Natural products are an important source for innovative drugs,but unclear molecular targets and mechanisms limit their further development and application.The authors proposed a new method for the target identification of natural products based on proteolysis-targeting chimera(PROTAC)technology and quantitative proteomics,and established the targeted degradomics(TGDO) technology for the identification of weak-affinity tar-gets.This article summarizes the standardized workflow and the application of TGDO for target identification of natural products.

BACKGROUND: The use of inserted sham acupuncture as a placebo in randomized controlled trials (RCTs) is controversial, because it may produce specific effects that cause an underestimation of the effect of acupuncture treatment. OBJECTIVE: This systematic survey investigates the magnitude of insert-specific effects of sham acupuncture and whether they affect the estimation of acupuncture treatment effects. SEARCH STRATEGY: PubMed, Embase and Cochrane Central Register of Controlled Trials were searched to identify acupuncture RCTs from their inception until December 2022. INCLUSION CRITERIA: RCTs that evaluated the effects of acupuncture compared to sham acupuncture and no treatment. DATA EXTRACTION AND ANALYSIS: The total effect measured for an acupuncture treatment group in RCTs were divided into three components, including the natural history and/or regression to the mean effect (controlled for no-treatment group), the placebo effect, and the specific effect of acupuncture. The first two constituted the contextual effect of acupuncture, which is mimicked by a sham acupuncture treatment group. The proportion of acupuncture total effect size was considered to be 1. The proportion of natural history and/or regression to the mean effect (PNE) and proportional contextual effect (PCE) of included RCTs were pooled using meta-analyses with a random-effect model. The proportion of acupuncture placebo effect was the difference between PCE and PNE in RCTs with non-inserted sham acupuncture. The proportion of insert-specific effect of sham acupuncture (PIES) was obtained by subtracting the proportion of acupuncture placebo effect and PNE from PCE in RCTs with inserted sham acupuncture. The impact of PIES on the estimation of acupuncture's treatment effect was evaluated by quantifying the percentage of RCTs that the effect of outcome changed from no statistical difference to statistical difference after removing PIES in the included studies, and the impact of PIES was externally validated in other acupuncture RCTs with an inserted sham acupuncture group that were not used to calculate PIES. RESULTS: This analysis included 32 studies with 5492 patients. The overall PNE was 0.335 (95% confidence interval [CI], 0.255-0.415) and the PCE of acupuncture was 0.639 (95% CI, 0.567-0.710) of acupuncture's total effect. The proportional contribution of the placebo effect to acupuncture's total effect was 0.191, and the PIES was 0.189. When we modeled the exclusion of the insert-specific effect of sham acupuncture, the acupuncture treatment effect changed from no difference to a significant difference in 45.45% of the included RCTs, and in 40.91% of the external validated RCTs. CONCLUSION The insert-specific effect of sham acupuncture in RCTs represents 18.90% of acupuncture's total effect and significantly affects the evaluation of the acupuncture treatment effect. More than 40% of RCTs that used inserted sham acupuncture would draw different conclusions if the PIES had been controlled for. Considering the impact of the insert-specific effect of sham acupuncture, caution should be taken when using inserted sham acupuncture placebos in RCTs. Please cite this article as: Luo XC, Liu JL, Yao MH, Chen YM, Fan AY, Liang FR, Zhao JP, Zhao L, Zhou X, Zhong XY, Yang JH, Li B, Zhang Y, Sun X, Li L. Specific effect of inserted sham acupuncture and its impact on the estimation of acupuncture treatment effect in randomized controlled trials: A systematic survey. J Integr Med. 2025; 23(6):630-640.
Acupuncture Therapy/methods* ; Humans ; Randomized Controlled Trials as Topic ; Placebo Effect ; Placebos ; Treatment Outcome

Alzheimer's disease(AD), a neurodegenerative disorder associated with aging, is the most prevalent form of dementia.As the aging population continues to expand, AD presents significant health and caregiving challenges for families and society, making it a pressing international public health concern.In recent years, numerous countries have implemented dementia prevention and treatment strategies that emphasize community-based comprehensive approaches.Currently, the community-based AD prevention and treatment model in China is still in the exploratory phase, with community efforts lacking organization.In alignment with China's action plan for advancing dementia prevention and treatment, and to achieve the strategic objective of "healthy aging, " this consensus is based on the principle of three-level prevention and is tailored to the characteristics of AD disease progression.It aims to develop a comprehensive prevention and treatment strategy for AD that is suitable for communities in China, providing technical guidance and support to establish a scientific basis for formulating community AD prevention and treatment models.

AIM To compare total sugar,total protein,total phenol,total flavonoid,calycosin-7-O-β-D-glucoside,liquiritin,lobetyolin,quercetin,isoferulic acid,hesperidin,glycyrrhizic acid contents and their antioxidant activities,hypoglycemic activities of big honey pill,small honey pill,water pill,concentrated pill,granule,mixture and decoction of Buzhong Yiqi Recipe.METHODS Anthraquinone-sulfuric acid method,Coomassie brilliant blue method,Folin-phenol colorimetry method,sodium nitrite-aluminum nitrate method and HPLC were adopted in the content determination of total sugar,total protein,total phenol,total flavonoid and seven constituents,respectively,after which the scavenging capacities,reducing powers on DPPH·free radical,ABTS+free radical,hydroxyl free radical,and inhibition capacity on α-glucosidase activity were detected.Subsequently,correlation analysis was performed.RESULTS Total sugar,total protein,total phenol and total flavonoid contents demonstrated significant differences among different dosage forms(P＜0.05,P＜0.01).Calycosin-7-O-β-D-glucoside,glycyrrhizin,codonoside and quercetin displayed the highest contents in the decoction,while those of isoferulic acid,hesperidin and glycyrrhizin were observable in the mixture.The water pill exhibited the strongest antioxidant activity,while those of the concentrated pill and mixture were weak;the big honey pill exhibited the strongest hypoglycemic activity,while that of the decoction was the weakest.Total protein,total phenol,total flavonoid and liquiritin contents displayed significant positive correlations between antioxidant activity(P＜0.05,P＜0.01),while hesperidin content displayed significant negative correlation between the latter(P＜0.05);total protein,calycosin-7-O-β-D-glucoside,codonoside and quercetin contents displayed significant negative correlations between hypoglycemic activity(P＜0.05,P＜0.01).CONCLUSION Active constituent contents and their biological activities of Buzhong Yiqi Recipe with different dosage forms exist differences,total sugar,total protein,total flavonoids,calycosin-7-O-β-D-glucoside,licorice glycoside,hesperidin,codonoside and quercetin can be taken as quality control indices for this prescription.

Natural products are an important source for innovative drugs,but unclear molecular targets and mechanisms limit their further development and application.The authors proposed a new method for the target identification of natural products based on proteolysis-targeting chimera(PROTAC)technology and quantitative proteomics,and established the targeted degradomics(TGDO) technology for the identification of weak-affinity tar-gets.This article summarizes the standardized workflow and the application of TGDO for target identification of natural products.

BACKGROUND:Induced resorption of herniated nucleus pulpous is a minimally invasive,non-invasive and innovative method for the treatment of cervical/lumbar intervertebral disc herniation.After induced resorption of herniated nucleus pulpous,the research about whether cervical/lumbar intervertebral disc can maintain the original biomechanical strength has not been reported.OBJECTIVE:To measure the height of adjacent vertebral centroid of cervical/lumbar intervertebral disc before and after induced resorption of herniated nucleus pulpous operation to analyze the changes of the biomechanical strength of the intervertebral disc after reclining and to provide a new basis for induced resorption of herniated nucleus pulpous treatment of cervical and lumbar intervertebral disc herniation.METHODS:A retrospective analysis was performed on 140 patients with cervical/lumbar intervertebral disc herniation who received induced resorption of herniated nucleus pulpous surgery in the First Affiliated Hospital of Zhengzhou University from January 2013 to January 2023.Related software was used to measure the height of adjacent vertebral centroid of cervical/lumbar intervertebral disc of patients at each follow-up time point before and after induced resorption of herniated nucleus pulpous surgery in Magnetic Resonance Imaging image data under Artificial Intelligence-assisted calibration.Unoperated T1/T2 and T12/L1 segments were taken respectively as controls.Those with preoperative height of adjacent vertebral centroid less than 8％of the corresponding T1/T2 or T12/L1 control segment were in the"height reduction group"(hereafter referred to as group A)and the rest were in the"height unchanged group"(hereafter referred to as group B).The difference of height of adjacent vertebral centroid before and after operation between the group A and the group B was statistically analyzed.Simultaneously,the correlation between the volume of cervical and lumbar herniated discs and the changes of height of adjacent vertebral centroid was analyzed according to the result measured by artificial intelligence.RESULTS AND CONCLUSION:(1)The study maintained a total of 140 patients,including 60 cases of cervical disc herniation and 80 cases of lumbar disc herniation.The postoperative follow-up period was 7 days to 12 months.(2)A total of 281 discs were measured in the cervical vertebra group,including 60 intervertebral discs in the control group.The mean value of height of adjacent vertebral centroid before and at the last postoperative follow-up was about 20.46 mm and 20.17 mm,respectively,with no statistical difference(P＞0.05).There were 162 cervical discs in group A.The average height of adjacent vertebral centroid before and after operation was 16.65 mm and 15.92 mm,respectively,with no statistically significant difference(P＞0.05).The mean cervical disc herniation volume before and after surgery was 510.28 mm3 and 364.76 mm3,respectively,which was not significantly correlated with height of adjacent vertebral centroid change(P＞0.05).There were 64 discs in the group B,with average of 20.15 mm before operation and 19.09 mm at the last follow-up,and there was no significant difference(P＞0.05).The mean volume of cervical disc herniation before and after surgery was 515.32 mm3 and 361.98 mm3,respectively,and there was no significant correlation with the change of height of adjacent vertebral centroid(P＞0.05).(3)A total of 258 discs were measured in the lumbar spine group,of which 80 intervertebral discs in the control group,the average height of adjacent vertebral centroid was 33.03 mm before operation and 32.40 mm at the last follow-up,and there was no significant difference.There were 59 discs in the group A,and the average height of adjacent vertebral centroid before and after operation was 30.08 mm and 31.67 mm,respectively,with no statistically significant difference.The mean volume of lumbar disc herniation before and after operation was 690.51 mm3 and 496.58 mm3,respectively,and there was no significant correlation with the change of height of adjacent vertebral centroid(P＞0.05).There were 119 discs in the group B,with an average height of adjacent vertebral centroid of 35.91 mm before surgery and 34.12 mm at the last follow-up.The mean volume of lumbar disc herniation before and after operation was 698.70 mm3 and 535.99 mm3,respectively,and there was no significant correlation with the change of height of adjacent vertebral centroid.(4)It is concluded that patients with cervical/lumbar intervertebral disc herniation can maintain the same intervertebral height level after induced resorption of herniated nucleus pulpous regardless of whether the intervertebral height has decreased before operation.It can be inferred that the resorption of the herniated disc does not affect its biomechanical strength.It suggests that induced resorption of herniated nucleus pulpous surgery should be performed before the intervertebral height of the degenerate segment has decreased.The induced resorption of herniated nucleus pulpous is more valuable to maintain the biomechanical strength of the resorptive disc.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective:To screen the optimal machine learning model for predicting the recurrence condition of hepatocellular carcinoma (HCC) at different time points post-surgery, based on the cutoff value of the Ki67 positive proliferation index condition calculated from recurrence-free survival and combined with various clinical features.Methods:retrospective study included initially treated patients with solitary HCC who underwent radical surgery at the Fifth Medical Center of the PLA General Hospital from January 2013 to March 2023. Data included general clinical data, preoperative laboratory parameters, and surgical pathology information about the subjects. The postoperative recurrence status was assessed by querying the medical record system or by telephone follow-up. The Ki67 positive index cutoff value was determined by the X-tile software based on the patient's recurrence-free survival status and time analysis. Survival rates were calculated using the Kaplan-Meier method, and survival curves were plotted. The study population was randomly divided into training and testing groups in a 7:3 ratio using a computer-generated random number method. The minimum redundancy maximum relevance (mRMR) method was used for feature variable selection. Predictive models for postoperative HCC recurrence conditions in patients with HCC were constructed using random forest, support vector machine, logistic regression, and gradient boosting decision tree machine learning algorithms. Inter-group comparisons for continuous data were performed using the t-test or Mann-Whitney U test. Inter-group comparisons of enumeration data were performed using the Pearson χ2 test, continuity-corrected χ2 test, or Fisher's exact test. Results:The cutoff values for the Ki67 positivity index were 0.3 and 0.5 in 510 cases, with a follow-up time ranging from 1.2 to 11.4 years (median: 6.2 years). The recurrence-free survival time was between 1 and 135 months (median: 32 months), with recurrence-free survival rates post-surgery at 1, 2, 3, and 5 years were 87.5%, 77.1%, 61.2%, and 54.5%, respectively. The top five variables predicted HCC recurrence and non-recurrence conditions following surgical follow-up at 6 months, 1 year, 2 years, and beyond 2 years, in accordance with information obtained by the mRMR screen out. The Ki67 positivity index screened a successfully constructed machine learning model to predict HCC recurrence and non-recurrence conditions following surgical follow-up at 6 months, 1 year, 2 years, and beyond 2 years. The machine learning model based on the gradient boosting decision tree algorithm had the best prediction performance among them (areas under the receiver operating characteristic curves for predicting HCC recurrence within six months in the training and validation sets were 0.996 and 0.946, and accuracies were 0.972 and 0.935, respectively).Conclusion:A machine learning model was successfully constructed using the Ki67 positivity index combined with four readily available clinical features to predict HCC recurrence. The machine learning model based on the gradient boosting decision tree algorithm demonstrated the best performance in terms of predicting HCC recurrence within six months after surgery.

Isoflavones which mainly distributed in leguminous plants have plenty of health benefits.Isoflavone synthase(IFS)is a membrane-associated cytochrome P450 enzyme(CYP450)which carries out the unique aryl-ring migration and hydroxylation.So far,few crystal structures of plant P450s have been obtained.We determined the crystal structure of IFS from Medicago truncatula at 1.9 ? by MAD method using a selenomethionine substituted crystal and conducted molecular docking and mutagenesis study.The structure of IFS complexed with imidazole exhibits the helix Ⅰa-loop-helix Ⅰβ motif which cor-responds to helix Ⅰ of other P450s.Compared with structures of common P450s,IFS/imidazole structure contains an extra domain,i.e.,the γ-domain.The structure reveals a homodimer in which the γ-domain of one molecule interacts with the β-domain of another.The plane of heme group makes an angle of ap-proximately 40° with the helix Ⅰa-loop-helix Ⅰβ motif.Molecular docking combined with mutagenesis study suggested that Trp-128 and Asp-300 might play important roles in substrate binding and recogni-tion.Phe-301,Ser-303 and Gly-305 from the helix Ⅰa-loop-helix Ⅰβ motif may play important roles in the aryl-ring migration.These novel structural features reveal insights into the unique reaction mechanism of IFS and provide a basis for engineering IFS in leguminous crops for health purpose.

BACKGROUND:With the continuous advancement of medical technology,the combination of oblique lumbar interbody fusion and percutaneous pedicle screw fixation has become a common method for treating lumbar degenerative diseases;however,there is still a lack of in-depth research on the relationship between changes in anterior convexity angles at different postoperative segments and fusion device settlement.OBJECTIVE:To explore the relationship between changes in anterior convexity angle of different segments and Cage subsidence after oblique lumbar interbody fusion combined with percutaneous pedicle screw fixation surgery.METHODS:Patients(93 cases)with lumbar degenerative diseases who underwent oblique lumbar interbody fusion combined with percutaneous pedicle screw fixation surgery in Weifang Hospital of Traditional Chinese Medicine from February 2019 to April 2023 were selected as the research subjects.According to the postoperative disc height loss value,they were divided into Cage subsidence group(25 cases,＞2 mm)and non-Cage subsidence group(68 cases,＜2 mm).Multiple Logistic regression analysis was used to analyze the risk factors for cage subsidence.Stepwise regression was utilized to evaluate the relationship of each risk factor and Cage subsidence.Risk prediction model was built and evaluated.RESULTS AND CONCLUSION:(1)After adjusting for confounding factors,there was still independent correlation between lumbar lordosis loss value and segmental lordosis improvement value and Cage subsidence risk(P＜0.05).(2)Age,oswestry disability index,disc height improvement value,segmental lordosis improvement value,and lumbar lordosis loss value were all independent influencing factors for the occurrence of Cage subsidence(P＜0.05).Among them,age,lumbar lordosis loss value,disc height improvement value,and segmental lordosis improvement value were most closely related to Cage subsidence.(3)The results of multivariate Logistic regression model analysis showed that when P=0.80,the Jordan index was the highest and the prediction effect was the best,with accuracy of 89.27％,sensitivity of 86.67％,and specificity of 89.89％.The model evaluation results showed that it had good discrimination and high accuracy.(4)As the lumbar lordosis loss value and segmental lordosis improvement value increase,the risk of Cage subsidence increases,which affects clinical efficacy.(5)It is indicated that age,lumbar lordosis loss value,disc height improvement value,and segmental lordosis improvement value are most closely related to Cage subsidence,and clinical doctors should pay more attention.