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.

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.

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 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 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.

Objective:To observe the epidemiological characteristics of spinal metastases by retrospectively analyzing the medical records of multicenter spinal metastases in China.Methods:Patients with spinal metastases were identified from several clinical centers between January 2007 and July 2019. A total of 1 976 patients were included in this study, including 1 129 males (57.14%) and 847 females (42.86%). The mean age was 58.6±11.6 years (range 13-92 years). The demographic characteristics, primary tumor types, spinal involvement of each patient were summarized and their clinical indicators were obtained by consulting medical records, including: Frankel grade, visual analog scale (VAS), metastatic spinal cord compression (MSCC), Tokuhashi revised score, the spinal instability neoplastic score (SINS), Karnofsky performance status (KPS), and history of malignant tumors. Finally, the intervention influencing factors of patients undergoing surgical treatment were statistically analyzed.Results:The ratio of male to female in 1 976 spinal metastases was 1.33∶1. The median age was 59.0, and most patients (63.71%) were in the ages range of 50-69. The average age of female was younger than male, and the difference was statistically significant. The proportion of male patients over 60 years old was higher than females, and the difference was statistically significant. The most common primary tumor was lung cancer (n=730, 36.94%), followed by unknown origin (n=326, 16.50%), breast cancer (n=159, 8.05%), kidney cancer (n=120, 6.07%), gastrointestinal cancer (n=109, 5.52%), etc. The most common primary tumor was lung cancer in both males and females, followed by unknown origin in males and breast cancer in females. In the past 10 years, the proportion of unknown origin has decreased, and the proportion of breast cancer has increased. According to the Tomita score, 1 284 patients (64.98%) were rapid growth tumors, 211 patients (10.68%) were moderate growth tumors, and 481 patients (24.34%) were slow growth tumors. There were 730 patients (57.14%) in the subgroup of the number<3, the most level of which was lumbar vertebrae, with 368 patients (32.60%). The remaining 847 patients (42.86%) were included in the subgroup of the number≥3, the most level of which was multiple-level of spine, with 617 patients (72.85%). Among the 1 976 patients, spinal cord injury occurred in 50.76% of patients, in which 77.18% of patients developed moderate and above pain, 14.02% of patients appeared metastatic spinal cord compression, and only 28.95% of patients had a clear history of primary tumor. In terms of treatment, 34.92% of patients underwent surgery, 5.97% underwent radiotherapy on spinal metastases, 6.02% underwent chemotherapy, and 1.77% underwent targeted therapy. Preoperative Frankel grade, SINS, and Tokuhashi revised score were important factors affecting the surgical treatment of patients.Conclusion:This study describes the epidemiological characteristics of multicenter spinal metastases in detail, which could assist orthopedic surgeons to understand the clinical characteristics of spinal metastases and was of great significance on guiding the clinical diagnoses and scientific researches.

Objective To evaluate the laparoscopic splenectomy and pericardial devascularization in patients with portal hypertension.Methods In this study,205 patients who underwent splenectomy and pericardial devascularization in the Second Hospital of Air Force Medical University between Jan 2013 and Jan 2018 were divided into 135 patients undergoing laparoscopic surgery(LSD group) and 70 patients undergoing open surgery (OSD group).Results Operation time,intraoperative blood loss,intraoperative blood infusion,time of postoperative abdominal drainage-tube removal,time of gastrointestinal function recovery and duration of hospital stay were respectively (150 ± 37) min,(223 ± 129) ml,(91 ± 138) ml,(4.0 ± 1.0)d,(33 ±9)h,(5.6 ± 1.0)d in the LSD group,(183 ±42) min,(346 ± 131) ml,(214 ± 182) ml,(5.5 ± 1.3)d,(42 ± 14)h,(7.5 ± 1.4)d in the OSD group,with statistically significant differences between groups(t =-2.203,-4.980,-2.830,-5.553,-2.307,-6.635,all P ＜ 0.05).The main complications included pancreatic fistula,intra-abdominal bleeding,intra-abdominal infection,pulmonary infection,refractory ascites,portal vein system thrombosis and incision infection,and there were respectively 0,1,2,2,3,13,0 in the LSD group and 3,4,6,6,7,14,3 in the OSD group,with statistically significant differences between groups (x2 =5.872,4.792,6.179,6.179,6.010,4.335,5.872,all P ＜ 0.05).All the 205 patients received follow-up for a median time of 38 months (12-72 months).Gastroscopy showed improvement of esophageal and gastric varices in postoperative 6 months.Conclusion Laparoscopic splenectomy and pericardial devascularization for the treatment of portal hypertension is safe,feasible and effective.

Objective To investigate the effect of repetitive transcranial magnetic stimulation (rTMS) on social function and life quality of schizophrenia in long-term hospitalization.Methods Sixty patients met with ICD-10 for schizophrenia in long-term hospitalization were enrolled in this study.The group was divided randomly into research (n =40) and control (n =40) groups.They were given rTMS or sham stimulation,respectively.The treatment was given 20 times,and the course of treatment was 4 weeks.The research and control groups were assessed with measured the scale of social function in psychosis inpatients and personal and social function scale and schizophrenia quality of life scale before and'after 4 weeks treatment.Each test result of all groups before and after treatment was compared with each other,respectively.Results Compared to rTMS before treatment,the study group scale of social function in psychosis inpatients (SSPI) total score,factor Ⅰ,Ⅱ and personal and social function scale (PSP) scores were significantly increased (P ＜ 0.05),no change of SSPI factor (P ＞ 0.05);the study group Schizophrenia Quality of Life Scale (SQLS) total score,psychological and social power,the energy scale scores were significantly reduced (P ＜ 0.05),SQLS symptoms and side effects scale showed no significant difference (P ＞ 0.05).No significant change was found in the scores of project SSPI,PSP and SQLS in control group before and after treatment (P ＞ 0.05);the difference of each parameter between two groups after treatment were statistically significant (P ＜ 0.05).Conclusions Repetitive transcranial magnetic stimulation could improve on social function and life quality of schizophrenia in long-term hospitalization,rTMS could provide a new way for the individual rehabilitation of schizophrenia in long-term hospitalization.

Objective To study the efficacy and safety of Shuganjieyu capsule alone or in combination with other antidepressants for the treatment of post-stroke depression (PSD).Methods Wanfang database,China National Knowledge Infrastructure (CNKI),Chinese VIP journals database,PubMed,EMbase,Cochrane Library,and Chinese dissertations full text database were retrieved by computers.The randomized controlled trials (RCTs) on Shuganjieyu capsule for the treatment of PSD from January 1995 to September 2017 were collected.After literature screening,data extraction,and methodological quality evaluation,RevMan 5.1 software was used to conduct a Meta-analysis.The bias was evaluated with the Stata 12.0 software using Begg's rank correlation and Egger's linear regression.Results A total of 19 RCTs were included,including 1 814 participants.The Meta-analysis results showed that compared with other antidepressants,there were no significant differences in the effective rate and cure rate of Shuganjieyu capsule (combinedeffects:RR=1.04 [95％ CI0.97-1.11],Z=0.99,P=0.32 and RR =1.06 [95％ CI 0.85-1.32];Z =0.52,P =0.60).Compared with other antidepressants,there were significant differences in the effective rate and cure rate of Shuganjieyu capsule in combination with other antidepressants (combined effects:RR =1.19 [95％ CI 1.13-1.26];Z =6.43,P ＜0.01 and RR =1.54 [95％ CI 1.26-1.88];Z =4.17,P ＜0.01).The incidence of adverse events of Shuganjieyu capsule alone was less than that of other antidepressants (combined effect:RR =0.39 [95％ CI 0.27-0.55];Z =5.30,P ＜ 0.01).The incidence of adverse events of Shuganjieyu capsule in combination with other antidepressants was the same as other antidepressants (combined effect:RR =0.99 [95％ CI 0.77-1.26];Z =0.10,P =0.92).Conclusions Shuganjieyu capsule is effective for post-stroke depression.The efficacy of Shuganjieyu capsule alone is as effective as other antidepressants,however,Shuganjieyu capsule in combination with other antidepressants is superior to other antidepressants,and the safety is better than other antidepressants.