OBJECTIVES: To investigate the expression of parathyroid hormone-like hormone (PTHLH) in hepatocellular carcinoma (HCC) and analyze its correlation with clinical prognosis, its regulatory effects on HCC cell behaviors, and the signaling pathways mediating its effects. METHODS: We analyzed the differential expression of PTHLH in HCC and adjacent tissues and its association with patient prognosis based on data from TCGA and GEO databases and from 70 HCC patients treated in our hospital. The effects of PTHLH knockdown and overexpression on proliferation, migration, and invasion of cultured HCC cells were investigated using CCK-8 assay, colony formation assay, Transwell migration and invasion assays, and the signaling pathways activated by PTHLH were detected using Western blotting. RESULTS: TCGA and GEO database analysis showed significant overexpression of PTHLH mRNA in HCC tissues, which was associated with poor prognosis of the patients (P<0.05). High PTHLH mRNA expression was a probable independent prognostic risk factor for HCC (P<0.05). In the clinical samples, PTHLH mRNA and protein expressions were significantly higher in HCC tissues than in the adjacent tissues (P<0.001 or 0.01). Univariate and multivariate Cox regression analyses suggested that high PTHLH mRNA expression was an independent risk factor to affect postoperative disease-free survival of HCC patients (P<0.05). The prognostic prediction model based on PTHLH mRNA expression showed an improved accuracy for predicting the risk of postoperative recurrence in HCC patients. In cultured HCC cells, PTHLH overexpression significantly promoted cell proliferation, colony formation, migration and invasion, and caused activation of the ERK/JNK signaling pathway in Huh7 and Hep3B cells. CONCLUSIONS High PTHLH expression promotes HCC progression and is associated with poor patient prognosis. Its pro-tumor effects may be mediated by activation of the ERK/JNK signaling pathway.
Humans ; Carcinoma, Hepatocellular/metabolism* ; Liver Neoplasms/metabolism* ; Prognosis ; Cell Proliferation ; Parathyroid Hormone-Related Protein/genetics* ; Cell Line, Tumor ; Cell Movement ; Disease Progression ; Signal Transduction ; Male ; RNA, Messenger/genetics* ; Female

OBJECTIVE: To explore the feasibility of incorporating simple bedside indicators into death predictive model for elderly critically ill patients based on interpretability machine learning algorithms, providing a new scheme for clinical disease assessment. METHODS: Elderly critically ill patients aged ≥ 65 years who were hospitalized in the intensive care unit (ICU) of Tacheng People's Hospital of Ili Kazak Autonomous Prefecture from June 2017 to May 2020 were retrospectively selected. Basic parameters including demographic characteristics, basic vital signs and fluid intake and output within 24 hours after admission, as well acute physiology and chronic health evaluation II (APACHE II), Glasgow coma score (GCS) and sequential organ failure assessment (SOFA) were also collected. According to outcomes in hospital, patients were divided into survival group and death group. Four datasets were constructed respectively, namely baseline dataset (B), including age, body temperature, heart rate, pulse oxygen saturation, respiratory rate, mean arterial pressure, urine output volume, infusion volume, and crystal solution volume; B+APACHE II dataset (BA), B+GCS dataset (BG), and B+SOFA dataset (BS). Then three machine learning algorithms, Logistic regression (LR), extreme gradient boosting (XGboost) and gradient boosting decision tree (GBDT) were used to develop the corresponding mortality predictive models within four datasets. The feature importance histogram of each prediction model was drawn by SHapley additive explanation (SHAP) method. The area under curve (AUC), accuracy and F1 score of each model were compared to determine the optimal prediction model and then illuminate the nomogram. RESULTS: A total of 392 patients were collected, including 341 in the survival group and 51 in the death group. There were statistically significant differences in heart rate, pulse oxygen saturation, mean arterial pressure, infusion volume, crystal solution volume, and etiological distribution between the two groups. The top three causes of death were shock, cerebral hemorrhage, and chronic obstructive pulmonary disease. Among the 12 prognostic models trained by three machine learning algorithms, overall performance of prognostic models based on B dataset was behind, whereas the LR model trained by BA dataset achieved the best performance than others with AUC of 0.767 [95% confidence interval (95%CI) was 0.692-0.836], accuracy of 0.875 (95%CI was 0.837-0.903) and F1 score of 0.190. The top 3 variables in this model were crystal solution volume with first 24 hours, heart rate and mean arterial pressure. The nomogram of the model showed that the total score between 150 and 230 were advisable. CONCLUSION The interpretable machine learning model including simple bedside parameters combined with APACHE II score could effectively identify the risk of death in elderly patients with critically illness.
Humans ; Critical Illness ; Machine Learning ; Aged ; Algorithms ; Intensive Care Units ; Retrospective Studies ; APACHE ; Prognosis ; Organ Dysfunction Scores ; Hospital Mortality ; Male ; Female

Organoids are three-dimensional (3D) cellular structures formed through the differentiation and self-organization of pluripotent stem cells or tissue-derived cells, showing considerable potential in the research on disease mechanism, personalized medicine, and developmental biology. However, the development of organoids is limited by the complex composition, batch-to-batch variations, and immunogenicity of basement-membrane matrix in the current culture system, which hinders the clinical translation and in vivo applications of organoids. Hydrogels are highly hydrated 3D polymer network materials, with modifiable mechanical and biochemical properties by engineering, representing an ideal alternative to basement-membrane matrix. This article reviews the research progress in engineered hydrogels with defined composition currently used in organoid culture. We introduce the structural characteristics and engineering design considerations of hydrogels, emphasize the latest research progress and specific application cases, and discuss the future development of these engineered hydrogels, provide valuable insights for the further advancement and optimization of engineered hydrogels for organoid.
Hydrogels/chemistry* ; Organoids/cytology* ; Tissue Engineering/methods* ; Humans ; Animals ; Pluripotent Stem Cells/cytology* ; Cell Culture Techniques, Three Dimensional/methods* ; Tissue Scaffolds

The main clinical research advances of critical care in 2023 includes: new trials of Chinese herbal medicine, hydroxocobalamin (vitamin B12), methylene blue as well glucocorticoids have shown the potential to improve outcomes of patients with sepsis and septic shock; international committees launched new global definition and managing recommendations for acute respiratory distress syndrome (ARDS). Besides, a cluster of new evidences has emerged in many aspects as following: fluid control strategy in sepsis (restrictive/liberative), antibiotic infusion strategy (continuous/intermittent), oxygen-saturation targets for mechanical ventilation (conservative/liberative), blood pressure targets after resuscitation from out-of-hospital cardiac arrest (hypotension/hypertension), blood pressure targets after successful stroke thrombectomy (intensive/conventional), and nutritional support strategies (low protein-calories/conventional protein-calories, fasting/persistent feeding before extubation). Thus, given above progress, carrying out high -quality domestic multi-center clinical registration researches, constructing shareable standardized databases, as well raising public awareness of sepsis, should be the essential steps to improve our level of intensive care medicine.

It is found that medicinal and food homologous Chinese materia medica such as Astragali Radix, Ginseng Radix et Rhizoma, Citri Reticulatae Pericarpium, Citri Fructus, Citri Sarcodactylis Fructus, Citri Exocarpium Rubrum, Curcumae Longae Rhizoma, Gardeniae Fructus, Glycyrrhizae Radix et Rhizoma, Puerariae Lobatae Radix, Portulacae Herba, Lycii Fructus and Piperis Longi Fructus have significant effects on the prevention and treatment of diabetic cardiomyopathy. Active components, including Astragalus polysaccharide, Astragalus agaloside, ginsenoside Rb1, ginsenoside Rg1 and naringin can prevent and treat myocardial damage in diabetes mellitus through mechanisms of anti-inflammation, anti-oxidative stress, inhibition of apoptosis, regulation of autophagy, anti-fibrosis, and regulation of energy metabolism, etc.

Objective To investigate the pathological damage to and inflammation of different intestinal segments in a rat model of severe hemorrhage,and to explore the effect of polarization of intestinal macrophage on the pathophysiology of intestinal inflammation.Methods Male Wistar rats were randomly divided into two groups:the sham operation group and hemorrhage group.In the hemorrhage group,40％of the total blood volume was lost in 25-30 minutes,while in the sham operation group,only the femoral artery and vein were intubated without bleeding.The rats were killed at 0,3,6,12 and 24 hours.The entire intestine was isolated quickly,and sections of the intestine were cut at the duodenum,jejunum,ileocecal junction,colon and rectum for histopathological evaluation.ELISA was adopted to determine related inflammation factors while multi-color immunohistochemistry was used to calculate macrophage surface markers.The data was statistically analyzed.Results(1)Compared with the sham group,there was no significant difference in colon histology at 3 h and 6 h,but significant difference was detected in rectum scores only at 24 h.The scores of other intestinal segments were significantly different at each time point.The severity of ileocecal and colonic lesions after bleeding increased with time.The duodenum,jejunum and ileocecum were more critically injured at 3 h than the rectum at 6 h.The injury to the duodenum,jejunum,ileum and colon was much more pronounced than to the rectum at 12 h.(2)The expressions of TNF-α and IL-1β in the rectum were increased significantly at 12 h post operation.The expressions of IL-1β,TNF-α in the jejunum increased obviously at 3 h and 6 h,respectively.(3)Three hours after severe bleeding,the level of macrophages in the jejunum and ileocececal area increased significantly,and the percentage of M1 macrophages was higher.After 6 hours,the proportion of M2 macrophages in the jejunum and M1 macrophages decreased significantly.After 3 hours,the percentage of M1 macrophages in the colon decreased,but that of M2 macrophages increased.The proportion of M2 polarized macrophages in the duodenum and rectum increased at 3 h after severe bleeding but decreased at 6 h.Conclusion Pathological damage to intestinal sections after bleeding varies depending on the time,and is correlated with the inflammatory level of macrophages.

The safety and efficacy of laparoscopic surgery for colorectal cancer has been confirmed by several large-scale clinical studies.Laparoscopy has become the main modality of surgical treatment for colorectal cancer in China.Based on evidence-based medicine and the experience accumulated in clinical practice,laparoscopic colorectal surgical techniques are still being continuously optimised and improved.The key techniques mainly revolve around the following three aspects:①complete surgical excision extension;②appropriate lymph node dissection area;③safe digestive tract reconstruction.Prioritizing the standardization of laparoscopic colorectal cancer surgery,promoting the consistent implementation of these procedures,establishing a scientific evaluation system,thoroughly assessing surgical outcomes,and conducting high-quality clinical research are essential for enhancing the standardization of laparoscopic colorectal cancer surgery in China.

The incidence of osteoporotic thoracolumbar vertebral fracture (OTLVF) in the elderly is gradually increasing. The kyphotic deformity caused by various factors has become an important characteristic of OTLVF and has received increasing attention. Its clinical manifestations include pain, delayed nerve damage, sagittal imbalance, etc. Currently, the definition and diagnosis of OTLVF with kyphotic deformity in the elderly are still unclear. Although there are many treatment options, they are controversial. Existing guidelines or consensuses pay little attention to this type of fracture with kyphotic deformity. To this end, the Lumbar Education Working Group of the Spine Branch of the Chinese Medicine Education Association and Editorial Committee of Chinese Journal of Trauma organized the experts in the relevant fields to jointly develop Clinical guidelines for the diagnosis and treatment of osteoporotic thoracolumbar vertebral fractures with kyphotic deformity in the elderly ( version 2024), based on evidence-based medical advancements and the principles of scientificity, practicality, and advanced nature, which provided 18 recommendations to standardize the clinical diagnosis and treatment.

Laparoscopic right hemicolectomy is currently the most commonly used surgical procedure for right-sided colon cancer. Although this procedure is maturing in terms of key tech-niques such as the extent of surgical resection, the extent of lymph node dissection, and the recons-truction of digestive tract, it still lacks a standardized surgical procedure and quality control system. In the pre-preparation phase of the COLOR Ⅳ study (an international, multicenter, randomized contro-lled trail comparing the efficacy of intracorporeal anastomosis versus extracorporeal anasto-mosis in laparoscopic right hemicolectomy for right-sided colon cancer), the research team of the authors formulates a standardized procedure for laparoscopic right hemicolectomy based on the Delphi survey, and develops a competency assessment tool for surgical ability and quality. Attempts are being made to automate the evaluation of surgical techniques using artificial intelligence. It is hoped that the above work will help colorectal surgeons to standardize surgical operations and reduce complications, provide support for the homogenization of multicenter clinical studies, and promote the implementation of structured training for this procedure.

Objective:To investigate the specimen quality of intersphincteric resection with transabdominal transanal mixed approach for rectal cancer in the Chinese Transanal Total Mesorectal Excision Registry Collaborative (CTRC) database.Methods:The retrospective case-control study was conducted. Based on the concept of real-world research, the clinicopathological data of 281 pati-ents with rectal cancer in the CTRC database who underwent intersphincteric resection with trans-abdominal transanal mixed approach in 19 medical centers, including the Beijing Friendship Hospital of Capital Medical University et al, from November 15,2017 to December 31,2023 were collected. There were 196 males and 85 females, aged 61(range, 27-87)years. Observation indicators: (1) preoperative examinations; (2) neoadjuvant therapy; (3) postoperative examinations; (4) analysis of influencing factors for positive circumferential margin in surgical specimen of intersphincteric resec-tion for rectal cancer. Measurement data with normal distribution were represented as Mean±SD. Measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers or percentages. The chi-square test was used for univariate analysis. Logistic regression model was used for multivariate analysis. Results:(1) Preoperative examinations. Of the 281 patients, 234 cases underwent preoperative pelvic magnetic resonance imaging (MRI) examina-tion. There were 2 cases in clinical stage T0, 3 cases in clinical stage T1, 58 cases in clinical stage T2, 137 cases in clinical stage T3, 24 cases in clinical stage T4, 3 cases in clinical stage Tx, 7 cases missing clinical T staging data. There were 87 cases in clinical stage N0, 68 cases in clinical stage N1, 60 cases in clinical stage N2, 9 cases in clinical stage Nx, 10 cases missing clinical N staging data. There were 30 cases with mesorectal fascia invasion, 53 cases with extramural venous invasion. The distance from lower margin of tumor to anal margin was 41.9(range, 1.0-80.0)mm. (2) Neoadjuvant therapy. Of the 281 patients, 125 cases underwent neoadjuvant therapy, including 39 cases receiving chemo-therapy alone, 6 cases receiving short-course simultaneous chemoradiotherapy, 5 cases receiving short-course simultaneous chemoradiotherapy and delayed surgery, 48 cases receiving long-course simultaneous chemoradiotherapy, 2 cases receiving other treatments, and 25 cases missing neoadju-vant therapy data. (3) Postoperative examinations. Of the 281 patients, 249 cases achieved R 0 resection, 9 cases achieved R 1 resection, and there were 23 cases missing surgical margin data. The maximum tumor diameter, the number of lymph nodes harvested and positive rate of vessel carcinoma embolus were 30.0(range, 0.5-200.0)mm, 13(range, 0-70) and 27.55%(73/265) in 281 patients. There were 252 patients with circumferential margin records, showing positive in 15 cases, with a positive rate as 5.95%(15/252). The minimum distance from deep part of tumor to circumferential margin was 7.0(range, 0-150.0)mm in 252 patients. There were 85 cases with distal margin records, showing positive in 1 case, and the distance from lower margin of tumor to distal margin was 10.0(range, 0-202.0)mm. There were 273 patients with specimen integrity records, which showed intact specimen in 208 cases, fair specimen in 58 cases, poor specimen in 4 cases, unevaluated specimen in 3 cases. There were 7 cases with rectal perforation. Of the 281 patients, cases in pathological stage T0, Tis, T1, T2, T3, T4 were 14, 5, 22, 107, 113, 12, respectively, and there were 8 cases missing pathological T staging data. Of the 281 patients, cases in pathological stage N0, N1a, N1b, N1c, N2a, N2b were 176, 27, 27, 11,20, 12, respectively, and there were 8 cases missing pathological N staging data. Of the 281 patients, there were 4 cases with distant metastasis, 262 cases without distant metastasis, 5 cases not evaluated, and 10 cases missing tumor metastasis data. Of the 125 patients undergoing neoadjuvant therapy, there were 85 cases with tumor regression grade records, including 16 cases as grade 1, 27 cases as grade 2, 19 cases as grade 3, 15 cases as grade 4, 8 cases as grade 5. (4) Analysis of influencing factors for positive circumferential margin in surgical specimen of intersphincteric resection for rectal cancer. Results of univariate analysis showed that preoperative T staging on preoperative pelvic MRI, mesorectal fascia invasion, extramural venous invasion, pathological T staging, and pathological N staging were related factors for positive circumferential margin in surgical specimen of intersphincteric resection for rectal cancer ( P<0.05). Conclusions:Intersph-incteric resection with transabdominal transanal mixed approach has good specimen quality and low positive rate of surgical margin. T staging on preoperative pelvic MRI may be related to positive circumferential margin after intersphincteric resection for rectal cancer.