Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.

Objective To investigate the MRI manifestations of acquired immunodeficiency syndrome complicated with subtentorial progressive multifocal leukoencephalopathy(PML).Methods Sixteen patients with acquired immunodeficiency syndrome complicated with subtentorial PML confirmed by surgery,pathology,or clinical diagnosis were selected.The MRI features of plain scan and enhanced scan were analyzed and summarized,retrospectively.Results Among the 16 acquired immunodeficiency syndrome patients complicated with subtentorial PML,in terms of lesion distribution,the left cerebellar hemisphere was involved in 10 cases(62.5％),and the right cerebellar hemisphere was involved in 10 cases(62.5％).The left pontine arm was involved in 11 cases(68.8％),the right pontine arm was involved in 10 cases(62.5％),the medulla oblongata was involved in 6 cases(37.5％),the pontine region was involved in 11 cases(68.8％),the midbrain was involved in 7 cases(43.8％),and the supratentorial lesions were involved in 5 cases(31.3％).Subtentorial lesions were found to be asymmetrically distributed in all patients.In terms of MRI imaging findings,acquired immunodeficiency syndrome patients complicated with subtentorial PML lesions exhibited low signal on T,WI and high signal on T2 WI/T2-fluid attenuated inversion recovery(FLAIR)images.The"shrimp sign"and"crescent cerebellar lesion"was respectively observed in 3 and 7 cases on T2 WI.There were no diffusion limitations on diffusion weighted imaging(DWI),no significant enhancement after contrast-enhanced scanning,and no mass effect in all the 16 cases.Conclusion The MRI imaging findings of acquired immunodeficiency syndrome complicated with subtentorial PML exhibit similar features to those observed in PML affecting the cerebral hemispheres.A characteristic"shrimp sign"is often observed on T2WI.The presence of typical MRI imaging findings,along with the patient's clinical history and the detection of JC virus deoxyribonucleic acid(DNA)in the cerebrospinal fluid(CSF),can aid in the accurate diagnosis of PML.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective:To explore the clinical application of the electronic portal imaging device (EPID) based on the linear accelerator produced by Shanghai United Imaging Healthcare Co., Ltd. (UIH) to in vivo dose verification. Methods:A total of 68 patients (32 cases with head and neck tumors, 16 cases with chest tumors, and 20 cases with abdomen and pelvis tumors) who were treated with volumetric modulated arc therapy (VMAT) in the Henan Provincial People′s Hospital were selected in this study. Each patient underwent the pre-treatment dose verification using an Arccheck device (Pre Arccheck), the pre-treatment dose verification using an EPID (Pre EPID), and the in vivo dose verification using an EPID (In vivo EPID). Moreover, the position verification based on fan beam computed tomography (FBCT) was also performed for each patient in the first three treatments and then once a week. The patients were treated when the setup error in any direction ( x: left-right, y: head-foot, z: vertical) was less than 3 mm; otherwise, position correction would be conducted. The three-dimensional setup deviation d was calculated according to setup errors x, y, and z. Results:The γ passing rates of dose verifications Pre EPID and In vivo EPID of 68 patients were (99.97±0.1)% and (94.15±3.84)%, respectively, significantly different from that (98.86±1.48)% of the Pre Arccheck dose verification ( t = -6.12, 9.43; P < 0.05). The γ passing rates of the chest, abdomen and pelvis, and head and neck in the In vivo EPID dose verification showed no significant differences ( P > 0.05). The difference in the γ passing rates (5.56±3.72)% between dose verifications Pre EPID and first In vivo EPID was unrelated to the three-dimensional setup deviation d (1.46±1.51 mm) ( P > 0.05). As the treatment proceeded, the γ passing rate of In vivo EPID gradually decreased from (94.15±3.84)% in the first week to (92.15±3.24)% in the fifth week. From the third week to the fifth week, the γ passing rates of In vivo EPID were significantly different from those in the first week ( t = 2.48, 2.75, 3.09, P < 0.05). Conclusions:The setup errors within 3 mm do not affect the γ passing rate of in vivo dose verification. The clinically acceptable threshold for the γ passing rate of in vivo EPID needs to be further determined. In addition, in vivo dose verification can support the clinical application of adaptive radiotherapy to a certain extent.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

Objective:To investigate the effect of different negative pressure level on drain volume after augmentation mammoplasty through inframammary fold incision, and try to put forward the appropriate negative pressure level for the best prognosis of patients.Methods:This was a randomized controlled clinical study. Patients who underwent prosthetic augmentation mammoplasty through inframammary fold incision in the Medical Beauty Center of the First Affiliated Hospital of Zhengzhou University from January 2019 to August 2021 were selected as the study subjects. Patients were divided into 4 groups by random number table method and different levels of negative pressure drainage were applied: 600 ml adjustable negative pressure drain bottle was used uniformly after operation by -80--85 kPa group, -40--60 kPa group, and -15--30 kPa group. In 0--5.2 kPa group, 300 ml drain drum was applied after operation. The criteria for drain removal was that the drain volume within 24 hours was less than 10 ml and the drainage fluid was clear. Daily drain volume, duration of drain placement, total drain volume, acceptance of the drain device and postoperative complications were recorded in the four groups. The corresponding indexes of each group were statistically analyzed by SPSS 21.0. Measurement data were expressed as Mean±SD. One-way analysis of variance was used for comparison between groups, and LSD- t test was used for pair comparison between groups. P<0.05 was considered statistically significant. Results:A total of 80 patients were included, 20 in each group. Inter-group equilibrium analysis: there was no significant difference in age, body mass index, distance from midclavicular point to nipple, distance from inferior mammary fold to nipple, and breast tissue thickness among 4 groups ( P>0.05). Evaluation of curative effect between groups: on the first and second day after operation, there was no significant difference in drain volume between -80--85 kPa group and -40--60 kPa group ( P>0.05), but there was significant difference among other groups ( P<0.05). There was significant difference in drain volume on the third day after operation, total drain volume and duration of drain placement between the four groups ( P<0.05). The lower the negative pressure level was, the less drain volume on the third day after surgery and the less total drain volume, and the shorter duration of drain placement. The duration of drain placement of the four groups were (5.6±0.7) d (-80--85 kPa group), (4.8±0.5) d (-40--60 kPa group), (4.0±0.5) d (-15--30 kPa group), and (3.2±0.4) d (0--5.2 kPa group), respectively. Safety evaluation: the complication rate of -80--85 kPa group, -40--60 kPa group, -15--30 kPa group and 0--5.2 kPa group were 2.5% (1/40), 2.5% (1/40), 0(0/40) and 15.0% (6/40), respectively. The complication rate of 0--5.2 kPa group was the highest. Investigation on the acceptance of the drainage device (no impact/dissatisfaction): 75 patients expressed dissatisfaction, with a dissatisfaction rate of 93.75%(75/80). Conclusion:In augmentation mammoplasty through inferior fold incision low negative pressure provides less drain volume, shorter drain placement. Negative pressure between -15 to -30 kPa is optimal.

Objective:To investigate the effect of different negative pressure level on drain volume after augmentation mammoplasty through inframammary fold incision, and try to put forward the appropriate negative pressure level for the best prognosis of patients.Methods:This was a randomized controlled clinical study. Patients who underwent prosthetic augmentation mammoplasty through inframammary fold incision in the Medical Beauty Center of the First Affiliated Hospital of Zhengzhou University from January 2019 to August 2021 were selected as the study subjects. Patients were divided into 4 groups by random number table method and different levels of negative pressure drainage were applied: 600 ml adjustable negative pressure drain bottle was used uniformly after operation by -80--85 kPa group, -40--60 kPa group, and -15--30 kPa group. In 0--5.2 kPa group, 300 ml drain drum was applied after operation. The criteria for drain removal was that the drain volume within 24 hours was less than 10 ml and the drainage fluid was clear. Daily drain volume, duration of drain placement, total drain volume, acceptance of the drain device and postoperative complications were recorded in the four groups. The corresponding indexes of each group were statistically analyzed by SPSS 21.0. Measurement data were expressed as Mean±SD. One-way analysis of variance was used for comparison between groups, and LSD- t test was used for pair comparison between groups. P<0.05 was considered statistically significant. Results:A total of 80 patients were included, 20 in each group. Inter-group equilibrium analysis: there was no significant difference in age, body mass index, distance from midclavicular point to nipple, distance from inferior mammary fold to nipple, and breast tissue thickness among 4 groups ( P>0.05). Evaluation of curative effect between groups: on the first and second day after operation, there was no significant difference in drain volume between -80--85 kPa group and -40--60 kPa group ( P>0.05), but there was significant difference among other groups ( P<0.05). There was significant difference in drain volume on the third day after operation, total drain volume and duration of drain placement between the four groups ( P<0.05). The lower the negative pressure level was, the less drain volume on the third day after surgery and the less total drain volume, and the shorter duration of drain placement. The duration of drain placement of the four groups were (5.6±0.7) d (-80--85 kPa group), (4.8±0.5) d (-40--60 kPa group), (4.0±0.5) d (-15--30 kPa group), and (3.2±0.4) d (0--5.2 kPa group), respectively. Safety evaluation: the complication rate of -80--85 kPa group, -40--60 kPa group, -15--30 kPa group and 0--5.2 kPa group were 2.5% (1/40), 2.5% (1/40), 0(0/40) and 15.0% (6/40), respectively. The complication rate of 0--5.2 kPa group was the highest. Investigation on the acceptance of the drainage device (no impact/dissatisfaction): 75 patients expressed dissatisfaction, with a dissatisfaction rate of 93.75%(75/80). Conclusion:In augmentation mammoplasty through inferior fold incision low negative pressure provides less drain volume, shorter drain placement. Negative pressure between -15 to -30 kPa is optimal.

Currently, there is still no effective curative treatment for the development of late-stage liver fibrosis. Here, we have illustrated that TB001, a dual glucagon-like peptide-1 receptor/glucagon receptor (GLP-1R/GCGR) agonist with higher affinity towards GCGR, could retard the progression of liver fibrosis in various rodent models, with remarkable potency, selectivity, extended half-life and low toxicity. Four types of liver fibrosis animal models which were induced by CCl₄, α-naphthyl-isothiocyanate (ANIT), bile duct ligation (BDL) and Schistosoma japonicum were used in our study. We found that TB001 treatment dose-dependently significantly attenuated liver injury and collagen accumulation in these animal models. In addition to decreased levels of extracellular matrix (ECM) accumulation during hepatic injury, activation of hepatic stellate cells was also inhibited via suppression of TGF-β expression as well as downstream Smad signaling pathways particularly in CCl₄-and S. japonicum-induced liver fibrosis. Moreover, TB001 attenuated liver fibrosis through blocking downstream activation of pro-inflammatory nuclear factor kappa B/NF-kappa-B inhibitor alpha (NFκB/IKBα) pathways as well as c-Jun N-terminal kinase (JNK)-dependent induction of hepatocyte apoptosis. Furthermore, GLP-1R and/or GCGR knock-down results represented GCGR played an important role in ameliorating CCl₄-induced hepatic fibrosis. Therefore, TB001 can be used as a promising therapeutic candidate for the treatment of multiple causes of hepatic fibrosis demonstrated by our extensive pre-clinical evaluation of TB001.

Osteoporotic vertebral compression fracture (OVCF) can lead to lower back pain and may be even accompanied by scoliosis, neurological dysfunction and other complications, which will affect the daily activities and life quality of patients. Vertebral augmentation is an effective treatment method for OVCF, but it cannot correct unbalance of bone metabolism or improve the osteoporotic status, causing complications like lower back pain, limited spinal activities and vertebral refracture. The post-operative systematic and standardized rehabilitation treatments can improve curative effect and therapeutic efficacy of anti-osteoporosis, reduce risk of vertebral refracture, increase patient compliance and improve quality of life. Since there still lack relevant clinical treatment guidelines for postoperative rehabilitation treatments following vertebral augmentation for OVCF, the current treatments are varied with uneven therapeutic effect. In order to standardize the postoperative rehabilitation treatment, the Spine Trauma Group of the Orthopedic Branch of Chinese Medical Doctor Association organized relevant experts to refer to relevant literature and develop the "Guideline for postoperative rehabilitation treatment following vertebral augmentation for osteoporotic vertebral compression fracture (2022 version)" based on the clinical guidelines published by the American Academy of Orthopedic Surgeons (AAOS) as well as on the principles of scientificity, practicality and advancement. The guideline provided evidence-based recommendations on 10 important issues related to postoperative rehabilitation treatments of OVCF.