Blinding assessment in clinical trials of traditional Chinese medicine: Exploratory principles and protocol.

As one of the key components of clinical trials, blinding, if successfully implemented, can help to mitigate the risks of implementation bias and measurement bias, consequently improving the validity and reliability of the trial results. However, successful blinding in clinical trials of traditional Chinese medicine (TCM) is hard to achieve, and the evaluation of blinding success through blinding assessment lacks established guidelines. Taking into account the challenges associated with blinding in the TCM field, here we present a framework for assessing blinding. Further, this study proposes a blinding assessment protocol for TCM clinical trials, building upon the framework and the existing methods. An assessment report checklist and an approach for evaluating the assessment results are presented based on the proposed protocol. It is anticipated that these improvements to blinding assessment will generate greater awareness among researchers, facilitate the standardization of blinding, and augment the blinding effectiveness. The use of this blinding assessment may further advance the quality and precision of TCM clinical trials and improve the accuracy of the trial results. The blinding assessment protocol will undergo continued optimization and refinement, drawing upon expert consensus and experience derived from clinical trials. Please cite this article as: Wang XC, Liu XY, Shi KL, Meng QG, Yu YF, Wang SY, Wang J, Qu C, Lei C, Yu XP. Blinding assessment in clinical trials of traditional Chinese medicine: Exploratory principles and protocol. J Integr Med. 2023; 21(6): 528-536.

Curcumol Exerts Antitumor Effect via Inhibiting EGFR-Akt-Mcl-1 Signaling.

Dysfunction of epidermal growth factor receptor (EGFR) signaling plays a critical role in the tumorigenesis of oral squamous cell carcinoma (OSCC). In the present study, the data analysis results of immunohistochemistry and the TCGA database verified that the expression of EGFR is significantly upregulated in OSCC tumor tissues, and depletion of EGFR inhibits the growth of OSCC cells in vitro and in vivo. Moreover, these results showed that the natural compound, curcumol, exhibited a profound antitumor effect on OSCC cells. Western blotting, MTS, and immunofluorescent staining assays indicated that curcumol inhibited cell proliferation and induced intrinsic apoptosis in OSCC cells via downregulating myeloid cell leukemia 1 (Mcl-1). A mechanistic study revealed that curcumol inhibited the EGFR-Akt signal pathway, which activated GSK-3[Formula: see text]-mediated Mcl-1 phosphorylation. Further research showed that curcumol-induced Mcl-1 Ser159 phosphorylation is required to disrupt the interaction between deubiquitinase JOSD1 and Mcl-1 and eventually induce Mcl-1 ubiquitination and degradation. In addition, curcumol administration can effectively inhibit CAL27 and SCC25 xenograft tumor growth and is well-tolerated in vivo. Finally, we demonstrated that Mcl-1 is upregulated and positively correlates with p-EGFR and p-Akt in OSCC tumor tissues. Collectively, the present results provide new insights into the antitumor mechanism of curcumol, identifying it as an attractive therapeutic agent that reduces Mcl-1 expression and inhibits OSCC growth. Targeting EGFR/Akt/Mcl-1 signaling could be a promising option in the clinical treatment of OSCC.

Predicting first session working alliances using deep learning algorithms: A proof-of-concept study for personalized psychotherapy.

OBJECTIVE: The aim of this proof-of-concept study is to develop a predictive model based on deep learning algorithms to predict working alliances after the first therapeutic session and to provide a basis for clinical decisions. METHODS: Using a sample of 325 patients and 32 psychotherapists from three university counseling centers, a deep learning algorithm known as fully connected neural networks (FCNNs) was adopted to construct data-driven predictive models. The performance differences between the model including only patient indicators and the model including both patient and therapist indicators were compared. The optimal model was further tested in a general hospital sample of 85 patients and 8 therapists. RESULTS: The model incorporating both patient indicators and therapist-level indicators (R²: 0.30 ± 0.02) performed better than the model incorporating only patient indicators (R²: 0.11 ± 0.02). The performance of this model decreased when being transferred to the independent general hospital sample, but still retained some predictive value (R² = 0.11). CONCLUSION: This study showed that the inclusion of therapist-level indicators can improve the performance of a predictive model in predicting working alliances. This model could assist clinical decisions on choosing psychotherapists for patients and may also initiate new possibilities for future research.

Right coronary artery-coronary sinus fistula diagnosed by three-dimensional echocardiography.

Right coronary artery-coronary sinus fistula is a very rare congenital anomaly in which a right coronary artery fistula drains into the right atrium, right ventricle, or pulmonary artery. A right coronary artery-coronary sinus fistula was diagnosed in a 44-year-old man by three-dimensional echocardiography and confirmed by computed tomography angiography and surgery. Relevant published experience in diagnosing this kind of anomaly is summarized.

Rupture of Aortic Sinus Aneurysms Diagnosed by Left Ventricular Opacification.

Rupture of aortic sinus aneurysms is a rare cardiac malformation that is commonly observed in the right coronary sinus but is rarely observed in the noncoronary sinus. Here, we report a case of aneurysm of the aortic sinus that ruptured into the left ventricular outflow tract and was diagnosed with left ventricular opacification. Left heart echocardiography can clearly demonstrate the structure of the heart and is one of the important diagnostic methods for diagnosing ruptured aortic sinus aneurysms. This observes the perfusion sequence of blood flow to clearly reveal the source, direction, and location of the ruptured aortic sinus aneurysm.

A Rare Case of Multiple Myxoma Involving Both Mitral Valve Leaflets.

Mitral valve myxoma is a very rare entity. Multiple myxomas with extensive involvement of the anterior and posterior leaflets of the mitral valve are exceedingly rare. We report a 58-year-old man who was admitted as sudden syncope. Thoracic echocardiography showed several masses adherent to the anterior and posterior leaflets and the mitral annulus with obvious mobility. Intraoperative probing revealed multiple tumors attached to the mitral annulus, valve leaflets, and tendinous cords. Mechanical mitral valve replacement was performed. Histopathological examination confirmed all tumors to be myxomas.

High peak power 2.8 µm Raman laser in a methane-filled negative-curvature fiber.

We demonstrate a 2.8 µm gas Raman laser in a methane-filled hollow-core negative-curvature fiber with average power of 113 mW, pulse energy of 113 µJ and estimated peak power of 9.5 MW. Raman quantum efficiency of 40% has been reached from the pump source at 1.064 µm to the 2nd order vibrational Stokes at 2.812 µm using 1.8 MPa methane gas. To our knowledge, this is the first high peak power fiber-based gas Raman laser in mid-infrared region and a range of applications in supercontinuum generation, laser surgery, molecular tracing and gas detection are in prospect.

Right-to-left shunt detection using contrast-enhanced transcranial Doppler: A comparison of provocation maneuvers between coughing and a modified Valsalva maneuver.

Contrast-enhanced transcranial Doppler (c-TCD) has been used to detect right-to-left shunts (RLS) because it is highly sensitive and cost-effective. The use of provocation maneuvers, such as physiologic maneuvers (e.g., coughing) and the Valsalva maneuver (VM) to transiently increase right atrial pressure and induce RLS increases the sensitivity of RLS detection. In this study, we sought to determine whether coughing is as effective as the VM in aiding the detection of RLS. We evaluated 162 subjects for RLS, using c-TCD under three different conditions: (i) resting state, (ii) coughing, and (iii) modified VM (m-VM), which involved blowing into a tube connected to a sphygmomanometer at 40 mmHg for 10 s. The positive rate of RLS detection with the m-VM was significantly higher than that with coughing. In addition, a difference between the two maneuvers was observed in terms of the degree of RLS seen. The m-VM should be widely used to detect RLS, because it is reliable, standardized, and cost-effective.

Synthesis and evaluation of adenosine containing 3-arylfuran-2(5H)-ones as tyrosyl-tRNA synthetase inhibitors.

Tyrosyl-tRNA synthetase (TyrRS) is an aminoacyl-tRNA synthetase family protein that possesses an essential role in bacterial protein synthesis. The synthesis, structure-activity relationship, and evolution of a novel series of adenosine-containing 3-arylfuran-2(5H)-ones as TyrRS inhibitors are described. Advanced compound d3 from this series exhibited excellent affinity for TyrRS with IC50 of 0.61 ± 0.04 µM. Bacterial growth inhibition assays demonstrated that d3 showed submicromolar antibacterial potency against Escherichia coli and Pseudomonas aeruginosa, and compared to the marketed antibiotics ciprofloxacin.

A case of familial Carney complex.

Carney complex is a syndrome characterized by skin pigmentation abnormalities, myxomas, endocrine tumors/overactivity, and schwannomas. It is caused by a mutation in the PRKAR1A gene that encodes the enzyme protein kinase A regulatory subunit type 1 alpha. A 23-year old male was diagnosed with Carney complex on the basis of spotty skin lentigines on his face and lips, multiple thyroid neoplasms, a right ventricular myxoma, and bilateral testicular tumors. A total bilateral orchectomy was performed and the pathological findings revealed Leydig's cell tumors on one side and a Sertoli cell tumor on the other side. When his first-degree relatives were examined, his mother was found to have Carney complex as well. This is the first reported case of familial Carney complex in China.

[Construction and expression of pir-b gene lentiviral vector].

The purpose of this research was to construct a lentiviral vector containing pir-b gene, and to detect the expression of pir-b gene in 293T cells. The open reading frame (ORF) of pir-b gene from the mRNA of mouse was cloned, then inserted into a sequencing vector. The pir-b gene was subcloned into the transfer plasmid of the lentivirus system, which was transfected together with the packaging plasmids into 293T cells by Lipofectin 2000, thereafter, the supernatant was collected and concentrated to transfect 293T cells. Western blot was used to detect the expression of the exogenous PIR-B after 293T cells were infected by the virus, while the lentivirus harboring egfp gene was packaged as the control group. The result indicated that the ORF of the pir-b gene was successfully cloned, the sequence of which was consistent to that was expected and the PIR-B protein could be expressed in 293T cells normally. It is concluded that the lentiviral vector containing pir-b gene was constructed successfully, which would contribute to illustrating the important role of pir-b gene in the immunological regulation.

Relationship and significance between anti-beta2-glycoprotein I antibodies and platelet activation state in patients with ulcerative colitis.

AIM: To study the relationship between anti-beta2-glycoprotein I (abeta2GPI) antibodies and platelet activation state in patients with ulcerative colitis (UC) and its significance. METHODS: Peripheral blood samples were collected from 56 UC patients (34 males and 22 females, aged 43.5 years, range 21-66 years), including 36 at active stage and 20 at remission stage, and 25 sex-and age-matched controls. The level of abeta2GPI was measured by ELISA. The platelet activation markers, platelet activation complex-I (PAC-I) and P-selectin (CD62P) were detected by flow cytometry. RESULTS: The A value for IgG abeta2GPI in the active UC group was 0.61 +/- 0.13, significantly higher than that in the remittent UC and control groups (0.50 +/- 0.13 and 0.22 +/- 0.14, P < 0.01). There was a significant difference between the two groups (P < 0.01). The A value for IgM abeta2GPI in the active and remittent UC groups was 0.43 +/- 0.13 and 0.38 +/- 0.12, significantly higher than that in the control group (0.20 +/- 0.12, P < 0.01). However, there was no significant difference between the two groups (P > 0.05). The PAC-I positive rate for the active and remittent UC groups was 30.6% +/- 7.6% and 19.6% +/- 7.8% respectively, significantly higher than that for the control group (6.3% +/- 1.7%, P < 0.01). There was a significant difference between the two groups (P < 0.01). The CD62P positive rate for the active and remittent UC groups was 45.0% +/- 8.8% and 31.9% +/- 7.8% respectively, significantly higher than that for the control group (9.2% +/- 2.7%, P < 0.01). There was a significant difference between the two groups (P < 0.01). In the active UC group, the more severe the state of illness was, the higher the A value for IgG abeta2GPI was, and the positive rate for PAC-I and CD62P was positively correlated with the state of illness (Fabeta2GPI = 3.679, P < 0.05; FPAC-I (%) = 5.346, P < 0.01; and FCD62P (%) = 5. 418, P < 0.01). Meanwhile, in the same state of illness, the A value for IgG abeta2GPI was positively correlated to the positive rates for PAC-I and CD62P. CONCLUSION: abeta2GPI level, platelet activation state and their relationship of them are closely correlated with the pathogenesis and development of UC.

[In situ raman spectroscopic study on the oxidation of HCHO on a roughened platinum electrode].

The electrooxidation behavior of HCHO on a roughened platinum electrode was studied by cyclic voltammetry. Two factors that influence the electrooxidation behavior of HCHO, i.e. the concentration of the supporting electrolyte and the structure of the electrode surface were taken into account. The dissociative adsorption behavior of HCHO on a roughened platinum electrode was investigated by confocal microprobe Raman spectroscopy in-situ, and the spontaneous dissociative adsorption behavior of HCHO on a roughened platinum electrode was found by CV and was confirmed at the molecule level by in-situ Raman spectra.

Studies on specific interaction of beta-2-glycoprotein I with HBsAg.

AIM: To observe the binding activity of beta-2-glycoprotein I(beta(2)GPI) to hepatitis B surface antigen (HBsAg) and the possible roles of beta(2)GPI in hepatitis B virus (HBV) infection. METHODS: The rationale of ELISA methods and ELISA-based research method and ligand-blotting technique were used to detect the specific interaction of beta(2)GPI with HBsAg. RESULTS: With the increase of rHBsAg, the binding of beta(2)GPI to rHBsAg elevated, and these changes had statistic significance. When we added non- biotinlyated beta(2)GPI, the OD value significantly decreased though they still were positively relevant to rHBsAg, suggesting non- biotinlyated beta(2)GPI competed with biotinlyated beta(2)GPI to saturate the binding sites on rHBsAg. Meanwhile BSA was used as negative control to substitute for rHBsAg coating the plates. The results indicated no interaction between beta(2)GPI and BSA, suggesting the affinity of beta(2)GPI to rHBsAg was specific. The ligand blotling indicated that beta(2)GPI might bind to rHBsAg no matter whether it was under reduced condition or not. CONCLUSION: The binding of beta(2)GPI to HBsAg suggests that beta(2)GPI may be a carrier of HBV and that beta(2)GPI may play important roles in HBV infection.