ObjectiveTo observe ovarian microvascular damage in rats with cold coagulation and blood stasis syndrome and to explore the mechanism by which Liangfang Wenjing decoction improves this condition in rats. MethodsFifty SPF female SD rats were randomly divided into a blank group， a model group， low-dose （8.1 g·kg^-1） and high-dose groups （16.2 g·kg^-1） of Liangfang Wenjing decoction， and a 4-phenylbutyric acid （0.1 g·kg^-1） group， with 10 rats in each group. The ice-water bath method was employed to establish the rat model of cold coagulation and blood stasis syndrome. Concurrent with modeling， Liangfang Wenjing decoction was administered continuously for 21 days， once daily. The rats' syndrome manifestations and estrous cycles were recorded. The enzyme-linked immunosorbent assay （ELISA） was used to detect serum reproductive hormone levels and levels of endothelin-1 （ET-1）， nitric oxide （NO）， thrombomodulin （TM）， and von Willebrand factor （vWF） in ovarian tissue. Prothrombin time （PT）， activated partial thromboplastin time （APTT）， thrombin time （TT）， and fibrinogen （FIB） were measured. The ovarian microcirculatory blood perfusion was detected by laser speckle contrast imaging. Hematoxylin-eosin （HE） staining was performed to observe the ovarian histopathology， flow cytometry to detect ovarian apoptosis rate， and transmission electron microscopy to observe the ultrastructure of ovarian microvascular endothelial cells. Western blot was employed to detect the protein expression of endothelial nitric oxide synthase （eNOS）， phosphorylated eNOS （p-eNOS）， Caspase-3， B-cell lymphoma-2 （Bcl-2）， Bcl-2-associated X protein （Bax）， glucose-regulated protein 78 （GRP78）， C/EBP homologous protein （CHOP）， inositol-requiring enzyme1α （IRE1α）， p-IRE1α， apoptosis signal-regulating kinase 1 （ASK1）， p-ASK1， c-Jun N-terminal kinase （JNK）， and p-JNK. Immunofluorescence was used to detect ovarian Bax and Bcl-2 expression in microvascular endothelial cells. ResultsCompared with the blank group， the model group showed signs of cold coagulation and blood stasis syndrome， prolonged estrus cycles， and reproductive hormone disorders. Histopathological results revealed a decrease in follicle counts at all stages and disorganized granulosa cell arrangement. Ovarian microcirculatory perfusion was significantly decreased （P<0.01）. PT， APTT， and TT were reduced （P<0.05， P<0.01）， while FIB levels were increased （P<0.05）. In ovarian tissue， NO content was decreased， while ET-1， vWF， and TM levels were increased significantly （P<0.01）. The apoptosis rate of ovarian cells was markedly increased （P<0.01）. Furthermore， p-eNOS/eNOS and Bcl-2 were decreased （P<0.05）， whereas Bax， cleaved-Caspase-3/Caspase-3， GRP78， CHOP， p-IRE1α/IRE1α， p-ASK1/ASK1， and p-JNK/JNK expression showed significant increases （P<0.05， P<0.01）. Compared with the model group， Liangfang Wenjing decoction intervention alleviated the symptoms of cold coagulation and blood stasis， gradually restored the estrus cycle， and improved ovarian histopathology and endothelial cell ultrastructure. Microcirculatory blood perfusion was significantly elevated （P<0.05）. NO content in ovarian tissue was elevated， while ET-1， vWF， and TM levels were significantly decreased （P<0.05， P<0.01）. The p-eNOS/eNOS ratio and Bcl-2 expression were significantly elevated （P<0.05）， while the expression of Bax， cleaved-Caspase-3/Caspase-3， GRP78， CHOP， p-IRE1α/IRE1α， p-ASK1/ASK1， and p-JNK/JNK was significantly decreased （P<0.05， P<0.01）. ConclusionLiangfang Wenjing decoction may regulate the IRE1α/ASK1/JNK signaling pathway to inhibit endoplasmic reticulum stress， attenuate apoptosis， and improve microvascular endothelial injury in ovaries of rats with cold coagulation and blood stasis syndrome.

Objective:To analyze the differentially diagnostic ability of metabolic parameters of 18F-fluorodeoxyglucose positron-emission tomography/computed tomography(18F-FDG PET/CT)in thymic epithelial tumors(TETs)of different histological types.Methods:A total of 72 patients who underwent 18F-FDG PET/CT examination and were confirmed as TETs before treatment at the Department of Nuclear Medicine of the First Medical Center of Chinese PLA General Hospital between January 2013 to May 2022 were analyzed.The patients were divided into thymic tumor with low risk group(9 cases),thymic tumor with high risk group(15 cases)and thymic cancer group(9 cases)according to histological type.The clinical data of patients were recorded,and the patients were staged according to pathological Masaoka-Koga staging of thymic tumor surgery.The maximum standardized uptake value(SUVmax),average standardized uptake value(SUVmean),metabolic tumor volume(MTV),total lesion glycolysis(TLG)and standardized uptake value ratio(SUVR)of the lesions were recorded respectively.The differences of metabolic parameters of various group were compared.The area under curve(AUC)value of receiver operating characteristic(ROC)curve was used to analyze the diagnostic efficacy of 18F-FDG PET/CT in TETs of different histological types.Results:The results of analyzing each metabolic parameter of three groups indicated that the SUVmax,SUVmean and SUVR values of thymic tumor with high risk group and thymic cancer group were significantly higher than them of thymic tumor with low risk group,and the differences were significant(F=10.315,8.336,11.593,P<0.05),respectively.SUVR has the highest diagnostic efficacy in the differential diagnosis for thymic tumor and thymic cancer(AUC:0.864,sensitivity:83.3%,specificity:75.0%),and for thymic tumor with high-risk and thymic cancer(AUC:0.832,sensitivity:56.3%,specificity:100.0%).In addition,SUVR has the highest diagnostic efficacy for thymic tumor with high-risk and thymic tumor with low-risk(AUC:0.748,sensitivity:80.0%,specificity:66.7%).Conclusion:The metabolic parameters of 18F-FDG PET/CT have a certain of differential and diagnostic value in identifying TETs of different histological types.

Objective:To investigate the therapeutic efficacy of different modes of neoadjuvant therapy for locally advanced rectal cancer (LARC) with proficient in mismatch repair intact (pMMR) or microsatellite stability (MSS).Methods:A retrospective case series study was conducted. A total of 210 LARC patients with pMMR or MSS admitted to the First Affiliated Hospital of Zhengzhou University from January 2020 to December 2022 were selected. Patients were divided into the chemotherapy alone group (98 cases) and the total neoadjuvant therapy (TNT) group (112 cases) based on different neoadjuvant treatment modes. The pathological complete remission (pCR) rate of both groups was compared. In the TNT group, 24 patients received short-course radiotherapy (SCRT) plus chemotherapy (group A), 62 patients received SCRT plus chemotherapy combined with immunotherapy (group B), 23 patients received long-course radiotherapy (LCRT) plus chemotherapy (group C), and 3 patients received LCRT plus chemotherapy combined with immunotherapy (group D). The pCR rate, tumor down-staging and the incidence of adverse reactions were compared between the 4 groups. A subgroup analysis was performed in 87 patients with the distance from the tumor site to anal verge >5 cm and T 2-3N 0-2M 0 TNM staging. And then 87 patients were divided into the chemotherapy alone group (47 cases) and the TNT group (40 cases), and the overall survival (OS) and disease-free survival (DFS) of patients were compared between the 2 groups. Results:Among the 210 LARC patients, 126 cases were male and 84 cases were female, with the age of (51±11) years. There were 3 cases in clinical stage Ⅱ and 207 cases in clinical stage Ⅲ; 68 cases with the distance from the tumor site to the anal verge <5 cm and 142 cases with the distance from the tumor site to the anal verge ≥ 5 cm. The pCR rate of the TNT group was higher than that of the chemotherapy alone group [40.2% (45/112) vs. 7.2% (7/98)], and the difference was statistically significant ( χ2 = 30.62, P < 0.001). In group D, 1 patient achieved pCR, but no statistical comparison was made due to the small sample size. There was no statistically significant difference in pCR rate between group A and group C [25.0% (6/24) vs. 21.7% (5/23), χ2 = 0.07, P = 0.792]. The pCR rate of group B was higher than that of group A and group C [53.2% (33/62) vs. 25.0% (6/24), 53.2% (33/62) vs. 21.7% (5/23)], and the differences were statistically significant ( χ2 = 5.56, P = 0.029; χ2 = 6.73, P = 0.013). However, there were no statistically significant differences in T and N down-staging among group A, group B and group C (all P > 0.05). During neoadjuvant treatment, the incidence of grade 3-4 myelosuppression was 10.7% (12/112) in the TNT group, and no grade 3-4 radiation proctitis was observed. The incidence of granulocytopenia in group B was lower than that in group A, and the incidence of thrombocytopenia in group was lower than that in group C; and the differences were statistically significant (all P < 0.05). In the subgroup analysis, there were no statistically significant differences in OS and DFS between the chemotherapy alone group and the TNT group ( χ2 = 2.17, P = 0.141; χ2 = 0.24, P = 0.624). Conclusions:The neoadjuvant treatment of SCRT combined with immunotherapy has a high pCR rate and a good safety in LARC patients with pMMR or MSS. TNT is not effective in improving the survival of low-risk LARC patients with tumors located in the mid to high segment of the rectum and may have the risk of overtreatment.

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 investigate the effect of lidocaine medicated plaster （LMP） combined with pregabalin （PGB） on patients with postherpetic neuralgia （PHN）, and the impact on serum pain mediators. Methods 108 PHN patients admitted in our hospital from January 2024 to December 2024 were selected and grouped according to the time point of receiving treatment, 54 PHN patients treated with PGB from January 2024 to June 2024 were included in the PGB group, and 54 PHN patients treated with LMP on top of the PGB group from July 2024 to December 2024 were included in the PGB+LMP group. Comparisons were made between the two groups in terms of pain score, serum pain mediator levels, dosage of PGB, and incidence of adverse reactions. Results After 4 weeks of treatment, both groups showed a decrease in Pain Rating Index scores （sensory score and affective score）, Present Pain Intensity score, Visual Analog Scale score, and total score. Meanwhile, above scores of the PGB+LMP group were lower than those of the PGB group （P<0.05）. After 4 weeks of treatment, the levels of substance P（SP） and neuropeptide Y （NPY） in both groups were lower than those before treatment, while serum 5-hydroxytryptamine （5-HT） levels were higher than those before treatment. Moreover, the levels of SP and NPY were lower, and 5-HT level was higher in the PGB+LMP group than in the PGB group （P<0.05）. The dosages of PGB in the PGB+LMP group at T1, T, T3 and T4 were significantly lower than those in the PGB group （P<0.05）. The incidence of adverse reactions was 1.85%（1/54） in the PGB+LMP group. Compared to 5.56%（3/54） in the PGB group, and the difference was not statistically significant （P>0.05）. Conclusion LMP combined with PGB was effective in the treatment of patients with PHN, which could effectively alleviate pain and lower the levels of serum pain mediators, with good safety.

Objective To observe the clinical efficacy of Bushen Tongmai Prescription in treating type 2 diabetes mellitus(T2DM)complicated with atherosclerotic cardiovascular disease(ASCVD)of kidney deficiency and blood stasis type,and to investigate its effect on serum microRNA-126(miR-126).Methods Sixty patients with T2DM complicated with ASCVD of kidney deficiency and blood stasis type who admitted to the outpatient and inpatient departments of the Department of Geriatric Medicine of Shenzhen Traditional Chinese Medicine Hospital from March 2023 to October 2023 were randomly divided into the study group and the control group according to random number table method,with 30 patients in each group.All patients in the two groups were required to take low-salt and low-fat diabetic diet and exercise for intervention,and were also given the conventional western medical treatment with hypoglycemic,lipid-lowering,antihypertensive,anti-platelet aggregation agents.Additionally,the study group was treated with Bushen Tongmai Prescription.The course of treatment for the two groups covered eight weeks.Before and after treatments,the two groups were observed in the changes of C-reactive protein(CRP),interleukin 1β(IL-1β),interleukin 6(IL-6),vascular cell adhesion molecule 1(VCAM1),miR-126,carotid intima-media thickness(CIMT),carotid plaque Crouse scores,and blood lipid indicators of total cholesterol(TC),triglycerides(TG),low-density lipoprotein cholesterol(LDL-C)and high-density lipoprotein cholesterol(HDL-C).After treatment,the therapeutic efficacy on carotid artery and drug safety in the two groups were evaluated.Results(1)After treatment,the serum miR-126 level in the study group was significantly increased compared with that before treatment(P＜0.01),but the level in the control group only showed a rising trend and the difference was not statistically significant(P＞0.05).The comparison between the two groups showed that the increase of serum miR-126 level in the study group was significantly superior to that in the control group(P＜0.05).(2)After treatment,the serum VCAM1 level in the study group was decreased significantly compared with that before treatment(P＜0.01),but the level in the control group only showed a rising trend and the difference was not statistically significant(P＞0.05).The comparison between the two groups showed that the decrease of serum VCAM1 level in the study group was significantly superior to that in the control group(P＜0.01).(3)After treatment,the serum CRP,IL-1 β,and IL-6 levels in the two groups were decreased compared with those before treatment(P＜0.05 or P＜0.01),and the decrease of serum IL-1β and IL-6 levels in the study group was significantly superior to that in the control group(P＜0.05).(4)After treatment,the TC,TG and LDL-C levels in the study group were decreased(P＜0.01)and the HDL-C level was increased compared with that before treatment(P＜0.01),but in the control group,the changes in the TC,TG,LDL-C,and HDL-C levels were not significant(P＞0.05).The comparison between the two groups showed that the decrease of TC and LDL-C levels in the study group was significantly superior to that in the control group(P＜0.05).(5)After eight weeks of treatment,the total effective rate of the study group was 90.00％(27/30),while that of the control group was 63.33％(19/30).The intergroup comparison(tested by chi-square test)showed that the therapeutic efficacy of the study group was significantly superior to that of the control group(P＜0.05).(6)During the treatment,no serious adverse reactions or toxic-side effects occurred in the two groups.Conclusion Bushen Tongmai Prescription combined with conventional western medicine treatment can up-regulate the level of miR-126,inhibit the expression of VCAM1,and decrease the levels of serum CRP,IL-1β,and IL-6,so as to inhibit inflammatory response and retard the progression of T2DM complicated with ASCVD.The combined therapy exerts certain clinical efficacy and higher safety in treating T2DM complicated with ASCVD.

Objective To investigate the value of CT radiomics for predicting effect of neoadjuvant chemotherapy(NACT)for locally advanced gastric cancer(LAGC).Methods Totally 325 LAGC patients who received NACT were retrospectively enrolled,among them 247 were taken as training set,while the rest 78 were taken as validation set.Tumor regression scale(TRG)was evaluated according to postoperation pathology after NACT,and the efficacy of NACT was evaluated.Univariate logistic regression was used to analyze and screen clinical predictors of effect of NACT,and clinical model was constructed.Radiomics features were extracted based on venous phase enhanced CT pre-and post-NACT,and Delta radiomics features(i.e.the ratio of the difference of pre-and post-NACT radiomics features and pre-NACT radiomics features)were calculated.The best features were screened based on pre-NACT,post-NACT and Delta radiomics features to construct radiomics labels,the optimal label was screened and used to construct combined model through combining clinical model.Receiver operating characteristic(ROC)curve was plotted,and the area under the curve(AUC)was calculated to evaluate predicting efficiency of the above models.Decision curve analysis(DCA)was performed to explore the clinical value of each model.Results In training set,significant effect was found in 67 cases,but not in 180 cases,while in validation set,significant effect was found in 18 cases but not in 60 cases.Borrmann classification of LAGC before NACT was the clinical predictor(P=0.031),and clinical model was constructed,which had AUC of 0.577 and 0.520 in training and validation sets,respectively.Based on pre-NACT,post-NACT and Delta radiomics features,19,14 and 17 best features were selected,and AUC of the established radiomics labels of Pre-Rad,Post-Rad and Delta-Rad in training set was 0.672,0.796 and 0.789,while in validation set was 0.558,0.805 and 0.666,respectively.Post-Rad was the optimal label,which was used to construct combined model.AUC of the obtained combined model in training and validation sets was 0.824 and 0.818,respectively,both higher than that of clinical model(both P＜0.001)but not different with that of Post-Rad(both P＞0.05).Taken 0.4 to 0.7 as the threshold,the combined model had higher clinical net benefit than the other two.Conclusion Venous CT radiomics could effectively predict effect of NACT for LAGC.Combining with clinical features could improve its predictive efficacy.

Objective:To construct a smart elderly education system that in line with the current situation under the Healthy China strategy and explore the constraints on its institutional implementation,in order to provide a basis for scientifically evaluating the implementation effect of this system.Methods:A questionnaire survey was conducted on 34 experts in related fields.The analytic hierarchy process(AHP)was used to perform quantitative and qualitative analyses on the construction of the smart elderly education system,and the weights of the importance of each scheme were obtained.Results:The constructed model of the smart elderly education system included 5 first-level indicators and 15 second-level indicators.Calculations of the judgment matrix for the 5 first-level indicators showed that the maximum eigenvalue(λmax)=5.071 4,the random consistency index(RI)=1.12,the consistency index(CI)=0.017 8,and the consistency ratio(CR)=0.015 9.With CR＜0.1,the result met the consistency requirement.For the second-level indicators under each first-level indicator,pairwise comparison judgment matrices were constructed.The CR values of all 5 judgment matrices were＜0.1.In summary,all judgment matrices passed the consistency test and were applicable.Among the first-level indicators,the top three by weights were guarantee mechanisms,demand orientation,and implementation effectiveness.Among the second-level indicators,the top three by combined weights were funding support capacity,health literacy improvement rate,and health demand identification mechanism.Conclusions:The indicator evaluation system for the smart elderly education system constructed based on AHP includes core dimensions such as guarantee mechanisms and demand orientation,responding to the key issues of institutional implementation.The selected indicators are both objective and practical,and can serve as reference tools for actual evaluation.

Objective:To construct a smart elderly education system that in line with the current situation under the Healthy China strategy and explore the constraints on its institutional implementation,in order to provide a basis for scientifically evaluating the implementation effect of this system.Methods:A questionnaire survey was conducted on 34 experts in related fields.The analytic hierarchy process(AHP)was used to perform quantitative and qualitative analyses on the construction of the smart elderly education system,and the weights of the importance of each scheme were obtained.Results:The constructed model of the smart elderly education system included 5 first-level indicators and 15 second-level indicators.Calculations of the judgment matrix for the 5 first-level indicators showed that the maximum eigenvalue(λmax)=5.071 4,the random consistency index(RI)=1.12,the consistency index(CI)=0.017 8,and the consistency ratio(CR)=0.015 9.With CR＜0.1,the result met the consistency requirement.For the second-level indicators under each first-level indicator,pairwise comparison judgment matrices were constructed.The CR values of all 5 judgment matrices were＜0.1.In summary,all judgment matrices passed the consistency test and were applicable.Among the first-level indicators,the top three by weights were guarantee mechanisms,demand orientation,and implementation effectiveness.Among the second-level indicators,the top three by combined weights were funding support capacity,health literacy improvement rate,and health demand identification mechanism.Conclusions:The indicator evaluation system for the smart elderly education system constructed based on AHP includes core dimensions such as guarantee mechanisms and demand orientation,responding to the key issues of institutional implementation.The selected indicators are both objective and practical,and can serve as reference tools for actual evaluation.

Objective To investigate the value of CT radiomics for predicting effect of neoadjuvant chemotherapy(NACT)for locally advanced gastric cancer(LAGC).Methods Totally 325 LAGC patients who received NACT were retrospectively enrolled,among them 247 were taken as training set,while the rest 78 were taken as validation set.Tumor regression scale(TRG)was evaluated according to postoperation pathology after NACT,and the efficacy of NACT was evaluated.Univariate logistic regression was used to analyze and screen clinical predictors of effect of NACT,and clinical model was constructed.Radiomics features were extracted based on venous phase enhanced CT pre-and post-NACT,and Delta radiomics features(i.e.the ratio of the difference of pre-and post-NACT radiomics features and pre-NACT radiomics features)were calculated.The best features were screened based on pre-NACT,post-NACT and Delta radiomics features to construct radiomics labels,the optimal label was screened and used to construct combined model through combining clinical model.Receiver operating characteristic(ROC)curve was plotted,and the area under the curve(AUC)was calculated to evaluate predicting efficiency of the above models.Decision curve analysis(DCA)was performed to explore the clinical value of each model.Results In training set,significant effect was found in 67 cases,but not in 180 cases,while in validation set,significant effect was found in 18 cases but not in 60 cases.Borrmann classification of LAGC before NACT was the clinical predictor(P=0.031),and clinical model was constructed,which had AUC of 0.577 and 0.520 in training and validation sets,respectively.Based on pre-NACT,post-NACT and Delta radiomics features,19,14 and 17 best features were selected,and AUC of the established radiomics labels of Pre-Rad,Post-Rad and Delta-Rad in training set was 0.672,0.796 and 0.789,while in validation set was 0.558,0.805 and 0.666,respectively.Post-Rad was the optimal label,which was used to construct combined model.AUC of the obtained combined model in training and validation sets was 0.824 and 0.818,respectively,both higher than that of clinical model(both P＜0.001)but not different with that of Post-Rad(both P＞0.05).Taken 0.4 to 0.7 as the threshold,the combined model had higher clinical net benefit than the other two.Conclusion Venous CT radiomics could effectively predict effect of NACT for LAGC.Combining with clinical features could improve its predictive efficacy.