One female patient with cancer pain due to bone metastasis from breast cancer was initially treated with Xinhuang tablets,diclofenac sodium double-release enteric-soluble capsules,paracetamol dihydrocodeine tablets and paracetamol oxycodone tablets,before being switched to controlled-release oxycodone hydrochloride tablets.She regularly took oxycodone hydrochloride sustained-release tablets 20 mg,q12h,no abnormalities were observed,and the dosage was increased to 40 mg,q12h due to poor pain control.The patient was diagnosed with 5-hydroxytryptamine syndrome after 1 d of intermittent recurrent tremor,myotonia,scalp sweating,restlessness and elevated blood pressure.When oxycodone hydrochloride sustained release tablet was adjusted to 20 mg,q12h and gabapentin capsule was added to 0.1 g,tid,the frequency of tremor and myotonia attacks slightly decreased,and sweating and agitation symptoms were not relieved.After 14 days,oxycodone hydrochloride sustained release tablets were stopped and morphine sulfate sustained release tablets 60 mg,q12h were replaced.Three days later,the patient's symptoms disappeared.During 5-month follow-up,the patient's pain was well-contrdled,with no change in the dose of morphine sulfate sustained-release tablets,and no adverse drug reactions observed.Using the Naranjo's Assessment Scale,the association between the patient's serotonin syndrome and the suspected drug oxycodone hydrochloride sustained-release tablets was evaluated as"probable".Thiscase highlights the importance for clinicians to closely monitor adverse reactions induced by rapid opioid dose escalation to ensure medication safety in patients.

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One female patient with cancer pain due to bone metastasis from breast cancer was initially treated with Xinhuang tablets,diclofenac sodium double-release enteric-soluble capsules,paracetamol dihydrocodeine tablets and paracetamol oxycodone tablets,before being switched to controlled-release oxycodone hydrochloride tablets.She regularly took oxycodone hydrochloride sustained-release tablets 20 mg,q12h,no abnormalities were observed,and the dosage was increased to 40 mg,q12h due to poor pain control.The patient was diagnosed with 5-hydroxytryptamine syndrome after 1 d of intermittent recurrent tremor,myotonia,scalp sweating,restlessness and elevated blood pressure.When oxycodone hydrochloride sustained release tablet was adjusted to 20 mg,q12h and gabapentin capsule was added to 0.1 g,tid,the frequency of tremor and myotonia attacks slightly decreased,and sweating and agitation symptoms were not relieved.After 14 days,oxycodone hydrochloride sustained release tablets were stopped and morphine sulfate sustained release tablets 60 mg,q12h were replaced.Three days later,the patient's symptoms disappeared.During 5-month follow-up,the patient's pain was well-contrdled,with no change in the dose of morphine sulfate sustained-release tablets,and no adverse drug reactions observed.Using the Naranjo's Assessment Scale,the association between the patient's serotonin syndrome and the suspected drug oxycodone hydrochloride sustained-release tablets was evaluated as"probable".Thiscase highlights the importance for clinicians to closely monitor adverse reactions induced by rapid opioid dose escalation to ensure medication safety in patients.

Objective: To analyze the disease burden of acute gastrointestinal illness (AGI) caused by non-typhoidal Salmonella and Vibrio Parahaemolyticus in Zhejiang Province, so as to provide the reference for the prevention and control of foodborne diseases. Methods: The detection rates of non-typhoidal Salmonella and Vibrio parahaemolyticus in 2022 were collected through the Zhejiang Foodborne Disease Outbreak Surveillance System. The number of cases, incidence and hospitalizations of AGI caused by non-typhoidal Salmonella and Vibrio parahaemolyticus were calculated. Disability-adjusted life years (DALY) were used to analyze the disease burden of AGI caused by non-typhoidal Salmonella and Vibrio parahaemolyticus among different age groups. Results: The number of AGI cases caused by non-typhoidal Salmonella in Zhejiang Province in 2022 was 889 500 person-times, the incidence rate was 1 352.42/105, the number of hospital visits was 328 900 person-times, the DALY was 972.69 (95%CI: 771.68-1 164.16) person-years, and the DALY rate was 1.48 (95%CI: 1.17-1.77) /105. The incidence rate and DALY rate were highest in the children aged under 5 years, reaching 3 989.51/105 and 13.93 (95%CI: 8.67-18.42) /105, respectively. The number of AGI cases caused by Vibrio parahaemolyticus in Zhejiang Province was 639 400 person-times, the incidence rate of 972.16/105,the number of hospital visits was 166 800 person-times, the DALY was 509.30 (95%CI: 411.75-699.62) person-years, and the DALY rate was 0.78 (95%CI: 0.63-1.06)/105. The incidence rate and DALY rate were highest in the residents aged 45 to <65 years, reaching 1 383.55/105 and 1.27 (95%CI: 1.14-1.96)/105, respectively. Conclusions The incidence and DALY of AGI caused by non-typhoidal Salmonella were relatively high in Zhejiang Province. The AGI caused by non-typhoidal Salmonella in the children under 5 years and the AGI caused by Vibrio parahaemolyticus in the residents aged 45 to <65 years need to be monitored with priority.

Epigenomic imbalance drives abnormal transcriptional processes,promoting the onset and progression of cancer.Although defective gene regulation generally affects carcinogenesis and tumor suppression networks,tumor immunogenicity and immune cells involved in antitumor responses may also be affected by epigenomic changes,which may have significant implications for the development and application of epigenetic therapy,cancer immunotherapy,and their combinations.Herein,we focus on the impact of epigenetic regulation on tumor immune cell function and the role of key abnormal epigenetic processes,DNA methylation,histone post-translational modification,and chromatin structure in tumor immunogenicity,and introduce these epigenetic research methods.We emphasize the value of small-molecule inhibitors of epigenetic modulators in enhancing antitumor immune responses and discuss the challenges of developing treatment plans that combine epigenetic therapy and immuno-therapy through the complex interaction between cancer epigenetics and cancer immunology.

Objective:To investigate the effect of CD226 gene knockout (CD226 -/-) on carbon tetrachloride (CCl 4) -induced liver fibrosis in mice. Methods:Eight 6-8 week-old male wild-type and CD226 -/- C57BL/6 mice were used, with weights of (22.16±2.24) g and (21.84±2.50) g, respectively. Four mice each from wild-type and CD226 -/- mice were injected intraperitoneally with CCl 4 to establish a liver fibrosis model, namely, the liver fibrosis group and the CD226 -/- liver fibrosis group, and the remaining four mice each corresponded to the control group and the CD226 -/- control group. The effect of CD226 -/- on liver mass, liver index and Ishak fibrosis score were observed. HE, Masson, and Sirius red staining were performed to observe the liver injury and liver fibrosis. Immunohistochemistry and Western blot were used to detect the protein expression levels of collagen type I (Collagen I) and α-smooth muscle actin (α-SMA) in liver tissues. Flow cytometry was used to analyze the proportion of T lymphocytes and their intracellular IFN-γ secretion levels in the peripheral blood and liver tissues. The mRNA expression level of transforming growth factor-β1 (TGF-β1) in the liver tissues was detected by real-time fluorescence quantitative PCR (qPCR). Results:Compared to the liver fibrosis group, the CD226 -/- liver fibrosis group showed an increase in liver mass [(2.00±0.14) g vs. (1.41±0.16) g] and liver index (7.25±0.59 vs. 5.33±0.30), and a decrease in Ishak's fibrosis score [(6.75±0.96) score vs. (10.00±1.41) score], and the differences were statistically significant (all P<0.05). HE staining showed disorganization of the liver tissue structure, and degeneration and necrosis of the hepatocytes both occurred in the liver fibrosis group and CD226 -/- liver fibrosis group, but the degree of inflammatory cell recruitment was milder in the CD226 -/- liver fibrosis group than the liver fibrosis group. Sirius red and Masson staining revealed reduced collagen fibre deposition in the CD226 -/- liver fibrosis group compared to the liver fibrosis group. Immunohistochemical staining showed that the expression of Collagen I [(4.38±0.51)% vs. (6.55±1.40)%] and α-SMA [(0.77±0.20)% vs. (1.20±0.24)%] were reduced in the CD226 -/- liver fibrosis group compared to the liver fibrosis group, and the differences were statistically significant (both P<0.05). Western blot indicated that the relative expression level of Collagen I was reduced in the CD226 -/- liver fibrosis group compared to the liver fibrosis group (0.35±0.14 vs. 1.66±0.73), and the difference was statistically significant ( P<0.05). Flow cytometry revealed increased intracellular IFN-γ secretion by T lymphocytes in the peripheral blood in the CD226 -/- liver fibrosis group compared to the liver fibrosis group. qPCR result revealed that the relative mRNA expressions of TGF-β1 was reduced in the CD226 -/- liver fibrosis group compared to the liver fibrosis group (0.38±0.18 vs. 0.61±0.28), and the difference was statistically significant ( P<0.05). Conclusion:CD226 -/- attenuates CCl 4-induced hepatic inflammatory infiltration and hepatic fibrosis, which may be related to its affected intrahepatic T lymphocytes and intracellular IFN-γ secretion.

Objective:To retrospectively analyze the patients with spinal metastases who received surgical intervention and summarize the evolution of their clinical and pathological characteristics and surgical methods.Methods:The data of 703 patients with spinal metastases from January 2007 to December 2018 were collected retrospectively. There were 395 males (56.19%, 395/703) and 308 females (43.81%, 308/703) with an average age of 58.14±11.46 years (range 13-84 years). According to the degree of invasion and thoroughness of tumor resection, the surgical methods could be divided into minimally invasive surgery, decompression surgery, separation surgery, piecemeal resection and total en-bloc spondylectomy surgery. The operative methods were minimally invasive surgery in 89 cases (12.66%), decompression surgery in 96 cases (13.66%), separation surgery in 303 cases (43.10%), piecemeal resection in 182 cases (25.89%) and total en-bloc spondylectomy in 33 cases (4.69%). To analyze the trend of the clinical, pathological types and surgical treatment of patients with spinal metastases over the years, and determine the relevant factors affecting the decision-making of surgical methods by multivariate logistic regression.Results:The ratio of male to female was 1.28:1. 39.54% (278/703) of patients with single-segment involvement in 703 patients, 24.04% (169/703) of patients with double-segment metastasis and 36.42% (256/703) of patients with multi-segment metastasis. The most common type of primary tumor was lung cancer (34.57%, 243/703), followed by breast cancer (8.25%, 58/703), myeloma (8.11%, 57/703), gastrointestinal tumor (6.82%, 48/703) and renal malignant tumor (6.40%, 45/703). From 2007 to 2018, there was no significant difference in the percentage change of different age, gender and primary tumor source composition (age: χ 2=14.01, P=0.233; gender: χ 2=35.73, P=0.341; primary tumor: χ 2=120.09, P=0.074). The percentage of patients with sacrococcygeal metastasis decreased from 20.00% in 2008 to 1.89% in 2017 and the difference was statistically significant (χ 2=8.09, P=0.005). The percentage of patients with multi-level metastasis increased from 26.67% in 2008 to 52.83% in 2017, and the difference was statistically significant (χ 2=7.23, P=0.007). The percentage of patients with minimally invasive surgery decreased from 25.00% in 2007 to 5.88% in 2018, and the percentage of patients with segmented resection decreased from 53.33% in 2008 to 10.29% in 2018. The proportion of the two surgical methods showed a significant downward trend, and the differences were statistically significant (minimally invasive surgery: χ 2=1.46, P=0.026; segmented resection surgery: χ 2=19.56, P<0.001). The percentage of patients undergoing separation surgery increased from 13.33% in 2008 to 64.71% in 2018, and the proportion of patients undergoing total en-bloc spondylectomy increased from 0 in 2007 to 10.29% in 2018. Both surgical methods showed a significant growth trend and the differences were statistically significant (separation surgery: χ 2=27.09, P<0.001; χ 2=4.16, P=0.042). Multivariate Logistic regression analysis showed that age, metastatic site, number of metastatic segments, pathological vertebral fractures, Frankel grade, SINS score and VAS score were independent factors influencing surgical decision-making ( P<0.05). Conclusion:With different time and age, the invasiveness and thoroughness of surgery are increasing, which shows that the percentage of patients who underwent separation surgery and to-tal en-bloc spondylectomy is significantly increasing. Age, metastatic site, number of metastatic segments, pathological vertebral fractures, Frankel grade, SINS score and VAS score are independent factors affecting surgical decision-making.

Objective:To explore the effect of mind mapping combined with scenario simulation teaching on probation teaching of abdominal trauma.Methods:The probation undergraduates from Batch 2017 five-year clinical medicine of Air Force Medical University were selected as research objects and randomly divided into experimental group ( n=98) and control group ( n=92). The experimental group was taught by mind mapping combined with scenario simulation teaching method, while the control group was taught by traditional teaching mode. After the end of the course, the effect of teaching was evaluated from two aspects: theoretical evaluation and teaching satisfaction evaluation. SPSS 19.0 was used for t test and chi-square test. Results:The results of theoretical test in the experimental group were significantly better than those of the control group [(84.03±8.99) vs. (78.53±8.97)], and the difference was statistically significant ( P<0.05). Compared with the control group, the experimental group had obvious advantages in learning interest, teamwork awareness and clear thinking, and achieved good teaching effect. Conclusion:Therefore, this teaching model helps to improve the teaching quality and provides some reference experience.

Objective:To evaluate the clinical value of the New England spinal metastasis score (NESMS) in predicting the prognosis of patients with spinal metastases by retrospectively analyzing the medical records of multicenter spinal metastases in China.Methods:The data of 179 patients with spinal metastases from January 2008 to December 2018 were retrospectively collected. There were 108 males (60.3%) and 71 females (39.7%) with an average age of 59.79±10.88 years old (range 27-84 years). The patient demographic characteristics, primary tumor type, spinal metastases and segments, vertebral pathological fractures, neurological Frankel classification, physical function status, Karnofsky performance scale (KPS), visual analogue score (VAS), the spinal instability neoplastic score (SINS), modified Bauer score, NESMS score, Tomita score and modified Tokuhashi score were collected. The clinical value of NESMS score, Tomita score and modified Tokuhashi score in predicting the survival of patients with spinal metastases were compared. The independent factors affecting survival in these patients were analyzed by Cox proportional hazards regression model.Results:Among the 179 patients, the peak incidence of spinal metastases was in the age group of 61-75 years (45.3%, 81/179) of all patients. Lung cancer was the most common primary tumor (46.9%, 84/179). 40.8% (73/179) of patients had multi-segment metastasisand thoracic spine was the most common site with single-site metastasis (26.3%, 47/179). 28.5% (51/179) of the patients had visceral metastases and 52.0% (93/179) of the patients had extraspinal bone metastases. 31.3% (56/179) of the patients had pathological fractures of the involved vertebral bodies.114 patients received surgical treatment (63.4%). The mortality rates in 3-months, 6-months and 1-year were 22.4% (40/179), 51.4% (92/179) and 77.1% (138/179), respectively. The median survival time of patients with NESMS score of 0-3 was 3, 4, 8, and 10 months respectively with the mean survival time was 3.60±2.10, 6.77±3.39, 9.69±5.71 and 10.53±6.25 months. The 1-year mortality rates were 100% (13/13), 87.5% (42/48), 71.6% (63/88) and 66.7% (20/30) respectively. The consistency of NESMS score, Tomita score and modified Tokuhashi score in predicting survival of all patients was 0.63, 0.58 and 0.55, respectively. For patients with spinal metastases, the NESMS score was better than the Tomita score and modified Tokuhashi score in predicting survival at 3-months (AUC=1.00, 0.63, 0.42) and 6-months (AUC=0.71, 0.63, 0.45). But the accuracy of Tomita score was best in predicting survival at 1-year (AUC=0.66, 0.61, 0.38). Multivariate Cox proportional hazards regression model analysis showed that growth rate of primary tumor, neurological function Frankel score, albumin level and surgical treatment were independent factors affecting the survival time of patients with spinal metastases ( P<0.05). Conclusion:The consistency and accuracy of NESMS score in predicting survival of patients with spinal metastases are better than Tomita score and modified Tokuhashi score, especially in predicting 3- and 6-month survival. The growth rate of primary tumor, Frankel classification, albumin level and surgical treatment were independent factors affecting the survival time of patients with spinal metastases.

Objective:To establish a risk prediction model of conversion to open surgery during laparoscopic splenectomy and esophagogastric devascularization (LSED) and evaluate the impact of this conversion on patients' short-term prognosis.Methods:A total of 358 cirrhotic portal hypertension patients admitted to the Department of General Surgery , Second Affiliated Hospital, Air Force Military Medical University from Feb 2011 to Nov 2020 were retrospectively analyzed. All patients underwent attempted LSED. Univariate and least absolute shrinkage and selection operator (LASSO) Logistic regression were used to analyze the independent risk factors for conversion to laparotomy, and the R language was used to build a nomogram prediction model for conversion to laparotomy. The intraoperative and postoperative conditions of the two groups were compared.Results:A total of 358 patients were included in this study, of which 31(8.7%). patients were converted to open surgery. In univariate analysis, high MELD score, BMI ≥24 kg/m 2, history of upper abdominal surgery, red sign of the varicose, low platelet count and prolonged PT are risk factors for conversion . LASSO regression finally identified 5 factors: MELD, BMI, PLT, history of surgery, and red sign. In the nomogram prediction model the area under ROC curve was 0.831. The conversion led to longer operation time; increased blood loss; prolonged postoperative abdominal drainage , longer hospital stay, and increased perioperative complications ( t=-2.167, P=0.031; Z=-4.350, P<0.01; Z=-3.102, P=0.002; Z=-3.454, P=0.001; χ2=8.773, P=0.003). Conclusions:LASSO regression selected five indicators with greatest impact on intraoperative conversion: MELD, BMI, PLT, red sign, and previous history of abdominal surgery. The nomogram prediction model established has good prediction ability. Patients converted to open surgery had worse short-term outcomes.