OBJECTIVE To investigate the effects of galangin （GLA） on autophagy and apoptosis of chondrocytes in knee osteoarthritis （KOA） rats by regulating the adenosine monophosphate-activated protein kinase （AMPK）/mammalian target of rapamycin （mTOR）/UNC-51-like kinase 1 （ULK1） signaling pathway. METHODS KOA rat model was constructed and separated into model group， L-GLA， M-GLA， H-GLA groups [subcutaneous injection of 100， 200， 400 μg/kg GLA]， GLA+Compound C group [subcutaneous injection of 400 μg/kg GLA+0.2 mg/kg AMPK inhibitor Compound C]， with 10 rats in each group. Additionally， 10 normally fed rats were selected as the sham operation group. After the last medication， the degree of knee joint swelling of rats in each group was detected； the pathology of knee joints in KOA rats was observed. The serum expressions of matrix metalloproteinase 13 （MMP-13） and interleukin-1β （IL-1β） in KOA rats were detected； the autophagy of chondrocytes in KOA rats was observed； the chondrocyte apoptosis in KOA rats was detected； the phosphorylation of AMPK/mTOR/ULK1 pathway-related proteins in cartilage tissue of knee joint were detected in rats. RESULTS Compared with the sham operation group， the arrangement of articular chondrocytes in the model group was disordered， with nuclear pyknosis and severe fibrosis of the articular cartilage layer， accompanied by a large amount of inflammatory cell infiltration； the degree of joint swelling， the number of autophagic vacuoles and apoptosis rate of chondrocytes， serum levels of MMP-13 and IL-1β， and the phosphorylation of mTOR protein in cartilage tissue of knee joint were all increased significantly （P＜0.05）， while the phosphorylation of AMPK and ULK1 protein were all decreased significantly in cartilage tissue of knee joint （P＜0.05）. Compared with the model group， L- GLA， M-GLA， H-GLA groups showed significant improvement in joint cartilage injury and reduced infiltration of inflammatory cells in rats. The above quantitative indicators were significantly reversed in a dose-dependent manner，except the number of autophagic vacuoles increased significantly （P＜0.05）. Compared with the H-GLA group， the GLA+ Compound C group showed aggravated cartilage tissue of joint cartilage injury and inflammatory cell infiltration in rats， and the above quantitative indicators were reversed significantly （P＜0.05）. CONCLUSIONS GLA can promote autophagy and inhibit apoptosis of chondrocytes in KOA rats， the mechanism of which may be associated with activating AMPK/mTOR/ULK1 signaling pathway.

The high-quality development requirements for public hospitals,national examination orientations,and DIP medical insurance payment reforms present significant challenges to the refined management of public hospitals.Therefore,it is essential to enhance the operational management of these institutions.This paper aims to develop an operation evaluation index system for clinical departments using the Delphi method for assessing the efficiency of resource input and output across various clinical departments.It provides a scientific basis for decision-making regarding resource allocation,transformation towards re-fined management,and the enhancement of operational guidance for departments.

Background::Ainuovirine (ANV) is a new generation of non-nucleoside reverse transcriptase inhibitor for the treatment of human immunodeficiency virus (HIV) type 1 infection. This study aimed to evaluate the population pharmacokinetic (PopPK) profile and exposure-response relationship of ANV among people living with HIV.Methods::Plasma concentration-time data from phase 1 and phase 3 clinical trials of ANV were pooled for developing the PopPK model. Exposure estimates obtained from the final model were used in exposure-response analysis for virologic responses and safety responses.Results::ANV exhibited a nonlinear pharmacokinetic profile, which was best described by a two-compartment model with first-order elimination. There were no significant covariates correlated to the pharmacokinetic parameters of ANV. The PopPK parameter estimate (relative standard error [%]) for clearance adjusted for bioavailability (CL/F) was 6.46 (15.00) L/h, and the clearance of ANV increased after multiple doses. The exposure-response model revealed no significant correlation between the virologic response (HIV-RNA <50 copies/mL) at 48 weeks and the exposure, but the incidence of adverse events increased with the increasing exposure ( P value of steady-state trough concentration and area under the steady-state curve were 0.0177 and 0.0141, respectively). Conclusions::Our PopPK model supported ANV 150 mg once daily as the recommended dose for people living with HIV, requiring no dose adjustment for the studied factors. Optimization of ANV dose may be warranted in clinical practice due to an increasing trend in adverse reactions with increasing exposure.Trial registration::Chinese Clinical Trial Registry https://www.chictr.org.cn (Nos. ChiCTR1800018022 and ChiCTR1800019041).

Objective:To explore the affects of the filling degree of the abdominal and pelvic cavity to the position of the diaphragm.Methods:The computed tomography (CT) images of 25 patients from 137 CT scans stored in the Picture Archiving and Communication System of the First Affiliated Hospital of Soochow University from March 2018 to September 2020 were reviewed and analyzed retrospectively. Every patient was scanned 4-7 times. The outline of the abdominal and pelvic cavity from the diaphragmatic dome to the superior margin of pubic symphysis was drawn at every cross section, and then the filling volumes of the abdominal and pelvic cavities and the overall filling volume were calculated. For the same patient within 4-7 CT scans, per pair of different images was compared randomly and 379 comparison pairs were obtained. The volume change rate (△ VR) of the abdominal and pelvic cavity and the height difference (△ H) of the diaphragmatic dome were calculated. The images with "larger overall filling volume of the abdominal and pelvic cavity and higher diaphragmatic dome" were defined as consistent group, and those with "larger overall filling volume and lower diaphragmatic dome" were defined as inconsistent group. The percentage of images in the consistent group in all samples and the percentage of images showing deep inspiration in the inconsistent group in all samples were calculated. △ VR and △ H were compared between the consistent and inconsistent groups. △ VR of the abdomen and pelvic cavities in the consistent group was compared using the Mann-Whitney test. The correlations between △ VR of the abdomen and pelvic cavities and the elevation of the diaphragmatic dome in the consistent group were analyzed using Spearman correlation analysis. The average elevation of the diaphragmatic dome in all samples and the consistent group was simulated if the filling volume of the abdomen and pelvic cavity was increased by 500 ml. Results:The percentage of images in the consistent group in all samples was 67.28%. The percentage of images showing deep inspiration in the inconsistent group in all samples was 26.39%. There were significant differences in △ VR and △ H of the abdomen and pelvic cavity between the consistent and inconsistent groups ( Z=-4.95, -5.49, P<0.05). In the consistent group, there were significant differences in △ VR between the abdominal cavity and pelvic cavity ( Z=-7.53, P<0.05), and the elevation of the diaphragmatic dome was correlated with the △ VR of the abdominal cavity ( rs=0.43, P<0.05). The simulated calculation showed that an average increase of 500 ml in the filling volume of the abdominal and pelvic cavity result ed in an average elevation of 4.54 and 8.43 mm in the diaphragmatic dome in all samples and the consistent group, respectively. Conclusions:The filling degree of the abdominal and pelvic cavity may be one of the main factors affecting the position of the diaphragm and the precision of radiotherapy for relevant organs near the diaphragm, especially the filling degree of the abdominal cavity. It is recommended to repeat the filling degree of the abdominal and pelvic cavity by CT localization scanning as much as possible during radiotherapy.

Objective:To analyze the activity of skin markers at different parts of the body surface and the correlations between their displacement deviations and pelvic filling volumes during conventional abdominal and pelvic radiotherapy.Methods:A retrospective analysis was conducted on 15 patients receiving abdominal and pelvic radiotherapy with four times of computed tomography (CT) in the First Affiliated Hospital of Soochow University from January 2020 to January 2022. All CT images were divided into nine parts from the upper edge of L3 to the upper edge of the pubic symphysis: upper, middle, and lower parts in the right portion; upper, middle, and lower parts in the central portion; and upper, middle, and lower parts in the left part portions, No. 1-9 in sequence. The same blood-vessel or fascia intersection points near the same skin parts receiving the same dose fraction were used as the markers for skin positioning during simulated radiotherapy. The relative coordinates of the markers were measured, with the same point at the lower edge behind the L5 vertebral body set as the coordinate origin. Through pairwise comparison of each patient′s four CT images, the three-dimensional displacement deviations and activity were calculated for all markers. In the left-right (L-R), superior-inferior (S-I), and anterior-posterior (A-P) directions, the differences in the displacement activity of the markers in the nine parts were compared using both the non-parametric Kruskal-Wallis test and the Descriptives. The correlations between the three-dimensional displacement deviations of all markers and the A-P displacement deviations of the No. 5 marker were analyzed using the Pearson correlation analysis.Results:Differences existed in the displacement activity of the nine-part markers in the L-R, S-I, and A-P directions ( H=36.66, 66.20, 92.15, P<0.05). No. 3 and 9 markers exhibited lower overall three-dimensional displacement activity (median: 2.40-3.75 mm) than other markers. The No. 5 marker manifested the highest A-P displacement activity, with a median of 9.20 mm. The A-P displacement deviation of No. 5 marker was correlated using the L-R displacement deviations of the No. 1, 2, 3, 7, 8 and 9 markers ( r=-0.36 to 0.49, P<0.05), the S-I displacement deviations of the No. 4, 5, 6, and 9 markers ( r=-0.34 to -0.24, P<0.05), and the A-P displacement deviations of the No. 1, 2, 3, 4, 6, 7, 8 and 9 markers ( r=0.33-0.91, P<0.05). Conclusions:Skin markers drawn in bilateral acetabular regions serve as the best choices for reposition in pelvic radiotherapy. Conventional skin markers made at the central parts are prone to suffer deviations in the S-I direction due to the influence of the abdominal and pelvic filling volumes.

Objective To investigate the clinical characteristics of patients with chronic myeloid leukemia (CML) in chronic phase with deletion and non-deletion of the argininosuccinate synthesis gene (ASS gene) on the derivative chromosome 9. Methods The clinical data of patients with CML initially treated with imatinib and BCR/ABL1/ASS1 3-color fusion probe to detect ASS gene deletion were analyzed. The patients were divided into deletion group (n=27) and non-deletion group (n=92). Clinical characteristics, treatment effects, and prognosis were analyzed. Results The average age of 119 patients was 37.22±12.72 years old. The sokal score differed between the deletion and non-deletion groups (χ²=4.304, P=0.038). No statistically significant difference in other general characteristics was found (P > 0.05). The 3-month CCyR rate, 6-month CCyR rate, and BCR-ABL^IS≤ 1% rate in the deletion group were lower than those in the non-deletion group (P < 0.05). The median follow-up of 119 patients was 35.0 (3.0-60.0) months. The PFS in the deletion group was lower than that in the non-deletion group (χ²=4.293, P=0.038). Overall survival was not significantly different between the two groups (χ²=0.008, P=0.931). Conclusion The deletion of the ASS gene in patients with chronic CML is related to the poor efficacy of imatinib treatment, poor prognosis, and high risk of disease progression.

During coronavirus disease 2019 epidemic, the treatment of severe trauma has been impacted. The Consensus on emergency surgery and infection prevention and control for severe trauma patients with 2019 novel corona virus pneumonia was published online on February 12, 2020, providing a strong guidance for the emergency treatment of severe trauma and the self-protection of medical staffs in the early stage of the epidemic. With the Joint Prevention and Control Mechanism of the State Council renaming "novel coronavirus pneumonia" to "novel coronavirus infection" and the infection being managed with measures against class B infectious diseases since January 8, 2023, the consensus published in 2020 is no longer applicable to the emergency treatment of severe trauma in the new stage of epidemic prevention and control. In this context, led by the Chinese Traumatology Association, Chinese Trauma Surgeon Association, Trauma Medicine Branch of Chinese International Exchange and Promotive Association for Medical and Health Care, and Editorial Board of Chinese Journal of Traumatology, the Chinese expert consensus on emergency surgery for severe trauma and infection prevention during coronavirus disease 2019 epidemic ( version 2023) is formulated to ensure the effectiveness and safety in the treatment of severe trauma in the new stage. Based on the policy of the Joint Prevention and Control Mechanism of the State Council and by using evidence-based medical evidence as well as Delphi expert consultation and voting, 16 recommendations are put forward from the four aspects of the related definitions, infection prevention, preoperative assessment and preparation, emergency operation and postoperative management, hoping to provide a reference for severe trauma care in the new stage of the epidemic prevention and control.

Objective:To investigate the variations and related influencing factors of the volumes, positions, and morphologies of geometries formed by surgical clips in intensity-modulated radiation therapy (IMRT) for whole breasts after breast-conserving surgery.Methods:A retrospective analysis was conducted on 18 patients treated with IMRT from October 2021 to September 2022 after breast-conserving surgery. Set-up errors were obtained by reading the coordinate information of tumor bed surgical clips according to the cone beam CT (CBCT) images at 0, 10, 20, 30, 40, and 50 Gy sequentially. Geometries were constructed using the convex hull program, and the volumes ( Vct and V0-5) of geometries were then calculated based on the localization CT images and the six CBCT images, respectively. The centroid displacements ( D0-5) and degrees of inclusion ( DI0-5) of these geometries were compared. The t-test or rank-sum test was used to analyze the effects of radiation doses on V0-5, D0-5, and DI0-5. The Pearson correlation analysis was conducted to analyze the correlations between D0-5 and corresponding set-up errors in three-dimensional directions, and the correlations of average V0-5 variation ( AV), average D0-5 ( AD), and average DI0-5 ( ADI) with the body mass index (BMI), the volume of a breast ( VB), the breast axial height ( H), and the time interval from surgery to radiotherapy ( T) each. The influences of quadrants ( Q) where geometries are located and states ( S) of geometries adhering to or away from the chest walls on AV, AD, and ADI were analyzed through one-way ANOVA. Results:The differences between D5 and D0, between D5 and D1, and between D5 and D2 were statistically significant ( t = -3.27, -4.52, -3.38, P < 0.05), respectively. The differences between DI5 and DI0, between DI5 and DI1, between DI5 and DI2 were statistically significant ( t = 2.53, 2.70, 2.64, P < 0.05), respectively. D1 and D4 correlated with the set-up errors in the superior-inferior dimension, and D3 correlated with the set-up errors in the left-right dimension ( r = 0.50, 0.56, 0.53, P < 0.05). The AD was related to BMI, VB, and H ( r = 0.54, 0.48, 0.50, P < 0.05). There were statistically significant differences in AV and ADI of geometries away from ( S3) and near ( S2) chest walls ( F = 2.66, 3.83, P < 0.05). The AD differences of geometries between S3 and the state adhering to chest walls ( S1) and between S3 and S2 were statistically significant ( F = 7.46, P < 0.05), respectively. Conclusions:The geometries are relatively constant volumes during whole-breast radiotherapy. However, their positions and morphologies vary greatly in the late course. The volume variation ratios, centroid displacements, and degrees of inclusion of geometries are all affected by the states of their attachments to the chest walls. The centroid displacements correlate with breast morphologies and BMI. The radiotherapy plan modification can be individualized.

Objective To investigate the postoperative complications of ex vivo liver resection combined with autologous liver transplantation in the treatment of end-stage hepatic alveolar echinococcosis at high altitude and related prevention and treatment strategies. Methods Surgical data and follow-up data were collected from 11 patients with end-stage hepatic alveolar echinococcosis who underwent autologous liver transplantation in Qinghai People's Hospital from January 2013 to March 2019, and intraoperative and postoperative conditions were analyzed. Results All 11 patients underwent autologous liver transplantation successfully, without intraoperative death, among whom 2(18.18%) underwent hemi-extracorporeal hepatectomy and 9 (81.82%) underwent total extracorporeal hepatectomy. For the reconstruction of the retrohepatic inferior vena cava, 2 patients (18.18%) underwent reconstruction with the autologous great saphenous vein, 4 patients (36.36%) underwent reconstruction with artificial vessels, and the autologous retrohepatic inferior vena cava was preserved in 5 patients (45.45%). For biliary reconstruction, 8 patients (72.73%) underwent choledochoenterostomy and 3 (27.27%) underwent choledochocholedochostomy. The main postoperative complications of the 11 patients included bleeding in 2 patients (18.18%), bile leakage and abdominal infection in 4 patients (36.36%), bilioenteric anastomotic stenosis in 1 patient (9.09%), thrombus in 2 patients (18.18%), pulmonary infection and pleural effusion in 2 patients (18.18%), and echinococcosis recurrence in 1 patient (9.09%). Of all 11 patients, 2 (18.18%) died during the perioperative period, and the other 9 patients (81.82%) were improved and discharged. Conclusion Bleeding, biliary complications, and infection are the main causes of death in patients undergoing autologous liver transplantation at high altitude. An accurate understanding of surgical indication, careful multidisciplinary evaluation before surgery, superb operation during surgery, standardized surgical procedures, and fine perioperative management are the key to reducing perioperative mortality, avoiding and reducing postoperative complications, and achieving good long-term survival in patients undergoing autologous liver transplantation.

Model informed precision dosing (MIPD) is a new concept to guide precision dosing for individual patient by modeling and simulation based on the available information about the individual patient, medications and the disease. Compared to the empirical dosing, MIPD could improve the efficacy, safety, economics and adherence of the pharmacotherapy according to the individual's pathophysiology, genotyping and disease progression. This consensus report provides a brief account of the concept, methodology and implementation of MIPD as well as clinical decision supporting systems for MIPD. The status and future advancing of MIPD was also discussed to facilitate the appropriate application and development of MIPD in China.