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

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.

AIM: To examine the effects of salidroside on choroidal thickness, hypoxia-inducible factor-1α(HIF-1α), dopamine(DA)and its D1 receptor expression in guinea pigs with lens-induced myopia(LIM).METHODS: A total of 18 two-week-old guinea pigs were randomly divided into the normal control(NC)group, the LIM group, and the LIM + salidroside(LIM+SA)group, with 6 guinea pigs in each group. The guinea pigs in the NC group were fed normally and intragastrically administered with 2 mL/d saline; those in the LIM group wore a -5D lens in front of their right eyes to establish a myopia model, then they were intragastrically administered with 2 mL/d saline. Finally, those in the LIM+SA group wore glasses along with intragastric administration of 2 mL/d salidroside at a dose of 100 mg/kg. The refraction, axial length, and choroidal thickness of guinea pigs in each group were measured 4wk following the establishment of the model. In addition, the relative mRNA expression and protein content of HIF-1α in the choroid and retina of guinea pigs in each group were detected by real-time quantitative PCR(qPCR)and immunohistochemistry(IHC). Finally, the DA concentration and its D1 receptor expression were detected by enzyme-linked immunosorbent assay(ELISA)and Western blot.RESULTS: At 4wk after model establishment, guinea pigs of LIM group and LIM+SA group exhibited increased negative refraction of the right eye, prolonged axial length, and decreased choroidal thickness compared to the NC group. The relative mRNA expression and protein content of HIF-1α in the choroid and retina of the guinea pigs increased. The concentration of DA and the expression of its D1 receptor both decreased. Moreover, compared to the LIM group, the diopter of the right eye of guinea pigs in LIM+SA group significantly reduced, the axial length was shorter, the thickness of choroid increased, the relative mRNA expression and protein content of HIF-1α in the choroid and retina decreased and the concentration of DA and the expression of its D1 receptor both increased.CONCLUSION: Salidroside can delay myopia progression in myopic guinea pigs by affecting choroidal thickness and the expression of HIF-1α, DA and its D1 receptor.

Objective:To analyze the clinical characteristics of elderly acute pulmonary thromboembolism(APE)patients complicated with preexisting atrial fibrillation(AF)and the impact of preexisting AF on in-hospital adverse outcomes in elderly patients with APE.Methods:A retrospective analysis was performed on elderly APE patients with preexisting AF hospitalized in Beijing Anzhen Hospital, Capital Medical University between January 1, 2008 and December 31, 2021.We compared the comorbidities, symptoms, signs, laboratory test results and echocardiographic features, simplified pulmonary embolism severity index(sPESI)scores and adverse in-hospital outcomes between the preexisting AF group and the non-AF group.Logistic regression was used to analyze the risk factors of in-hospital adverse outcomes in elderly patients with APE.Results:A total of 240 patients diagnosed with APE were enrolled.There were 120 patients in the AF group and 120 patients in the non-AF group.For patients in the AF group and the non-AF group, the proportions with chronic heart failure were 38.3%(46/120)and 15.8%(19/120), the proportions with lower extremity deep vein thrombosis(DVT)were 36.7%(44/120)and 65.8%(79/120), the left ventricular ejection fractions(LVEF)were(59±10)% and(62±7)%, and hospital stays were(15±7)and(11±4)days, respectively, and the differences were statistically significant( χ2=15.381, 20.429, t=2.527, -4.710, all P<0.05). The incidences of in-hospital adverse outcomes in the AF group and the non-AF group were 4.2%(5/120)and 3.3%(4/120), respectively, with no significant difference( χ2=0.000, P=1.000). The overall incidence of in-hospital adverse outcomes was 3.8%(9/240). Multivariate Logistic regression analysis showed that elevated lactic acid was an independent risk factor for in-hospital adverse outcomes( OR=2.753, 95% CI: 1.367-5.542, P=0.005). However, AF( OR=2.880, 95% CI: 0.587-14.141, P=0.192)and sPESI score( OR=2.056, 95% CI: 0.904-4.673, P=0.086)were not associated with in-hospital adverse outcomes. Conclusions:Elderly APE patients with preexisting AF have a relatively low incidence of DVT, but a higher proportion have concurrent chronic heart failure and need a longer hospital stay.Elevated lactic acid is an independent risk factor for in-hospital adverse outcomes of elderly APE patients with preexisting AF.However, preexisting AF has no predictive value for in-hospital adverse outcomes in elderly patients with APE.

Limb length discrepancy(LLD) is a common complication after total hip arthroplasty (THA). Good positioning of the prosthesis and suitable soft tissue tension are essential to ensure hip joint stability. Patients will be more satisfied if almost the same length of both lower extremities is achieved. Preoperative comprehensive evaluation of patients is helpful to prevent the occurrence of LLD after surgery. Therefore, the pelvic spine conditions, as well as type and cause of LLD should be analyzed in detail before surgery. During operation, limb length should be adjusted by touching the position of patella, Kirschner's wires positioning and referring to the relationship between the center of femoral head and the tip of greater trochanter. After surgery, it is necessary to clearly distinguish true LLD from functional LLD, and make a reasonable therapeutic plan according to patient's symptoms and the range of differences in limb length. This article reviews the latest literatures based on clinical practice experience and summarizes the research status of LLD after THA, which helps joint surgeons to have an in-depth understanding of this postoperative complication.
Humans ; Arthroplasty, Replacement, Hip/adverse effects* ; Femur ; Femur Head ; Lower Extremity ; Pelvis

Humans ; Gemcitabine ; Neoplasms

Objective: To analyze the effect of a comprehensive intervention on the accuracy of children s body size perception, so as to provide a theoretical basis for child body size perception improvement. Methods: The participants were selected from a cluster randomized controlled trial (September 2018 to June 2019). A total of 1 287 children in 24 primary schools (clusters) equally distributed among three regions (Beijing, Changzhi and Urumqi) were selected, which included 12 intervention schools (648 students) and 12 control schools (639 students). The accuracy of body size perception was measured by Ma figural stimuli. A linear mixed model was employed to analyze the effect of the comprehensive intervention on the accuracy of children s body size perception. Results: At baseline, the accuracy rate of body size perception among children in the intervention group and the control group was 56.6% and 51.5%, respectively. The underestimation rate was 42.0% and 47.7%, and the overestimation rate was 1.4% and 0.8%. After the intervention, compared with the control group, the inaccuracy rate ( OR=0.50, 95%CI=0.37-0.68, P <0.01) and the underestimation rate in the intervention group decreased ( OR=0.37, 95%CI=0.26-0.54, P <0.01). There was no significant difference in the overestimation rate between the two groups( P =0.51). The results of the stratified analysis showed that the intervention could improve the accuracy of children s body size perception, regardless of their gender, nutritional status, region, or whether or not they were only child( P >0.05). Conclusion The inaccuracy rate of children s body size perception, which mainly involved underestimation was high. A comprehensive intervention can effectively reduce body size underestimation and improve the accuracy of children s body size perception.