Objective:To evaluate the efficacy and safety of oliceridine for treatment of moderate to severe pain after surgery with general anesthesia in patients.Methods:The patients with moderate to severe pain (numeric pain rating scale ≥4) after abdominal surgery with general anesthesia from 14 hospitals between July 6, 2021 and November 9, 2021 were included in this study. The patients were assigned to either experiment group or control group using a random number table method. Experiment group received oliceridine, while control group received morphine, and both groups were treated with a loading dose plus patient-controlled analgesia and supplemental doses for 24 h. The primary efficacy endpoint was the drug response rate within 24 h after giving the loading dose. Secondary efficacy endpoints included early (within 1 h after giving the loading dose) drug response rates and use of rescue medication. Safety endpoints encompassed the development of respiratory depression and other adverse reactions during treatment.Results:After randomization, both the full analysis set and safety analysis set comprised 180 cases, with 92 in experiment group and 88 in control group. The per-protocol set included 170 cases, with 86 in experiment group and 84 in control group. There were no statistically significant differences between the two groups in 24-h drug response rates, rescue analgesia rates, respiratory depression, and incidence of other adverse reactions ( P>0.05). The analysis of full analysis set showed that the experiment group had a higher drug response rate at 5-30 min after giving the loading dose compared to control group ( P<0.05). The per-protocol set analysis indicated that experiment group had a higher drug response rate at 5-15 min after giving the loading dose than control group ( P<0.05). Conclusions:When used for treatment of moderate to severe pain after surgery with general anesthesia in patients, oliceridine provides comparable analgesic efficacy to morphine, with a faster onset.

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.

Objective:To evaluate the possible mediation effect of smoking and healthy diet score on the association between educational level and the risk of lung cancer incidence.Methods:After excluding individuals with missing educational levels and cancer information at baseline, 446?772 participants in the UK Biobank (UKB) prospective cohort study were included. Cox regression models were used to investigate the associations of educational level and smoking and healthy diet score with the incidence of lung cancer. Mediating effect analysis was conducted to analyze the mediating effect of smoking and healthy diet score on the correlation between educational level and lung cancer.Results:During a median follow-up of 7.13 years, 1?994 new- onset lung cancer cases were observed. Per 1 standard deviation (5 years) increase in educational level was associated with a 12% lower risk of lung cancer ( HR=0.88, 95% CI: 0.84-0.92). The corresponding level 1-5 in the International Standard Classification for Education (ISCED) were mapped to UKB self‐report highest qualification to estimate the educational level. A higher rank means a higher educational level. Compared with level ISCED-1, the HR(95% CI) of level ISCED-2, ISCED-3, ISCED-4 and ISCED-5 were respectively 0.83 (0.72-0.94), 0.67 (0.53-0.85), 0.76 (0.65-0.89) and 0.72 (0.64-0.80) for lung cancer. Education years were negatively correlated with smoking, with β coefficients (95% CI) being -0.079 (-0.081- -0.077), but positively correlated with healthy diet score ( β=0.042, 95% CI: 0.039-0.045). Analysis of mediating effect indicated that the association of educational level with lung cancer risk was mediated by smoking and healthy diet score, the proportions of mediating effect were 38.952% (95% CI: 31.802%-51.659%) and 1.784% (95% CI: 0.405%-3.713%), respectively. Conclusion:Smoking and healthy diet score might mediate the effect of educational level on the incidence of lung cancer, indicating that improving the level of education can reduce the risk of lung cancer by changing lifestyles such as smoking and diet.

Although genome-wide association studies have identified more than eighty genetic variants associated with non-small cell lung cancer (NSCLC) risk, biological mechanisms of these variants remain largely unknown. By integrating a large-scale genotype data of 15 581 lung adenocarcinoma (AD) cases, 8350 squamous cell carcinoma (SqCC) cases, and 27 355 controls, as well as multiple transcriptome and epigenomic databases, we conducted histology-specific meta-analyses and functional annotations of both reported and novel susceptibility variants. We identified 3064 credible risk variants for NSCLC, which were overrepresented in enhancer-like and promoter-like histone modification peaks as well as DNase I hypersensitive sites. Transcription factor enrichment analysis revealed that USF1 was AD-specific while CREB1 was SqCC-specific. Functional annotation and gene-based analysis implicated 894 target genes, including 274 specifics for AD and 123 for SqCC, which were overrepresented in somatic driver genes (ER = 1.95, P = 0.005). Pathway enrichment analysis and Gene-Set Enrichment Analysis revealed that AD genes were primarily involved in immune-related pathways, while SqCC genes were homologous recombination deficiency related. Our results illustrate the molecular basis of both well-studied and new susceptibility loci of NSCLC, providing not only novel insights into the genetic heterogeneity between AD and SqCC but also a set of plausible gene targets for post-GWAS functional experiments.
Adenocarcinoma of Lung/genetics* ; Carcinoma, Non-Small-Cell Lung/genetics* ; Carcinoma, Squamous Cell/genetics* ; Genetic Heterogeneity ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Humans ; Lung Neoplasms/genetics* ; Polymorphism, Single Nucleotide

Objective To synthesize and investigate cytotoxicity of an indole-chalcone derivative FC58. Methods The target compound was synthesized through the Aldol condensation with 1-(3,4,5-trimethoxyphenyl)ethan-1-one and 1H-indole-3-carbaldehyde. The Cell Titer-Blue method was used to determine in vitro cytotoxicity. The cell cycle experiment was performed to analyze the action characteristics of FC58. Results FC58 exhibited high cytotoxicity against various leukemia cells and resulted in G2/M phase arrest. It showed stronger drug resistant index than traditional tubulin inhibitors such as paclitaxel, vinblastine and doxorubicin. Conclusion FC58 represents a promising lead compound for multi-drug resistant leukemia.

Objective: To explore the effect of Qishen-Xiaodian Decoction combined with laser acupoint irradiation on oxidative stress and renal function on children with recurrent henoch schonlein purpura (HSP). Methods: A total of 120 children with recurrent HSP in the dermatology department clinic of Hospital of Xinle City from January 2015 to November 2017 were divided into two groups according to the random number table method, with 60 cases in each group. The control group took loratadine, Troxerutin and vitamin C orally, while the treatment group took Chinese medicine combined with laser acupoint irradiation based onthe control group. Drugs were taken orally for 4 weeks, laser acupoint irradiation treatment for 2 weeks. The level of glutathione peroxidase (GSH-Px) in plasma was detected by ELISA, the levels of MDA and SOD in plasma were detected by thiobarbituric acid colorimetry and hydroxylamine method, the level of IgG, micro albumin (Alb), β2-microglobulin (β2-MG) in urine were detected by radioimmunoassay, and the clinical effect was evaluated. The recurrence was recorded. Results: After treatment, the plasma GSH-Px (90.45 ± 15.36 μmol/L vs. 81.62 ± 13.68 μmol/L, t=3.318), SOD (99.64 ± 18.66 IU/ml vs. 84.21 ± 16.73 IU/ml, t=4.769) in the treatment group were significantly higher than the control group (P<0.01); the MDA (5.58 ± 1.31 μmol/L vs. 4.37 ± 1.36 μmol/L, t=4.964) was significantly lower than the control group (P<0.01); the ratio of urine IgG (3.48 ± 0.95 mg/L vs. 6.56 ± 1.47 mg/L, t=13.630), Alb (7.80 ± 2.94 mg/L vs. 12.73 ± 4.26 mg/L, t=7.378), β2-MG (4.02 ± 1.61 mg/L vs. 6.95 ± 2.10 mg/L, t=8.577) were significantly lower than those of the control group (P<0.01). The total effective rate was 95.0% (57/60) in the treatment group and 80.0% (48/60) in the control group. There was statistically significant difference between two groups (χ²=6.171, P=0.013). Follow-up of 6 and 12 months, the recurrence rate of the treatment group were significantly lower than that of the control group (χ² value were 4.931, 4.574, P<0.05). Conclusions Qishen-Xiaodian Decoction combined with laser acupoint irradiation can improve the oxidative stress of children with recurrent HSP, protect the renal function, improve the clinical efficacy and reduce the recurrence rate.

Patient-specific volumetric modulated arc therapy (VMAT) quality assurance (QA) process is an important component of the implementation process of clinical radiotherapy. The tolerance limit and action limit of discrepancies between the calculated dose and the delivered radiation dose are the key parts of the VMAT QA processes as recognized by the AAPM TG-218 report, however, there is no unified standard for these two values among radiotherapy centers. In this study, based on the operational recommendations given in the AAPM TG-218 report, treatment site-specific tolerance limits and action limits of gamma pass rate in VMAT QA processes when using ArcCHECK for dose verification were established by statistical process control (SPC) methodology. The tolerance limit and action limit were calculated based on the first 25 in-control VMAT QA for each site. The individual control charts were drawn to continuously monitor the VMAT QA process with 287 VMAT plans and analyze the causes of VMAT QA out of control. The tolerance limits for brain, head and neck, abdomen and pelvic VMAT QA processes were 94.56%, 94.68%, 94.34%, and 92.97%, respectively, and the action limits were 93.82%, 92.54%, 93.23%, and 90.29%, respectively. Except for pelvic, the tolerance limits for the brain, head and neck, and abdomen were close to the universal tolerance limit of TG-218 (95%), and the action limits for all sites were higher than the universal action limit of TG-218 (90%). The out-of-control VMAT QAs were detected by the individual control chart, including one case of head and neck, two of the abdomen and two of the pelvic site. Four of them were affected by the setup error, and one was affected by the calibration of ArcCHECK. The results show that the SPC methodology can effectively monitor the IMRT/VMAT QA processes. Setting treatment site-specific tolerance limits is helpful to investigate the cause of out-of-control VMAT QA.
Calibration ; Humans ; Quality Assurance, Health Care ; Radiotherapy Dosage ; Radiotherapy Planning, Computer-Assisted ; Radiotherapy, Intensity-Modulated

Objective To investigate the effects of insulin-like growth factor 1 (IGF 1) and transforming growth factor beta 1 (TGF-β1) in he pathogenesis of children with allergic purpura kidney damage.Methods 135 henoch-schonlein purpura (HSP) children with kidney damage were divided into HSP and HSPN group according to whether associated with renal damage,blood IGF 1,TGF-β1,urinary inhibition C (Cys C),creatinine (SCr) and content of urea nitrogen (BUN) were compared,and blood IGF-1,TGF-β1 and Cys C content of HSPN patients in different pathological grading were compared,the correlation of blood IGF 1,TGF-β1 and Cys C content of the HSPN group were analyzed,Results Blood IGF 1,TGF-β1 and Cys C content of the control group(117.2±18.8 ng/L,164.2±18.4 ng/L,0.9±0.2 mg/L),the HSP group(131.7±19.6 ng/L,282.1±28.3 ng/L,1.1±0.2 mg/L) and the HSPN group (205.3±24.5 ng/L,489.2±32.7 ng/L,1.3±0.3 mg/L) showed a trend of increasing gradually (F=4.824～45.066,P value＜0.01),the HSP group and the HSPN group were higher than that of the control group (q=3.397～58.931,P value＜0.01),the HSPN group was higher than that of the HSP group (q=16.997,35.193,P value＜0.01),the difference was statistically significant.Blood IGF-1 (level Ⅱ 175.6 ± 20.4 ng/L,level m198.5±23.3 ng/L,level Ⅳ241.7±25.1 ng/L),TGF-β1(level Ⅱ 392.8±38.9 ng/L,level Ⅲ 481.3± 44.03 ng/L,level Ⅳ 537.6±42.9 ng/L),Cys C (level 11 1.1±0.3 mg/L,level Ⅲ 1.3±0.4 mg/L,level Ⅳ1.6±0.4 mg/L) content of children with HSPN increased with the increase of renal pathology classification (F=6.594～ 28.317,P value ＜0.01),blood IGF-1,TGF-β1 and Cys C content of kidney pathology classification of Ⅵ level in children was higher than that of the level of Ⅱ and Ⅲ in children (q=2.415～11.818,P＜0.05 or P＜0.01),while the contern of blood IGF-1,TGF-β1 and Cys C of level Ⅲ in children was higher than that of the level Ⅱ in children (q=2.577～6.244,P＜0.05 orP＜ 0.01),the difference was statistically significant.Blood IGF-1,TGF-β1 content of children with HSPN were positively correlated with Cys C content of children (r=0.648,0.719,P＜0.05),but blood IGF 1 content was significantly positive correlated with TGF-β1 content (r=0.748,P＜0.05).Conclusion IGF 1 and TGF-β31 partieipated in the pathogenesis of HSPN,and both were correlated with the degree of the pathological damage.

OBJECTIVETo establish a diet-induced obesity model in zebrafish larvae.

METHODSAt 7 days post-fertilization (dpf), 200 zebrafish larvae with normal development were randomly allocated to two groups with the feeding quantity of 30 mg per day (normal feeding group) or 180 mg per day (overfed group) for 20 days. The weight, length, BMI, triglyceride (TG) and total cholesterol (TCH) of each group were measured. Whole-mount Oil Red O staining, frozen Oil Red O staining and hematoxylin-eosin (HE) staining were used to estimate the rate of hepatic steatosis and liver histology of the zebrafish. The dynamic change of hepatic lipid droplets and distribution of adipose tissue were observed with Nile Red staining in overfed zebrafish in vivo.

RESULTSThe weight, length, BMI and TG of overfed zebrafish were significantly increased compared with those in normal feeding group. Whole-mount Oil Red O staining showed that the percent of hepatic steatosis in overfed group (89.4%) was markedly higher than that in normal feeding group (20.7%). Macrovesicular steatosis was observed in the liver of the overfed larvae. Nile Red staining visualized hepatic lipid droplets and the distribution of larval adipose tissue, which increased with feeding time in the overfed zebrafish. Starving larvae showed depletion of fat and hepatic lipid, and adipose tissue was induced after refeeding.

CONCLUSIONSWe successfully established an diet-induced obesity model in zebrafish larva, in which Nile Red staining allows in vivo observation of the adipocytes and hepatic lipid droplets.

Adipose Tissue ; Animals ; Cholesterol ; Diet ; adverse effects ; Disease Models, Animal ; Fatty Liver ; Larva ; Lipids ; Obesity ; pathology ; Triglycerides ; Zebrafish

OBJECTIVEThis study aimed to induce carcinogenesis of lingual mucosa in C57BL/6 mice by feeding them 4-nitroquinoline 1-oxide (4NQO) solution.

METHODSA total of 85 C57BL/6 mice were randomly divided into distilled water control group (DD group, n=5), 1,2-propylene glycol control group (PG group, n=5), and experimental group (EP group, n= 75). The mice in the experimental group were medially fed in 15 cages. By contrast, the mice in DD, EP, and PG groups were watered with distilled water, 50 mg.L-1 4NQO solution, and 1,2-propylene glycol solution. The mice in EP group were executed every two weeks from week 0, and the mice in the control groups were sacrificed at the 28th week. The mice were weighed. Mucosal lesions were measured by macroscopic observation and histopathologic detection.

RESULTSOne mouse in EP group died of unknown reason. The weight of the mice in EP group presented weight loss compared with the mice in DD and PG groups after the 24th week. Seventy-nine macroscopic lesions were observed in the lingual mucosa, oral floor, and upper palatal and buccal mucosa. A total of 70 macroscopic lesions (88.6%) were located in the lingual mucosa. Mucosal lesions changed from simple hyperplasia to squamous cell carcinomas. Well-differentiated squamous cell carcinomas were observed in all mice of EP group by pathological section at the 28th week. No lesion was found in the mice of DD and PG groups.

CONCLUSIONThe animal model of lingual squamous cell carcinomas was successfully established. The periods from 12th to 16th week and 20th to 28th week were the ideal times for the research on pathogenesis of early and medial-advanced stage during carcinogenesis of squamous cell carcinomas.

4-Nitroquinoline-1-oxide ; Animals ; Cell Transformation, Neoplastic ; Disease Models, Animal ; Mice ; Mice, Inbred C57BL ; Mouth Mucosa ; Tongue