OBJECTIVE To investigate the efficacy and safety of ropivacaine combined with oxycodone for the analgesia of iliac fascia nerve block in patients undergoing hip replacement. METHODS Sixty-six patients who underwent hip replacement at the Central Hospital of Enshi Tujia and Miao Autonomous Prefecture from October 2023 to April 2024 were selected and randomly divided into observation group and control group， with 33 cases in each group. Before induction of anesthesia， ultrasound-guided iliac fascial nerve block was performed. Patients in the observation group were treated with 0.33% ropivacaine+0.1 mg/kg oxycodone injection mixture 30 mL， and patients in the control group were treated with 0.33% ropivacaine injection 30 mL. The time of first postoperative rescue analgesia， 24 h postoperative analgesic drug consumption， sensory block and motor block effective and maintenance time， satisfaction degree， numerical rating scale （NRS） pain score， Ramsay sedation score， muscle strength score， heart rate （HR）， mean arterial pressure （MAP）， oxygen saturation（SpO2）， sleep score， anxiety score， and the occurrence of adverse reactions in the two groups were all recorded. RESULTS Compared with the control group， the first rescue analgesia time after operation was significantly prolonged in the observation group， and 24 h postoperative analgesic drug consumption after operation decreased； the effective time of sensory block was significantly shortened， and the maintenance time of sensory block was significantly prolonged， and the satisfaction score was higher； the NRS pain score after iliac fascia nerve block was lower， HR and MAP were lower， and the anxiety score and sleep score 24 and 48 h after operation were lower （P＜0.05）. In terms of safety， patients in both groups had adverse reactions after operation， such as hypertension， nausea， vomiting， and dizziness， but there was no significant difference in the incidence of adverse reactions between the two groups （P＞0.05）. CONCLUSIONS Oxycodone combined with ropivacaine shows good efficacy and safety for iliac fascial nerve block analgesia in patients undergoing hip replacement， can significantly prolong the analgesic time of ropivacaine， reduce postoperative analgesic drug consumption， improve the sleep quality of patients， and promote the rapid recovery of patients.

OBJECTIVE To investigate the clinical characteristics of drug-induced liver injury （DILI） induced by glucagon- like peptide-1 receptor agonists （GLP-1RAs）， and to provide a reference for safe clinical medication. METHODS Using search terms such as “GLP-1”“GLP-1RAs”“semaglutide” “drug-induced liver injury”， relevant studies from PubMed， Embase， the Cochrane Library， CNKI， Wanfang Data and VIP were retrieved. Descriptive analysis was performed on cases of DILI induced by GLP-1RAs. RESULTS A total of 11 studies， comprising 11 patients， were included. Among them， 4 were male （36.4%） and 7 were female （63.6%）. Patient ages ranged from 17 to 64 years； 5 patients （45.5%） were between 50 and 65 years old. Six patients were treated for diabetes， and five for weight loss. Ten patients had underlying diseases. The shortest time to the onset of DILI was 5 days after medication， while the longest was approximately 180 days. The DILIs induced by GLP-1RAs were mainly hepatocellular injury type （6 cases）； severity levels included severe （3 cases）， moderate （6 cases）， and mild （2 cases）. Gastrointestinal symptoms and jaundice were the most common clinical manifestations. The association between DILI and GLP- 1RAs was assessed as “probable” in 10 cases and “possible” in 1 case. All 11 patients improved after drug discontinuation and （or） corresponding treatment. CONCLUSIONS DILI induced by GLP-1RAs is relatively concentrated in patients aged 50-65， with a higher incidence in females. The risk may be further increased in patients with underlying diseases. Clinical use of these agents should enhance pharmaceutical care， including identification of high-risk populations and patient education （especially symptom recognition）. When relevant symptoms appear， the drug should be discontinued immediately， with liver-protective therapy initiated when necessary， to ensure patient safety of drug use.

ObjectiveTo observe the effects of Hedysari Radix polysaccharide on the apoptosis of gastric sinus smooth muscle cells and explore the underlying mechanism via the insulin-like growth factor-1 （IGF-1）/phosphatidylinositol 3-kinase （PI3K）/serine-threonine kinase （Akt） pathway in the rat model of diabetic gastroparesis （DGP）. MethodSixty-two Wistar male rats were randomized into a blank group （n=12） and a modelling group （n=50）. The rat model of DGP was established by small-dose multiple intraperitoneal injections of streptozotocin combined with an irregular high-fat and high-sugar diet for 4 weeks. The modeled rats were randomized into model group， mosapride citrate （1.35 mg·kg^-1）， and high-， medium-， and low-dose （200， 100， and 50 mg·kg^-1， respectively） Hedysari Radix polysaccharide groups. The rats were administrated with corresponding drugs by gavage， and those in the blank and model groups with equal volumes of pure water by gavage once a day for 8 consecutive weeks. The random blood glucose and body mass were measured every 2 weeks， and gastric emptying rate was calculated. Hematoxylin-eosin （HE） staining was used to observe the pathological changes of smooth muscle in gastric antrum， and terminal deoxynucleoitidyl transferase-mediated nick-end labeling （TUNEL） was employed to detect the apoptosis of smooth muscle cells in the gastric antrum. The expression of IGF-1， phosphorylated （p）-PI3K， and p-Akt in the smooth muscle of gastric sinus tissue was detected by immunohistochemistry. Western blot was employed to determine the protein levels of IGF-1， p-PI3K/PI3K， p-Akt/Akt， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein （Bax） in the smooth muscle of the gastric antrum. ResultCompared with the blank group， the model group showed elevated random blood glucose at all time points （P<0.01）， decreased body mass and gastric emptying rate （P<0.01）， increased apoptotic index of smooth muscle cells in the gastric antrum （P<0.01）， down-regulated protein levels of IGF-1， p-PI3K/PI3K， p-Akt/Akt， and Bcl-2， and up-regulated protein level of Bax （P<0.01）. Compared with the model group， the 8 weeks of drug administration lowered the random blood glucose， increased the body mass and gastric emptying rate （P<0.05， P<0.01）， decreased the apoptotic index of smooth muscle cells in the gastric antrum （P<0.05， P<0.01）， up-regulated the protein levels of IGF-1， p-PI3K/PI3K， p-Akt/Akt， and Bcl-2， and down-regulated the protein level of Bax （P<0.05， P<0.01）. Compared with the mosapride citrate group，the administration of low-dose Hedysari Radix polysaccharide for 6 and 8 weeks lowered the random blood glucose and decreased the body mass （P<0.05， P<0.01），low and medium-dose Hedysari Radix polysaccharide decreased the gastric emptying rate and the apoptotic index of smooth muscle cells in the astragaloside low-dose group decreased （P<0.05）. The protein levels of IGF-1，p-PI3K/PI3K，p-Akt/Akt and Bcl-2（low dose）were down-regulated and the protein level of Bax was up-regulated by low doses of Hedysari Radix polysaccharide （P<0.05， P<0.01）. Compared with high-dose Hedysari Radix polysaccharide， low-dose Hedysari Radix polysaccharide elevated random blood glucose and reduced body mass after 6 and 8 weeks of administration （P<0.05， P<0.01）， and the low and medium doses decreased the gastric emptying rate， increased the apoptotic index of smooth muscle cells in the gastric antrum （P<0.05， P<0.01）， down-regulated the protein levels of IGF-1， p-PI3K/PI3K， p-Akt/Akt， and Bcl-2， and up-regulated the protein level of Bax （P<0.05， P<0.01）. Compared with the medium-dose group，the low-dose group of Hedysari Radix polysaccharide had lower body mass，lower gastric emptying rate in rats，higher apoptotic index of smooth muscle cells in gastric sinus tissue after 6 and 8 weeks of administration （P<0.05， P<0.01）， and lower protein expression of IGF-1，p-PI3K/PI3K，p-Akt/Akt. ConclusionHedysari Radix polysaccharide protects the smooth muscle cells in gastric antrum against apoptotic injury and promotes gastric motility by activating the IGF-1/PI3K/Akt signaling pathway， as manifested by the up-regulated expression of IGF-1， p-PI3K， p-Akt， and Bcl-2 and down-regulated expression of Bax.

ObjectiveTo provide technical support for the molecular surveillance of pathogenic bacteria strains carrying mobile colistin resistance-1 （mcr⁃1） gene isolate from inlet of wastewater treatment plants （WWTP）. MethodsThe Enterobacteriaceae strains carrying mcr⁃1 resistance gene isolate from inlet of WWTP during April 1 to June 30， 2023 in Shanghai were cultured on blood-rich and SS culture medium and were identified using a mass spectrometry analyzer. The mcr⁃1 gene and copy number were detected by real-time fluorescence quantitative PCR. Drug susceptibility test was performed by microbroth dilution method. The copy numbers of Escherichia coli carrying mcr⁃1 gene isolated from wastewater and human fecel were statistically analyzed by SPSS 25.0. ResultsA total of 14 strains carrying the mcr⁃1 gene were isolated from 49 WWTP samples， and the positive isolation rate was 28.6%， including 12 non-diarrheal E. coli strains and 2 Klebsiella pneumoniae strains. The drug susceptibility results showed that all 14 strains were multi-drug resistant bacteria. They were all sensitive to imipenem and tigecycline， but were ampicillin- and cefazolin-resistant. There was no significant difference in the copy number between human-sourced diarrheal E. coli and wastewater-sourced non-diarrheal E. coli （t=0.647， P>0.05）. ConclusionThe isolation and identification of strains carrying the mcr⁃1 gene from inlet of WWTP samples were firstly established in Shanghai. The multi-drug resistance among the isolated strains is severe. To effectively prevent and control the spread of colistin-resistant bacteria， more attention should be paid to the surveillance of mcr⁃1 gene.

Tumor cells use glycolysis to provide material and energy under hypoxic conditions to meet the energy requirements for rapid growth and proliferation， namely the Warburg effect. Even under aerobic conditions， tumor cells mainly rely on glycolysis to provide energy. Therefore， glucose transporter protein 1（GLUT1）， which is involved in the process of glucose metabolism， plays an important role in tumorigenesis， development and drug resistance， and is considered to be one of the important targets in the treatment of malignant tumors. In recent years， research on tumor glucose metabolism has gradually become a hot spot. It has been shown that various factors are involved in the regulation of tumor energy metabolism， among which the role of GLUT1 is the most critical. In this paper， the authors reviewed the latest research progress of GLUT1-targeted traditional Chinese medicine（TCM） active ingredient nano-delivery system in tumor therapy， aiming to reveal the feasibility and effectiveness of this system in the delivery of chemotherapeutic drugs. The GLUT1-targeted TCM active ingredient nano-delivery system can overcome the bottleneck of the traditional targeting strategy as well as the high-permeability long retention（EPR） effect. In summary， the authors believe that the GLUT1-targeted TCM active ingredient nano-delivery system provides a new strategy for targeted treatment of tumors and has a broad application prospect in tumor prevention and treatment.

Depression is a prevalent mental illness worldwide, its multifaceted pathogenesis is still in the exploratory stage. MicroRNA (miRNA), as a crucial epigenetic regulator, plays an important role in depression. miR-124 is one of the most abundant miRNAs in the central nervous system including neurons and microglia, and involved in various biological events like neuron development and differentiation, synaptic and axonal growth, neural plasticity, inflammation and autophagy. Recent studies have reported abnormal expression of miR-124 in both depression patients and animal models. Most of the studies showed that miR-124 is upregulated in the hippocampus or prefrontal cortex in stress-induced rodent depression animal models such as CUMS, CSDS, CORT, CRS and LH but some evidence for divergence. Upregulation of miR-124 expression may be involved in depression-like behavior via CREB/BDNF/TrkB pathway, GR pathway, SIRT1 pathway, apoptosis and autophagy pathways by directly targeting these genes including Creb, Bdnf, Sirt1, Nr3c1, Ezh2 and Stat3. The downregulation of miR-124 expression in neurons is mainly involved in the neurogenesis and neuroplasticity impairments in depression by targeting the Notch signaling pathway and DDIT4/TSC1/2/mTORC1 pathway. The downregulation of miR-124 expression also was found in the activated microglia in the stress-induced models, and resulted in neuroinflammation. In summary, the abnormal expression of miR-124 in the brain of depression-related models and its related mechanisms are complex and even contradictory, and still need further research. This review provides a summary of the research progress of miR-124 in depression.

Objective:To investigate the current status of endoscopic treatment for gastroesophageal varices in portal hypertension in China, and to provide supporting data and reference for the development of endoscopic treatment.Methods:In this study, initiated by the Liver Health Consortium in China (CHESS), a questionnaire was designed and distributed online to investigate the basic condition of endoscopic treatment for gastroesophageal varices in portal hypertension in 2022 in China. Questions included annual number and indication of endoscopic procedures, adherence to guideline for preventing esophagogastric variceal bleeding (EGVB), management and timing of emergent EGVB, management of gastric and isolated varices, and improvement of endoscopic treatment. Proportions of hospitals concerning therapeutic choices to all participant hospitals were calculated. Guideline adherence between secondary and tertiary hospitals were compared by using Chi-square test.Results:A total of 836 hospitals from 31 provinces (anotomous regions and municipalities) participated in the survey. According to the survey, the control of acute EGVB (49.3%, 412/836) and the prevention of recurrent bleeding (38.3%, 320/836) were major indications of endoscopic treatment. For primary [non-selective β-blocker (NSBB) or endoscopic therapies] and secondary prophylaxis (NSBB and endoscopic therapies) of EGVB, adherence to domestic guideline was 72.5% (606/836) and 39.2% (328/836), respectively. There were significant differences in the adherence between secondary and tertiary hospitals in primary prophylaxis of EGVB [71.0% (495/697) VS 79.9% (111/139), χ2=4.11, P=0.033] and secondary prophylaxis of EGVB [41.6% (290/697) VS 27.3% (38/139), χ2=9.31, P=0.002]. A total of 78.2% (654/836) hospitals preferred endoscopic therapies treating acute EGVB, and endoscopic therapy was more likely to be the first choice for treating acute EGVB in tertiary hospitals (82.6%, 576/697) than secondary hospitals [56.1% (78/139), χ2=46.33, P<0.001]. The optimal timing was usually within 12 hours (48.5%, 317/654) and 12-24 hours (36.9%, 241/654) after the bleeding. Regarding the management of gastroesophageal varices type 2 and isolated gastric varices type 1, most hospitals used cyanoacrylate injection in combination with sclerotherapy [48.2% (403/836) and 29.9% (250/836), respectively], but substantial proportions of hospitals preferred clip-assisted therapies [12.4% (104/836) and 26.4% (221/836), respectively]. Improving the skills of endoscopic doctors (84.2%, 704/836), and enhancing the precision of pre-procedure evaluation and quality of multidisciplinary team (78.9%, 660/836) were considered urgent needs in the development of endoscopic treatment. Conclusion:A variety of endoscopic treatments for gastroesophageal varices in portal hypertension are implemented nationwide. Participant hospitals are active to perform emergent endoscopy for acute EGVB, but are inadequate in following recommendations regarding primary and secondary prophylaxis of EGVB. Moreover, the selection of endoscopic procedures for gastric varices differs greatly among hospitals.

Objective To monitor and evaluate the synergistic antitumor effects of programmed death-1(PD-1)checkpoint inhibitor combined with radiation therapy through whole-body dynamic 18 F-Fluorodeoxy glucose positron emission computed tomography(18F-FDG PET/CT)and Patlak multi-parametric analysis.Methods B16F10 mel-anoma dual-tumor mouse model was established and randomly divided into control,PD-1 monoclonal antibody,ra-diation-only,and combination groups(n=6).Whole-body 18F-FDG PET/CT imaging was performed before and 24 hours post-treatment.The changes of maximum standardized uptake value(SUVmax)and metabolic rate of FDG(MRFDG)changes were analyzed and compared.Mice were then euthanized,tumors excised and underwent histo-pathology with HE,CD8,Ki-67 staining to assess immune infiltration and proliferation.Distal tumor volumes were monitored during treatment.Results At 24 hours post-treatment,in the primary tumors,SUVmax and MRFDG values increased compared to pre-treatment in the control group(P＜0.000 1),while they decreased in the combination treatment group(P＜0.000 1),with statistically significant differences.In the distal tumors,SUVmax and MRFDG values increased compared to pre-treatment in the control group,PD-1 monoclonal antibody group,and radiothera-py-alone group.The SUVmax differences were statistically significant in the control group before and after treatment(P＜0.000 1).MRFDG values in the distal tumors showed statistically significant differences in all three groups(P＜0.01 or P＜0.000 1).In the combination treatment group,SUVmax and MRFDG values in the distal tumors de-creased significantly compared to pre-treatment(P＜0.000 1).Post-treatment comparison of SUVmax and MRFDG values in the distal tumors showed that statistically significant differences in SUVmax and MRFDG values were observed among all groups except between the radiotherapy-alone and PD-1 monoclonal antibody groups(all P＜0.05).Im-munohistochemistry results showed that the mean absorbance value of CD8 T lymphocytes in the distal tumor was significantly higher than that in the other three groups(P＜0.001);the mean absorbance value of Ki-67 immuno-histochemistry in the distal tumor proliferation index was significantly lower than that in the other three groups(P＜0.001).Conclusion The synergistic effects of combined treatment reduced distal tumor growth.Whole-body 18F-FDG PET/CT Patlak multi-parametric imaging can monitor the synergistic effects of PD-1 antibody and radiotherapy in B16F10 melanoma,providing reliable imaging parameters for optimizing combinatorial therapies.

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.

Background::Findings on the association of genetic factors and colorectal cancer (CRC) survival are limited and inconsistent, and revealing the mechanism underlying their prognostic roles is of great importance. This study aimed to explore the relationship between functional genetic variations and the prognosis of CRC and further reveal the possible mechanism.Methods::We first systematically performed expression quantitative trait locus (eQTL) analysis using The Cancer Genome Atlas (TCGA) dataset. Then, the Kaplan-Meier analysis was used to filter out the survival-related eQTL target genes of CRC patients in two public datasets (TCGA and GSE39582 dataset from the Gene Expression Omnibus database). The seven most potentially functional eQTL single nucleotide polymorphisms (SNPs) associated with six survival-related eQTL target genes were genotyped in 907 Chinese CRC patients with clinical prognosis data. The regulatory mechanism of the survival-related SNP was further confirmed by functional experiments.Results::The rs71630754 regulating the expression of endoplasmic reticulum aminopeptidase 1 ( ERAP1) was significantly associated with the prognosis of CRC (additive model, hazard ratio [HR]: 1.43, 95% confidence interval [CI]: 1.08-1.88, P = 0.012). The results of dual-luciferase reporter assay and electrophoretic mobility shift assay showed that the A allele of the rs71630754 could increase the binding of transcription factor 3 (TCF3) and subsequently reduce the expression of ERAP1. The results of bioinformatic analysis showed that lower expression of ERAP1 could affect the tumor immune microenvironment and was significantly associated with severe survival outcomes. Conclusion::The rs71630754 could influence the prognosis of CRC patients by regulating the expression of the immune-related gene ERAP1. Trial Registration::No. NCT00454519 (https://clinicaltrials.gov/)