ObjectiveTo explore the mechanism by which Xiaoyaosan regulates HPT axis dysfunction in the rat model with the syndrome of liver depression and spleen deficiency by observing its effect on the glycoprotein hormone α-subunit （CGA）/glutathione peroxidase 2 （GPX2）/thyroid-stimulating hormone β-subunit （TSHβ） pathway for thyroid hormone synthesis. MethodsSeventy-two male SD rats were randomized into six groups： normal， model， high-dose （16.7 g·kg^-1）， medium-dose （8.35 g·kg^-1）， and low-dose （4.175 g·kg^-1） Xiaoyaosan， and fluoxetine （0.001 8 g·kg^-1） groups， with 12 rats in each group. The rat model of liver depression and spleen deficiency was induced by chronic restraint stress for 21 days. The intervention groups were treated with Xiaoyaosan decoctions or fluoxetine suspension， respectively. After modeling， hematoxylin-eosin staining was employed to observe morphological changes in the thyroid and pituitary tissue of the rats. Serum levels of triiodothyronine （T3）， tetraiodothyronine （T4）， and thyroid-stimulating hormone （TSH） were measured by enzyme-linked immunosorbent assay （ELISA）. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot were employed to determine the mRNA and protein levels， respectively， of TSH receptor （TSHR） in the thyroid tissue， thyrotropin-releasing hormone receptor （TRHR） and TSHβ in the pituitary tissue， and thyrotropin-releasing hormone （TRH）， CGA， GPX2， and TSHβ in the hypothalamic tissue. ResultsCompared with the normal group， the model group showed significant atrophy and irregularity of thyroid follicles， a marked reduction in colloid secretion， extensive vacuolar degeneration of adenocytes in the anterior pituitary， lowered serum levels of T3， T4， and TSH （P<0.01）， and down-regulated mRNA and protein levels of TSHR in the thyroid tissue， TRHR and TSHβ in the pituitary tissue， and TRH， CGA， GPX2， and TSHβ in the hypothalamic tissue （P<0.01）. Compared with the model group， high- and medium-dose Xiaoyaosan and fluoxetine alleviated the pathological changes in the thyroid and pituitary tissue， outperforming the low-dose Xiaoyaosan group. Moreover， they elevated the serum levels of T3， T4， and TSH （P<0.05， P<0.01）. The serum TSH level was also elevated in the low-dose Xiaoyaosan group （P<0.05）. The mRNA and protein levels of TSHR in the thyroid， TRHR and TSHβ in the pituitary， and TRH， CGA， GPX2， and TSHβ in the hypothalamus were up-regulated in the high- and medium-dose Xiaoyaosan groups （P<0.05， P<0.01）. Additionally， the mRNA and protein levels of TSHβ in the hypothalamus were up-regulated in the low-dose Xiaoyaosan group （P<0.01）. In the fluoxetine group， the mRNA and protein levels of TSHR in the thyroid， TRHR in the pituitary， and TRH， CGA， and GPX2 in the hypothalamus were up-regulated （P<0.05， P<0.01）. ConclusionThe downregulation of CGA/GPX2/TSHβ pathway may be one of the biological mechanisms underlying HPT axis dysfunction in the rat model with the syndrome of liver depression and spleen deficiency. Xiaoyaosan may regulate the HPT axis dysfunction by up-regulating the CGA/GPX2/TSHβ pathway.

BACKGROUND:Finite element analysis is a commonly used mathematical modeling method to analyze the biomechanics of the lumbar spine.By constructing finite element models of the complex tissues such as muscles,blood vessels,and nerves in the lumbar region,mechanical analysis is performed to elucidate the pathogenesis of lumbar spine disorders and the mechanical mechanisms of treatment approaches. OBJECTIVE:To review the progress of finite element analysis in understanding the pathogenesis and treatment modalities of lumbar spine disorders,and to propose a new clinical workflow for the implementation of finite element analysis,aiming to provide a reference for future studies and promote the widespread utilization of finite element analysis in clinical diagnosis and treatment. METHODS:The PubMed database was searched using English keywords"finite element analysis,lumbar vertebra",while the WanFang and China National Knowledge Infrastructure(CNKI)databases were searched using Chinese keywords"finite element analysis,lumbar vertebra".A total of 73 articles were included for review. RESULTS AND CONCLUSION:(1)Lumbar spine degeneration in non-slipped patients typically originates from the posterior annulus fibrosus,while in patients with lumbar spine spondylolisthesis,degeneration starts from the lumbar facet joints due to abnormal mechanical mechanisms.(2)Restoring vertebral body height can prevent adjacent-level degeneration,and finite element analysis-measured vertebral compression strength can serve as an effective predictor of fracture risk,replacing bone density measurements.(3)In lumbar spine fusion surgery,selecting fusion devices of appropriate height and placing them transversely can prevent device subsidence.Increased intervertebral strain,circumferential stress,and intervertebral pressure in adjacent segments after fusion surgery may contribute to the occurrence of degenerative changes in neighboring segments.(4)Finite element analysis results suggest that preoperative planning for transforaminal endoscopic surgery should include considerations for osteotomy size to avoid excessive destruction of the articular process,and intraoperatively,preferential selection of a technique that traverses the superior articular process for foraminal dilatation.(5)In percutaneous kyphoplasty,bilateral pedicle screw augmentation should be performed,distributing bone cement on both sides of the pedicle.More advanced non-aluminum glass polyalkenoate cement materials should be selected.(6)Traction therapy should be personalized based on individual patient characteristics,including customized traction angles and forces,to achieve optimal therapeutic effects.(7)Manual therapy can induce relative displacement between the herniated intervertebral disc and the nerve root,thereby reducing compression.(8)The workflow involving CT/MR-AI Plus FEA-AI Plus Surgical robots can enable more precise diagnosis and treatment.

Objective To verify the mechanism of Buyang Huanwu decoction in the treatment of spinal cord injury based on network pharmacology and molecular docking.Methods The active ingredients and targets of Buyang Huanwu decoction were screened out by TCMSP,SymMap,PubChem and Swiss Target Prediction databases.Spinal cord injury targets were retrieved from OMIM,GeneCards,TTD,and DrugBank databases.Through venny software,the intersection target of Buyang Huanwu decoction and spinal cord injury was obtained.The active ingredient-target network for the treatment of spinal cord injury was constructed with Cytoscape software.Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis of common targets were carried out by DAVID,and the binding ability of drugs and targets was analyzed by molecular docking technology.Results A total of 106 active ingredients and 225 targets of Buyang Huanwu decoction,1315 targets of spinal cord injury and 112 targets of drug-disease intersection were obtained.The active ingredients of Buyang Huanwu decoction were quercetin,kaempferol,ellagic acid,luteolin and hederagenin in the treatment of spinal cord injury.Conclusion Buyang Huanwu decoction can achieve the purpose of treating spinal cord injury through various signal pathways.

This article introduces a high-magnification electronic endoscope system that utilizes a continuous zoom optical design,enabling high-magnification imaging at the cellular level.By selecting an appropriate initial retrofocus structure,the optimized modulation transfer function(MTF)curve of the zoom objective lens approaches the diffraction limit.Additionally,the tip and operation parts of the system incorporate modular gas-tight sealing and multiple layers of protective structure.The design employs efficient sealing materials and precise packaging techniques to ensure the system's sealing performance.The experimental results indicate that,under conventional imaging,the resolution is equivalent to 39.37 μm in object space,and the field of view angle is larger than 140 degrees.At magnified imaging,the resolution is equivalent to 2.78 μm in object space,and the observed actual field of view is greater than 800 μm×700 μm.When used with a 26-inch display monitor,the high-magnification electronic endoscope can achieve 500×optical magnification,allowing for the observation of features at the cellular level.Currently,this product has successfully achieved mass production and has undergone multiple animal trials,demonstrating its wide range of potential applications and significant clinical value.

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.

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 expression，prognosis and biological role of hepatocyte nuclear factor 4A (HNF4A) in gastric cancer，and to study its effect on the proliferation of gastric cancer cells． Methods: Tumor Immune Estimation Resource 2. 0 (TIMER2. 0) and Gene Expression Profiling Interactive Analysis ( GEPIA2) databases were used to analyze the relative expression levels of HNF4A in gastric cancer and normal tissue，KM Plotter was used to analyze the correlation between the expression level of HNF4A and the survival rate of gastric cancer patients，TISIDB database and R language (4. 1. 2) were used to analyze whether HNF4A was involved in the immune regulation process of gastric cancer．cBioPortal database was used to analyze the mutations of HNF4A in gastric cancer，GSEA 4. 2 was used to analyze the functional enrichment of HNF4A，and LinkedOmics database was used to predict the genes that might be regulated by HNF4A．The relative expression of HNF4A in gastric cancer and adjacent tissues was detected by qRT-PCR , Western blot and immunohistochemistry (IHC) ．The proliferation and cell cycle of gastric cancer cells were analyzed by CCK-8，EdU，colony forming assay and flow cytometry. Results : The expression of HNF4A increased in gastric cancer tissues (P ＜0. 05) ，and the overall survival rate of gastric cancer patients with high HNF4A expression was worse (P＜0. 001) ．HNF4A was mainly missense mutated in gastric cancer．Immune cell infiltration showed that HNF4A was associated with B lymphocytes，CD8 + T cells， neutrophils，macrophages and dendritic cells ( all P ＜0. 001) ． HNF4A was also associated with tumor mutation burden (r = 0. 28，P＜0. 0001) and microsatellite instability (r = 0. 13，P＜0. 01) ．After knockdown of HNF4A， cell proliferation ability was significantly inhibited ，and cell cycle was arrested at G0 / G1 phase． Conclusion HNF4A expression significantly increased in gastric cancer tissues，which is associated with poor prognosis ，and may also be involved in immune regulation． Knockdown of HNF4A can inhibit the proliferation of gastric cancer cells.

Objective:To analyze the clinicopathological characteristics, treatment responses and kidney outcomes of patients with atypical membranous nephropathy (MN), and to provide information for the clinical practice.Methods:The clinical data of patients with atypical MN and synchronous primary MN who were diagnosed, treated and followed up in Peking University First Hospital from January 2008 to June 2020 were retrospectively collected and analyzed. Clinicopathological features, treatment responses and kidney prognosis were compared between the two groups. The expression of phospholipase A2 receptor (PLA2R) in kidney tissues was detected by immunofluorescence. Serum anti-PLA2R antibody was detected by enzyme-linked immunosorbent assay. Clinicopathological indexes were compared between PLA2R-related MN group and non-PLA2R-related MN group. Kaplan-Meier (Log-rank test) survival curve and multivariate Cox regression analysis methods were used to analyze the influencing factors of kidney prognosis in patients with atypical MN. The primary endpoint of renal adverse outcome was renal insufficiency, defined as end-stage renal disease or estimated glomerular filtration rate (eGFR) decline>30% baseline and<60 ml·min -1·(1.73 m 2) -1. Results:A total of 65 atypical MN patients were enrolled in this study. Compared with primary MN ( n=324), patients with atypical MN had younger age ( Z=-4.229, P<0.001), higher proportion of hematuria ( χ2=5.555, P=0.018), higher level of urinary protein ( Z=2.228, P=0.026) and lower level of eGFR ( t=-5.108, P<0.001); the proportion of IgG4 deposition in kidneys was lower ( χ2=8.081, P=0.004), and the proportions of IgA ( χ2=16.969, P<0.001) and IgM ( χ2=9.281, P=0.002) deposition were higher. There was no significant difference on gender, serum albumin, positive proportion of anti-PLA2R antibody, anti-PLA2R antibody level and kidney C3/C1q deposition between the two groups (all P>0.05). The proportions of atypical MN patients receiving renin-angiotensin aldosterone system inhibitors (49.3% vs 57.1%), calcineurin inhibitors (27.7% vs 19.1%) and cyclophosphamide (21.5% vs 23.8%) were comparable to those of primary MN patients (all P>0.05). The rates of clinical remission (80.0% vs 77.2%), partial remission (44.6% vs 44.1%), complete remission (35.4% vs 33.1%), spontaneous remission (36.9% vs 42.6%), response to cyclophosphamide (85.7% vs 81.8%), response to calcineurin inhibitor (88.9% vs 79.0%), and relapse (30.8% vs 26.8%) in atypical MN patients were comparable to those in primary MN patients (all P>0.05). During the follow-up 30.0(21.5, 61.5) months, 15 atypical MN patients (23.1%) had eGFR reduction>30%, among whom 7 patients (10.8%) had eGFR reduction>50% and 3 patients (4.6%) had end-stage kidney disease. There was no significant difference on poor kidney prognosis between the two groups (all P>0.05). Kaplan-Meier survival curve showed that patients with age>39 years old ( χ2=10.092, P=0.001), eGFR≤100 ml·min -1·(1.73 m 2) -1( χ2=5.491, P=0.019), tubular interstitial lesion ( χ2=6.999, P=0.008) and no nephropathy remission ( χ2=22.952, P<0.001) had earlier poor renal prognosis. Multivariate Cox regression analysis showed that no nephropathy remission ( HR=12.604, 95% CI 2.691-59.037, P=0.001) was an independent influencing factor for poor renal prognosis in atypical MN patients. Conclusion:No significant difference is found between atypical MN and primary MN on treatment responses and kidney prognosis, which implies that clinical practice of atypical MN can be performed by referring to the guidelines and experience of primary MN.

Objective:To investigate the clinical efficacy and prognosis of simultaneous resection of synchronous colorectal liver metastasis in patients admitted in different phases.Methods:The retrospective cohort study was conducted. The clinicopathological data of 346 patients who underwent simultaneous resection of synchronous colorectal liver metastasis in the First Affiliated Hospital of Naval Medical University (Changhai Hospital of Shanghai) from January 2000 to April 2021 were collected. There were 217 males and 129 females, aged (58±12)years. Patients under-went simultaneous resection of synchronous colorectal liver metastasis. Observation indicators: (1) clinicopathological features of patients with synchronous colorectal liver metastasis in 2000?2010 and 2011?2021; (2) surgical and postoperative situations of patients with synchronous colorectal liver metastasis in 2000?2010 and 2011?2021; (3) analysis of prognosis of patients with synchro-nous colorectal liver metastasis in 2000?2010 and 2011?2021. Follow-up was conducted using telephone interview or outpatient examination to detect survival of patients. The follow-up was performed once every 3 months, including blood routine test, liver and kidney function test, car-cinoembryonic antigen (CEA) test, CA19-9 test, abdominal B-ultrasound examination, and once every 6 months, including chest computed tomography (CT) plain scan, liver magnetic resonance imaging (MRI) and/or CT enhanced scan, abdominal or pelvic MRI and/or CT enhanced scan, within postoperative 2 year. The follow-up was performed once every 6?12 months within postoperative 2?5 years including above reexaminations. Electronic colonoscopy was performed once a year after operation. The follow-up was up to November 12, 2021. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distuibution were represented as M(range). Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test. Comparison of ordinal data was conducted using the rank sum test. Kaplan-Meier method was used to calculate survival rates and draw survival curves, and Log-Rank test was used to conduct survival analysis. Results:(1) Clinicopathological features of patients with synchronous colorectal liver metastasis in 2000?2010 and 2011?2021. Of the 346 patients, 59 cases underwent simultaneous resection within 2000?2010 and 287 cases underwent simultaneous resection within 2011?2021. The gender (males and females), cases with or without fundamental diseases, cases with the number of lymph nodes harvested in primary lesion as <12 or ≥12, the tumor diameter of primary lesion, the tumor diameter of liver metastasis lesion, the number of liver metastasis lesions, cases with or without preoperative treatment, cases with or without postoperative treatment, cases with adjuvant therapy as perioperative treatment, surgery or other treatment were 47, 12, 36, 23, 19, 40, (5.5±2.4)cm, (2.1±0.7)cm, 1.6±0.5, 59, 0, 16, 16, 0, 16, 43 in patients admitted in 2000?2010, respectively. The above indicators in patients admitted in 2011?2021 were 170, 117, 121, 166, 58, 229, (4.2±2.0)cm, (3.0±2.0)cm, 1.9±1.4, 208, 79, 34, 235, 74, 29, 184, respectively. There were significant differences in the above indicators between patients admitted in 2000?2010 and 2011?2021 ( χ2=8.73, 7.02, 4.07, t= 4.40, ?6.04, ?3.10, χ2=21.05, 28.82, 26.68, P<0.05). (2) Surgical and postoperative situations of patients with synchronous colorectal liver metastasis in 2000?2010 and 2011?2021. Cases with surgical methods as complete open surgery or laparoscopy combined with open surgery, the operation time, time to postoperative initial liquid food intake, cases with or without postoperative complications, cases with postoperative duration of hospital stay as ≤10 days or >10 days were 58, 1, (281±57)minutes, (5±1)days, 33, 26, 14, 45 in patients admitted in 2000?2010, respec-tively. The above indicators in patients admitted in 2011?2021 were 140, 147, (261±82)minutes, (3±1)days, 233, 54, 198, 89, respectively. There were significant differences in the above indicators between patients admitted in 2000?2010 and 2011?2021 ( χ2=49.04, t=2.24, 7.53, χ2=17.56, 26.02, P<0.05). There was no death in the 346 patients. (3) Analysis of prognosis of patients with synchro-nous colorectal liver metastasis in 2000?2010 and 2011?2021. Of the 346 patients, 295 cases were followed up for 47(range, 1?108)months. Of the 29 patients admitted in 2000?2010 who were followed up, there were 27 cases died. The median survival time, 1-, 3-, 5-year overall survival rates, 1-, 3-, 5-year disease free survival rates of patients admitted in 2000?2010 were 18.0 months (95% confidence interval as 12.7?23.3 months), 82.8%, 11.5%, 3.8%, 53.6%, 8.3%, 4.2%, respec-tively. Of the 266 patients admitted in 2011?2021 who were followed up, there were 109 cases died. The median survival time, 1-, 3-, 5-year overall survival rates, 1-, 3-, 5-year disease free survival rates of patients admitted in 2011?2021 were 54.0 months (95% confidence interval as 38.1?70.4 months), 93.3%, 61.8%, 47.0%, 68.2%, 33.7%, 28.3%, respectively. There were significant differences in overall survival rate and disease free survival rate between patients admitted in 2000?2010 and 2011?2021 ( χ2=47.57, 9.17, P<0.05). Conclusions:With the increase of the operation volume of simultaneous resection of synchronous colorectal liver metastasis, the operation time, time to postoperative initial liquid food intake, postoperative duration of hospital stay and postoperative complications have significantly decreased, while the overall survival rate and disease free survival rate have significantly increased.

The etiology and pathogenesis of keloid are still not clear. It is believed that the formation of keloid is due to the joint action of many factors, during which process the external factor of fibroblast play an important role. Reprogramming of glucose metabolism in keloid fibroblasts is a new research direction. TGF-β 1 and its related TGF-β 1/Smad signalling pathway are considered to be the most closely related to the formation of keloid. This article reviews the research progress on extracellular factors, glucose metabolism and signaling pathways of keloids.