It has been proposed by Basic Questions On Proper Therapies for Different Diseases Geographically （《素问·异法方宜论篇》） that "wei （痿） diseases should be treated by Daoyin （导引）". Furthermore， it is clarified that the indications of Daoyin are those conditions related to spleen and dampness caused by dampness pathogen， excessive food intake and less exercise， and mainly manifested as heavy limbs， fatigue and flaccidity， which is similar to the metabolic imbalance in the early stage of glucose or lipid metabolism disorder in modern medicine. Based on modern clinical and basic research evidence， Daoyin can inhibit the response of inflammation， alleviate oxidative stress， regulate intestinal microbiota， and modulate gene expression to improve metabolic abnormalities， and this will provide ideas for researches on the indications of Daoyin.

Objective: To investigate the symptoms of depression and anxiety and their influencing factors in adolescents undergoing facial scar plasty, so as to provide insights into psychological interventions among them. Methods: The patients with facial scars who were 14 to 25 years old and admitted to the Department of Plastic Surgery, Hospital of Dermatology Chinese Academy of Medical Sciences and Peking Union Medical College were selected. General information and scar condition were collected through questionnaire surveys. Symptoms of depression and anxiety were assessed using the Self-rating Depression Scale (SDS) and Self-rating Anxiety Scale (SAS). The patients who scored 50 points and over in both SDS and SAS were identified as having depression and anxiety symptoms. Factors affecting depression and anxiety symptoms were identified using a multivariable logistic regression model. Results: A total of 108 adolescents undergoing facial scar plasty were surveyed, with a mean age of (19.16±2.03) years. There were 50 boys (46.30%) and 58 girls (53.70%). Depression and anxiety symptoms were detected in 62 cases, accounting for 57.41%. Multivariable logistic regression analysis showed that girls (OR=1.547, 95%CI: 1.072-2.231), unhealthy diet (OR=1.428, 95%CI: 1.120-1.820), high scores of pain (OR=1.677, 95%CI: 1.120-2.511) and high scores of scar severity (OR=1.629, 95%CI: 1.112-2.387) were associated with increased risks of depression and anxiety symptoms in adolescents undergoing facial scar plasty, while high scores of social support (OR=0.569, 95%CI: 0.348-0.931) and high scores of resilience (OR=0.465, 95%CI: 0.252-0.858) were associated with decreased risks. Conclusion Depression and anxiety symptoms are relatively prevalent in adolescents undergoing facial scar plasty, and are influenced by gender, diet, pain degree, scar severity, social support and resilience.

Objective To evaluate the effects of triple therapy combined with betahistine on cerebral blood circulation and cutaneous sympathetic response (SSR) in patients with residual dizziness after reposition of benign paroxysmal positional vertigo. Methods A total of 196 patients with residual dizziness after reposition of benign paroxysmal positional vertigo were randomly divided into two groups, with 98 cases in each group. Control group was treated with betahistine, while experimental group was treated with betahistine and triple therapy (compound manipulation, transcranial magnetic stimulation and specific body position), and both groups were treated for 2 courses of treatment, with 7 days as a course of treatment. Efficacy, duration of residual dizziness, the scores of the Dizziness Handicap Inventory (DHI), the Visual Analogue Scale (VAS), the Activity Balance Confidence (ABC), the Hamilton Anxiety Scale (HAMA) and the Vestibular Symptom Index (VSI) before treatment and after the course of the treatment, SSR, and values of mean blood flow velocity (V_m) of cerebral vertebral artery (VA) and basilar artery (BA) were compared between the two groups. Results The duration of residual dizziness in the experimental group was (10.25±3.74) days, which was significantly shorter than (15.26±2.98) days in the control group (P < 0.001); the total treatment effective rate of the experimental group was 93.88%, which was significantly higher than 79.59% of the control group (P < 0.05). At the end of the course, the scores of the three dimensions of the DHI in the experimental group were significantly lower than those in the control group (P < 0.05). At the end of the course, the VAS, the HAMA and the VSI scores in the experimental group were significantly lower than those in the control group, while the ABC score was significantly higher than that in the control group (P < 0.05). At the end of the course, the SSR amplitude value in the experimental group was significantly lower than that in the control group, while the SSR latency value was significantly higher than that in the control group (P < 0.05). At the end of the course, the values of V_m of VA and BA in the experimental group were significantly higher than those in the control group (P < 0.05). Conclusion The combination of triple therapy and betahistine has a definite therapeutic effect on residual dizziness after reposition of benign paroxysmal positional vertigo, which can alleviate dizziness and vestibular symptoms, enhance activity balance confidence, relieve anxiety degree, and improve SSR and cerebral blood circulation.

The well-known insulin-like growth factor 1 (IGF1)/IGF-1 receptor (IGF-1R) signaling pathway is overexpressed in many tumors, and is thus an attractive target for cancer treatment. However, results have often been disappointing due to crosstalk with other signals. Here, we report that IGF-1R signaling stimulates the growth of hepatocellular carcinoma (HCC) cells through the translocation of IGF-1R into the ER to enhance sarco-endoplasmic reticulum calcium ATPase 2 (SERCA2) activity. In response to ligand binding, IGF-1Rβ is translocated into the ER by β-arrestin2 (β-arr2). Mass spectrometry analysis identified SERCA2 as a target of ER IGF-1Rβ. SERCA2 activity is heavily dependent on the increase in ER IGF-1Rβ levels. ER IGF-1Rβ phosphorylates SERCA2 on Tyr⁹⁹⁰ to enhance its activity. Mutation of SERCA2-Tyr⁹⁹⁰ disrupted the interaction of ER IGF-1Rβ with SERCA2, and therefore ER IGF-1Rβ failed to promote SERCA2 activity. The enhancement of SERCA2 activity triggered Ca²⁺_ER perturbation, leading to an increase in autophagy. Thapsigargin blocked the interaction between SERCA2 and ER IGF-1Rβ and therefore SERCA2 activity, resulting in inhibition of HCC growth. In conclusion, the translocation of IGF-1R into the ER triggers Ca²⁺_ER perturbation by enhancing SERCA2 activity through phosphorylating Tyr⁹⁹⁰ in HCC.

Objective:To investigate the application value of the Nottingham Hip Fracture Score (NHFS) in China and establish a formula specifically designed to assess the risk for 30-day mortality after surgery for hip fracture patients in China.Methods:A retrospective study was conducted to analyze the clinical data of 824 hip fracture patients who had been treated at Department of Orthopaedics, The First Hospital Affiliated to Zhengzhou University from August 2019 to May 2022. There were 312 males and 512 females with a median age of 73 (63, 82) years. The clinical data were compared between patients with different survival outcomes. The 30-day mortality was calculated by the formula according to the patients' NHFS, and compared with the actual one to validate the effectiveness of the original prediction model. The patients were divided into a training group ( n=577) and a validation group ( n=247). Binary logistic regression analysis was performed to establish a new prediction model for the patients in the training group. The discrimination, calibration, and clinical effectiveness of the predictive model were assessed in both the training and validation groups. Results:Multivariate logistic regression analysis showed that advanced age (≥86 years old) ( OR=3.775, 95% CI: 1.099 to 12.972, P=0.035), male ( OR=3.151, 95% CI: 1.574 to 6.306, P=0.001), admission hemoglobin concentration ≤100 g/L ( OR=2.402, 95% CI: 1.189 to 4.850, P=0.015), dependence on others for care before admission ( OR=2.673, 95% CI: 1.298 to 5.505, P=0.008), and comorbidities ≥2 ( OR=4.988, 95% CI: 1.874 to 13.274, P=0.001) were identified as risk factors for postoperative 30-day mortality (all P<0.05). In validation of the original prediction model, the C-index was found to be 0.764, indicating good discrimination. However, there was a significant discrepancy between the mortality forecast by the original prediction model and the actual mortality ( P<0.05), indicating poor calibration. After the prediction model was recalibrated, 30-day mortality (%) = 100/[1 + e (5.818-NHFS×0.599)]. After the new prediction model was validated in both the training and validation groups, the C-indexes were 0.762 and 0.780, indicating a good level of discrimination. The predicted 30-day mortality by the prediction model was closely aligned with the actual mortality ( P>0.05), demonstrating good calibration. When the threshold probabilities of the training and the validation groups were 0 to 26% and 0 to 35%, respectively, the patients might benefit from clinical intervention, showing clinical effectiveness of the model. Conclusions:The NHFS can predict the risk for 30-day mortality after hip fracture surgery. The new NHFS prediction model after calibration has a good predictive value for 30-day mortality after hip fracture surgery in Chinese population.

Insulin-like growth factor-1 receptor (IGF-1R) has been made an attractive anticancer target due to its overexpression in cancers. However, targeting it has often produced the disappointing results as the role played by cross talk with numerous downstream signalings. Here, we report a disobliging IGF-1R signaling which promotes growth of cancer through triggering the E3 ubiquitin ligase MEX3A-mediated degradation of RIG-I. The active β-arrestin-2 scaffolds this disobliging signaling to talk with MEX3A. In response to ligands, IGF-1Rβ activated the basal βarr2 into its active state by phosphorylating the interdomain domain on Tyr64 and Tyr250, opening the middle loop (Leu130‒Cys141) to the RING domain of MEX3A through the conformational changes of βarr2. The models of βarr2/IGF-1Rβ and βarr2/MEX3A could interpret the mechanism of the activated-IGF-1R in triggering degradation of RIG-I. The assay of the mutants βarr2^Y64A and βarr2^Y250A further confirmed the role of these two Tyr residues of the interlobe in mediating the talk between IGF-1Rβ and the RING domain of MEX3A. The truncated-βarr2 and the peptide ATQAIRIF, which mimicked the RING domain of MEX3A could prevent the formation of βarr2/IGF-1Rβ and βarr2/MEX3A complexes, thus blocking the IGF-1R-triggered RIG-I degradation. Degradation of RIG-I resulted in the suppression of the IFN-I-associated immune cells in the TME due to the blockade of the RIG-I-MAVS-IFN-I pathway. Poly(I:C) could reverse anti-PD-L1 insensitivity by recovery of RIG-I. In summary, we revealed a disobliging IGF-1R signaling by which IGF-1Rβ promoted cancer growth through triggering the MEX3A-mediated degradation of RIG-I.

The grading of evidence is an important factor in clinical decision-making. The current evidence grading system based on western medicine is limited in the clinical practice of traditional Chinese medicine （TCM）， therefore we propose the solutions to the development of grading system for TCM interventional evidence， following the international evidence grading standards， taking into considerations of the unique characteristics of TCM practice， based on the Grades of recommendation， assessment， development and evaluation （GARDE） evaluation system， and integrating with grading system regarding TCM classical literature and empirical evidence from modern famous doctors. The evidence from classical literature is suggested to be evaluated from three aspects including source of ancient medical records， comprehensive of treatment details， and the inheritance. The qualification of famous doctors， content integrity， and inheritance of experiences will be used to evaluate the evidence from famous doctors' experience. The multi-sourced evidence such as TCM classical literature， experience of modern famous doctors， and modern researches is mainly integrated in a qualitative way， and the overall level of evidence of TCM interventions will be graded consistently with the GRADE system based on modern research. The evidence from classical literature and modern famous doctors' experience will be assessed and considered as supplementary evidence， which will make the evaluation of clinical evidence more objectively and comprehensively， thereby guiding clinical practice further.

BACKGROUND: Progressive lipid loss of adipose tissue is a major feature of cancer-associated cachexia. In addition to systemic immune/inflammatory effects in response to tumor progression, tumor-secreted cachectic ligands also play essential roles in tumor-induced lipid loss. However, the mechanisms of tumor-adipose tissue interaction in lipid homeostasis are not fully understood. METHODS: The yki -gut tumors were induced in fruit flies. Lipid metabolic assays were performed to investigate the lipolysis level of different types of insulin-like growth factor binding protein-3 (IGFBP-3) treated cells. Immunoblotting was used to display phenotypes of tumor cells and adipocytes. Quantitative polymerase chain reaction (qPCR) analysis was carried out to examine the gene expression levels such as Acc1 , Acly , and Fasn et al . RESULTS: In this study, it was revealed that tumor-derived IGFBP-3 was an important ligand directly causing lipid loss in matured adipocytes. IGFBP-3, which is highly expressed in cachectic tumor cells, antagonized insulin/IGF-like signaling (IIS) and impaired the balance between lipolysis and lipogenesis in 3T3-L1 adipocytes. Conditioned medium from cachectic tumor cells, such as Capan-1 and C26 cells, contained excessive IGFBP-3 that potently induced lipolysis in adipocytes. Notably, neutralization of IGFBP-3 by neutralizing antibody in the conditioned medium of cachectic tumor cells significantly alleviated the lipolytic effect and restored lipid storage in adipocytes. Furthermore, cachectic tumor cells were resistant to IGFBP-3 inhibition of IIS, ensuring their escape from IGFBP-3-associated growth suppression. Finally, cachectic tumor-derived ImpL2, the IGFBP-3 homolog, also impaired lipid homeostasis of host cells in an established cancer-cachexia model in Drosophila . Most importantly, IGFBP-3 was highly expressed in cancer tissues in pancreatic and colorectal cancer patients, especially higher in the sera of cachectic cancer patients than non-cachexia cancer patients. CONCLUSION Our study demonstrates that tumor-derived IGFBP-3 plays a critical role in cachexia-associated lipid loss and could be a biomarker for diagnosis of cachexia in cancer patients.
Humans ; Insulin-Like Growth Factor Binding Protein 3/metabolism* ; Culture Media, Conditioned/pharmacology* ; Cachexia/pathology* ; Gastrointestinal Neoplasms ; Somatomedins/metabolism* ; Insulins/metabolism* ; Lipids

A rapid determination of methamphetamine, amphetamine, 6-monoacetylmorphine, and morphine in hair samples by UPLC-MS/MS was established and optimized.The concentration of target compounds in the hair of drug abusers and drug laboratory technicians was investigated and the cut-off value was evaluated.After cleaned hair was extracted by grinding with methanol-water (7∶3) at 3 000 r/min for 100 s, the final solution after adjusting the volume to methanol-water (1∶1) was analyzed by UPLC-MS/MS.The analytes were gradient eluted on a Waters Acquity BEH C18 (2.1 mm × 100 mm, 1.7 μm) column with 5 mmol/L ammonium formate-0.1% formic acid aqueous solution and acetonitrile as mobile phase at a flow rate of 0.4 mL/min. The ESI+ ion source and multiple reaction monitoring (MRM) were used to select the qualitative and quantitative ion pairs of the four target compounds. All analytes showed good linearity (R2 ≥ 0.999 6) in the range of 0.01-5 ng/mg (except amphetamine in 0.01-4 ng/mg), limit of the quantitation was 0.01 ng/mg, and the limit of detection was 0.001-0.008 ng/mg.The accuracy, precision, matrix effect, and recovery all met the requirements of biological sample methodology.According to the comprehensive consideration of the receiver operating characteristic (ROC) curve, Youden index, law enforcement cost and intensity, the reference cut-off values were methamphetamine ≥ 0.1 ng/mg; amphetamine ≥ 0.025 ng/mg; 6-monoacetylmorphine ≥ 0.05 ng/mg; morphine ≥ 0.05 ng/mg.The method established in our research can quickly and accurately detect the contents of methamphetamine, amphetamine, 6-monoacetylmorphine, and morphine in hair.This study provides some reference for the public security system to make more rational cut-off values in the norm of drug-related personnel hair samples detection in the future.

Objective:To investigate the expression and clinical significance of peptide/histidine transporter solute carrier family 15 member 4 (SLC15A4) in peripheral blood mononuclear cells (PBMCs) of patients with systemic lupus erythematosus (SLE).Methods:Fifty-five patients with SLE were divided into active SLE group and stable SLE group according to SLE disease activity index (SLEDAI) score, and 13 healthy volunteers were used as controls. The expression of SLC15A4 in PBMCs were detected by Western blot method. Moreover, the correlation between the expression of SLC15A4 and clinical and laboratory parameters of SLE patients were analyzed. The expression of SLC15a4 in the three groups was compared based on one-way analysis of variance (ANOVA), and the correlation between SLC15A4 expression level and clinical indicators was analyzed by Pearson correlation.Results:The expression levels of SLC15A4 in active SLE group, stable SLE group and healthy control group were (0.96±0.19), (0.88±0.14), (0.78±0.24), respectively. The expression level of SLC15A4 in SLE with active disease was higher than that in healthy controls ( F=4.47, P=0.015). In addition, the expression of SLC15A4 in PBMCs of SLE patients was positively correlated with the quantity of anti-double stranded DNA (anti-dsDNA) antibody, erythrocyte sedimentation rate (ESR) and systemic lupus erythematosus disease activity index (SLEDAI) ( r=0.29, P=0.031; r=0.36, P=0.007; r=0.32, P=0.017, respectively). However, the expression of SLC15A4 in PBMCs had no significant correlation with 24-h urinary protein ( r=0.45, P=0.127) and C3 ( r=0.20, P=0.133). Conclusion:SLC15A4 is involved in the pathogenesis of SLE and its expression in PBMCs of SLE patients can be used as an index to evaluate disease activity.