1.Research progress of pyroptosis in tumor immunity
Yuting HAN ; Dongdong LI ; Peimin LIU
Chinese Journal of Immunology 2024;40(11):2421-2426
Pyroptosis,as the main mechanism of host defense,is the key link between innate immunity and adaptive immunity.Pyroptosis is accompanied by membrane rupture,and the cells release a large number of inflammatory mediators,which recruit inflam-matory cells and activate the inflammatory response.Tumor immunotherapy utilizes the natural defense mechanism of the host to ad-minister certain immunomodulators,antibodies or stimulation-adjusted immune cells to obtain stronger anti-tumor effects.Recent stud-ies have shown that pyroptosis has a positive regulatory effect on tumor immunotherapy,including immune checkpoint inhibitors and chimeric antigen receptor T-cell immunotherapy,etc.In this paper,based on the published experimental studies,the mechanism of pyroptosis and its correlation with tumor immunotherapy.In this paper,based on the published experimental studies,the mechanism of cellular apoptosis in tumor immunity is elucidated on the basis of the mechanism of apoptosis and the correlation between tumor im-munotherapy,in order to provide new ideas for the basic and clinical research of malignant tumors.
2.Construction and validation of a prediction model for prolonged hospitalization in patients with severe acute pancreatitis
Qianqian LIU ; Liuyi MA ; Dongdong HAN ; Min GAO ; Yuan TIAN ; Xiaoyan ZHOU
Chinese Critical Care Medicine 2024;36(11):1174-1178
Objective:To construction the risk factors associated with prolonged hospitalization in patients with severe acute pancreatitis (SAP) and develop a prediction model for assessing these risks.Methods:SAP patients admitted to the department of emergency of Hebei Province Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine from January 2015 to December 2023 were retrospectively selected as the study subjects. The 75% of hospital stay was used as the cut-off point, and the patients were categorized into a normal group and an extended group. Clinical indicators of patients were collected, and independent risk factors for prolonged hospital stay in SAP patients were analyzed using multifactor Logistic regression. A prediction model was established, and a nomogram was created. The efficiency of the prediction model was evaluated using a receiver operator characteristic curve (ROC curve). The accuracy of the model was assessed using Hosmer-Lemeshow goodness-of-fit test. Decision curve analysis (DCA) was employed to evaluate the clinical applicability of the model. Finally, internal validation of the model was conducted using Bootstrap method.Results:A total of 510 patients with SAP were included, and the length of hospital stay was 18 (6, 44) days, including 400 cases in the normal group (<24 days) and 110 cases in the extended group (≥24 days). Multivariate Logistic regression analysis showed that abdominal effusion [odds ratio ( OR) = 4.163, 95% confidence interval (95% CI) was 2.105-8.234], acute physiology and chronic health evaluation Ⅱ (APACHEⅡ; OR = 1.320, 95% CI was 1.185-1.470), C-reactive protein (CRP; OR = 1.006, 95% CI was 1.002-1.011), modified CT severity index (MCTSI; OR = 1.461, 95% CI was 1.213-1.758), procalcitonin (PCT; OR = 1.303, 95% CI was 1.095-1.550) and albumin ( OR = 0.510, 95% CI was 0.419-0.622) were independent risk factors for prolonged hospital stay in SAP patients (all P < 0.01). ROC curve analysis showed that the area under the curve (AUC) of the model was 0.922 (95% CI was 0.896-0.947), the optimal cut-off value was 0.726, the sensitivity was 87.3%, and the specificity was 85.3%. Hosmer-Lemeshow test showed that χ 2 = 5.79, P = 0.671. It showed that the prediction model had good prediction efficiency and fit degree. The DCA curve showed that the prediction probability of the model could bring more clinical benefits to patients at 0.1 to 0.7. Bootstrap internal verification showed that the model had a high consistency (AUC = 0.916). Conclusions:Abdominal effusion, high APACHEⅡ score, high CRP, high MCTSI, high PCT and low albumin level are significantly associated with prolonged hospital stay in SAP patients. The prediction model can help clinicians make more scientific clinical decisions for SAP patients.
3.The relationship between the decrease of end expiratory carbon dioxide during liver transplantation and the occurrence of acute kidney injury after surgery
Yongyi CHEN ; Yaqi XU ; Shiwei YANG ; Dongdong HAN ; Jun DUAN
Journal of Chinese Physician 2024;26(4):538-542
Objective:To investigate whether end-tidal carbon dioxide (etCO 2) is associated with acute kidney injury (AKI) after liver transplantation. Methods:Clinical data of 83 patients undergoing classic allogeneic liver transplantation were retrospectively collected. Patients were divided into AKI group and non AKI group based on changes in serum creatinine levels within 48 hours after surgery, and differences in baseline data, intraoperative etCO 2 decrease rate [ΔetCO 2(%)], and postoperative creatinine values were analyzed between the groups. Results:The incidence of AKI within 48 hours after liver transplantation in 83 patients was 56.6%(47/83). The proportion of male patients in the AKI group was higher ( P=0.003), and the ΔetCO 2(%) in the anhepatic phase of AKI group patients was higher than that of non AKI patients [(0.26±0.08)% vs (0.22±0.07)%, P=0.024]. There was no statistically significant difference in ΔetCO 2(%) between the two groups during pre liver, inferior vena cava (IVC) occlusion, and new liver phase (all P>0.05). On the 7th day after surgery, the creatinine value in the AKI group was significantly higher than that in the non AKI group [68.7(55.4, 92.6)]μmol/L vs 52.7(44.1, 69.3)μmol/L, P<0.001], at a 3-month follow-up, creatinine levels in 43 patients (91.5%) in the AKI group returned to normal. Conclusions:The decrease in ΔetCO 2(%) during the anhepatic phase of liver transplantation reflects to some extent the severe fluctuations in circulation during the operation, which may be related to the occurrence of AKI within 48 hours after surgery.
4.Medication rules of famous Beijing TCM doctor Wang Pei in the treatment of colon cancer based on data mining
Dongdong LU ; Xiping GUO ; Yuewan FU ; Han LIU ; Jie WANG ; Yichao WU ; Jianwei SHANG ; Yaosheng ZHANG
International Journal of Traditional Chinese Medicine 2023;45(1):90-94
Objective:To explore the medication rules of Professor Wang Pei in the treatment of colon cancer.Methods:The medical records of Professor Wang Pei's outpatient treatment for colon cancer were collected, entered into the Traditional Chinese Medicine Inheritance Computing Platform V3.0, and the laws of the prescription's nature, flavor, meridian, drug frequency, drug combination, association rules, and cluster analysis were explored.Results:A total of 65 prescriptions were collected, including 150 Chinese materia medica. The medicinal properties of these Chinese materia medica are mainly warm, cold and flat, the tastes were mainly sweet, bitter and pungent, and the meridians were mainly liver, spleen and kidney meridians. Dampness category and blood circulation promoting and blood stasis category were mainly used, and the most frequently used drugs include Poria, Polyporus, Scutellariae Barbatae Herba, Astragali Radix, Curcumae Rhizoma, and the pairs of Polyporus- Poria, Astragali Radix- Astragali Radix Praeparata cum Melle, Scutellariae Barbatae Herba- Curcumae Rhizoma. Twenty nine high-related drug pairs were obtained from association rules, including Polyporus- Astragali Radix Praeparata cum Melle- Astragali Radix, Poria- Scutellariae Barbatae Herba- Polyporus, Scutellariae Barbatae Herba- Curcumae Rhizoma- Polyporus. The cluster analysis showed the combination of 6 types of medicines mainly focuses on strengthening the spleen and removing dampness, nourishing qi and promoting blood, clearing heat and detoxifying, and astringing the intestines to stop bleeding. Conclusion:Professor Wang Pei mostly discusses the treatment of colon cancer from "spleen dampness, rectification deficiency, heat toxin, blood stasis, bleeding", and the treatment is "invigorating the spleen and removing dampness, invigorating Qi and strengthening the body, clearing away heat and detoxifying, promoting blood circulation and removing blood stasis, and astringent intestines to stop bleeding", which is in line with the thought of Traditional Chinese Medicine treatment of tumors, strengthening the righteousness and eliminating pathogenic factors, and and can be used for clinical reference.
5.Establishment of prediction model for severe acute pancreatitis complicated with abdominal hypertension
Liuyi MA ; Qianqian LIU ; Dongdong HAN ; Min GAO ; Yuan TIAN ; Xiaoyan ZHOU
Chinese Journal of Pancreatology 2023;23(4):272-277
Objective:To construct the prediction model of SAP complicated with intra-abdominal hypertension (IAH), and evaluate the prediction efficiency of the model.Methods:The clinical data of 322 SAP patients admitted to the emergency department of Cangzhou Hospital of Integrated Chinese and Western Medicine in Hebei Province from January 2017 to December 2021 were retrospectively analyzed. They were divided into IAH group ( n=153) and control group ( n=169) according to whether they had IAH complications or not. The clinical characteristics and laboratory test results of the two groups were compared. Multifactor logistic step-up regression was used to analyze the risk factors of SAP patients complicated with IAH. A nomogram model for predicting SAP complicated with IAH was established by using R software. The receiver operating characteristic curve (ROC) of the model was plotted, and the area under the curve (AUC) was calculated to evaluate its prediction efficiency. Calibration chart, Hosmer-Lemesshow test and decision curve analysis were used to evaluate the prediction accuracy and clinical application value of the model. The Bootstrap method was applied to verify the model internally. Results:In IAH group, cases with body mass index, CRP, procalcitonin (PCT), WBC, acute physiological and chronic health assessmentⅡ (APACHEⅡ) score, modified CT Severity Index score (MCTSI), incidence of complications (abdominal effusion, abdominal infection, gastrointestinal dysfunction, shock, multiple organ dysfunction syndrome), mechanical ventilation, the number of high-volume fluid reactivation (24 h≥4 L) were more than those in control group; serum albumin and serum calcium in IAH group were lower than those in control group, and the differences were statistically significant (all P value <0.05). Multivariate logistic regression analysis showed that serum albumin ( OR=0.815, 95% CI 0.710-0.937), CRP ( OR=1.005, 95% CI 1.002-1.008), MCTSI ( OR=2.043, 95% CI 1.695-2.463), complication of gastrointestinal dysfunction ( OR=4.179, 95% CI 2.170-8.049), and high-volume fluid resuscitation ( OR=4.265, 95% CI 2.269-8.015) were independent risk factors for IAH in SAP.The Nomogram prediction model was established using the five factors above as parameters, and the AUC value for predicting IAH complication was 0.886. The Hosmer-Lemesshow test showed a high consistency between the prediction results and the actual clinical observation results ( P=0.189). The results of decision curve analysis showed that the prediction probability of the model was between 10% and 85%, which could bring more benefits to patients. Conclusions:The early prediction model of SAP with concurrent IAH is successfully established, which can better predict the risk of SAP with concurrent IAH.
6.Estimation model for the exposure of mycophenolic acid in early renal transplant recipients
Hanjuan ZHANG ; Jianqiang DING ; Wenchao HAN ; Yongyan CHEN ; Gaobiao WANG ; Rui DING ; Dongdong YUAN
China Pharmacy 2023;34(20):2530-2534
OBJECTIVE To establish the estimation model for the exposure of mycophenolic acid (MPA) in early renal transplant recipients [calculated by the area under the plasma concentration-time curve with 12 h (AUC0-12 h)]. METHODS Twenty kidney transplant recipients, who received triple immunosuppressive therapy of mycophenolate mofetil (MMF)+tacrolimus+ methylprednisolone, were selected and given MMF dispersible tablets (750 mg, q12 h) on the 15th day after the operation; the blood samples were collected from the patients before and 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 12.0 hours after the administration, respectively. The blood concentration of MPA was determined, and the pharmacokinetic parameters of MPA were calculated. The multivariate linear stepwise regression analysis method was used to fit an estimation formula for the finite sampling method suitable for MPA-AUC0-12 h of the recipients. Bland-Altman analysis was used to evaluate the agreement between the estimation formula and the classical pharmacokinetic method. RESULTS The main pharmacokinetic parameters of MPA in 20 renal transplant recipients: c0 was (1.53±0.84) μg/mL, cmax was (12.07±5.97) μg/mL, t1/2 was (5.41±3.67) h, tmax was (1.58±0.75) h, and the average AUC0-12 h calculated by the classical pharmacokinetic method was (33.95±13.40) μg·h/mL. MPA-AUC0-12 h was estimated with sampling points of “4.0, 8.0, 12.0 h”; the simplified calculation formula was AUC0-12 h=12.058+2.819c4.0+7.045c8.0+ 3.879c12.0 (R 2=0.934). The predicted value had a good correlation and consistency with the measured value, and 95.0% of predicted values did not exceed the x±1.96SD (standard deviation) range. CONCLUSIONS The estimation model is established successfully for the exposure of MPA in early renal transplant recipients; the model has better prediction accuracy and fewer sampling points.
7.Construction and clinical application of An analytical method for rapidly detecting sulfamethoxazole plasma concentration in heart transplant patients
WANG Gaobiao ; ZHANG Hanjuan ; CHEN Yongyan ; HAN Wenchao ; DING Rui ; YUAN Dongdong
Chinese Journal of Modern Applied Pharmacy 2023;40(13):1853-1857
OBJECTIVE To explore and establish an analysis method for sulfamethoxazole blood concentration in patients with heart transplantation to guide clinical rational drug use. METHODS A new two-dimensional liquid chromatograph (2D-LC-UV) based on column switching technology was used. The on-line solid-phase extraction of sulfamethoxazole in serum was performed using a one-dimensional column Aston SC2(3.5 mm×25 mm, 5 μm), then it was intercepted and retained through the middle column Aston SBR(3.5 mm×10 mm, 5 μm), and the target analytes were completely separated and detected by transfer to the second-dimension column Aston SNX4(4.6 mm×130 mm, 5 μm). The chromatographic conditions were obtained by optimization. The one-dimensional mobile phase was acetonitrile-methanol-H2O(10:10:70), the flow rate was 0.8 mL·min-1; the two-dimensional mobile phase ratio was BPI-1 basic mobile phase-API-3 acidic mobile phase-methanol(20:40:40) the flow rate was 1.2 mL·min-1. The UV detection wavelength was 240 nm. RESULTS The correlation coefficient between the concentration of sulfamethoxazole and peak area was in the range of 9.96‒200.04 μg·mL-1 with R2=0.999 6, it showed a good linear relationship. The intra-day and inter-day precisions(RSD) at low, medium and high concentrations were <15%, and the relative recoveries were between 85%‒115%. The blood concentration of 56 patients in the hospital was measured, and only 30 patients(53.57%) had the blood sample sulfamethoxazole concentration of 100‒150 μg·mL-1, and the rest were not comfortable about the concentration treatment window; there were 0 cases of grade III-IV adverse reactions in the urinary system/blood system/liver, etc. CONCLUSION This method has a simple pre-treatment, high automation, can be sampled in large volumes, and has high accuracy and sensitivity. It can meet the requirements of clinical applications. The research results can provide a methodological reference for clinical therapeutic drug monitoring..
8.Excerpt from the 2023 American Association for the Study of Liver Diseases practice guideline: prevention, diagnosis, and treatment of hepatocellular carcinoma
Zhengyu WANG ; Dongdong XIA ; Guohong HAN
Chinese Journal of Hepatology 2023;31(12):1262-1265
The 2023 American Association for the Study of Liver Diseases practice guidelines (hereinafter referred to as the Guidelines) provide the latest approach for the prevention, diagnosis, and treatment of hepatocellular carcinoma. The prior American Association for the study of Liver Diseases (AASLD) HCC guidelines have been updated to reflect the clinically significant advances in multiple fields of HCC. Notable examples of these updates include recommendations for the use of ultrasound and alpha-fetoprotein for HCC monitoring, the expansion of surgical treatment indications, the addition of immunosuppressive therapy as first-line systemic therapy, and the implementation of clear multidisciplinary care and proactive care planning.
9.Effects of transcutaneous electrical acupoint stimulation on emergence agitation in patients undergoing thoracoscopic surgery
Xiangshuo MENG ; Jianli LI ; Jing ZHANG ; Shuang HAN ; Dongdong YU
Chinese Journal of Anesthesiology 2022;42(2):147-150
Objective:To evaluate the effect of transcutaneous electrical acupoint stimulation (TEAS) on emergence agitation in the patients undergoing thoracoscopic surgery.Methods:Eighty patients of both sexes, aged 25-64 yr, with body mass index of 18-30 kg/m 2, of American Society of Anesthesiologists physical status Ⅱ or Ⅲ, undergoing elective thoracoscopic surgery under general anesthesia, were divided into 2 groups ( n=40 each) by a random number table method: TEAS group (group T) and control group (group C). In group T, the Hegu (L14), Zusanli (ST36) and Sanyinjiao (SP6) were stimulated starting from 30 min before induction of anesthesia until the end of operation, with a frequency of 2/100 Hz and disperse-dense waves.The intensity of stimulation was the maximum current that patients could tolerate.In group C, stimulating electrodes were placed at the same acupoints before induction, but no electrical stimulation was applied.Ramsay sedation score and VAS score were recorded.and emergence agitation was assessed using RSS agitation score.Blood samples from the median cubital vein or internal jugular vein were collected before anesthesia induction (T 1), at the end of surgery (T 2), immediately after removal of tracheal tube (T 3) and at 15 min after removal of tracheal tube (T 4) for determination of serum interleukin-6 (IL-6) and IL-10 concentrations by enzyme-linked immunosorbent assay.The intraoperative consumption of propofol, remifentanil and sufentanil was recorded.Adverse reactions such as tachycardia, bradycardia, hypertension, hypotension, respiratory depression, delay of awakening and nausea and vomiting were recorded after operation. Results:Compared with group C, the amount of intraoperative remifentanil consumed was significantly decreased, serum IL-6 concentrations were decreased, and the serum IL-10 concentration was increased T 2-4, Ramsay sedate score was increased, and the incidence of agitation was decreased in group T ( P<0.05). There was no significant difference in VAS score and incidence of postoperative adverse reactions between the two groups ( P>0.05). Conclusions:TEAS can reduce the development of emergence agitation in the patients undergoing thoracoscopic surgery, which is related to inhibition of inflammatory responses.
10.Value of Modified Response Evaluation Criteria in Solid Tumors response in predicting the prognosis of patients with unresectable hepatocellular carcinoma patients after transarterial chemoembolization
Dandan HAN ; Zhexuan WANG ; Enxin WANG ; Dongdong XIA ; Qiuhe WANG ; Wei BAI ; Yong CHEN ; Guohong HAN
Journal of Clinical Hepatology 2021;37(3):616-620
ObjectiveTo investigate the association of Modified Response Evaluation Criteria in Solid Tumors (mRECIST) response with the prognosis of patients with unresectable hepatocellular carcinoma (HCC) after transarterial embolization (TACE). MethodsA retrospective analysis was performed for the clinical data of 190 patients with unresectable HCC who were consecutively admitted to Department of Liver Disease and Digestive Interventional Radiology, The First Affiliated Hospital of Air Force Medical University, and treated with TACE from January 2010 to December 2014. The mRECIST criteria were used to evaluate imaging response after TACE; the patients with complete response (CR) or partial response (PR) were enrolled as response group(n=89), and those with progressive disease (PD) or stable disease (SD) were enrolled as non-response group(n=101). The Kaplan-Meier method was used to calculate median survival time, and the log-rank test was used for comparison between groups; the Cox regression model was used to identify the influencing factors for prognosis. ResultsAccording to the mRECIST criteria, 39 patients (20.5%) achieved CR, 50 (26.3%) achieved PR, 67 (35.3%) had SD, and 34 (17.9%) had PD. The objective response rate based on mRECIST was 46.8% for the whole population. The response group had a significantly longer survival time than the non-response group, and the median survival time was 29.9 (95% confidence interval [CI]: 25.0-34.8) months for the response group and 7.5 (95% CI: 5.7-9.3) months for the non-response group (P<0.001). The multivariate analysis showed that mRECIST response (hazard ratio [HR]=2.02, P<0.001), hepatitis B (HR=4.03, P<0.001), and portal invasion (HR=2.12, P=0.008) were independent risk factors for survival. ConclusionThe mRECIST response has a certain value in predicting the prognosis of patients with unresectable HCC after TACE.


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