (53.1%(17/32)), chronic inflammation (46.9%(15/32)) and inflammatory granuloma (43.8%(14/32)). Oval or round spore with apparent septum could be seen by special staining. In AIDS with intestinal TM infection group, 27 patients were cured or improved, five patients died or deteriorated, while all patients in the AIDS without intestinal TM infection group improved after treatment without death. Conclusions:There are no specific gastrointestinal symptoms in AIDS patients with intestinal TM infection, while the patients present with decreased immunological cells and multiple colony pathological features. Specific fungal spores can be seen.

The foreign body reaction refers to a chronic inflammatory reaction and a wound-healing reaction that mainly involve macrophages and foreign body giant cells, which occur after a biological material is implanted into the body. Since macrophages in the foreign body reaction are recruited to the surface of the material after implantation of the material, subsequent secretion of a series of inflammatory factors and fusion into foreign body giant cells may lead to the degradation of the biological materials and environmental stress cracking. Moreover, the prolongation of macrophage polarization and the influence of related receptors may also lead to the phenomenon of fiber encapsulation, resulting in poor prognosis. Some scholars are committed to reducing the response of foreign bodies from the perspective of macrophages and foreign body giant cells, specifically by regulating the secretion of related inflammatory factors, reducing the subtypes of M1 macrophages, promoting their polarization to M2 macrophages, and regulating the fusion of macrophages and selective expression of macrophage-associated receptors to regulate fibrosis. The new immunological view holds that macrophages have the potential to repair bone tissue via angioplasts and osteogenesis in foreign body reactions. Therefore, the gold standard that has long been considered in regenerative medicine, which is that an inert material does not cause a foreign body reaction, is expected to be gradually replaced by tissue engineering that regulates tissue activity and function.

Extracellular vesicles (EVs) are lipid bilayers secreted by a variety of cells that contain nucleic acids, proteins, etc. They can be used as a carrier for cell-to-cell communication. In related research on bone regeneration, mechanisms for transmitting regeneration signals to target cells to achieve the desired goal of osteogenesis have become one of the most important and unsolved topics. Therefore, this review aims to explore the role of mesenchymal stem cells and EVs derived from osteoblasts in bone regeneration in four processes, immunity, angiogenesis, osteogenesis and mineralization, and to provide new ideas for basic and clinical research.