Acute liver failure (ALF) is a life-threatening condition associated with macrophage-mediated inflammatory responses. Effective therapies and drugs are still lacking to date. Here, we reveal that a derivative of xanthohumol, CAM12203, alleviates lipopolysaccharide (LPS) + d-galactosamine (D-GalN)-induced ALF through limiting macrophage-mediated inflammation, with the most significant impact on interleukin-1β (IL-1β) transcription. Through biotin labeling-mediated pull-down and LC-MS/MS analysis, diacylglycerol kinase ζ (DGKζ), a lipid-metabolizing kinase, is identified as the direct target of CAM12203. Mechanistically, DGKζ is induced in macrophages upon inflammatory stimuli and is upregulated observed on clinical liver failure samples. Its product phosphatidic acid (PA) boosts phospholipase C (PLC)-inositol 1,4,5-trisphosphate (IP₃)-Ca²⁺ signaling and subsequent janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) cascade, ultimately promoting IL-1β production and liver failure. DGKζ knockdown/ablation or inhibition significantly impairs the DGKζ-STAT3-IL-1β pathway along with ALF progression. Finally, CAM12203 is confirmed to be a new DGKζ inhibitor and acts against inflammation in a DGKζ-reliant manner. Taken together, CAM12203 inhibits IL-1β transcription in macrophages by binding to DGKζ and blocking the DGKζ-STAT3 axis, thereby exerting an ameliorative effect on ALF. These results not only highlight CAM12203 as a promising lead compound for ALF treatment, but also define DGKζ as a novel therapeutic target.

Peroxisome proliferator activated receptor-α (PPAR-α) is significantly expressed in various tissues such as the liver, kidney, myocardium, and skeletal muscle, which plays a central role in the development of various diseases by regulating key physiological processes such as energy homeostasis, redox balance, inflammatory response, and ferroptosis. As an important metabolic and excretory organ of the body, renal dysfunction can lead to water and electrolyte imbalance, toxin accumulation, and multiple system complications. The causes of kidney injury are complex and diverse, including acute injury factors (such as ischemia/reperfusion, nephrotoxic drugs, septic shock, and immune glomerulopathy), as well as chronic progressive causes [such as metabolic disease-related nephropathy, hypertensive nephropathy (HN)], and risk factors such as alcohol abuse, obesity, and aging. This review briefly describes the structure, function, and activity regulation mechanism of PPAR-α, systematically elucidates the molecular regulatory network of PPAR-α in the pathological process of kidney injury including acute kidney injury (AKI) such as renal ischemia/reperfusion injury (IRI), drug-induced AKI, sepsis-associated acute kidney injury (SA-AKI), glomerulonephritis, chronic kidney disease (CKD) such as diabetic nephropathy (DN), HN, and other kidney injury, and summarizes the mechanisms related to PPAR-α regulation of kidney injury, including regulation of metabolism, antioxidation, anti-inflammation, anti-fibrosis, and anti-ferroptosis. This review also evaluates PPAR-α's medical value as a novel therapeutic target, and aims to provide theoretical basis for the development of kidney protection strategies based on PPAR-α targeted intervention.
Humans ; PPAR alpha/metabolism* ; Acute Kidney Injury/therapy* ; Animals ; Kidney/metabolism*

OBJECTIVES: Long noncoding RNAs (lncRNA) play important roles in the pathological processes of angiogenesis-related diseases such as cancer and diabetic retinopathy. This study aims to identify global research trends and hotspots in the field of lncRNAs in angiogenesis-related diseases and to explore future research directions. METHODS: Relevant literature published between 2012 and 2022 was retrieved from the Web of Science Core Collection (WoSCC). A total of 1 516 articles on lncRNAs and angiogenesis-related diseases were included for bibliometric analysis. CiteSpace and VOSviewer were used to analyze publication countries, institutions, journals, authors, co-cited references, and key words. RESULTS: The number of publications in this field has shown a steadily increasing trend from 2012 to 2022, peaking in 2021. China has the highest number of publications, while the United States ranked highest in centrality. Nanjing Medical University was the most prolific institution. Liu Y was the most productive author, while Wang Y ranked first in co-citation frequency. Cell was the most frequently cited journal. The latest terms of burst key words were vascular remodeling, dysfunction, heart, target, suppress, and pulmonary arterial hypertension. CONCLUSIONS From 2012 to 2022, research on lncRNAs in angiogenesis-related diseases has grown significantly. China leads in publication volume, while the United States holds the most academic influence. Emerging research hotspots such as vascular remodeling and dysfunction point to key directions for future research.
Bibliometrics ; RNA, Long Noncoding/genetics* ; Humans ; Neovascularization, Pathologic/genetics* ; Neoplasms/genetics* ; Diabetic Retinopathy/genetics* ; Biomedical Research/trends* ; China ; Angiogenesis

Objective:To evaluate the safety and feasibility of laparoscopic radical anterograde modular pancreatosplenectomy (Lap-RAMPS).Methods:From Jan 2014 to Dec 2020, the clinical data of 83 patients who underwent laparoscopic radical resection for pancreatic tail cancer in LiHuili Hospital of Ningbo Medical Center were retrospectively analyzed.Results:Eighty-three cases were divided into Lap-RAMPS group (44 cases) and laparoscopic conventional distal pancreatectomy and splenectomy(Lap-CDP) group (39 cases). There were no significant differences in the duration of surgery [(245.34±70.30) min vs. (239.87±68.10) min], intraoperative blood lose [(159.32±115.60) ml vs. (208.97±161.70) ml] and intraoperative transfusions (2 cases vs. 3 cases) between the two groups ( P>0.05). There were no statistical significance in both groups in postoperative pancreatic fistula, postoperative bleeding grade, postoperative gastric emptying delay, Clavien-Dindo complication and postoperative hospital stay ( P>0.05). There were statistically significant differences in the negative margin rate (93.2% vs. 76.9%),lymph node harvest(12.91±8.24 vs. 8.49±6.85) and median survival time (25.0 months vs. 15.0 months) between the two groups ( P<0.05). Conclusion:Lap-RAMPS for pancreatic tail cancer is safe and feasible, increasing the negative rate of pancreatic margins, improving the lymph node harvest, and prolonging patients' survival time.

Objective:To explore the clinical and endoscopic features of patients with autoimmune gastritis (AIG) and to improve the accuracy of clinical diagnosis of AIG.Methods:From January 3, 2020 to November 25, 2021, the general information (gender, age), laboratory examination indicators and endoscopic findings of 179 AIG patients diagnosed at the Second Affiliated Hospital of Chongqing Medical University were retrospectively analyzed. The laboratory examination indicators included hemoglobin, gastrin-17, pepsinogen (PG), anemia combination indicators (ferritin, vitamin B 12), thyroid function indicators (thyroid-stimulating hormone, thyroglobulin antibody and thyroid peroxidase antibody), Helicobacter pylori, and anti-parietal cell antibody and anti-intrinsic factor antibody. Descriptive methods were used for statistical analysis. Results:Among the 179 AIG patients, there were 42 males (23.5%) and 137 females (76.5%), with an average age of (55.23±12.04) years old. The gastrin-17 level of AIG patients was 195.31 ng/L (143.64 ng/L, 273.61 ng/L), PG Ⅰ level and PG Ⅰ/PG Ⅱ ratio were 12.40 μg/L (7.65 μg/L, 19.40 μg/L) and 1.03 (0.66, 1.52), respectively. There were 15.3% (18/118) of the AIG patients with iron deficiency anemia, and 16.1% (19/118) with megaloblastic anemia. The positive rate of anti-parietal cell antibody was 71.8% (51/71), and the positive rate of anti-intrinsic factor antibody was 25.4% (18/71). The serum thyroid-stimulating hormone level increased in 27.3% (15/55) of the patients, and the positive rates of thyroglobulin antibody and thyroid peroxidase antibody were 31.6% (12/38) and 47.4% (18/38), respectively. The positive rate of Helicobacter pylori was 29.7% (38/128). The endoscopic appearance of AIG indicated reverse atrophy, characterized by obvious atrophy in gastric fundus and gastric body mucosa, however the atrophy of gastric antrum was not obvious. Under endoscopy yellow-white turbid mucus, which was difficult to be washed, was found in 67.0% (120/179) of the patients, and under endoscopy the residual gastric fundus glands could be seen in 19.6% (35/179) of the patients. Among 179 AIG patients, 7 cases (3.9%) of neuroendocrine tumor (NET), 7 cases (3.9%) of early gastric adenocarcinoma (including 1 case of poorly differentiated adenocarcinoma), 1 case (0.6%) of adenoma, and 14 cases (7.8%) of hyperplastic polyps were found. Except for the case of poorly differentiated adenocarcinoma undergoing surgery, the others were treated with endoscopic resection. Conclusions:When unexplained iron deficiency anemia, megaloblastic anemia, or reverse atrophy is found, AIG should be considered. AIG patients are at high risk for gastric cancer and NET, and should be closely followed up, and active treatment should be given before anemia and neurological symptoms appear.

Objective To investigate the expression level of calcitonin gene-related peptide-receptor component protein (CRCP) in hepatocellular carcinoma (HCC) tissue and adjacent tissue and its association with the clinicopathological features and prognosis of patients. Methods HCC and adjacent tissue samples were collected from 79 HCC patients who underwent surgical resection in Eastern Hepatobiliary Surgery Hospital, Navy Medical University, from June 2003 to September 2009. Tissue microarray was prepared, and immunohistochemistry was used for quantitative analysis. Related proteins were extracted and measured by Western blot, and the expression of CRCP was compared between HCC tissue and adjacent tissue. The chi-square test was used for comparison of categorical data between groups. The receiver operating characteristic (ROC) curve analysis was performed to obtain the area under the ROC curve (AUC), and goodness of fit was evaluated. Youden index was used to determine the optimal cut-off value. and the Kaplan-Meier survival analysis was used to analyze the association of CRCP expression with the recurrence and prognosis of HCC, and the log rank test was used for comparison between the two groups. Results Among the 79 HCC patients, there were 67 male patients and 12 female patients, with an age of 10-72 years, and 20 patients had portal vein tumor thrombus. As for pathological grade, 1 had grade 4 HCC, 61 had grade 3 HCC, and 17 had grade 2 HCC; as for BCLC stage, 5 had BCLC stage 0 HCC, 55 had BCLC stage A HCC, 11 had BCLC stage B HCC, and 8 had BCLC stage C HCC. Western blot showed that the expression level of CRCP in HCC tissue was lower than that in adjacent tissue in 4 patients, and immunohistochemistry showed that the expression level of CRCP in HCC tissue was significantly lower than that in adjacent tissue in 75.9% of the patients. Low CRCP expression was associated with CK19 positivity, incomplete tumor capsule, presence of portal vein tumor thrombus, and high pathological grade ( χ 2 =6.410, 4.829, 9.319, and 9.083, all P < 0.05). Compared with the low CRCP expression group, the high CRCP expression group had a significantly longer overall survival time and a significantly lower recurrence rate ( P < 0.001 and P =0.009). Conclusion Patients with low CRCP expression in HCC tissue tend to have a poorer prognosis than those with high CRCP expression, and CRCP may participate in the development, progression, and metastasis of HCC, suggesting that this molecule can be used as a potential biomarker to predict the prognosis of HCC patients.

Objective:To propose a markless patient setup workflow based on the optical surface monitoring system (AlignRT) and open-face mask immobilization for whole-course head tumor radiotherapy, assess the setup time and repositioning frequency of the proposed workflow, and conduct a comparative analysis of the differences, correlation, and consistency of the setup errors of the AlignRT and cone beam CT (CBCT) systems.Methods:A retrospective analysis was conducted for the data on the errors of 132 fractionated setup based on open-face mask immobilization of 33 head tumor patients. AlignRT-guided markless patient setup workflow was applied throughout the radiotherapy. Meanwhile, the body structures automatically generated by the treatment planning system were used as body references. The 6-degree-of-freedom (6DoF) setup errors (lateral, vertical, longitudinal, rotation, pitch, roll, and yaw directions), setup time, and repositioning frequency of the AlignRT and CBCT systems were recorded and analyzed. The Wilcoxon and Spearman analyses were used to statistically assess the differences and correlation of the setup errors of the two systems. Moreover, the Bland-Altman analysis was employed to evaluate the consistency of the two systems.Results:The 6DoF setup errors of CBCT were within the clinical tolerance (linear motions: -0.30 to 0.30 cm; rotational motions: -2.0° to 2.0°). The setup time and repositioning frequency of CBCT were (98 ± 31) s and 1.51% (2/132), respectively. There was no significant difference in setup errors between the two systems except those in x-axis ( Z = -3.11, P= 0.002), y-axis ( Z = -7.40, P<0.001), and Pitch ( Z= -4.48, P<0.001). There was a significant positive correlation between the setup errors along lateral ( rs = 0.47, P<0.001) and vertical ( rs = 0.29, P = 0.001) directions, rotation (Rtn; rs = 0.47, P<0.001), pitch (Pitch; rs = 0.28, P = 0.001) and roll (Roll; rs = 0.45, P<0.001) of the two systems. The 95% limits of agreement (95% LoA) of 6DoF setup errors were -0.12 to 0.09 cm, -0.07 to 0.17 cm, -0.19 to 0.20 cm, -1.0° to 0.9 °, -1.0° to 1.5°, and -0.9° to 1.0°, respectively. The 95% confidence interval (95% CI) of 95% LoA was -0.14 to 0.11 cm, -0.09 to 0.19 cm, -0.23 to 0.23 cm, -1.2° to 1.1°, -1.2° to 1.7°, and-1.0° to 1.1°, respectively, all of which were within the permissible error ranges. The 6DoF setup error difference of 3.41% (27/792< 5%) was beyond the 95% LoA. The maximum absolute differences of 6DoF setup errors within the 95% LoA were 0.12, 0.16, 0.19 cm, 0.9°, 1.5°, and 1.0°, respectively. Conclusions:The proposed markless setup workflow based on AlignRT combined with open-face mask immobilization for whole-course head tumor radiotherapy exhibits reasonable agreement and consistency with the patient setup using CBCT, with acceptable clinical efficiency. It can be applied to the first radiotherapy and the real-time monitoring of therapy to improve the safety and thus is of value in clinical applications.

Objective To study dynamic compression performance of adipose tissues, so as to further reveal the damage mechanism, and provide references for medical treatment.Methods Based on the improved split Hopkinson pressure bar (SHPB) experimental device, the adipose tissue dynamic compression experiment was conducted. The stress-strain curves of adipose tissues at different strain rates were obtained. Then the numerical model of SHPB was established, and the experimental process was simulated and analyzed. The numerical simulation for penetration process of 32 mm diameter rubber non-lethal projectile into the simulated target in human abdomen was carried out.Results Adipose tissues had a noticeable strain rate effect. The stress-strain curves at two high strain rates were approximately straight lines. The slope was similar, and the elastic modulus was 3.25 MPa, which was about 6 times of that under a quasi-static state. The simulation curves of fat SHPB were consistent with the experimental curves, which verified correctness of the constitutive model. In the process of non-lethal projectile penetrating human abdomen, an annular convex area similar to water wave appeared on skin surface, and the fat layer absorbed about 67% of the impact kinetic energy.Conclusions The experimental data of adipose tissues are very accurate. Numerical simulation can reproduce the penetration process well, and provide references for studying the damaging effect of non-lethal weapons on human body.

Objective:To analyze the clinical efficacy and pregnancy outcomes of gonadotropin-releasing hormone agonist (GnRH-a) based fertility-sparing re-treatment in women with endometrial carcinoma (EC) and atypical endometrial hyperplasia (AEH) who failed with oral progestin therapy.Methods:Forty cases with EC or AEH who failed to respond to oral progestin were included from January 2012 to December 2020 at Peking Union Medical College Hospital. Combination of GnRH-a with levonorgestrel-releasing intrauterine system (group GLI: a subcutaneous injection of GnRH-a every 4 weeks and LNG-IUS insertion constantly) or the combination of GnRH-a with aromatase inhibitor (group GAI: a subcutaneous injection of GnRH-a every 4 weeks and oral letrozole 2.5 mg, daily) were used for these patients. Histological evaluation were performed at the end of each course (every 3-4 months) by hysteroscopy and curettage. After the complete remission (CR), all patients were followed up regularly.Results:(1) Clinical characteristics:among the 40 patients with EC or AEH, the median age at diagnosis was 31 years (range: 22-40 years) and the median body mass index was 24.7 kg/m 2 (range: 18.9-39.5 kg/m 2). (2) Efficacy of fertility-sparing re-treatment: 37 (92%, 37/40) patients achieved CR, 6 (6/7) in AEH and 31 (94%, 31/33) in EC patients. The CR rate was 93% (26/28) and 11/12 in group GLI and GAI, respectively. The median time to CR was 5 months (range: 3-12 months). At the end of the first therapy course, the CR rates in AEH and EC were 5/7 and 42% (14/33), at the second course, the CR rates were 6/7 and 82% (27/33), respectively. (3) Recurrence: after 25 months of median follow-up duration (range: 10-75 months), 8 (22%, 8/37) women developed recurrence, 1/6 in AEH and 7 (23%, 7/31) in EC patients, with the median recurrence time of 18 months (range: 9-26 months). Among them, two cases who had completed childbirth chose to receive hysterectomy directly. Six patients met the criteria of fertility-preserving therapy and received conservative treatment again and 5 (5/6) of them achieved CR. (4) Pregnancy: of the 37 patients with CR, 33 desired to conceive. Ten women attempted to get pregnancy spontaneously and 23 cases with assisted reproductive technology. Fourteen (42%, 14/33) patients became pregnant, including 9 (27%, 9/33) live births, 3 (9%, 3/33) missed abortions, and 2 (6%, 2/33) miscarriages at the second trimester. Conclusions:GnRH-a based fertility-sparing re-treatment in AEH or EC patients who failed with oral progestin therapy achieved good treatment effect and reproductive outcomes. It is an encouraging alternative regime for patients who failed with oral progestin therapy.

Objective:To build patient setup workflow based on the optical surface monitoring system (OSMS) in postoperative radiotherapy for breast cancer, and compare the setup accuracy and PTV margin between OSMS based setup and conventional skin marker based method.Methods:The setup data of 20 cases of postoperative radiotherapy for breast cancer were retrospectively analyzed and divided into two groups: OSMS setup group and conventional skin marker setup group with 10 patients in each group. All CBCT rigid registration values in six dimensions ( x, y, z, Rtn, Pitch, Roll) were obtained, and the absolute value and distribution of errors were statistically analyzed by single sample t-test and χ2-test respectively. Finally, the CTV-PTV margins were compared using the extension formula. Results:The mean values in OSMS setup group and conventional skin marker setup group in sixdirections were 0.18 and 0.18 cm, 0.12 and 0.13 cm, 0.13 and 0.23 cm, 0.55° and 0.74°, 0.63° and 0.99°, 0.67° and 0.68°, respectively, while the standard deviations were 0.13 and 0.12 cm, 0.09 and 0.09 cm, 0.11 and 0.16 cm, 0.37° and 0.55°, 0.53° and 0.65°, 0.42° and 0.55°, respectively. The setup error differed in both z and Pitch directions( t=3.53, 2.98, P<0.05), while the error distribution rate difference was statistically significant between two groups in z direction( χ2=11.090, P<0.05). The CTV-PTV margins in OSMS setup group and conventional skin marker setup group were 0.28 and 0.26 cm, 0.21 and 0.20 cm, 0.24 and 0.35 cm, respectively. Conclusions:The proposed OSMS-based patient setup work flow is better than the conventional skin marker based method in setup accuracy, with significant setup error differences in z and Pitch directions. The proposed OSMS workflow is of potential clinical benefit.