ObjectiveAt present, the most commonly used photosensitizers in photodynamic therapy are still chemical photosensitizers, such as porphyrin and methylene blue, in order to specifically target cellular tissues, and thus poison cells, chemical photosensitizers need to use antibody conjugation or a transgenically encoded tag with affinity for the modified photosensitizing ligand, e.g. FlAsH, ReAsh or Halo Tag. Gene-encoded photosensitizers can directly poison cells by targeting specific cell compartments or organelles. However, currently developed gene-encoded photosensitizers have low reactive oxygen species production and low cytotoxicity, so it is necessary to continue to develop and obtain photosensitizers with higher reactive oxygen species production for the treatment of microbial infections and tumors. MethodsIn this study, we developed a photosensitizer LovPSO2 based on the light-oxygen-voltage (LOV) structural domain of phototropin-1B-like from Oryza sativa japonica. LovPSO2 was expressed in E. coli BL21(DE3) and purified to obtain protein samples, the purified protein samples were added 3 µmol/L singlet oxygen probe of SOSG and 5 µmol/L superoxide anion probe of DHE after fixed to A₄₄₅=0.063±0.003, respectively, then measured every 2 min of singlet oxygen production for 10 min and every 1 min of superoxide anion production for 5 min under blue light irradiation at 445 nm, 70 µmol·m^-2·s^-1. ResultsThe results showed that LovPSO2 could produce a large amount of singlet oxygen under blue light irradiation at 445 nm, 70 µmol·m^-2·s^-1, and its singlet oxygen quantum yield was 0.61, but its superoxide anion yield was low, so in order to improve the superoxide anion yield of LovPSO2, a mutant with a relatively high superoxide anion yield was obtained by further development and design on its basis LovPRO2. The stability of proteins is crucial for research in drug development and drug delivery, among others. Temperature and light are the key factors affecting the production of reactive oxygen species (ROS) by photosensitive proteins and their stability, while the temperature in cell culture and mammals in vivo is about 37°C, and the temperature inside tumor cells is about 42-45°C. Therefore, we further analyzed the photostability of miniSOG, SOPP3, LovPSO2, and LovPRO2 and their thermostability at 37℃ and 45℃. The analysis of proteins thermostability showed that LovPSO2 and LovPRO2 had better thermostability at 37℃ and 45℃, respectively. Analysis of the photostability of the proteins showed that LovPRO2 had better photostability. In addition, to further determine the phototoxic effects of photosensitizers, LovPSO2 and LovPRO2 were expressed in E. coli BL21(DE3) and HeLa cells, respectively. The results showed that LovPSO2 and LovPRO2 had better phototoxicity to E. coli BL21(DE3) under blue light irradiation, and the cellular phototoxicity lethality was as high as 90% after 30 min of continuous light irradiation, but the phototoxicity was weaker in HeLa cells. The reason for this result may be that the intracellular environment exacerbated the photobleaching of FMN encapsulated by LovPSO2 and LovPRO2, respectively, which attenuated the damage of reactive oxygen species to animal cellular tissues, limiting its use as a mechanistic tool to study oxidative stress. ConclusionLovPSO2 and LovPRO2 can be used as antibacterial photosensitizers, which have broader application prospects in the food and medical fields.

OBJECTIVE: Angiogenesis is a critical target for hepatocellular carcinoma (HCC) treatment. The previous studies indicated that Jiedu Fang (JDF) could inhibit hypoxia-induced angiogenesis through interleukin-8 (IL-8). Therefore, the present study further explores the mechanisms behind JDF's inhibition of HCC angiogenesis. METHODS: Angiogenesis was assessed with the capillary-like tube formation assay in vitro and the matrigel plug angiogenesis assay in vivo. A liver cancer-related gene set and genes associated with angiogenesis and the hypoxic microenvironment were analyzed using a bioinformatics platform. Real-time reverse transcription-polymerase chain reaction and Western blotting assays were used to assess the targeted mRNA and protein levels, respectively. The Transwell assay was used to assess the migration and invasion potential of EA.hy 926 cells. The orthotopic tumor xenograft model was established, and immunohistochemistry and immunofluorescence assays were used to detect cluster of differentiation 31 and angiopoietin 2 expression, while an enzyme-linked immunosorbent assay was used to detect vascular endothelial growth factor and IL-8 protein levels. RESULTS: In vitro and in vivo assays showed that IL-8 promoted angiogenesis, and JDF could antagonize this effect. Bioinformatics analysis indicated that aurora kinase A (Aurora A) was an important candidate, which can promote IL-8 expression through activation of signal transducer and activator of transcription 3 (STAT3). The overexpression of Aurora A increased IL-8 secretion and promoted HCC migration, invasion, and angiogenesis, which was partly inhibited by JDF. Such effects were validated by in vivo assays. Further validation using the STAT3 inhibitor S3I-201 demonstrated that STAT3 was regulated by Aurora A. CONCLUSION JDF exhibits efficacy in reducing hypoxia-induced angiogenesis in HCC through a mechanism involving the Aurora A/STAT3/IL-8 signaling pathway. Therefore, JDF holds promise as a potential therapeutic approach for targeting HCC angiogenesis. Please cite this article as: Zhong MF, Luo YJ, Guo YY, Xiang S, Lin WF. Jiedu Fang inhibits hypoxia-induced angiogenesis in hepatocellular carcinoma by targeting Aurora A/STAT3/IL-8 signaling pathway. J Integr Med. 2025; 23(6):683-693.
Carcinoma, Hepatocellular/blood supply* ; Humans ; STAT3 Transcription Factor/metabolism* ; Interleukin-8/metabolism* ; Liver Neoplasms/blood supply* ; Aurora Kinase A/metabolism* ; Neovascularization, Pathologic/drug therapy* ; Animals ; Signal Transduction/drug effects* ; Mice ; Drugs, Chinese Herbal/therapeutic use* ; Cell Line, Tumor ; Mice, Inbred BALB C ; Mice, Nude ; Angiogenesis

Objective:To explore the relationship between weight change and the development of hyperuricemia (HUA) in adults receiving health checkups.Methods:A retrospective cohort study. A total of 37 722 subjects who underwent two or more health checkups at the Health Management Center of the Second Affiliated Hospital of Dalian Medical University from January 2014 to December 2022 were included, and the general information and laboratory findings at the time of the initial health checkups and follow-up were collected. Weight change was defined as the ratio of difference between the weight at the last follow-up and the baseline weight to baseline weight. The subjects were grouped with weight change: significant weight loss group (weight change ≤-5.0%), mild weight loss group (-5.0%

Objective To evaluate the pharmacokinetic characteristics and safety of single and multiple oral azvudine tablets in healthy young and elderly Chinese subjects.Methods This was a open-label and parallel-group study.The trial consisted of two groups:healthy young subjects group and healthy elderly subjects group,with 12 subjects in each group.Enrolled subjects were first given a single dose,fasting oral azvudine tablet 5 mg,after a 3-day cleansing period entered the multiple dose phase,fasting oral azvudine tablet 5 mg·d-1 for 7 days.Results After a single dose of azvudine 5 mg,Cmax and AUC0-∞ were(4.76±2.12)ng·mL-1,(6.53±2.20)ng·mL-1·h,and Tmax,t1/2 were 0.75,1.87 h in young subjects;Cmax and AUC0-∞ were(6.40±3.25)ng·mL-1,(9.50±3.70)ng·mL-1·h,and Tmax,t1/2 were 0.63,2.66 h in elderly subjects.After a multiple dose of azvudine 5 mg·d-1 for 7 d,Cmax and AUC0-∞ were(3.26±1.61)ng·mL-1,(5.38±2.19)ng·mL-1·h,and Tmax,ss,t1/2,ss were 0.88,2.13 h in young subjects;Cmax,ss and AUC0-∞,ss were(3.97±2.09)ng·mL-1,(6.71±3.26)ng·mL-1·h,and Tmax,ss,t1/2,ss were 0.75,2.56 h in elderly subjects.Elderly/young geometric mean ratios and 90％CIs were 128.37％(88.23％-186.76％),139.93％(105.42％-185.72％),140.03％(106.33％-184.41％)for azvudine Cmax,AUC0-t,AUC0-∞ after a single dose,and were 118.66％(80.83％-174.20％),118.41％(83.60％-167.69％),118.95％(84.78％-166.89％)for azvudine Cmax,AUC0-t,AUC0_∞ after a multiple dose of azvudine 5 mg·d-1 for 7 d.Conclusion After single and multiple oral administration of azvudine tablets,systemic exposure to azvudine was higher in healthy elderly subjects compared with healthy young subjects.After taking azvudine tablets,the types,severity and incidence of adverse events and adverse drug reactions in healthy elderly people were not significantly different from those in healthy young subjects.Azvudine was found to be safe and well tolerated in healthy elderly subjects.

Objective To investigate the safety and efficacy of novel bioabsorbable vascular scaffold(BVS)in the treatment of patients with complex coronary artery disease.Methods This was a retrospective,matched,single-center observational study.45 patients with coronary atherosclerotic cardiopathy received BVS treatment in the cardiovascular medicine department Department of the Affiliated Hospital of Guangdong Medical University from June 2020 to June 2021(BVS),and 45 patients treated with drug-eluting stents(DES)group were selected according to matching study requirements during the same period.Baseline,surgical,and follow-up data were compared between the two groups to evaluate safety and efficacy.The main measures of safety were:surgical time,intraoperative adverse events,etc.,and the end point of efficacy was target lesion failure(TLF),including cardiac death,target vessel myocardial infarction,and ischa-driven target lesion revascularization.Results A total of 90 patients were enrolled in this study,all of whom were followed up for at least 3 years.There were 20 cases of bifurcation lesions and 25 cases of diffuse long lesions in the two groups,and 50 cases of imaging were reviewed among the 90 patients.The proportion of stable coronary heart disease,history of diabetes,history of hypertension,history of smoking,pre-dilated balloon pressure and postoperative diastolic blood pressure in BVS group was higher than that in DES group,and the proportion of family history was lower than that in DES group(all P＜0.05).There were no statistically significant differences in the rates of cardiac death,target vessel myocardial infarction,and ischemia-driven revascularization of target lesions between the two groups(all P＞0.05).Binary Logistic regression model analysis showed that the diameter stenosis ratio of target lesions was an independent risk factor for intrastent restenosis(OR 2.786,95％CI 1.096-7.081,P=0.031).Conclusions Compared with traditional DES,BVS implantation has consistent safety and efficacy in the treatment of complex coronary artery disease within 3 years.The diameter stenosis ratio of target lesions was an independent risk factor for intrastent restenosis.

Objective To establish a cost-benefit evaluation (CBE) index system which is suitable for health enterprise construction, and provide an effective tool for conducting economic evaluation of health enterprise development. Methods The index pool of CBE index system for health enterprise construction was initially established by comprehensive use of field surveys, key informant interviews and literature review. The improved Delphi method was used to conduct two rounds of expert correspondences with 21 experts, through which the evaluation indicator system was adjusted and refined based on the experts' opinions, ultimately the CBE indicator system suitable for health enterprise construction was determined. Results The effective questionnaire recovery rates of the two rounds of expert consultations were 100.0%. The expert authority coefficients was 0.88, and the Kendall's W coordination coefficients of the cost input indicator and benefit indicator in the second round of expert consultation were 0.14 and 0.15 (all P<0.001), with Cronbach's α coefficient of reliability evaluation of index system were all >0.80. The final CBE index system for health enterprise construction includes cost input indicators focusing on four dimensions: “improving management systems”, “building a healthy environment”, “enhancing health management and services”, and “cultivating a healthy culture”. It covered four primary indicators, ten secondary indicators, and 22 tertiary indicators. The benefit indicators mainly focused on the four primary indicators, including “health productivity”, “clinical output”, “economic output”, and “cultural output”, ten secondary indicators, and 23 tertiary indicators. Conclusion The CBE indicator system for health enterprise construction developed in this study is highly reliable, scientific, and practical. It can serve as a tool for the preliminary evaluation and general application of the cost-benefit evaluation of health enterprise construction and provide strong support for future research.

OBJECTIVE: Tumor-derived exosomes (TDEs) play crucial roles in intercellular communication. Hypoxia in the tumor microenvironment enhances secretion of TDEs and accelerates tumor metastasis. Jiedu recipe (JR), a traditional Chinese medicinal formula, has demonstrated efficacy in preventing the metastasis of hepatocellular carcinoma (HCC). However, the underlying mechanism remains largely unknown. METHODS: Animal experiments were performed to investigate the metastasis-preventing effects of JR. Bioinformatics analysis and in vitro assays were conducted to explore the potential targets and active components of JR. TDEs were assessed using nanoparticle tracking analysis (NTA) and Western blotting (WB). Exosomes derived from normoxic or hypoxic HCC cells (H-TDEs) were collected to establish premetastatic mouse models. JR was intragastrically administered to evaluate its metastasis-preventive effects. WB and lysosomal staining were performed to investigate the effects of JR on lysosomal function and autophagy. Bioinformatics analysis, WB, NTA, and immunofluorescence staining were used to identify the active components and potential targets of JR. RESULTS: JR effectively inhibited subcutaneous-tumor-promoted lung premetastatic niche development and tumor metastasis. It inhibited the release of exosomes from tumor cells under hypoxic condition. JR treatment promoted both lysosomal acidification and suppressed secretory autophagy, which were dysregulated in hypoxic tumor cells. Quercetin was identified as the active component in JR, and the epidermal growth factor receptor (EGFR) was identified as a potential target. Quercetin inhibited EGFR phosphorylation and promoted the nuclear translocation of transcription factor EB (TFEB). Hypoxia-impaired lysosomal function was restored, and secretory autophagy was alleviated by quercetin treatment. CONCLUSION JR suppressed HCC metastasis by inhibiting hypoxia-stimulated exosome release, restoring lysosomal function, and suppressing secretory autophagy. Quercetin acted as a key component of JR and regulated TDE release through EGFR-TFEB signaling. Our study provides a potential strategy for retarding tumor metastasis by targeting H-TDE secretion. Please cite this article as: Jia WT, Xiang S, Zhang JB, Yuan JY, Wang YQ, Liang SF, Lin WF, Zhai XF, Shang Y, Ling CQ, Cheng BB. Jiedu recipe, a compound Chinese herbal medicine, suppresses hepatocellular carcinoma metastasis by inhibiting the release of tumor-derived exosomes in a hypoxic microenvironment through the EGFR-TFEB signaling pathway. J Integr Med. 2024; 22(6): 697-709.
Exosomes/drug effects* ; Animals ; Carcinoma, Hepatocellular/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Liver Neoplasms/pathology* ; Tumor Microenvironment/drug effects* ; Mice ; Humans ; Cell Line, Tumor ; Mice, Inbred BALB C ; Neoplasm Metastasis ; Male ; Mice, Nude

Objective To compare the prevalence and disease burden of thyroid cancer and their trends between China and the globe from 1990 to 2019.Methods With the global disease burden data in 2019,Joinpoint was used to predict the trends of the disease burden of thyroid cancer in China and the globe from 1990 to 2019,and logarithmic linear model was used to test the predicted trends.The R language was used for predictive analysis and graphic plotting of the disease burden from 2020 to 2035.Results From 1990 to 2019,the standardized incidence rate and the standardized mortality rate of thyroid cancer in China were lower than those in the globe.The standardized incidence rate in China and the globe showed an increasing trend(with the increases of 102.65% and 40.65%,respectively),while the standardized mortality rate showed a decreasing trend(with the decreases of 7.63% and 4.91%,respectively).Compared with those of the female population,the standardized incidence and mortality rates of the Chinese male population increased significantly from 1990 to 2019(the rates of change in the male population were 48.65% and 214.60%,respectively;and the rates of change in the female population were -39.01% and 60.44%,respectively).China's overall standardized years of life lost(YLL),years lived with disability(YLD),and disability-adjusted life years(DALY)rates during the 30-year period were lower than the global average.The Chinese and global populations showed the standardized YLL rate decreasing by 16.61% and 6.88% and the standardized DALY rate decreasing by 10.77% and 3.65%,respectively,while the rates of standardized YLD increased by 128.91% and 46.89%,respectively.The magnitude of DALY in China and the world was mainly influenced by YLL.The standardized incidence,mortality,and DALY rates of the Chinese male population were gradually approaching the global levels.From 1990 and 2019,thyroid cancer showed a higher mortality rate in the population with the age ≥ 75 years and a higher incidence rate in the population with the age <75 years.It is projected that from 2020 to 2035,the standardized incidence rates in China and the world will increase by 36.66% and 21.15%,respectively;the standardized mortality rates will decrease by 20.19% and 3.46%,respectively;and the standardized DALY rate is expected to decrease by 7.08% in China and increase by 4.35% in the world.Conclusions From 1990 to 2019,China's standardized incidence rate of thyroid cancer increased and had a higher increase than the global level,and the standardized mortality rate decreased,with a slightly higher decrease than the global level.However,the increases in the standardized incidence rate and mortality rate of this disease in China's ≥75 years male population were severe.Although China's disease burden of thyroid cancer showed a decreasing trend in line with the global trend as a whole,the disease burden in the Chinese males was higher than that in the females.Specifically,the disease burden due to premature death was predominant,and the burden in specific populations requires policy attention.
Male ; Humans ; Female ; Aged ; Quality-Adjusted Life Years ; Reference Standards ; Cost of Illness ; China/epidemiology* ; Thyroid Neoplasms/epidemiology* ; Incidence

OBJECTIVE: To compare and analyze the early clinical effect of direct superior approach(DSA) and posterior lateral approach (PLA) in hemiarthroplasty for elderly patients with femoral neck fracture. METHODS: The clinical data of 72 elderly patients with femoral neck fracture who underwent hemiarthroplasty from January 2020 to December 2021 were retrospectively analyzed. Among them, 36 patients were operated through minimally invasive DSA including 10 males and 26 females with an average age of (82.82±4.05) years old; the other 36 patients underwent traditional PLA including 14 males and 22 females with an average age of (82.79±3.21) years old. The perioperative related indexes and Harris scores during follow-up between two groups were compared. RESULTS: Comparison of operation time between two groups, (79.41±17.39) min of DSA group was shorter than(98.45±26.58) min of PLA group;incision length (8.33±2.69) cm was shorter than (11.18±1.33) cm of PLA group;intraoperative blood loss (138.46±71.58) ml was less than (173.51±87.17) ml of PLA group, initial landing time (3.04±0.95) d was earlier than (4.52±1.10) d of PLA group, hospitalization time (8.70±1.89) d was shorter than (10.67±2.35) d of PLA group(P<0.05). There was no statistical difference in Harris score between two groups before operation(P>0.05), but Harris score in DSA group was higher than that of PLA group at 1 month after operation(P<0.05), but at 12 months after operation, the difference was not statistically significant between two groups(P>0.05). CONCLUSION Compared with PLA, DSA is superior in clinical indexes such as operation time, intraoperative blood loss, incision length, first landing time, length of hospitalization and Harris score in the first month after operation in hemi hip replacement, and has comparative advantages in promoting early postoperative rehabilitation of elderly patients with femoral neck.
Male ; Female ; Humans ; Aged ; Aged, 80 and over ; Blood Loss, Surgical ; Hemiarthroplasty ; Retrospective Studies ; Arthroplasty, Replacement, Hip ; Femoral Neck Fractures/surgery* ; Treatment Outcome

AIM:To investigate the effects and mechanisms of curcumin on apoptosis of retinal ganglion cells(RGCs)in chronic ocular hypertension rats.METHODS:A total of 21 Spraque-Dawley(SD)rats were randomly divided into 3 groups with 7 rats in each group. The rat models of chronic ocular hypertension were established by cauterization of the superior scleral veins in the high intraocular pressure model group and the curcumin treatment group, and the sham operation group only cut the conjunctiva without the cauterization of the superior scleral veins; the rats in the curcumin treatment group were intragastrically treated with curcumin at a dose of 4mL/kg, and the rats in the sham operation group and the high intraocular pressure model group were treated with pure water at a dose of 4mL/kg for 3wk. After 3wk, HE staining was used to observe the morphological and pathological changes of retina, the number of RGCs and the thickness of ganglion cell layer(GCL)in each group of rats; TUNEL staining was used to observe the apoptosis of RGCs and retinal cells in each group of rats; the expression levels of glutamate-cysteine ligase modifier subunit(GCLM)and heme oxygenase-1(HO-1)in the retina of each group of rats were detected by real-time fluorescence quantitative PCR, immunohistochemical staining and Western blot.RESULTS:Compared with the sham operation group, the retinal morphology of rats in the high intraocular pressure model group and the curcumin treatment group was disorganized, the number of RGCs was reduced, the GCL was thinner, the apoptosis rate of RGCs and retinal cells increased, and the expression levels of GCLM and HO-1 increased. Compared with the high intraocular pressure model group, the retinal morphology of rats in the curcumin treatment group was basically normal, the number of RGCs increased, the GCL thickened, the apoptosis rate of RGCs and retinal cells decreased, and the expression levels of GCLM and HO-1 increased.CONCLUSION:Curcumin can inhibit the apoptosis of RGCs in the rat model of chronic ocular hypertension by up-regulating the expression of antioxidant genes GCLM and HO-1.