Objective To analyze the PLCβ4 gene mRNA expression and its clinical significance in hepatocellular carcinoma (HCC) based on TCGA database. Methods Based on the data on 424 clinical samples (including 374 cases of HCC tissues and 50 cases of nontumor liver tissues) in the TCGA database, Kaplan–Meier method, Cox regression analysis, and immune infiltration analysis were performed to evaluate the relationship between PLCβ4 gene and the clinical characteristics and survival prognosis of HCC patients. Correlation analysis between PLCβ4 gene and 24 types of immune cells was applied to investigate the relationship between PLCβ4 gene and immune cell infiltration and mRNA expression level of TP53 gene, a high-frequency mutation gene in HCC. In addition, paraffin sections of highly, moderately, and poorly differentiated tumor tissues and normal liver tissues from HCC patients were collected. The histopathological observation was carried out via HE staining method, and the expression levels of PLCβ4 and Ki-67 proteins in each clinical sample were verified through the immunohistochemical method. Results The expression level of PLCβ4 gene in HCC was significantly higher than that in normal tissues (P<0.01), and all patients in the PLCβ4 high-expression group had a significantly longer overall survival than those in the low-expression group (P<0.05), which suggested that PLCβ4 substantially affected the prognosis of HCC patients. Correlation analysis showed that the expression level of PLCβ4 gene was highly correlated with immune cell infiltration and the expression level of TP53 gene. As verified by clinical sample experiments, HE staining experiments and immunohistochemical results revealed that PLCβ4 gene expression in HCC tissue samples was significantly higher than that in normal tissues (P<0.001), and it was negatively correlated with the degree of differentiation. Conclusion PLCβ4 may serve as an independent prognostic factor in HCC and is expected to be a novel molecular target for HCC treatment.

With the increasing proportion of human papilloma virus(HPV)infection in the pathogenic factors of oro-pharyngeal cancer,a series of changes have occurred in the surgical treatment.While the treatment mode has been im-proved,there are still many problems,including the inconsistency between diagnosis and treatment modes,the lack of popularization of reconstruction technology,the imperfect post-treatment rehabilitation system,and the lack of effective preventive measures.Especially in terms of treatment mode for early oropharyngeal cancer,there is no unified conclu-sion whether it is surgery alone or radiotherapy alone,and whether robotic minimally invasive surgery has better func-tional protection than radiotherapy.For advanced oropharyngeal cancer,there is greater controversy over the treatment mode.It is still unclear whether to adopt a non-surgical treatment mode of synchronous chemoradiotherapy or induction chemotherapy combined with synchronous chemoradiotherapy,or a treatment mode of surgery combined with postopera-tive chemoradiotherapy.In order to standardize the surgical treatment of oropharyngeal cancer in China and clarify the indications for surgical treatment of oropharyngeal cancer,this expert consensus,based on the characteristics and treat-ment status of oropharyngeal cancer in China and combined with the international latest theories and practices,forms consensus opinions in multiple aspects of preoperative evaluation,surgical indication determination,primary tumor re-section,neck lymph node dissection,postoperative defect repair,postoperative complication management prognosis and follow-up of oropharyngeal cancer patients.The key points include:① Before the treatment of oropharyngeal cancer,the expression of P16 protein should be detected to clarify HPV status;② Perform enhanced magnetic resonance imaging of the maxillofacial region before surgery to evaluate the invasion of oropharyngeal cancer and guide precise surgical resec-tion of oropharyngeal cancer.Evaluating mouth opening and airway status is crucial for surgical approach decisions and postoperative risk prediction;③ For oropharyngeal cancer patients who have to undergo major surgery and cannot eat for one to two months,it is recommended to undergo percutaneous endoscopic gastrostomy before surgery to effectively improve their nutritional intake during treatment;④ Early-stage oropharyngeal cancer patients may opt for either sur-gery alone or radiation therapy alone.For intermediate and advanced stages,HPV-related oropharyngeal cancer general-ly prioritizes radiation therapy,with concurrent chemotherapy considered based on tumor staging.Surgical treatment is recommended as the first choice for HPV unrelated oropharyngeal squamous cell carcinoma(including primary and re-current)and recurrent HPV related oropharyngeal squamous cell carcinoma after radiotherapy and chemotherapy;⑤ For primary exogenous T1-2 oropharyngeal cancer,direct surgery through the oral approach or da Vinci robotic sur-gery is preferred.For T3-4 patients with advanced oropharyngeal cancer,it is recommended to use temporary mandibu-lectomy approach and lateral pharyngotomy approach for surgery as appropriate;⑥ For cT1-2N0 oropharyngeal cancer patients with tumor invasion depth＞3 mm and cT3-4N0 HPV unrelated oropharyngeal cancer patients,selective neck dissection of levels ⅠB to Ⅳ is recommended.For cN+HPV unrelated oropharyngeal cancer patients,therapeutic neck dissection in regions Ⅰ-Ⅴ is advised;⑦ If PET-CT scan at 12 or more weeks after completion of radiation shows intense FDG uptake in any node,or imaging suggests continuous enlargement of lymph nodes,the patient should undergo neck dissection;⑧ For patients with suspected extracapsular invasion preoperatively,lymph node dissection should include removal of surrounding muscle and adipose connective tissue;⑨ The reconstruction of oropharyngeal cancer defects should follow the principle of reconstruction steps,with priority given to adjacent flaps,followed by distal pedicled flaps,and finally free flaps.The anterolateral thigh flap with abundant tissue can be used as the preferred flap for large-scale postoperative defects.

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.

Gastric ulcer is a common digestive system disease,and the long-term use of non-steroidal anti-inflammatory drugs(NSAIDs)is the second most important cause.NSAID-induced gastric ulcer animal models are key experimental tools for studying the pathogenesis,corresponding treatment method,and effective mechanisms of NSAID-induced gastrointestinal injury.However,there are currently a lack of reviews on NSAID-induced gastric ulcer animal models.This review summarizes and compares the relevant literature on animal research into indomethacin-and aspirin-induced gastric ulcers in the past 10 years,including the selection of experimental animals,drug solvents,and specific modeling method.The limitations of current models,such as the cumbersome modeling method,incomplete modeling details,inadequate models for clinical use,and lack of comparative drug research,are discussed.Feasible solutions are proposed with the aim of providing an effective reference for research in this field.

Severe pneumonia is one of the most common infectious diseases and the leading cause of sepsis and septic shock. Preventing infection, balancing the patient's immune status, and anti-coagulation therapy are all important elements in the treatment of severe pneumonia. As multi-target agents, Xuebijing injection (XBJ) has shown unique advantages in targeting complex conditions and saving the lives of patients with severe pneumonia. This review outlines progress in the understanding of XBJ's anti-inflammatory, endotoxin antagonism, and anticoagulation effects. From the hundreds of publications released over the past few years, the key results from representative clinical studies of XBJ in the treatment of severe pneumonia were selected and summarized. XBJ was observed to effectively suppress the release of pro-inflammatory cytokines, counter the effects of endotoxin, and assert an anticoagulation effect in most clinical trials, which are consistent with experimental studies. Collectively, this evidence suggests that XBJ could play an important and expanding role in clinical medicine, especially for sepsis, septic shock and severe pneumonia. Please cite this article as: Zhang M, Zheng R, Liu WJ, Hou JL, Yang YL, Shang HC. Xuebijing injection, a Chinese patent medicine, against severe pneumonia: Current research progress and future perspectives. J Integr Med. 2023; 21(5): 413-422.
Humans ; Nonprescription Drugs ; Shock, Septic/drug therapy* ; Sepsis/drug therapy* ; Endotoxins ; Anticoagulants/therapeutic use*

Objective:To investigate the clinical effect of "ladder reduction method" in the treatment of iliac fracture combined anterior dislocation of sacroiliac joint.Methods:The retrospective analysis was performed on 10 cases of iliac fracture combined anterior sacroiliac joint dislocation admitted to the Affiliated Hospital of Yunnan University from February 2010 to January 2022, among which 5 cases were males and 5 cases were females, aged ranging from 22 to 52 years, with an average age of 38.8 years. All patients were injured in car accidents including 5 cases of C1.2, 3 cases of C2, and 2 cases of C3 fractures according to Tile classification. All patients were treated with the "ladder reduction method" with plate and screw fixation. In the first step, 1-2 Schanz pins were inserted into the iliac crest to control the ilium, and the Schanz pins were appropriately pulled laterally; in the second step, the periosteal stripper was used to pry the reduction between the sacrum and ilium; in the third step, for the patients who still could not be reduced, a 2.5 mm diameter Kirschner wire was placed on the sacrum close to the iliac crest, and a periosteal stripper was inserted between the sacrum and iliac crest, with its tip against the Kirkner wire, and the iliac crest as the fulcrum for pry pulling to separate the two. In the fourth step, the pry was maintained, and then another 2.5 mm diameter Kirschner wire was placed on the sacrum close to the internal margin of the iliac bone. The periosteal stripper was continued to pry between the sacrum and the iliac bone, and the operation was repeated. At the same time, the anterior dislocation of the sacroiliac joint was reduced with traction of the lower limb. Postoperatively, the quality of reduction was evaluated by the Matta score, and the degree of functional recovery after pelvic fracture was evaluated by the Majeed score.Results:Four patients completed the reduction through the first and second steps, and 6 cases of refractory sacroiliac joint anterior dislocation were successfully reduced through the first to fourth steps. The fracture reduction time of 6 patients with refractory anterior sacroiliac joint dislocation was 39.67±3.09 min (range, 35-44 min), with intraoperative blood loss of 300.00±141.42 ml (range, 150-600 ml); in the other 4 cases, the fracture reduction time was 36.75±4.38 min (range, 30-42 min), and the intraoperative blood loss was 225.00±44.30 ml (range, 200-300 ml). All 10 patients were followed up for 12.9±3.7 months (range, 9-20 months). The anterior and posterior pelvic ring fractures were healed in all patients, and the fracture healing time was 12.77±1.62 weeks (range, 10.71-15.28 weeks). At the last follow-up, Matta evaluation was excellent in 5 cases, good in 1 case, and excellent in the other 4 cases. The Majeed scores of 6 cases were 86.50±6.08 points (range, 74-92 points), of which 5 cases were excellent and 1 case was good. The other 4 cases were 81.5±9.39 scores (range, 71-94), of which 2 were excellent and 2 were good.Conclusion:The "ladder reduction method" is a safe, effective and easy-to-operate method for the treatment of iliac fracture combined anterior dislocation of the sacroiliac joint, especially for refractory anterior dislocation of the sacroiliac joint, which can still obtain satisfactory curative effects.

This study aims to explore the effect of tryptanthrin on potential metabolic biomarkers in the serum of mice with ulcerative colitis(UC) induced by dextran sulfate sodium(DSS) based on liquid chromatography-mass spectrometry(LC-MS) and predict the related metabolic pathways. C57BL/6 mice were randomly assigned into a tryptanthrin group, a sulfasalazine group, a control group, and a model group. The mouse model of UC was established by free drinking of 3% DSS solution for 11 days, and corresponding drugs were adminsitrated at the same time. The signs of mice were observed and the disease activity index(DAI) score was recorded from the first day. Colon tissue samples were collected after the experiment and observed by hematoxylin-eosin(HE) staining. The levels of interleukin-4(IL-4), interleukin-10(IL-10), tumor necrosis factor-α(TNF-α), interleukin-6(IL-6), and interleukin-8(IL-8) in the serum were measured by enzyme linked immunosorbent assay(ELISA). The serum samples were collected from 6 mice in each group for widely targeted metabolomics. The metabolic pathways were enriched by MetaboAnalyst 5.0. The results showed that compared with the model group, tryptanthrin treatment decreased the DAI score(P<0.05), alleviated the injury of the colon tissue and the infiltration of inflammatory cells, lowered the levels of proinflammatory cytokines, and elevated the levels of anti-inflammatory cytokines in the serum. The metabolomic analysis revealed 28 differential metabolites which were involved in 3 metabolic pathways including purine metabolism, arachidonic acid metabolism, and tryptophan metabolism. Tryptanthrin may restore the metabolism of the mice with UC induced by DSS to the normal level by regulating the purine metabolism, arachidonic acid metabolism, and tryptophan metabolism. This study employed metabolomics to analyze the mechanism of tryptanthrin in the treatment of UC, providing an experimental basis for the utilization and development of tryptanthrin.
Mice ; Animals ; Colitis, Ulcerative/drug therapy* ; Tryptophan ; Arachidonic Acid/metabolism* ; Mice, Inbred C57BL ; Colon ; Cytokines/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Interleukin-6/metabolism* ; Metabolomics ; Purines/therapeutic use* ; Dextran Sulfate/metabolism* ; Disease Models, Animal ; Colitis/chemically induced*

Interleukin-1 receptor associated kinase 4 (IRAK-4), acting as a serine threonine kinase, is considered as a key signal node for the transduction of IL-1R family and TLRs signal pathway. Studies have found that IRAK-4 has a hand in many signal pathways, involving the inflammatory response of human joints, intestines, liver and nervous system, as well as other autoimmune diseases. It is also one of the causes of drug resistance of some cancer cells. Therefore, IRAK-4 tends to be an effective therapeutic target for inflammatory diseases and cancer. The prospects for the development of drugs in this pathway is to develop novel IRAK-4 small molecule inhibitors and investigate their safety and effectiveness, enrich the clinical treatment of inflammatory and cancer diseases finally. This paper classified and summarized the latest research progress on small molecule inhibitors of IRAK-4 signaling pathway according to structures of the compounds, in order to provide assistances and references for the research and development of related drugs.

OBJECTIVE To explore the efficacy of Sour Jujube Seed Decoction combined with Huanglian Wendan Decoction on adult chronic insomnia and its effect on hypnotic withdrawal.METHODS 187 patients with chronic insomnia were included for anal-ysis,including 102 in the traditional Chinese medicine(TCM)group and 85 in the western medicine group.The TCM group was trea-ted with Sour Jujube Seed Decoction combined with Huanglian Wendan Decoction,while the western medicine group was treated with benzodiazepine under the consideration of doctor.The intervention period was 1 month,with assessments using the Pittsburgh Sleep Quality Index(PSQI)conducted before and after the intervention.Follow-up evaluations were performed at 3 months and 6 months re-spectively after the intervention.RESULTS There was no significant difference between the two groups at baseline.After the inter-vention,the PSQI scores of patients in both groups were significantly improved(P<0.01).Among them,the TCM group was better than the western medicine group in the improvement of sleep quality and sleeping pills,total PSQI score reduction(P<0.01).The re-sults of linear regression analysis showed that after controlling for confounding factors,the regression coefficients of the TCM group in two different models were1.821 and 1.922 respectively,and the former was statistically significant(P<0.05).By screening patients who took hypnotics at baseline in the TCM group and comparing them with those in the western medicine group,the influencing factors of hypnotic withdrawal were analyzed.During the 3-month follow-up,25 out of 39 patients in the TCM group and 17 out of 80 patients in the western medicine group had hypnotic withdrawal(χ2= 19.25,P<0.001);during the 6-month follow-up,23 of the 39 patients in the TCM group and 18 of the 79 patients in the western medicine group had hypnotic withdrawal(χ2= 13.53,P<0.001),the with-drawal rate of patients in the TCM group was significantly higher than that in the western medicine group.Further regression analysis showed that after adjusting for confounding factors,the results showed that the western medicine group had a significantly higher rate of not withdrawal than the TCM group at 3 months(OR=5.50,95%CI:2.30～13.72)and 6 months(OR=6.43,95%CI:2.54～17.77),and the results were statistically different(P<0.05).CONCLUSION Sour Jujube Seed Decoction combined with Huangli-an Wendan Decoction is effective in treating adult chronic insomnia and assisting in hypnotic withdrawal.

Objective:To analyze and summarize the clinical effects of 3D printed porous titanium-alloy prosthesis implantation in the treatment of long bone defects of lower extremities.Methods:We retrospectively studied the clinical cases with lower extremity bone defect treated by 3D printed porous titanium prostheses from December 2017 to November 2021. 18 patients who were followed up for more than 12 months were included in this study. The enrolled patients included 12 males and 6 females, with an average of 48.9±22.5 years (range, 13-79 years), and an average body mass index of 23.1±4.3 kg/m 2 (range, 17.2-27.1 kg/m 2). There were 14 osteomyelitis-derived bone defects and 4 nonunion-derived bone defects. The bone defect locations included 10 cases of femur and 8 cases of tibia. The average bone defect distance was 13.9±9.7 cm (range, 5.8-31.2 cm), and the proportion of the defect length to the long bone (femur of tibia) was average 33.7%±16.8% (range, 15.0%-63.0%). The clinical efficacy was comprehensively evaluated through gross observation, imaging evaluation, changes in the total length of lower extremities and long bones, femorotibial angle (FTA) measurement, lower extremity functional scale (LEFS), satisfaction, complications and other indicators, focusing on the stabilization mechanism of the prosthesis and the regeneration of new bone. Results:All 18 patients were followed up for 12-35 months, with an average of 16.3 months. Postoperative X-rays at 1, 3, 12 and 24 months showed that new bone could gradually creep along the prosthesis surface. The preoperative bone defect length of long bone and total length of lower limb were respectively 39.4±4.0 cm and 80.5±5.7 cm, which were different from those of the healthy side by 1.6±1.0 cm and 1.5±1.1 cm. One week after implantation, the length of long bone and lower limb was 39.9±3.5 cm and 80.9±6.2 cm, respectively, and the average difference was 1.0±0.6 cm and 0.9±1.1 cm compared with the healthy side. At the last follow-up, the length of long bone and lower limb was 39.7±3.6 cm and 80.9±7.8 cm, with an average difference of 1.8±1.1 cm and 1.0±0.7 cm from the healthy side. There were no significant differences in the length of long bone and lower limbs at the three time points before surgery, one week after surgery and the last follow-up ( F=0.12, 0.04; P>0.05). The average FTA of the affected limb was 174.7° (173.9°, 175.5°), 175.2°(173.5°, 176.4°), and 175.0°(173.5°, 176.3°) at three time nodes, before surgery, one week after surgery and the last follow-up, respectively, and there was no significant statistical difference in pairwise comparison ( Z=0.01, P>0.05). Patients had a mean LEFS score of 50 (46, 51) at the last follow-up, significantly higher than the preoperative score of 20 (17, 21) ( Z=-5.56, P<0.001). The mean satisfaction score of the 18 patients at the last follow-up was 9.7. Two patients (11.1%) had screw fractures but all 3D printed porous titanium alloy prostheses remained stable without significant loosening or displacement. Two patients (11.1%) had nail channel infection of external fixator, all patients with channel infection were cured by intravenous antibiotics combined with local disinfection and dressing change. Conclusion:The implantation of 3D printed porous titanium-alloy prosthesis could efficiently and safely repair the long bone defects of the lower extremities. The prosthesis could maintain stable in the early and middle postoperative period. The length of the long bones and lower limbs did not change significantly with the weight-bearing and functional exercise of the limbs. The new bone could gradually crawl and grow from both ends of the defect, and the patient's limb function recovered significantly, and the patient's satisfaction was high.