This article summarized the current status and challenges of manipulation therapy for musculoskeletal pain and its placebo effect in clinical trials, analyzing the impact of the placebo effect on the evaluation of therapeutic efficacy. The efficacy of different manual manipulation techniques remains uncertain, and the degree of blinding and patient expectations play a crucial role in efficacy assessment. The article suggested improving trial design through standardized placebo intervention design, comprehensive investigation of patient expectations and psychological states, rigorous training of practitioners, and optimized diagnostic and treatment scenarios and doctor-patient relationship, to ensure consistency between intervention and placebo groups. Specific measures include the application of the DITTO (Deconstruct, Identify, Take out, Think, Optimize) framework, the use of standardized questionnaire tools, and multi-center, large-sample randomized controlled trials to enhance the external validity and statistical power of research results, thereby providing more scientifically reliable evidence for clinical practice.

The placebo effect in manual therapy is analyzed, suggesting that it is not only a control tool in experiments but also a key to the success of manual therapy. By analyzing the impact of multiple dimensions of the placebo effect, such as psychological and social factors, behavioral responses, and expectation effects, on treatment outcomes, it is pointed out that the professional image of the therapist and the patients' positive expectations of the treatment are the core elements to activate the placebo effect. At the same time, individual differences in treatment responses are also emphasized as a crucial aspect that cannot be ignored. It is suggested to reposition the placebo effect, incorporate it into the overall framework of manual therapy, and further explore its mechanism to provide a theoretical basis for the scientific and precise development of manual therapy.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Abstract To understand the relationship between cardiovascular disease (CVD) and adverse childhood experiences (ACEs), the present review aims to describe the burden and influencing factors of CVD, epidemiological characteristics and burden of ACEs, current research on the relationship between ACEs and CVD, and the mechanism of ACEs leading to CVD. It is proposed that further assessment of the relationship is warranted through identifying blood biomarkers, conducting prospective cohort studies and intervention studies. Such efforts would provide valuable scientific insights for primary prevention strategies for cardiovascular disease.

Cerebral edema is characterized by fluid accumulation, and the glymphatic system (GS) plays a pivotal role in regulating fluid transport. Using the Tenecteplase system, magnesium salt of salvianolic acid B/ginsenoside Rg1 (SalB/Rg1) was injected intravenously into mice 4.5 h after middle cerebral artery occlusion and once every 24 h for the following 72 h. GS function was assessed by Evans blue imaging, near-infrared fluorescence region II (NIR-II) imaging, and magnetic resonance imaging (MRI). SalB/Rg1 had significant effects on reducing the infarct volume and hemorrhagic transformation score, improving neurobehavioral function, and protecting tissue structure, especially inhibiting cerebral edema. Meanwhile, the influx/efflux drainage of GS was enhanced by SalB/Rg1 according to NIR-II imaging and MRI. SalB/Rg1 inhibited matrix metalloproteinase-9 (MMP-9) activity, reduced cleaved β-dystroglycan (β-DG), and stabilized aquaporin-4 (AQP4) polarity, which was verified by colocalization with CD31. Our findings indicated that SalB/Rg1 treatment enhances GS function and attenuates cerebral edema, accompanying the regulation of the MMP9/β-DG/AQP4 pathway.
Animals ; Ginsenosides/administration & dosage* ; Brain Edema/etiology* ; Male ; Benzofurans/administration & dosage* ; Glymphatic System/diagnostic imaging* ; Mice ; Infarction, Middle Cerebral Artery/drug therapy* ; Aquaporin 4/metabolism* ; Disease Models, Animal ; Mice, Inbred C57BL ; Matrix Metalloproteinase 9/metabolism* ; Neuroprotective Agents/pharmacology* ; Depsides

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Objective To analyze the methodology and reporting quality of acupuncture related randomized controlled trials(RCTs)in order to provide a basis for improving the design and reporting of acupuncture studies.Methods Literatures on RCTs included in acupuncture were obtained from two systematic reviews of acupuncture studies.Two reviewers were selected independently according to the exclusion criteria,and RoB2.0,CONSORT statement and STRICTA criteria were used to evaluate the methodology and report quality.Results 95 literatures on acupuncture RCTs were included,including 51 in Chinese and 44 in English,involving 38 diseases and 54 outcome indicators.CONSORT declared that there were 8 items with high reporting rate,15 items with low reporting rate and 2 items with medium reporting rate in the evaluation.The STRICTA criteria included 8 items with high reporting rate,4 items with low reporting rate,and 4 items with medium reporting rate.As for RoB2.0 bias risk assessment,11.6%of the literature in the overall bias area that served as a summary was high risk,50.5%was likely risk,and 37.9%was low risk.Conclusion The current published RCTs research methodology and report quality evaluation are not high,the future research should improve the scientific and rigorous program design,to form a transparent and complete research report.

Objective:To investigate the factors influencing recurrence and metastasis and prognosis of early breast cancer patients after surgery and the significance of all-foci radiotherapy after recurrence and metastasis.Methods:A retrospective cohort study was conducted. A total of 554 patients with stage T 1-2N 0M 0 breast cancer after surgery who were admitted to Weihai Municipal Hospital, Cheeloo College of Medicine, Shandong University from January 2006 to January 2019 were collected. The clinicopathological features were compared between patients with and without recurrence and metastasis after surgery. Kaplan-Meier method was used to analyze the overall survival (OS) and disease-free survival (DFS) of patients. The univariate analysis of prognostic factors was conducted using log rank test, while the multivariate analysis was conducted using Cox proportional hazards model. Patients with recurrence and metastasis are grouped according to whether the recurrence and metastasis lesions had received radiotherapy, patients with radiotherapy for all recurrence and metastasis lesions were classified as the all-foci radiotherapy group, patients with radiotherapy for partial recurrence and metastasis lesions were classified as non-all-foci radiotherapy group, and patients without radiotherapy for all recurrence and metastasis lesions were classified as non-radiotherapy group. The OS and progression free survival (PFS) were compared between groups. Results:The 554 patients were (49±10) years old, including 56 patients (10.1%) with recurrence and metastasis after surgery. There were statistically significant differences in menopausal status, pathological type, differentiation degree, estrogen receptor or progesterone receptor expression, pathological stage, postoperative adjuvant chemotherapy, postoperative adjuvant radiotherapy, and postoperative adjuvant endocrine therapy (all P < 0.05). The 5-year OS and DFS were 96.9% and 95.9%, respectively. The multivariate Cox regression analysis showed that the high differentiation ( HR = 0.300, P = 0.011), no postoperative adjuvant radiotherapy ( HR = 0.097, P < 0.001) and no postoperative endocrine therapy ( HR = 0.421, P = 0.040) were independent risk factors for DFS. The high differentiation ( HR = 0.266, P = 0.003) and no postoperative adjuvant radiotherapy ( HR = 0.225, P = 0.003) were independent risk factors for OS. OS in all-foci radiotherapy group was better than that in non-all-foci radiotherapy group, and the difference was statistically significant ( χ2 = 6.73, P = 0.010), but there was no significant difference in PFS between the two groups ( χ2 = 3.51, P = 0.061). There was no statistically significant difference in OS and PFS between the all-foci radiotherapy group and the non-radiotherapy group (both P > 0.05). Conclusions:Menopausal status, pathological classification, differentiation degree, estrogen receptor or progesterone receptor expression, pathological stage, postoperative adjuvant chemotherapy, postoperative adjuvant radiotherapy, and postoperative adjuvant endocrine therapy may affect the occurrence of postoperative recurrence and metastasis in stage T 1-2N 0M 0 breast cancer patients after surgery. The prognosis of stage T 1-2N 0M 0 breast cancer patient with high differentiation, no postoperative adjuvant radiotherapy and no postoperative endocrine therapy is poor. The OS of early breast cancer patients with recurrence and metastasis may be prolonged by all-foci radiotherapy compared with non-all-foci radiotherapy.

Taking Xiaochaihu Decoction as an example,the application differences of classical prescriptions in modern medical context and Chinese medicine practice are compared and analyzed from the aspects of clinical application scope,understanding of pre-scription connotation,dosage specification,dosage form and decoction method.Strategies to solve the differences in efficacy are pro-posed:integrating the wisdom of classical prescriptions and reshaping the framework of Chinese medicine diagnosis and treatment;transforming the results of modern pharmacology and exploring the principles of classical prescriptions;controlling drug quality stand-ards and exploring new uses and dosages of classical prescriptions;keeping pace with the times in Chinese medicine decoction and strengthening management and control to ensure efficacy.It is believed that combining the essence of Chinese medicine with modern technology can make the application of classical prescriptions maintain traditional characteristics while meeting modern clinical require-ments.This can not only improve the adaptability of classical prescriptions to modern complex diseases,but also provide a reference for the modernization of traditional medicine.