BACKGROUND:Curcumin is the main active ingredient of turmeric and has significant medicinal value in anti-tumor,anti-inflammatory,antioxidant and other aspects.However,its poor water solubility,unstable chemical properties and easy decomposition lead to difficulty in extracting curcumin and low extraction yield.Therefore,it is particularly important to optimize the curcumin extraction method.OBJECTIVE:To enhance the extraction yield and utilization value of curcumin and optimize the curcumin extraction process and curcumin nanoparticle preparation process.METHODS:Curcumin was extracted from turmeric by ethanol extraction,ultrasonic extraction,ionic liquid extraction,enzyme extraction,and ionic liquid combined with ultrasonic assisted enzyme extraction.The curcumin extraction yield was detected by high performance liquid chromatography;the best extraction method was determined,and subsequent process optimization experiments were carried out.The curcumin extraction yield was the response value with the type of ionic liquid,reaction temperature,ultrasonic time,liquid-to-solid ratio,ionic liquid concentration,and enzyme-drug mass ratio as parameters.The optimal production process of ionic liquid combined with ultrasonic assisted enzyme extraction was determined by single factor combined response surface experiment.The optimal process for preparing curcumin nanoparticles by ionic crosslinking method was determined by single factor combined response surface experiment with acetic acid concentration,chitosan to sodium tripolyphosphate mass ratio,stirring rate,curcumin mass concentration,sodium tripolyphosphate mass concentration,and chitosan mass concentration as parameters,and drug encapsulation efficiency as response value.Curcumin nanoparticles were prepared under the optimal process,and the particle size,polydispersity index,Zata potential value,drug loading,stability,hemolysis rate,and antioxidant capacity in vivo and in vitro of the nanoparticles were detected.RESULTS AND CONCLUSION:(1)Among the five extraction methods,the curcumin yield of ionic liquid combined with ultrasound-assisted enzyme extraction was the highest,and this method was selected as the curcumin extraction method for subsequent experiments.The results of single factor combined response surface experiment showed that the optimal process for curcumin extraction was:ionic liquid selected 1-hexyl-3-methylimidazolium chloride,reaction temperature 55 ℃,liquid-to-solid ratio 40 mL/g,ultrasound time 57 minutes,ionic liquid concentration 57％,enzyme-drug mass ratio 3.5:10,and the obtained turmeric extraction yield was 3.10％.The optimal preparation process of curcumin nanoparticles was:glacial acetic acid concentration 0.5％,chitosan and sodium tripolyphosphate mass ratio 5.0:1,stirring speed 150 r/min,curcumin mass concentration 2.23 mg/mL,sodium tripolyphosphate mass concentration 1.45 mg/mL,chitosan mass concentration 3.63 mg/mL,and the obtained drug encapsulation efficiency was 90.61％.(2)The drug loading of curcumin nanoparticles was(14.49±0.23)％,the average particle size was(76.95±1.65)nm,the polydispersity coefficient was 0.15±0.02,and the Zata potential value was(32.37±1.46)mV.The curcumin nanoparticles had good stability and blood compatibility,did not induce hemolysis,and had stronger antioxidant capacity in vivo and in vitro than free curcumin.(3)The results show that the process optimization not only solves the problems of low extraction yield,poor solubility,and low bioavailability of curcumin,but also enhances its antioxidant activity in vivo and in vitro.

BACKGROUND:Curcumin is the main active ingredient of turmeric and has significant medicinal value in anti-tumor,anti-inflammatory,antioxidant and other aspects.However,its poor water solubility,unstable chemical properties and easy decomposition lead to difficulty in extracting curcumin and low extraction yield.Therefore,it is particularly important to optimize the curcumin extraction method.OBJECTIVE:To enhance the extraction yield and utilization value of curcumin and optimize the curcumin extraction process and curcumin nanoparticle preparation process.METHODS:Curcumin was extracted from turmeric by ethanol extraction,ultrasonic extraction,ionic liquid extraction,enzyme extraction,and ionic liquid combined with ultrasonic assisted enzyme extraction.The curcumin extraction yield was detected by high performance liquid chromatography;the best extraction method was determined,and subsequent process optimization experiments were carried out.The curcumin extraction yield was the response value with the type of ionic liquid,reaction temperature,ultrasonic time,liquid-to-solid ratio,ionic liquid concentration,and enzyme-drug mass ratio as parameters.The optimal production process of ionic liquid combined with ultrasonic assisted enzyme extraction was determined by single factor combined response surface experiment.The optimal process for preparing curcumin nanoparticles by ionic crosslinking method was determined by single factor combined response surface experiment with acetic acid concentration,chitosan to sodium tripolyphosphate mass ratio,stirring rate,curcumin mass concentration,sodium tripolyphosphate mass concentration,and chitosan mass concentration as parameters,and drug encapsulation efficiency as response value.Curcumin nanoparticles were prepared under the optimal process,and the particle size,polydispersity index,Zata potential value,drug loading,stability,hemolysis rate,and antioxidant capacity in vivo and in vitro of the nanoparticles were detected.RESULTS AND CONCLUSION:(1)Among the five extraction methods,the curcumin yield of ionic liquid combined with ultrasound-assisted enzyme extraction was the highest,and this method was selected as the curcumin extraction method for subsequent experiments.The results of single factor combined response surface experiment showed that the optimal process for curcumin extraction was:ionic liquid selected 1-hexyl-3-methylimidazolium chloride,reaction temperature 55 ℃,liquid-to-solid ratio 40 mL/g,ultrasound time 57 minutes,ionic liquid concentration 57％,enzyme-drug mass ratio 3.5:10,and the obtained turmeric extraction yield was 3.10％.The optimal preparation process of curcumin nanoparticles was:glacial acetic acid concentration 0.5％,chitosan and sodium tripolyphosphate mass ratio 5.0:1,stirring speed 150 r/min,curcumin mass concentration 2.23 mg/mL,sodium tripolyphosphate mass concentration 1.45 mg/mL,chitosan mass concentration 3.63 mg/mL,and the obtained drug encapsulation efficiency was 90.61％.(2)The drug loading of curcumin nanoparticles was(14.49±0.23)％,the average particle size was(76.95±1.65)nm,the polydispersity coefficient was 0.15±0.02,and the Zata potential value was(32.37±1.46)mV.The curcumin nanoparticles had good stability and blood compatibility,did not induce hemolysis,and had stronger antioxidant capacity in vivo and in vitro than free curcumin.(3)The results show that the process optimization not only solves the problems of low extraction yield,poor solubility,and low bioavailability of curcumin,but also enhances its antioxidant activity in vivo and in vitro.

Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

ObjectiveTo evaluate the clinical efficacy and safety of Qidan Tangshen Granules （芪丹糖肾颗粒， QTG） in the treatment of early diabetic kidney disease （DKD） with qi deficiency， blood stasis， and kidney deficiency syndrome， and to explore its mechanism. MethodsA double-blind， double-simulated method was used to enroll 200 patients with early DKD and qi deficiency， blood stasis， and kidney deficiency syndrome. Patients were randomly assigned in a 1∶1 ratio to the treatment group （100 cases） and the control group （100 cases）. The treatment group received QTG plus a valsartan capsule simulant， while the control group received valsartan capsules plus a QTG simulant， both for 12 weeks. The primary outcome was the urinary albumin-to-creatinine ratio （UACR）. Secondary outcomes included estimated glomerular filtration rate （eGFR）， fasting blood glucose （FBG）， 2-hour postprandial blood glucose （PBG）， glycated hemoglobin （HbA1c）， and traditional Chinese medicine （TCM） syndrome scores （including individual symptom scores for fatigue， dull complexion， soreness and weakness of the waist and knees， headache and chest pain， irritability， spontaneous sweating， thirst and polydipsia， polyphagia， polyuria， numbness of the limbs， and the total TCM syndrome score）. Oxidative stress markers including serum 8-hydroxy-2'-deoxyguanosine （8-OHDG）， 3-nitrotyrosine （3-NT）， and superoxide dismutase （SOD） were also assessed. Clinical efficacy and TCM syndrome efficacy were evaluated after treatment， and routine blood tests， urinalysis， and liver function tests were conducted and adverse reaction during the tria was recorded to assess safety. ResultsA total of 191 patients completed the study （95 in the treatment group and 96 in the control group）. The treatment group showed significant reductions in UACR， FBG， PBG， and HbA1c levels after treatment （P＜0.05 or P＜0.01）. The single TCM symptom scores except for polyphagia and total TCM syndrome scores significantly decreased （P＜0.05 or P＜0.01）. Compared to the control group， the treatment group had signi-ficantly lower UACR， FBG， PBG levels， and total TCM syndrome scores， sinlge symptoms scores except for polyphagia and limb numbness （P＜0.05 or P＜0.01）. Among 40 randomly selected patients （21 cases in the treatment group and 19 cases in the control group） for oxidative stress analysis， there were no significant differences in SOD， 3-NT， and 8-OHDG levels before and after treatment within or between groups （P＞0.05）. The overall effective rate in the treatment group was 64.2% （61/95） and 39.6% （38/96） in the control group， while the TCM syndrome efficacy rates were 80.0% （76/95） and 24.0% （23/96）， respectively， with the treatment group showing superior efficacy （P＜0.01）. No significant differences were observed in routine blood tests， urinalysis， or liver function indices before and after treatment in either group （P＞0.05）. The incidence of adverse reactions was 8.4% （8/95） in the treatment group and 9.4% （9/96） in the control group， with no statistically significant difference （P＞0.05）. ConclusionQTG can effectively reduce UACR and blood glucose levels， alleviate clinical symptoms， and improve clinical efficacy in patients with early DKD with qi deficiency， blood stasis， and kidney deficiency syndrome. The treatment is well-tolerated and safe， with no significant impact on oxidative stress markers.

Objective To investigate the effect of diosgenin on the proliferation and apoptosis of breast cancer cells and its potential molecular mechanism. Methods The breast cancer cell line MCF-7 was treated with low, medium, and high doses of diosgenin, and cell proliferation was detected through the MMT method. Flow cytometry was used to detect cell apoptosis. Nuclear-cytoplasmic-protein separation method was applied to detect the subcellular localization of death associated protein (DAXX). qRT-PCR and Western blot were used to detect the expressions of DAXX and c-Jun N-terminal kinase pathway (JNK)-related proteins. Results Diosgenin considerably inhibited the proliferation of MCF-7 cells and promoted cell apoptosis in a concentration-dependent manner. Diosgenin can promote the movement of DAXX from nucleus into the cytoplasm. Diosgenin upregulated the expression of cell surface death receptor (Fas), increased the phosphorylation levels of JNK and mitogen activated protein kinase (p38), and activated the JNK/p38 signaling pathway with concentration dependence. Conclusion Diosgenin inhibits the proliferation and promotes the apoptosis of the breast cancer cell line MCF-7, whose mechanism may be related to the regulation of DAXX subcellular localization and the activation of JNK/p38 signaling pathway.

Objective:To investigate the feasibility of segmented total marrow and lymphoid irradiation(TMLI)using Helical TomoTherapy(HT)in adults,and to analyze the impact of positional errors in the treatment on the actually received dose.Methods:Imaging data from four adult patients with acute myeloid leukemia were treated at the First Medical Center of the Chinese PLA General Hospital between November 2022 and December 2024 were retrospectively selected.The prescribed dose was 12 Gy in 3 fractions,and the heights range of patient was from 162 to 178 cm.The planning target volume(PTV)included the entire bone marrow and lymphatic drainage regions.The mid-femur was used as the dividing landmark,and the segmented location of head-in first(upper segmentation)and foot-in first(lower segmentation)were adopted to design plan for each segmentation.The upper segmentation used helical tomotherapy,and the lower segmentation used tomo direct therapy.The dosimetric parameters of planning target volume,and organ at risk(OAR)included eye lens,testicles and lungs were analyzed.The located computed tomography(CT)images of patients were used to simulate the changes of dosimetric parameters of each planning target region and OAR when the positions of patients moved 3,5,10 and 15 mm to outside of rack aperture.The changes of dose distribution of connection region of upper and lower segmentation were further analyzed.Results:The segmented irradiation technique can better achieve the cover(95%)of whole target region of TMLI under the condition of protecting normal organs.Under the condition with different position errors,the cover rate of the most of target region significant decreased.The largest dose of right lens increased 9.272%than primary under the 5 mm position error,and that of left and right lens increased respectively 40.199%and 67.898%under the 10 mm position error,and the max dose and mean dose of testicles increased respectively 5.847%and 5.240%under the 3mm position error.The mean dose of whole lung increased all under the error at different grades,which increased 3.021%under the 10mm position error.The non-uniformity of dose distribution of connection region increased after the position error was introduced,and the largest variation range reached to 4 Gy.Conclusion:The technique of segmented radiotherapy of Helical Tomotherapy has feasibility for TMLI of adult.But the error of the position of patients can reduce the cover of target region,and decrease the control rate for target region,and can lead to the occurrences of excessive doses on eye lens,testicles,lung and other OAR at the same time,which can increase the probability of occurring OAR injury.It should be high pay attention in treatment and implementation.

Fracture healing is a complex process that necessitates the synergistic action of various cells and molecules. Macrophages play an indispensable and crucial regulatory role in the process of fracture repair, influencing stages such as inflammatory modulation, angiogenesis, and tissue remodeling. This article delves into the functional characteristics of macrophages and their roles at different stages of fracture healing. Additionally, it explores the impact of aging macrophages on the healing process. Furthermore, the potential of emerging therapies, such as hydrogel-based treatments and exosomes, in modulating macrophage responses is analyzed. This study provides a theoretical foundation for the development of innovative therapies aimed at enhancing the efficacy of fracture healing.

Objective To explore the influencing factors of poor prognosis after successful recanalization of symptomatic acute internal carotid artery occlusion(AICAO)by applying endovascular therapy(EVT)technology.Methods We made a retrospective analysis of the clinical and imaging data of 62 symptomatic AICAO patients.After collateral evaluation and recanalization therapy,we obtained flat CT and DSA images,together with the findings of the collateral circulation assessment.At 24.0±6.0 hours after surgery,head plain CT scans were reexamined,and at 14 days after surgery or at discharge,neurological function was assessed using the NIHSS scale.Using the modified Rankin scale,we assessed neurological function and prognosis over a 90-day period.Results Each of the 62 patients had a TICI grade of 2b or 3 and was successfully recanalized.On average,it took 124.36±66.31 minutes from puncture to recanalization.Two instances involved iatrogenic dissection,while twelve cases had intraoperative distal thrombus escape episodes.Of all the patients,32 ones(51.6％)had a fair prognosis,whereas 30 patients(48.4％)had a bad prognosis.The two patient groups differed significantly in the ASPECT score,preoperative NIHSS score,intraoperative balloon catheter usage,postoperative 24 hour and 14 days NIHSS score,postoperative 14 days neurological function,and all-cause mortality within 90 days(all P＜0.05).The best intervention threshold for preoperative NIHSS score was 11.5 points,and both the preoperative NIHSS score and intraoperative BGC utilization were independent predictors influencing poor outcome.Conclusion The preoperative NIHSS score and intraoperative BGC usage are independent predictors of 90-day poor prognosis in AICAO patients with symptomatic AICAO who underwent successful recanalization via endovascular therapy.

Objective To explore the influencing factors of poor prognosis after successful recanalization of symptomatic acute internal carotid artery occlusion(AICAO)by applying endovascular therapy(EVT)technology.Methods We made a retrospective analysis of the clinical and imaging data of 62 symptomatic AICAO patients.After collateral evaluation and recanalization therapy,we obtained flat CT and DSA images,together with the findings of the collateral circulation assessment.At 24.0±6.0 hours after surgery,head plain CT scans were reexamined,and at 14 days after surgery or at discharge,neurological function was assessed using the NIHSS scale.Using the modified Rankin scale,we assessed neurological function and prognosis over a 90-day period.Results Each of the 62 patients had a TICI grade of 2b or 3 and was successfully recanalized.On average,it took 124.36±66.31 minutes from puncture to recanalization.Two instances involved iatrogenic dissection,while twelve cases had intraoperative distal thrombus escape episodes.Of all the patients,32 ones(51.6％)had a fair prognosis,whereas 30 patients(48.4％)had a bad prognosis.The two patient groups differed significantly in the ASPECT score,preoperative NIHSS score,intraoperative balloon catheter usage,postoperative 24 hour and 14 days NIHSS score,postoperative 14 days neurological function,and all-cause mortality within 90 days(all P＜0.05).The best intervention threshold for preoperative NIHSS score was 11.5 points,and both the preoperative NIHSS score and intraoperative BGC utilization were independent predictors influencing poor outcome.Conclusion The preoperative NIHSS score and intraoperative BGC usage are independent predictors of 90-day poor prognosis in AICAO patients with symptomatic AICAO who underwent successful recanalization via endovascular therapy.

Objective:To investigate the feasibility of segmented total marrow and lymphoid irradiation(TMLI)using Helical TomoTherapy(HT)in adults,and to analyze the impact of positional errors in the treatment on the actually received dose.Methods:Imaging data from four adult patients with acute myeloid leukemia were treated at the First Medical Center of the Chinese PLA General Hospital between November 2022 and December 2024 were retrospectively selected.The prescribed dose was 12 Gy in 3 fractions,and the heights range of patient was from 162 to 178 cm.The planning target volume(PTV)included the entire bone marrow and lymphatic drainage regions.The mid-femur was used as the dividing landmark,and the segmented location of head-in first(upper segmentation)and foot-in first(lower segmentation)were adopted to design plan for each segmentation.The upper segmentation used helical tomotherapy,and the lower segmentation used tomo direct therapy.The dosimetric parameters of planning target volume,and organ at risk(OAR)included eye lens,testicles and lungs were analyzed.The located computed tomography(CT)images of patients were used to simulate the changes of dosimetric parameters of each planning target region and OAR when the positions of patients moved 3,5,10 and 15 mm to outside of rack aperture.The changes of dose distribution of connection region of upper and lower segmentation were further analyzed.Results:The segmented irradiation technique can better achieve the cover(95%)of whole target region of TMLI under the condition of protecting normal organs.Under the condition with different position errors,the cover rate of the most of target region significant decreased.The largest dose of right lens increased 9.272%than primary under the 5 mm position error,and that of left and right lens increased respectively 40.199%and 67.898%under the 10 mm position error,and the max dose and mean dose of testicles increased respectively 5.847%and 5.240%under the 3mm position error.The mean dose of whole lung increased all under the error at different grades,which increased 3.021%under the 10mm position error.The non-uniformity of dose distribution of connection region increased after the position error was introduced,and the largest variation range reached to 4 Gy.Conclusion:The technique of segmented radiotherapy of Helical Tomotherapy has feasibility for TMLI of adult.But the error of the position of patients can reduce the cover of target region,and decrease the control rate for target region,and can lead to the occurrences of excessive doses on eye lens,testicles,lung and other OAR at the same time,which can increase the probability of occurring OAR injury.It should be high pay attention in treatment and implementation.