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

Amoenucles A-F (1-6), six previously undescribed nucleoside derivatives, and two known analogs (7 and 8) were isolated from the culture of Aspergillus amoenus TJ507. Their structures were elucidated through spectroscopic analysis, single-crystal X-ray crystallography, and chemical reactions. Notably, 3 and 4 represent the first reported instances of nucleosides with an attached pyrrole moiety. Of particular significance, the absolute configuration of the sugar moiety of 1-4 was determined using nuclear magnetic resonance (NMR), electric circular dichroism (ECD) calculations, and a hydrolysis reaction, presenting a potentially valuable method for confirming nucleoside structures. Furthermore, 1, 2, and 5-8 exhibited potential tumor necrosis factor α (TNF-α) inhibitory activities, which may provide a novel chemical template for the development of agents targeting autoimmune and inflammatory diseases.
Aspergillus/chemistry* ; Tumor Necrosis Factor-alpha/antagonists & inhibitors* ; Molecular Structure ; Nucleosides/isolation & purification* ; Crystallography, X-Ray ; Animals ; Humans ; Mice ; Magnetic Resonance Spectroscopy

OBJECTIVE: The study aim was to investigate the effects of exposure to multiple environmental organic pollutants on cardiopulmonary health with a focus on the potential mediating role of oxidative stress. METHODS: A repeated-measures randomized crossover study involving healthy college students in Beijing was conducted. Biological samples, including morning urine and venous blood, were collected to measure concentrations of 29 typical organic pollutants, including hydroxy polycyclic aromatic hydrocarbons (OH-PAHs), bisphenol A and its substitutes, phthalates and their metabolites, parabens, and five biomarkers of oxidative stress. Health assessments included blood pressure measurements and lung function indicators. RESULTS: Urinary concentrations of 2-hydroxyphenanthrene (2-OH-PHE) ( β = 4.35% [95% confidence interval ( CI): 0.85%, 7.97%]), 3-hydroxyphenanthrene ( β = 3.44% [95% CI: 0.19%, 6.79%]), and 4-hydroxyphenanthrene (4-OH-PHE) ( β = 5.78% [95% CI: 1.27%, 10.5%]) were significantly and positively associated with systolic blood pressure. Exposures to 1-hydroxypyrene (1-OH-PYR) ( β = 3.05% [95% CI: -4.66%, -1.41%]), 2-OH-PHE ( β = 2.68% [95% CI: -4%, -1.34%]), and 4-OH-PHE ( β = 3% [95% CI: -4.68%, -1.29%]) were negatively associated with the ratio of forced expiratory volume in the first second to forced vital capacity. These findings highlight the adverse effects of exposure to multiple pollutants on cardiopulmonary health. Biomarkers of oxidative stress, including 8-hydroxy-2'-deoxyguanosine and extracellular superoxide dismutase, mediated the effects of multiple OH-PAHs on blood pressure and lung function. CONCLUSION Exposure to multiple organic pollutants can adversely affect cardiopulmonary health. Oxidative stress is a key mediator of the effects of OH-PAHs on blood pressure and lung function.
Humans ; Oxidative Stress/drug effects* ; Male ; Cross-Over Studies ; Female ; Young Adult ; Environmental Pollutants/toxicity* ; Environmental Exposure/adverse effects* ; Biomarkers/blood* ; Adult ; Blood Pressure/drug effects* ; Polycyclic Aromatic Hydrocarbons/urine* ; Beijing

Cancer brings about an enormous threat to human health,making the exploration of its mechanisms and therapeutic strategies a current focal point and challenge in research.Bacteriophages are integral components of the human microbiome,and studies have shown their influences on tumor growth and metastasis and their pivotal role in cancer treatment.This article elucidates the mechanisms by which bacteriophages impact the occurrence and development of cancer from their interactions with cancer cells,effects on bacteria,and influence on the immune system.Additionally,it explores bacteriophage-based strategies in cancer treatment and their potential in this field.This article aims to bring new thoughts and insights to the research in this field.
Humans ; Bacteriophages ; Microbiota ; Neoplasms/therapy* ; Phage Therapy

OBJECTIVE: To investigate the effect of zedoarondiol on neovascularization of atherosclerotic (AS) plaque by exosomes experiment. METHODS: ApoE^-/- mice were fed with high-fat diet to establish AS model and treated with high- and low-dose (10, 5 mg/kg daily) of zedoarondiol, respectively. After 14 weeks, the expressions of anti-angiogenic protein thrombospondin 1 (THBS-1) and its receptor CD36 in plaques, as well as platelet activation rate and exosome-derived miR-let-7a were detected. Then, zedoarondiol was used to intervene in platelets in vitro, and miR-let-7a was detected in platelet-derived exosomes (Pexo). Finally, human umbilical vein endothelial cells (HUVECs) were transfected with miR-let-7a mimics and treated with Pexo to observe the effect of miR-let-7a in Pexo on tube formation. RESULTS: Animal experiments showed that after treating with zedoarondiol, the neovascularization density in plaques of AS mice was significantly reduced, THBS-1 and CD36 increased, the platelet activation rate was markedly reduced, and the miR-let-7a level in Pexo was reduced (P<0.01). In vitro experiments, the platelet activation rate and miR-let-7a levels in Pexo were significantly reduced after zedoarondiol's intervention. Cell experiments showed that after Pexo's intervention, the tube length increased, and the transfection of miR-let-7a minics further increased the tube length of cells, while reducing the expressions of THBS-1 and CD36. CONCLUSION Zedoarondiol has the effect of inhibiting neovascularization within plaque in AS mice, and its mechanism may be potentially related to inhibiting platelet activation and reducing the Pexo-derived miRNA-let-7a level.
Animals ; MicroRNAs/genetics* ; Exosomes/drug effects* ; Plaque, Atherosclerotic/genetics* ; Neovascularization, Pathologic/genetics* ; Human Umbilical Vein Endothelial Cells/metabolism* ; Humans ; Blood Platelets/drug effects* ; Apolipoproteins E/deficiency* ; Thrombospondin 1/metabolism* ; CD36 Antigens/metabolism* ; Platelet Activation/drug effects* ; Male ; Mice ; Mice, Inbred C57BL

OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

Fifty whitespotted bamboo sharks (Chiloscyllium playgiosum) of both sexes were used to establish a large capacity variable domain of the new antigen receptor (VNAR) library with a total capacity of over 10⁹ colony-forming units (CFU). It was applied to screen VNARs against human serum albumin (HSA) and human transcription factor EB (TFEB), respectively. Meanwhile, VNAR libraries specific to HSA and TFEB with capacities above 10⁸ CFU were obtained following conventional immunization. These two approaches were systematically studied in terms of VNAR yield and composition. By comparing the VNAR sequences obtained from naïve and antigen-immunized libraries, we found that the complementary-determining region 3 (CDR3) of the former differs in composition from that of the latter. It shares a higher degree of homology with the naïve library. Meanwhile, the binding efficiency assessed by ELISA is also different between the naïve and antigen-immunized libraries. The binding of VNARs from the TFEB-immunized library appeared to surpass that observed with the naïve libraries, whereas the performance of VNARs from the HSA-immunized library indicated that both the immunized and naïve libraries for HSA had positive binding responses in polyclonal and monoclonal ELISA. The results are useful to develop novel diagnostic and therapeutic products based on shark VNARs.

Objective:To discuss the correlation of International Society of Urological Pathology (ISUP) pathological grading with 18F-prostate specific membrane antigen (PSMA)-1007 positron emission tomography-computed tomography (PET/CT) parameters and serum total prostate specific antigen (tPSA) in prostate cancer, and assess the clinical value of PET/CT combined with tPSA in predicting the ISUP pathological grade of prostate cancer. Methods:The correlation of ISUP pathological grade with primary parameters of PET/CT images and serum tPSA of 117 patients diagnosed with prostate cancer at Shanxi Cancer Hospital from August 2018 to February 2023 and taken 18F-PSMA-1007 PET/CT imaging were retrospectively analyzed. Univariate and multivariate logistic regressions were used to identify the independent influencing factors for ISUP pathological grading of prostate cancer. The receiver operating characteristic (ROC) curves were used to predict the efficacy between the high and low ISUP grades for prostate cancer. Results:Of the 117 patients, 20 were in ISUP Group 1, 25 in Group 2, 18 in Group 3, 32 in Group 4, and 22 in Group 5. Of these, 63 were in the low-grade group (Groups 1-3) and 54 were in the high-grade group (Groups 4-5). The tumor long diameter was 3.10 (2.05, 4.25) cm, the prostate volume was 40.11 (33.13, 51.85) cm 3, the serum tPSA was 19.71 (12.25, 42.83) ng/ml, the prostate specific antigen density (PSAD) was 0.51 (0.31, 1.01) ng·ml -1·cm -3, the maximum standard uptake value of the lesion (SUVmax) was 15.24 (10.87, 22.03), and the tumor/spleen uptake ratio (TSR) was 1.61 (1.08, 2.15) in the 117 patients. The correlation analysis displayed that the SUVmax, TSR, and tPSA were positively correlated with ISUP groups ( r=0.640, 0.619, and 0.500, P＜0.01). The differences among SUVmax, TSR, long diameter, tPSA, and PSAD were statistically significant when compared among the five ISUP groups ( H=48.98, 45.63, 26.82, 33.95, and 23.81, P＜0.001). The differencesin serum tPSA ( z=5.19), PSAD ( z=4.64), long diameter ( z=3.19), SUVmax ( z=5.57), and TSR ( z=5.53) of the patients between the low-grade group and the high-grade group were statistically significant ( P＜0.01). In multivariate analysis, TSR ( OR=4.172, 95% CI: 2.095-8.308, P＜0.001) and the serum tPSA ( OR=1.042, 95% CI: 1.014-1.070, P＜0.01) were independent influencing factors for ISUP grades. ROC analysis revealed that the area under the curve for the 18F-PSMA-1007 PET/CT parameters SUVmax and TSR to predict low- or high-grade ISUP for prostate cancer was 0.800 (95% CI: 0.717-0.883) and 0.797 (95% CI: 0.713-0.881), respectively. Among the 70 patients who underwent radical prostatectomy, the postoperative recurrence rate of high-grade ISUP patients was higher than that of low-grade patients (54.8% and 25.6%, χ 2=6.21, P＜0.05). Conclusions:18F-PSMA-1007 PET/CT has good application in predicting ISUP grading of prostate cancer. TSR and the serum tPSA are independent predictors for the pathological grade.

Objective:To discuss the correlation of pathologic findings after radical prostatectomy and preoperative 18F-PSMA-1007 PET/CT parameters with the prognosis of patients with prostate cancer. Methods:A retrospective case series study was conducted. The clinicopathological data of 48 patients with prostate cancer who underwent radical prostatectomy in Shanxi Province Cancer Hospital between January 2019 and August 2023 were retrospectively analyzed. All patients underwent 18F-PSMA-1007 PET/CT imaging before surgery. The age, the preoperative serum total prostate-specific antigen (tPSA), prostate-specific antigen density (PSAD), prostate volume, tumor diameter, TNM staging, the pathologic data after radical prostatectomy [International Society of Urological Pathology (ISUP) grade, resection margin status, nerve invasion], and preoperative maximum standard uptake value (SUV max) were collected. The receiver operating characteristic (ROC) curves were used to evaluate the efficacy of PET/CT parameter SUV max in predicting tumor recurrence after prostate cancer surgery. The recurrence-free survival (RFS) was analyzed by using the Kaplan-Meier method and log-rank test was performed. Cox proportional risk model was used to analyze the factors influencing RFS after radical prostatectomy. Results:All 48 patients were acinar adenocarcinoma. The median level of the patients' serum tPSA was 19.16 (10.50, 30.99) ng/ml; the median prostate volume was 36.20 (31.83, 45.48) ml; the median tumor diameter was 2.80 (1.60, 4.00) cm; the median PSAD was 0.48 (0.31,1.02) ng·ml -1·cm -3. The primary SUV max of prostate cancer was 13.61 (8.10, 20.20) . Of the 48 patients, 1 case died of heart disease and 1 case died of COVID-19 within 3 to 6 months after surgery, and the rest 46 patients were analyzed for prognosis. Among 46 cases, 26 were in the ISUP low-grade group and 20 were in the high-grade group; 17 were positive and 29 were negative for nerve invasion; 7 were positive and 39 were negative for margin status. The median follow-up time was 18.5 (8-64) months. There were 30 recurrence-free patients and 16 recurrent patients by the follow-up in April 2024. The median RFS time was 15 months; and there were statistically significant differences in RSF among the ISUP high-grade and low-grade groups, preoperative SUV max ≥ 16.77 and < 16.77 groups, positive and negative resection margin groups (all P < 0.01). SUV max was positively correlated with ISUP pathological grade and tPSA level ( r value was 0.634, 0.584, respectively; both P < 0.01). The differences in preoperative serum tPSA level, PSAD, tumor diameter, and SUV max were statistically significant between the ISUP low-grade group and the high-grade group (all P < 0.01); the differences in preoperative serum tPSA, PSAD, and tumor diameter were statistically significant between the nerve invasion positive group and nerve invasion negative group (all P < 0.01); the differences in preoperative serum tPSA, PSAD, tumor diameter, and SUV max between patients with positive resection margins or not were not statistically significant (all P > 0.05). Multivariate Cox regression analysis showed that the tumor resection margin status (negativity vs. positivity: HR = 7.82,95% CI: 1.97-31.07, P < 0.01), ISUP pathological grade (low grade vs. high grade: HR = 4.34,95% CI:1.21-15.62, P < 0.05), and the preoperative SUV max (<16.77 vs. ≥ 16.77: HR = 4.18, 95% CI:1.36-12.85 , P < 0.05) were independent influencing factors for RFS in patients with prostate cancer after radical prostatectomy. Conclusions:Pathological grading after radical prostatectomy and the preoperative 18F-PSMA-1007 PET/CT parameters are associated with the prognosis of patients with prostate cancer.

To investigate the pathogenic mechanisms of a patient with type 1 diabetes mellitus (T1DM) complicated with fibrocalculous pancreatic diabetes at Tianjin Medical University General Hospital Airport Site in June 2024, clinical and genetic characteristic analyses were performed. Potential pathogenic genes were screened by whole-exome sequencing (WES), and Sanger sequencing validated the identified genetic variants within the family. The proband exhibited elevated blood glucose levels and positivity for tyrosine phosphatase antibodies, suggesting a diagnosis of T1DM. Multiple calcifications in the pancreas were observed in the proband. Genetic testing revealed that the proband carried two variants in the serine peptidase inhibitor Kazal type 1 (SPINK1) gene, namely, c.194+2T>C and c.-215G>A. According to the American College of Medical Genetics and Genomics (ACMG) guidelines, the c.194+2T>C mutation is preliminarily classified as pathogenic, while the c.-215G>A variant is classified as a variant of uncertain significance (VUS). Bioinformatics analysis indicated that the c.194+2T>C variant in the SPINK1 gene results in a truncated protein, affecting the three-dimensional structure and activity of the protein. This mutation is in complete linkage disequilibrium with the c.-215G>A variant, which may have a protective function and influence the clinical phenotype. Given that the patient also has T1DM and FCPD, there should be increased awareness of the co-occurrence of both types of diabetes to prevent misdiagnosis and underdiagnosis.