Pristimerin, which is one of the compounds present in Celastraceae and Hippocrateaceae, has antitumor effects. However, its mechanism of action in esophageal squamous cell carcinoma (ESCC) remains unclear. This study aims to investigate the efficacy and mechanism of pristimerin on ESCC in vitro and in vivo. The inhibitory effect of pristimerin on cell growth was assessed using trypan blue exclusion and colony formation assays. Cell apoptosis was evaluated by flow cytometry. Gene and protein expressions were analyzed through quantitative reverse transcription-polymerase chain reaction (qRT-PCR), Western blotting, and immunohistochemistry. RNA sequencing (RNA-Seq) was employed to identify significantly differentially expressed genes (DEGs). Cell transfection and RNA interference assays were utilized to examine the role of key proteins in pristimerin?s effect. Xenograft models were established to evaluate the antitumor efficiency of pristimerin in vivo. Pristimerin inhibited cell growth and induced apoptosis in ESCC cells. Upregulation of Noxa was crucial for pristimerin-induced apoptosis. Pristimerin activated the Forkhead box O3a (FoxO3a) signaling pathway and triggered FoxO3a recruitment to the Noxa promoter, leading to Noxa transcription. Blocking FoxO3a reversed pristimerin-induced Noxa upregulation and cell apoptosis. Pristimerin treatment suppressed xenograft tumors in nude mice, but these effects were largely negated in Noxa-KO tumors. Furthermore, the chemosensitization effects of pristimerin in vitro and in vivo were mediated by Noxa. This study demonstrates that pristimerin exerts an antitumor effect on ESCC by inducing AKT/FoxO3a-mediated Noxa upregulation. These findings suggest that pristimerin may serve as a potent anticancer agent for ESCC treatment.
Forkhead Box Protein O3/genetics* ; Humans ; Apoptosis/drug effects* ; Esophageal Squamous Cell Carcinoma/physiopathology* ; Esophageal Neoplasms/physiopathology* ; Pentacyclic Triterpenes ; Animals ; Cell Line, Tumor ; Proto-Oncogene Proteins c-bcl-2/genetics* ; Mice ; Signal Transduction/drug effects* ; Mice, Nude ; Cell Proliferation/drug effects* ; Triterpenes/pharmacology* ; Xenograft Model Antitumor Assays ; Mice, Inbred BALB C ; Male ; Gene Expression Regulation, Neoplastic/drug effects*

Humans ; Artificial Intelligence ; Algorithms ; Brain ; Head

Objective:To propose a novel refined subtyping of Neer type Ⅵ proximal humerus fracture-dislocation and explore its clinical application.Methods:A retrospective study was conducted to analyze the data of 36 patients who had been admitted to Department of Orthopaedics, Beijing Friendship Hospital between January 2018 and December 2022 for surgical treatment with proximal humeral internal locking system (PHILOS) for Neer type Ⅵ proximal humerus fracture-dislocation. There were 25 males and 11 females with an age of (46.1±4.7) years. According to the fracture-dislocation and the separation between the humeral head and the stem, the patients with Neer type Ⅵ proximal humerus fracture-dislocation were further subdivided into 3 subtype groups (known as STAB subtypes): subtype-T group (dislocation of the shoulder joint with macro-capitellar fracture, n=14), subtype-A group (proximal humerus fracture-dislocation without separation of the humeral head from the humeral stem, n=12), and subtype-B group (dislocation of the proximal humerus fracture with separation of the humeral head from the humeral stem, n=10). STAB subtyping was performed on the same imaging data from all the patients at admission and 2 weeks later by 4 surgeons with different qualifications. Interobserver and intraobserver agreements of the STAB typing were verified. The operation time, fracture healing time, visual analogue scale (VAS) pain score, Constant-Murley score, and complications were recorded for patients in the 3 subtype groups. Results:The differences in the preoperative general data were not statistically significant between the 3 subtype groups, indicating comparability ( P>0.05). All patients were followed up for (11.2±4.2) months. The inter-observer and intra-observer Kappa values for STAB subtyping were 0.94 and 0.95, respectively. For subtype-T group, subtype-A group, and subtype-B group, respectively, the operation time was (68.9±5.6) min, (90.0±5.2) min, and (113.0±9.2) min; the fracture healing time was (9.0±0.8) weeks, (10.3±1.2) weeks, and (11.8±0.9) weeks; the VAS scores at the last follow-up were 1.0(1.0, 2.0) points, 2.0(1.0, 2.0) points, 2.0(2.0, 3.0) points; the Constant-Murley scores at the last follow-up were (83.6±2.8) points, (74.5±3.0) points, and (62.7±5.5) points. The differences between the 3 subtype groups in the above items were statistically significant ( P<0.05). The overall success rate of closed reduction was 61.1% (22/36). In subtype-T, subtype-A, and subtype-B groups, respectively, the number of patients with successful closed reduction was 13, 7, and 2, while complications occurred in 2, 3, and 6 patients. The differences in closed reduction and complications among the 3 groups were statistically significant ( P<0.05). Conclusions:The STAB subtyping proposed in this study demonstrates strong intra- and inter-group consistency. Because the refined STAB subtyping can reveal differences among all the Neer type Ⅵ proximal humeral fractures and dislocations, it may provide more precise guidance for personalized clinical decision-making.

Objective:To establish a nomogram prediction model for recurrence within 2 years after radical resection of hepatocellular carcinoma (HCC) based on clinical and ultrasonographic characteristics.Methods:Clinical data from 405 HCC patients (including 327 males and 78 females), aged 60 (53, 66) years old, who underwent radical hepatectomy in the Zhongshan Hospital, Fudan University, from January to December 2021, were retrospectively collected. The patients were divided into two groups: the training group ( n=283) and the validation group ( n=122). Based on recurrence within 2 years after surgery, the 283 patients in the training group were further categorized into the recurrence group ( n=73) and the non-recurrence group ( n=210). Among the 122 patients in the validation group, 33 had recurrence within 2 years, while 89 did not. Data on age, microvascular invasion, alpha-fetoprotein (AFP), AFP lentil lectin-reactive fraction (AFP-L3), protein induced by vitamin K absence or antagonist-II (PIVKA-II), tumor number, and enhancement homogeneity were collected. Logistic regression analysis was performed on the training group to identify risk factors associated with postoperative recurrence, and a nomogram model for predicting HCC recurrence was constructed based on these factors. Calibration curves were used to compare the consistency between predicted and actual outcomes in both the training and validation groups. Results:Multivariate logistic regression analysis revealed that younger age ( OR=0.976, 95% CI: 0.953-1.000, P=0.004), higher AFP-L3 ( OR=1.066, 95% CI: 1.014-1.120, P=0.012), higher PIVKA-II ( OR=1.000, 95% CI: 1.000-1.001, P=0.042), multiple tumors ( OR=0.399, 95% CI: 0.225-0.706, P=0.038), and heterogeneous enhancement ( OR=0.472, 95% CI: 0.243-0.916, P=0.045) were significant risk factors for recurrence after partial hepatectomy in HCC patients. The nomogram constructed based on these variables had a C-index of 0.87 (95% CI: 0.81-0.93) in the training group and 0.83 (95% CI: 0.77-0.89) in the validation group. The calibration curves for predicting recurrence within 2 years after partial hepatectomy in HCC patients showed a high degree of fit in both the training and validation groups, indicating a good agreement between predicted and actual outcomes. Conclusion:The nomogram model constructed based on preoperative clinical and ultrasonographic characteristics can effectively predict the risk of recurrence within 2 years after radical resection of HCC.

Objective To quantitatively study the influence of changes in probe position on the quality control test results of dental panoramic radiography and to provide a reference for analyzing the sources of deviations in quality control test results. Methods Eight different models of dental panoramic X-ray machines were selected for this study. The film analysis method was used to determine the position of the central axis of the main beam on the image detector. The position of the probe was accurately controlled through an auxiliary moving device. The tube voltage, radiation output, and half-value layer of the useful beam were measured for positions at the center of the beam; 1 cm upward, downward, left, and right from the center of the beam; and 2 cm upward, downward, left, and right from the center of the beam. Results The tube voltage, radiation output, and half-value layer had a maximum value at the center of the beam, with a decrease in the value as the position deviated from the center. There were significant differences in the probe position sensitivity between different models of dental panoramic radiography equipment. A 2 cm deviation in the probe position resulted in an impact on the measured tube voltage of less than 5.3 kV (5.8%) for less sensitive equipment. A 2 mm deviation in the probe position resulted in an impact on the measured tube voltage of less than 5.4 kV (6.0%) for sensitive equipment. Conclusion The probe position can lead to deviation in the quality control test results of dental panoramic photography. Therefore, determining the position of the central axis of the main beam on the image detector for accurate positioning of the probe is crucial for quality control testing.

Circular RNAs (circRNAs) are endogenous non-coding RNAs with covalently closed structures, which have important functions in plants. However, their biogenesis, degradation, and function upon treatment with gibberellins (GAs) and auxins (1-naphthaleneacetic acid, NAA) remain unknown. Here, we systematically identified and characterized the expression patterns, evolutionary conservation, genomic features, and internal structures of circRNAs using RNase R-treated libraries from moso bamboo (Phyllostachys edulis) seedlings. Moreover, we investigated the biogenesis of circRNAs dependent on both cis- and trans-regulation. We explored the function of circRNAs, including their roles in regulating microRNA (miRNA)-related genes and modulating the alternative splicing of their linear counterparts. Importantly, we developed a customized degradome sequencing approach to detect miRNA-mediated cleavage of circRNAs. Finally, we presented a comprehensive view of the participation of circRNAs in the regulation of hormone metabolism upon treatment of bamboo seedlings with GA and NAA. Collectively, our study provides insights into the biogenesis, function, and miRNA-mediated degradation of circRNAs in moso bamboo.
RNA, Circular/metabolism* ; Multiomics ; Poaceae/metabolism* ; Seedlings/genetics* ; Hormones/metabolism* ; MicroRNAs/metabolism* ; Gene Expression Regulation, Plant

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection, of which the pathogenesis is complex and the mortality rate is high. However, current basic research is facing the dilemma of high heterogeneity and difficult translation to clinical practice. In-depth basic research is one of the most important ways to break through the "bottleneck" of clinical diagnosis and treatment of sepsis. The purpose of this review is to analyze the current progress and challenges in the field of basic research on sepsis, and look forward to the potential research directions in the future. Cell function, energy metabolism, microbiota, epigenetics and recovery period of sepsis may be the research priorities.

Sepsis is defined as life-threatening organ dysfunction secondary to a dysregulated host response to infection.It is considered a major cause of death and health loss worldwide.Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021, released in October 2021, included 93 total statements, which addressed screening and initial resuscitation, infection, hemodynamics, ventilation, additional therapies, and goals of care and long-term outcomes.This review interpreted the content ofthe guidelines and also analyzed the underlying issues.The guidelines provide a more accurate framework and guidance for the diagnosis and treatment of sepsis, and may also provide an opportunity to urge researchers in the field of sepsis worldwide to implement further individualized research.

Minimally invasive surgery helps enhance postoperative recovery and improve quality of life of the patients by minimizing surgical trauma and decreasing incisional pain. Minimally invasive pulmonary resection, including both video-assisted thoracoscopic surgery and robotic surgery, is mainly used for surgical management of peripheral early stage lung cancers. Because of tumor location, lymph node involvement, and treatment modalities, surgery for central lung cancers is often technically demanding. Open thoracotomy is still the dominant approach for these tumors, especially when complex procedures such as sleeve lobectomy or pneumonectomy are needed. With the advent of surgical techniques, minimally invasive techniques have started to be tried in treatment of central lung cancers. Initial results have proven their feasibility and safety in sleeve lobectomy and pneumonectomy, showing a great potential of minimally invasive surgery in the future. Further study is necessary to prove its functionally superiority and oncological equivalence to open surgery, so that more lung cancer patients could benefit for minimally invasive surgery.

Objective To present clinical effects of debridement, antibiotics, irrigation and retention of implant (DAIR) with integrated antibiotics application in treating periprosthetic joint infection (PJI) occurred within 3 months after primary surgery. Methods We retrospectively analyzed patients who received DAIR between January 2011 and October 2015. A total of 49 pa?tients with a mean age of 62.38±14.56 years (range, 26-82 years) were included in this study, including 29 males and 20 females. There are 27 knees and 22 hips. Twenty?three patients has sinus tract. Failure was defined as subsequent surgical intervention for infection after the index procedure; persistent fistula, drainage, or excessive joint pain at the last follow?up; death related to the PJI; chronic suppression with antibiotics. Results There were 18 (36.7%) culture negative cases and 31 (63.3%) culture positive cases, including 28.6% (14/49) methicillin?sensitive staphylococcus aureus, 4% (2/49) methicillin?resistant staphylococcus aure?us, 2% (1/49) methicillin?resistant staphylococcus epidermidis, 2%(1/49) mixed infection with fungus and so on. Within the 68.34± 14.02 months (range, 39-94 months) follow?up duration, the Knee Society Score (KSS) score was improved from 38.37 ± 12.39 points (range, 18-62 points) pre?operatively to 82.26±10.50 points (range, 49-96 points) post?operatively (t=-17.09, P<0.001). KSS function score was improved from 42.19±10.14 points (range, 26-67 points) pre?operatively to 75.22±11.60 points (range, 41-90 points) post?operatively (t=-12.53, P<0.001). Harris hip score was improved from 47.41±8.39 points (range, 32-58 points) pre?operatively to 86.41±6.07 points (range, 71-96 points) post?operatively (t=-23.38, P<0.001). There were 6 patients receiving sub?sequent surgical intervention as failure. The mean duration from the index surgery to failure was 5.75±3.00 months (range, 1.5-10 months). Conclusion The present protocol of DAIR for dealing with early?stage PJI, which is less than 3 months after primary TKA or THA, is fairly effective.