The past, present and future of heart transplantation / 器官移植

Heart transplantation is one of the most effective strategies to treat end-stage heart failure. Multiple challenges, such as difficulty in preservation of heart allograft, rejection and postoperative complications, emerge in heart allotransplantation. After decades of research and practice, most problems have been resolved. Nevertheless, the shortage of donor organs has become increasingly prominent. To alleviate the shortage of donor organs, artificial heart and heart xenotransplantation have captivated attention, and obtained significant progress in recent years. The application of artificial heart in clinical practice has significantly enhanced the survival rate of patients with end-stage heart failure, which is expected to become the standard treatment for end-stage heart failure. Heart xenotransplantation still faces many challenges, which is still far from clinical application. In this article, the history of heart transplantation, development of heart allotransplantation, use of artificial heart and research progress on heart xenotransplantation were reviewed, and the future development direction of heart transplantation was predicted.

A consensus on the management of allergy in kindergartens and primary schools / 中国学校卫生

Abstract@#Allergic diseases can occur in all systems of the body, covering the whole life cycle, from children to adults and to old age, can be lifelong onset and even fatal in severe cases. Children account for the largest proportion of the victims of allergic disease, Children s allergies start from scratch, ranging from mild to severe, from less to more, from single to multiple systems and systemic performance, so the prevention and treatment of allergic diseases in children is of great importance, which can not only prevent high risk allergic conditions from developing into allergic diseases, but also further block the process of allergy. At present, there is no consensus on the management system of allergic children in kindergartens and primary schools. The "Consensus on Allergy Management and Prevention in Kindergartens and Primary Schools", which includes the organizational structure, system construction and management of allergic children, provides evidence informed recommendations for the long term comprehensive management of allergic children in kindergartens and primary schools, and provides a basis for the establishment of the prevention system for allergic children.

Advances in analytical methods for endogenous bile acids based on UPLC-MS/MS technology / 药学学报

Bile acids (BAs) are a group of endogenous steroid molecules that regulate lipid, glucose and energy metabolism. They play an important role in maintaining body homeostasis and physiological functions as key signaling molecules for host and gut microbial metabolism. The accurate characterization and quantification of BAs in vivo is of great importance in basic and clinical research. Over the past decades, enzymatic assay, enzyme-linked immunoassay, nuclear magnetic resonance (NMR), chromatography, and other related techniques have been developed and applied to the detection of BAs. The diverse structures of BAs, the existence of isomers and the complex matrix of biological samples pose great challenges for the detection of endogenous BAs. Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) is a robust analytical technique that combines the rapid separation capacities of UPLC with the powerful structural identification capabilities of MS/MS, facilitating the more rapid separation, characterization and accurate quantitative of target analytes in biological samples. UPLC-MS/MS has been widely used in the quantitative analysis of BAs in recent years for its high selectivity, high sensitivity, and high accuracy. This paper summarized the biosynthetic pathways of BAs, sample pretreatment methods, common analytical detection techniques, and highlights the current status of the application of UPLC-MS/MS technology in the analysis of endogenous BAs over the past five years, to provide a reference for the accurate detection of endogenous BAs and further research development and application.

Influence of small-group experiential learning of integrated traditional Chinese and Western medicine on the oral health knowledge, beliefs, and behaviors of elderly patients with diabetes

SUMMARY OBJECTIVE: This study aimed at the oral health problems of elderly patients with diabetes. A training course of integrated traditional Chinese and Western medicine was constructed, helping patients improve their oral health quality of life. METHODS: A randomized controlled prospective experimental study was conducted. A total of 190 elderly patients were divided randomly into an observation group and a control group with 95 cases in each. The control group received regular health education, while the observation group was based on the control group to implement the integrated experiential learning of traditional Chinese and Western medicine in small groups. The oral health knowledge, attitude, behavior, and blood glucose control status along with the oral health quality of life of the two groups were compared before the intervention and at 3-month postintervention. RESULTS: Three months after the intervention, the fasting blood glucose control and the 2-h postprandial blood glucose/glycosylated hemoglobin levels in the observation group were significantly better than in the control group, and the difference was statistically significant (p<0.05). The oral health quality of life in the observation group was significantly better than in the control group, and the difference was statistically significant (p<0.05). CONCLUSION: The small-group experiential learning model of integrated Chinese and Western medicine can promote the transformation of knowledge-beliefs-behaviors in elderly patients with diabetes, which is conducive to controlling blood sugar levels and improving the quality of oral health.

Prognostic value of PCSK9 and blood lipid in patients with sepsis / 中华危重病急救医学

Objective:To investigate the prognostic value of proprotein convertase subtilisin/kexin type 9 (PCSK9) and blood lipid indexes in patients with sepsis.Methods:Patients with sepsis or septic shock who were ≥ 18 years old and met the Sepsis-3.0 diagnostic criteria admitted to the department of critical care medicine of Binzhou Medical University Hospital from January to October 2021 were enrolled. Healthy adults at the same period were selected as healthy control group. Baseline characteristics, acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) and sequential organ failure assessment (SOFA) score were recorded. Venous blood samples were collected within 24 hours after diagnosis, and serum PCSK9 was determined by enzyme-linked immunosorbent assay (ELISA) at 1, 3 days and 5 days. Meanwhile, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglyceride (TG) and lipoprotein A were detected. The differences of each index between sepsis group (28-day death group and survival group) and healthy control group were compared. Meanwhile, the indexes of patients with different severity and 28-day prognosis in sepsis group were compared. Receiver operator characteristic curve (ROC curve) was drawn to evaluate the predictive value of PCSK9 and blood lipid for the prognosis of sepsis. Multivariate Logistic regression was used to analyze the influencing factors for the prognosis of sepsis, and the Kaplan-Meier survival curve at 28th day was drawn.Results:There were 50 patients in sepsis group (including 19 patients with sepsis, 31 patients with septic shock) and 27 patients in healthy control group. In the sepsis group, 19 patients died and 31 patients survived within 28 days. The serum PCSK9 in the sepsis group was significantly higher than that in the healthy control group [μg/L: 223.09 (198.47, 250.82) vs. 188.00 (165.27, 214.90), P < 0.01], and HDL-C, LDL-C, TC and lipoprotein A were significantly lower than those in the healthy control group [HDL-C (mmol/L): 0.82±0.35 vs. 1.45±0.24, LDL-C (mmol/L): 1.53 (1.14, 2.47) vs. 2.89 (2.55, 3.19), TC (mmol/L): 2.03 (1.39, 2.84) vs. 4.24 (3.90, 4.71), lipoprotein A (g/L): 8.80 (5.66, 17.56) vs. 27.03 (14.79, 27.03), all P < 0.01]. PCSK9 in the sepsis death group was higher than that in the survival group [μg/L: 249.58 (214.90, 315.77) vs. 207.01 (181.50, 244.95), P < 0.01], and the HDL-C, LDL-C and TC were lower than those in the survival group [HDL-C (mmol/L): 0.64±0.35 vs. 0.93±0.30, LDL-C (mmol/L): 1.32±0.64 vs. 2.08±0.94, TC (mmol/L): 1.39 (1.01, 2.23) vs. 2.69 (1.72, 3.81), all P < 0.01]. With the progression of the disease, the PCSK9 in the sepsis death group and the survival group was significantly lower than that within 1 day of diagnosis (all P < 0.05). ROC curve analysis showed that PCSK9 had higher predictive value of 28-day death than HDL-C, LDL-C, TC [area under ROC curve (AUC) and 95% confidence interval (95% CI): 0.748 (0.611-0.885) vs. 0.710 (0.552-0.868), 0.721 (0.575-0.867), 0.702 (0.550-0.854)]. Multivariate Logistic regression analysis showed that PCSK9 was an independent risk factor affecting the 28-day prognosis of sepsis (β value was 1.014, P = 0.020). Kaplan-Meier survival curve analysis showed that when PCSK9 ≥ 208.97 μg/L, with the increase of PCSK9, the 28-day survival rate of sepsis patients decreased significantly. Conclusions:PCSK9, HDL-C, LDL-C and TC can all predict the 28-day prognosis of patients with sepsis. The prognostic value of PCSK9 is the highest. PCSK9 is an independent risk factor affecting the prognosis of sepsis. In the early stage of the disease, PCSK9 may have a good predictive value for the prognosis of sepsis. When PCSK9 ≥ 208.97 μg/L, the 28-day survival rate decreased significantly.

Thymosin alpha 1 for the adjuvant treatment of coronavirus disease 2019: a retrospective cohort study / 中华危重病急救医学

Objective:To evaluate the effect of thymosin alpha 1 on the prognosis of patients with coronavirus disease 2019 (COVID-19).Methods:A retrospective cohort study was performed to collect clinical data of 95 patients treated by Shanghai Aid Medical Team in Wuhan Third Hospital during January 31, 2020 and March 4, 2020, who were confirmed COVID-19. They were divided into two groups according to whether they were treated with thymosin alpha 1 after admission. The 28-day mortality (primary outcome), and 28-ventilator-free-day, lymphocyte count (LYM) level, C-reactive protein (CRP) level (secondary outcomes) were compared between two groups. Survival analysis was performed using the Kaplan-Meier curve. The effect of thymosin alpha 1 on 28-day survival was evaluated with Cox regression model.Results:Among the 95 patients, there were 31 cases in thymosin group and 64 cases in non-thymosin group; 29 patients died 28 days after admission, including 11 cases (35.5%) in thymosin group and 18 cases (28.1%) in non-thymosin group. Kaplan-Meier survival curve showed that thymosin alpha 1 could improve the 28-day survival of patients with COVID-19, but the univariate Cox model analysis showed that the difference was not statistically significant [hazard ratio ( HR) = 0.48, 95% confidence interval (95% CI) was 0.20-1.14, P = 0.098]; multivariate Cox model analysis showed that thymosin alpha 1 was the factor to improve the 28-day mortality ( HR = 0.15, 95% CI was 0.04-0.55, P = 0.004), old age ( HR = 1.10, 95% CI was 1.05-1.15, P < 0.001), accompanied by chronic renal dysfunction ( HR = 42.35, 95% CI was 2.77-648.64, P = 0.007), decrease of LYM at admission ( HR = 0.15, 95% CI was 0.04-0.60, P = 0.007) and the use of methylprednisolone ( HR = 4.59, 95% CI was 1.26-16.67, P = 0.021) were also risk factors for the increase of 28-day mortality. The use of immunoglobulin and antiviral drugs abidol and ganciclovir did not affect the 28-day mortality. After adjustment for age, gender, LYM and other factors, weighted multivariate Cox analysis model showed thymosin alpha 1 could significantly improve the 28-day survival of COVID-19 patients ( HR = 0.45, 95% CI was 0.25-0.84, P = 0.012). In terms of secondary outcomes, no statistical difference (all P > 0.05) was found between two groups in days without ventilator at 28 days after admission (days: 17.97±13.56 vs. 20.09±12.67) and the increase of LYM at 7 days after admission [×10 9/L: -0.07 (-0.23, 0.43) vs. 0.12 (-0.54, 0.41)]. But the decrease of CRP at 7 days after admission in thymosin alpha group was significantly greater than that in non-thymosin group [mg/L: 39.99 (8.44, 82.22) vs. 0.53 (-7.78, 22.93), P < 0.05]. Conclusion:Thymosin alpha 1 may improve 28-day mortality and inflammation state in COVID-19 patients.

Effect of different connection schemes of continuous renal replacement therapy and extracorporeal membrane oxygenation on arterial and venous pressure: an in vitro and in vivo study / 中华危重病急救医学

Objective:To investigate the effects of different connection schemes of continuous renal replacement therapy (CRRT) and extracorporeal membrane oxygenation (ECMO) on arterial pressure (PA), venous pressure (PV), and transmembrane pressure (TMP), and to provide a theoretical basis for choosing a suitable connection scheme.Methods:① In vitro study: the different connection schemes of CRRT and ECMO were simulated and divided into 6 schemes according to the connection between CRRT and ECMO circuits at different positions. Scheme A: connected to the front and back points of the oxygenator; scheme B: connected to the points behind and in front of the oxygenator; scheme C: connected to the points in front of the oxygenator and in front of the centrifugal pump; scheme D: connected to the points behind the oxygenator and in front of the centrifugal pump; scheme E: connected to the points in front of the oxygenator and the return catheter; scheme F: connected to the points after the oxygenator and the return catheter. Each set of ECMO circuits was measured 5 times under each connection scheme and different flow rates (2, 3, 4, 5, 5.5 L/min). Six ECMO circuits for a total of 30 measurements, and the PA, PV, and TMP of the 6 schemes were compared. ② In vivo study: the patients who were treated with ECMO combined with CRRT in the department of critical care medicine of the First Affiliated Hospital of Wannan Medical College from August 2017 to August 2021 changed the connection scheme due to high PA or PV (from scheme A or B to scheme E or F) were retrospectively analyzed. The changes of PA and PV before and after changing the scheme were compared. Results:① In vitro study results: there was no significant difference in PA between schemes A and B, C and D, E and F under different ECMO blood flow (2-5.5 L/min). The PA of schemes C and D was the lowest, followed by schemes E and F. PV of scheme B was higher than that of scheme A under different ECMO blood flow (2-5.5 L/min). There was no significant difference in PV between schemes C and D, E and F under high ECMO blood flow (3-5.5 L/min), and the absolute value of PV was lowest in schemes E and F. Compared with schemes A and B [partial PA > 300 mmHg (1 mmHg≈0.133 kPa) at high flow rate], C and D (partial PV > 350 mmHg at high flow rate), schemes E and F were more reasonable connection schemes. TMP was negative in schemes C and D at ECMO blood flow of 5 L/min and 5.5 L/min (mmHg; 5 L/min: scheme C was -29.14±11.42, scheme D was -42.45±15.70; 5.5 L/min: scheme C was -35.75±13.21, scheme D was -41.58±15.42), which indicated the presence of dialysate reverse filtration. Most of the differences in TMP among schemes A, B, E, and F under different ECMO blood flow (2-5.5 L/min) were statistically significant, and the absolute value of mean fluctuation was 9.89-49.55 mmHg, all within the normal range. ② In vivo study results: a total of 10 patients who changed the connection scheme (from scheme A or B to E or F) due to high PA or PV were enrolled, including 8 males and 2 females; 7 cases of venous-arterial ECMO (VA-ECMO) and 3 cases of venous-venous ECMO (VV-ECMO), all used continuous veno-venous hemodiafiltration (CVVHDF) mode. After changing the scheme, both PA and PV decreased significantly as compared with those before changing [PA (mmHg): 244.00±22.58 vs. 257.20±21.92, PV (mmHg): 257.20±18.43 vs. 326.40±15.41, both P < 0.01], and PV decreased more significantly than PA [difference (mmHg): 69.20±6.55 vs. 13.20±5.45, P < 0.01]. Conclusion:For patients treated with ECMO in combination with CRRT, the scheme of connecting the access line of CRRT to the pre-oxygenator or post-oxygenator and connecting the return line to the point of the return catheter can significantly reduce PA and PV and maintains normal CRRT operation even running high-flow ECMO.

Clinicopathological features and prognosis analysis of patients with gastric gastrointestinal stromal tumor combined with digestive tract cancer / 中华消化外科杂志

Objective:To investigate the clinicopathological features and prognosis of patients with gastric gastrointestinal stromal tumor (GIST) combined with digestive tract cancer.Methods:The retrospective cohort study was conducted. The clinicopathological data of 1 163 patients with gastric GIST who were admitted to the Union Hospital admitted to Tongji Medical College of Huazhong University of Science and Technology from January 2002 to December 2021 were collected. There were 606 males and 557 females, aged 59(range,20?94)years. Of the 1 163 patients, 129 cases with gastric GIST combined with other digestive tract cancer were divided into the combined group, and 1 034 cases with only gastric GIST were divided into the non-combined group. Observation indicators: (1) clinicopathological features of patients; (2) surgical situations and postoperative complications; (3) follow-up and survival of patients; (4) analysis of prognosis associated affecting factors. Follow-up was conducted using outpatient examination, telephone and online interview to detect survival of patients up to January 2022. The overall survival time was defined as the time from surgery to the last tine of follow-up or the outcome events, such as death of patient, loss of follow-up, etc. Measurement data with normal distribution were represented as Mean± SD, and measure-ment data with skewed distribution were represented as M(range). Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test. Com-parison of ordinal data was conducted using the non-parameter Mann-Whitney U test. Kaplan-Meier method was used to draw survival curves and calculate survival rates, and Log-Rank test was used to conduct survival analysis. The COX proportional hazard model was used for univariate and multivariate analyses. Results:(1) Clinicopathological features of patients. Of the 129 patients in the combined group, there were 81 cases combined with gastric cancer, 39 cases combined with esophageal cancer, 8 cases combined with colon cancer and 1 case combined with rectal cancer. Gender (male, female), cases with age ≤60 years or>60 years, cases without or with clinical symp-toms before surgery, cases with tumor diameter of gastric GIST as<2 cm, 2?5 cm, 5?10 cm,>10 cm, cases with mitotic index as <5/50× high power field, 5?10/50× high power field, >10/50× high power field, cases with cell proliferation index of Ki-67 as ≤5% or >5%, cases classified as extremely low risk, low risk, medium risk and high risk of the modified national institutes of health (NIH) risk classification, cases with or without tumor necrosis of the gastric GIST, cases without or with adjuvant imatinib therapy, cases with the expression of DOG-1 detected by immunohistochemical staining as positive or negative, cases with the expression of CD34 as positive or negative were 92, 37, 30, 99, 9, 120, 114, 10, 3, 2, 126, 1, 2, 122, 2, 112, 8, 5, 4, 129, 0, 121, 8, 118, 3, 117, 12 in the combined group, versus 514, 520, 585, 449, 194, 840, 383, 360,201, 90, 799, 155, 80, 851, 143, 337, 308, 192, 197, 960, 74, 769, 265, 850, 80, 990, 44 in the non-combined group, showing significant differences in the above indicators between the two groups ( χ2=21.46, 51.11, 11.06, Z=?10.27, ?5.34, χ2=15.94, Z=?10.61, χ2=9.86, 24.10, 5.52, 6.37, P<0.05). Of the 1 163 patients, there were 12 cases of the combined group suspected diagnosed as gastric GIST before surgery and 1 case of the combined group dia-gnosed as gastric GIST by gastroscopy and pathological examination before surgery. The rest of 1 150 patients were diagnosed as gastric GIST by intraoperative exploration or postoperative pathological examination. (2) Surgical situations and postoperative complications. Of the 129 patients in the combined group, 72 cases underwent open surgery and 57 cases underwent laparoscopic or thoracoscopic surgery including 3 cases converted to open surgery. Of the 1 034 patients in the non-combined group,207 cases underwent endoscopic surgery, 371 cases underwent open surgery, and 456 cases underwent laparoscopic or thoracoscopic surgery including 8 cases converted to open surgery. Incidence of postoperative complications was 10.078%(13/129) in the combined group, versus 2.321%(24/1 034) in the non-combined group, showing a significant difference between the two groups ( χ2=22.40, P<0.05). (3) Follow-up and survival of patients. Of the 1 163 patients, 1 046 cases were followed up for 44(range, 1?220)months, with the postoperative 5-year overall survival rate as 87.2%. The postoperative 5-year overall survival rate was 51.2% in the combined group, versus 91.4% in the non-combined group, showing a significant difference between the two groups ( χ2=169.07, P<0.05). (4) Analysis of prognosis associated affecting factors. Results of univariate analysis showed that gender, age, tumor diameter of gastric GIST as 2?5 cm, 5?10 cm and >10 cm, combined with other digestive tract cancer, mitotic index as >10/50× high power field and tumor necrosis of the gastric GIST were related factors affecting the postoperative 5-year overall survival rate of patients with gastric GIST ( hazard ratio=2.16, 2.27, 0.46, 0.57, 1.75, 7.58, 2.70, 1.80, 95% confidence intervals as 1.52?3.07, 1.60?3.22, 0.29?0.71, 0.34?0.94, 1.11?2.77, 5.29?10.85, 1.67?4.38, 1.08?2.98, P<0.05). Results of multivariate analysis showed that gender, age, tumor diameter of gastric GIST, combined with other digestive tract cancer and mitotic index were independent factors affecting the post-operative 5-year overall survival rate of patients with gastric GIST ( hazard ratio=1.91, 1.82, 2.10, 7.11, 2.75, 95% confidence intervals as 1.33?2.75, 1.27?2.62, 1.14?3.87, 4.58?11.04, 1.50?5.03, P<0.05). Conclusions:The tumor diameter of gastric GIST is short in patients combined with other digestive tract cancer, and the risk grade of modified NIH risk classification is lower. Gender, age, tumor diameter of gastric GIST, combined with other digestive tract cancer and mitotic index are independent factors affecting the postoperative 5-year overall survival rate of patients with gastric GIST.

Research progress of the FLOT regimen in neoadjuvant treatment for gastric cancer / 中华消化外科杂志

With the deepening research of comprehensive treatment for gastric cancer, the FLOT regimen has begun to be used for the treatment of gastric cancer patients. FLOT neoadjuvant regimen can significantly improve the R 0 resection rate and prolong the overall survival time of locally advanced gastric cancer patients. FLOT regimen combined with immune-checkpoint inhibi-tors, targeted therapy and hyperthermic intraperitoneal chemotherapy have great potential in neo-adjuvant therapy for gastric cancer. The authors systematically analyse the development history and latest clinical research progress of FLOT neoadjuvant regimen for gastric cancer based on their clinical practice experience.

Application of ternary linkage continuation nursing model based on cognitive balance theory in patients with rheumatoid arthritis / 中国实用护理杂志

Objective:To explore the application effect of the ternary linkage continuation care model based on cognitive balance theory in patients with rheumatoid arthritis (RA), and to provide a reference for the continuation care model of RA patients.Methods:The convenience sampling method was adopted. A total of 72 RA patients who were treated in Huainan First People's Hospital, Anhui Province from January to December 2020 were selected as the research objects, and they were divided into observation group and control group by random number table method with 36 cases in each group. The control group was given regular discharge guidance and health education, and the observation group was given ternary continuous care based on cognitive balance theory on the basis of the control group. The intervention time was 3 months. The fatigue state, pain catastrophe, exercise self-efficacy and hope index was evaluated by the Bristol Rheumatoid Arthritis Fatigue Multi-Dimensional Questionnaire (BRAF-MDQ), the Pain Catastrophic Scale (PCS), the Self-Efficacy for Exercise Chinese version(SEE-C), and the Herth Hope Index Scale-Chinese version (HHI-C) and the results were compared between the two groups before and after the intervention.Results:There was no significant difference in the score of BRAF-MDQ, PCS, SEE-C, HHI-C before the intervention between the two groups( P>0.05). The scores of physical fatigue, life fatigue, cognitive fatigue and emotional fatigue of BRAF-MDQ in the observation group after the intervention were (10.02 ± 0.85), (6.33 ± 0.58), (3.31 ± 0.48), (4.25 ± 0.56) points, respectively, significantly lower than those in the control group (12.97 ± 1.89), (8.94 ± 0.97), (6.55 ± 0.97), (5.92 ± 0.87) points, and the differences were statistically significant ( t values were 8.54-17.96, all P<0.05). The scores of contemplation, exaggeration, and helplessness of PCS in the observation group after the intervention were (5.66 ± 0.43), (4.12 ± 0.36), (3.31 ± 0.41) points, respectively, which were significantly lower than those in the control group (8.41 ± 0.88), (5.74 ± 0.85), (5.52 ± 0.86) points, and the differences were statistically significant ( t=16.85, 10.53, 13.92, all P<0.05). The scores of SEE-C and HHI-C were (60.22 ± 7.89), (37.48 ± 5.79) points in the observation group after the intervention, which were significantly higher than those in the control group (46.98 ± 5.84), (34.21 ± 4.93) points, and the differences were statistically significant ( t=8.09, 2.58, both P<0.05). Conclusions:The ternary linkage continuation nursing model based on the cognitive balance theory has a significant effect on alleviating the fatigue state and pain catastrophe of RA patients, and helps to improve the patients' hope level and exercise self-efficacy.

Efficacy of postoperative radiotherapy based on modified clinical target volume according to high-frequency recurrence regions in patients with esophageal squamous cell carcinoma / 国际肿瘤学杂志

Objective:To analyze the survival efficacy, prognostic factors and failure patterns of patients with esophageal squamous cell carcinoma (ESCC) underwent postoperative radiotherapy (PORT) using modified clinical target volume (CTV) based on postoperative high-frequency recurrence regions, so as to provide reference for the further optimization of CTV of PORT.Methods:The patients with ESCC underwent radical operation in Comprehensive Cancer Center of Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School from April 28, 2014 to November 29, 2018 were retrospectively analyzed. Patients with stage pT 3-4aN 0 or N +, who underwent PORT with modified CTV based on postoperative high-frequency recurrence regions, were included in the study. Kaplan-Meier method was used to calculate overall survival (OS) and locoregional recurrence free survival (LRFS) , adverse events of patients were evaluated, Cox proportional hazards model was used for univariate and multivariate survival analysis, and the failure patterns of patients after PORT were analyzed. Results:A total of 85 patients were included in this study, and the median follow-up time was 52.6 months. The median OS of the whole group was 74.1 months. The 1-year, 2-year and 3-year OS rates were 97.6%, 84.7% and 71.7% respectively. The median LRFS was not reached, and the 1-year, 2-year and 3-year LRFS rates were 92.9%, 78.6% and 71.5% respectively. The incidence of grade 3-4 adverse events was 17.6% (15/85) , mainly including lymphopenia, bone marrow suppression, gastrointestinal reaction and skin reaction. Univariate analysis of OS after PORT showed that the degree of differentiation (set G1+G1-2+G2 group as the control group, G2-3+G3 group HR=4.19, 95% CI: 1.91-9.17, P<0.001; NA+basal-like group HR=4.16, 95% CI: 1.29-13.44, P=0.017) and postoperative stage ( HR=2.19, 95% CI: 1.09-4.39, P=0.030) were the influencing factors of OS. Cox multivariate analysis showed that the degree of differentiation was an independent prognostic factor for OS after PORT (set G1+G1-2+G2 group as the control group, G2-3+G3 group HR=5.24, 95% CI: 2.30-11.93, P<0.001; NA+basal-like group HR=4.83, 95% CI: 1.33-17.62, P=0.017) . The first failure patterns analysis showed that 39 cases (45.9%) had recurrence, among which, 22 cases (25.9%) had locoregional recurrence with the median onset time of 15.2 months after operation, 19 cases (22.4%) had distant metastasis with the median onset time was 14.1 months after operation, and 2 cases (2.4%) were mixed failure mode. Among the locoregional recurrence, 16 cases (72.7%) recurred in the radiation field. Among all the local recurrence sites, the lymph node drainage regions in the supraclavicular, upper middle mediastinum and upper abdominal perigastric/celiac artery trunk areas were the most common sites. Among the distant metastatic organs, lung, bone and liver metastases were the most common. Conclusion:Patients of ESCC with high risk of recurrence after radical esophagectomy have long survival time and high safety after PORT with modified CTV according to the high-frequency recurrence regions. It is worthy of further confirmation by multicenter, large sample and prospective clinical trials.

Risk factors of death and prognostic scores of patients with liver cirrhosis undergoing TIPS / 国际生物医学工程杂志

Objective:To analyze the risk factors of death within two years of the patients with liver cirrhosis after transjugular intrahepatic portosystemic shunt(TIPS), and to explore the predictive value of 6 common clinical evaluation systems on the risk of death after TIPS.Methods:TIPS clinical data from 132 patients with liver cirrhosis were analyzed retrospectively. According to the 2-year clinical outcome after TIPS, the patients were divided into the death group and the survival group. Logistic regression was used to analyze the risk factors of death within 2 years after TIPS. According to the scores of CTP, MELD, MELD Na, BioCliM, FIB-4, and ALBI evaluation systems, the prediction efficiency of death risk of the six evaluation systems was evaluated by using the receiver operating characteristic (ROC) curves and the area under the curve (AUC).Results:During the 2-year follow-up period after TIPS, the age, urea nitrogen level, platelet count, and proportion of hepatic encephalopathy in the death group were higher than those in the survival group one month after TIPS, and the serum sodium level was lower than those in the survival group (all P<0.05). Multivariate analysis showed that the elderly and hepatic encephalopathy one month after operation were independent risk factors for death (all P<0.05). At 1 week after the surgery, there were significant differences in CTP, MELD, and MELD-Na scores between the survival group and the death group (all P<0.05). One week after operation, the AUC of ROC of CTP, MELD, MELD-Na, and ALBI scores were 0.685, 0.721, 0.805, and 0.658 respectively, and the optimal critical values were 8.5, 12.99, 14.51 and -1.52 respectively. Conclusions:The elderly and the occurrence of hepatic encephalopathy one month after TIPS are independent risk factors for the death of liver cirrhosis patients after TIPS. The evaluation of CTP, MELD, MELD-Na, and ALBI one week after TIPS can predict the death risk of decompensated liver cirrhosis patients within 2 years after TIPS, and MELD-Na has the best predictive effect.

Safety and efficacy of Compound Huangdai Tablets combined with all-trans retinoic acid for treatment of acute promyelocytic leukemia: Clinical evidence and potential mechanisms / 中草药·英文版

Objective: To evaluate the safety and efficacy of Compound Huangdai Tablets (Realgar-Indigo Naturalis formula, RIF) combined with all-trans retinoic acid (ATRA) to treat acute promyelocytic leukemia (APL). Methods: This study was registered in PROSPERO (CRD42018108118). The relevant literatures on RIF treatment of APL were systematically searched in the following databases: China National Knowledge Infrastructure, Wanfang, VIP Medical Information System, Chinese Biomedical Database, EMBASE, Cochrane Library, and PubMed. The quality of the included studies was evaluated and Review Manager 5.3 software and Stata 13.0 software were used to perform the Meta-analysis. In addition, this study used the method of network pharmacology to conduct a preliminary exploration of the mechanism of RIF on APL. Results: The study included 12 studies involving 775 APL patients. The Meta-analysis showed that there was no significant difference (P 0.05) between the RIF group and the arsenic trioxide (ATO) group for primary outcomes, secondary outcomes apart from liver dysfunction. The incidence of liver dysfunction (P = 0.006) in the RIF group were significantly lower than those in the ATO group. In addition, the cost of maintenance therapy in the RIF group was significantly lower (P 0.05) than the ATO group. Besides, the active ingredients in RIF mainly act on targets proteins such as ACHE, NCOA2, RXRA, and then play a role in the treatment of APL through regulating multiple molecular mechanisms, such as TP53 regulates transcription of cell cycle genes, nuclear receptor transcription pathway. Conclusion: There was no significant difference in efficacy of oral RIF combined with ATRA compared with intravenous ATO combined with ATRA for the treatment of APL. The oral RIF exposed patients to less risk, offered more convenience and had lower prices. RIF can treat APL by multi-target and multi-pathway interventions that inducing apoptosis of APL cells and inhibiting the proliferation of APL cells, and so on. Therefore, oral RIF in the treatment of APL is worthy of further research and development.

The protective effect of schisandrol A against senecionine-induced hepatotoxicity in mice / 药学学报

Hepatotoxicity induced by herbal medicines such as Gynura japonica, which contains large amount of pyrrolizidine alkaloids (PAs) such as senecionine (SEN), is among the most serious problems of herbal drug-induced liver injury, yet there is no effective treatment in clinic. We have previously reported that ritonavir (the well-known CYP3A4 inhibitor) protected rats against Gynura japonica-induced liver injury in rats, which was closely related to the inhibition of the metabolic activation of PAs. A large number of lignans have been identified in Schisandrae Chinensis Fructis and are reported to attenuate drug-induced liver injuries by modulating the drug metabolism enzymes. Therefore, the present study investigated the protective effect and potential mechanism of schisandrol A (SoA, a representative lignan identified in Schisandrae Chinensis Fructis) against SEN-induced hepatotoxicity in mice. All experiments were approved by the Animal Research Committee of Shanghai University of Traditional Chinese Medicine (PZSHUTCM210604002). Animal welfare and the animal experimental protocols were strictly consistent with related ethics regulations of Shanghai University of Traditional Chinese Medicine. Liver injury was induced by a single gavage of SEN (150 μmol·kg-1); mice in the protection group were gavaged with SoA (116 μmol·kg-1) 7 days before SEN treatment. The results show that SoA dramatically alleviated SEN-induced liver injury in mice. Mice in the protection group showed decreased serum activities for alanine aminotransferase and aspartate aminotransferase; in addition, the hepatic necrosis and sinusoidal hemorrhage in SEN-treated mice were markedly attenuated in the protection group. The serum contents of SEN metabolites in mice were decreased. In vitro studies were performed by using human liver microsomes and proved that SoA inhibits CYP3A4 to decrease the metabolism of SEN. These studies indicate that SoA attenuated SEN-induced liver injury in mice, which was closely related to the inhibition of the metabolic activation of SEN. These results provide a better understanding of the relationship between CYP3A4 and PA-induced toxicity. This work also will be helpful in developing effective treatments for SEN-induced liver injury based on inhibition of its metabolic activation, and in making reasonable evaluations of the safety of herbal medicines containing PAs such as G. japonica.

Panax notoginseng saponins ameliorated LPS-induced acute lung injury in mice by inhibiting the activation of NF-κB / 药学学报

Acute lung injury (ALI) is a kind of lung disease mainly caused by excessive inflammatory reaction. At present, there is a lack of effective therapeutic drugs in clinic. The aim of this study was to investigate the improvement effect of Panax notoginseng saponins (PNS) on ALI and its potential mechanism. The model of wild-type C57BL/6J mice was established by intratracheal instillation of 50 μL 25 mg·mL-1 lipopolysaccharide (LPS). 24 h later, 200 and 400 mg·kg-1 PNS was given intragastric, respectively. 24 h after administration, the improvement effect of PNS on ALI mice was evaluated by lung function, wet-to-dry weight ratio (W/D), total protein, interleukin 6 (IL6) and tumor necrosis factor α (TNFα) concentration of bronchoalveolar lavage fluid (BALF), expression levels of IL6 and TNFα in lung tissues, pathological changes of lung tissues and expression of inflammatory cells in BALF. The protein expression levels of NF-κB and its upstream kinases in Raw264.7 cells and ALI mice lung tissues were further detected to evaluate the potential mechanism of PNS improving ALI mice. The experimental scheme was approved by the Animal Experiment Ethics Committee of Shanghai University of Traditional Chinese Medicine. It was found that 400 mg·kg-1 PNS could significantly improve the lung function of ALI mice, reduce the contents of W/D, BALF total protein, IL6 and TNFα, neutrophils expression in BALF and the infiltration of inflammatory cells in lung tissue. In Raw264.7 cells and ALI mice lung tissue, PNS significantly reduced the expression of NF-κB, reduced the protein expression and phosphorylation of NF-κB, promoted the expression of IκBα, and inhibited the inflammatory response. This study showed that PNS can improve ALI by inhibiting the activity of NF-κB, inhibiting the release of inflammatory factors and inflammatory cells infiltration, alleviating lung inflammation.

Meta-analysis of acupuncture intervening exercise-induced fatigue / 针灸推拿医学（英文版）

Objective: To systematically evaluate the impact of acupuncture on exercise-induced fatigue (EIF). Methods: Scopus, Springer Link, Web of Science, PubMed, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Academic Journal Full-text Database (Wanfang), Chongqing VIP Database (CQVIP), and China Biology Medicine Disc (CBM) were systematically searched to identify randomized controlled trials (RCTs) studying acupuncture treatment of EIF from the inception till August 2020. The risk of bias in the included studies was assessed using the Cochrane handbook. RevMan 5.3 was used to conduct statistical analysis on the extracted data. Results: A total of 11 RCTs were included for meta-analysis, involving 531 patients. It was revealed that acupuncture produced more significant effects in alleviating subjective fatigue [standardized mean difference (SMD)=-3.08, 95％ confidence interval (CI) (-4.35, -1.81), P<0.001], increasing the hemoglobin content [weighted mean difference (WMD)=3.89, 95％CI (1.37, 6.42), P=0.003], reducing the lactate dehydrogenase content [WMD=-10.63, 95％CI (-17.67, -3.59), P=0.003], reducing the blood lactic acid content [SMD=-2.65, 95％CI (-4.47, -0.83), P=0.004], and down-regulating the levels of serum creatine kinase [SMD=-0.79, 95％CI (-1.10, -0.48), P<0.001] and blood urea nitrogen [WMD=-1.47, 95％CI (-1.84, -1.11), P<0.001] than the control groups. Conclusion: Based on the existing evidence, acupuncture can be recognized as effective in improving EIF and is worthy of promotion in clinical settings.

Glymphatic system in Parkinson′s disease / 中华神经科杂志

Parkinson′s disease is a degenerative disease of the central nervous system with abnormal protein deposition in the brain as the main pathological changes. The onset of Parkinson′s disease is related to abnormal deposition protein removal disorders, and the relevant mechanisms are still unclear. The glymphatic system is a metabolic waste and abnormal protein deposition removal system in the brain. In recent years, studies have shown that the changes of aquaporin 4, perivascular space and dural lymphatic vessels in Parkinson′s disease are closely related to the level of relevant pathological proteins in cerebrospinal fluid, leading to the occurrence and development of Parkinson′s disease. The researches on structure and biomarkers of the glymphatic system in Parkinson′s disease in recent years are reviewed in this article.

Mechanism of penehyclidine hydrochloride alleviating endotoxin-induced lung injury in rats: relationship with Toll-like receptor 4 / 中华麻醉学杂志

Objective:To evaluate the role of Toll-like receptor 4 (TLR4) in the mechanism by penehyclidine hydrochloride alleviating lipopolysaccharide (LPS)-induced acute lung injury(ALI)in rats.Methods:Twenty-four healthy male Sprague-Dawley rats, aged 10 weeks, weighing 220-250 g, were divided into 4 groups ( n=6 each) according to the random number table method: normal saline group (NS group), endotoxin-induced ALI group (ALI group), penehyclidine hydrochloride + normal saline group (PHC+ NS group) and penehyclidine hydrochloride + endotoxin-induced ALI group (PHC+ ALI group). ALI was induced by intratracheal instillation of LPS 5 mg/kg in anesthetized animals. In group PHC+ ALI, penehyclidine hydrochloride 2 mg/kg was intraperitoneally injected immediately after intratracheal instillation of LPS. The equal volume of normal saline was injected into the airway in group NS, and penehyclidine hydrochloride 2 mg/kg was intraperitoneally injected immediately after intratracheal instillation of normal saline in group PHC+ NS. The rats were sacrificed at 6 h after intratracheal instillation of LPS or normal saline, and lungs were removed. The lung was lavaged and broncho-alveolar lavage fluid (BALF) was collected for determination of concentrations of tumor necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1β) by enzyme-linked immunosorbent assay. Lung tissues were obtained for microscopic examination of the pathological changes (with a light microscope) and for determination of wet to dry lung weight ratio (W/D ratio) and TLR4 protein and mRNA expression (by immuno-histochemistry or real-time polymerase chain reaction). Results:Compared with group NS and group PHC+ NS, the W/D ratio and concentrations of TNF-α and IL-1β in BALF were significantly increased, the expression of TLR4 protein and mRNA in lung tissues was up-regulated ( P<0.01), and the pathological changes of lung tissues were aggravated in group ALI . Compared with group ALI, the W/D ratio and concentrations of TNF-α and IL-1β in BALF were significantly decreased, the expression of TLR4 protein and mRNA in lung tissues was down-regulated ( P<0.01), and the pathological changes of lung tissues were significantly mitigated in group PHC+ ALI. Conclusions:The mechanism by which penehyclidine hydrochloride reduces endotoxin-induced lung injury may be related to reduction of TLR4 activity and thus inhibition of pulmonary inflammatory responses in rats.

Comparison of effects of different lung recruitment maneuvers in infants undergoing laparoscopic surgery / 中华麻醉学杂志

Objective:To compare the effects of different lung recruitment maneuvers in infants undergoing laparoscopic surgery.Methods:A total of 70 pediatric patients of either sex, aged 1-6 yr, weighing 10-24 kg, of American Society of Anesthesiologists physical status Ⅰ or Ⅱ, scheduled for elective laparoscopic surgery from September 2020 to June 2021 with expected operation time≤2 h, were divided into 2 groups ( n=35 each) by a random number table method: recruitment maneuver using incremental positive end-expiratory pressure (PEEP) group (PV group) and recruitment maneuver using controlled lung expansion group (RM group). The children underwent pressure-controlled ventilation after tracheal intubation, and lung recruitment was performed at 20 min after pneumoperitoneum, immediately after pneumoperitoneum, and at the end of operation and before tracheal extubation.In PV group, PEEP was gradually increased, the upper limit of airway pressure was 35 mmHg, PEEP was increased by 5 cmH 2O, ventilation was performed for 30 s, then PEEP was increased to 15 cmH 2O, ventilation was continued for 30 s, then the parameters were adjusted to the original ones, and ventilation was continued until the next lung recruitment.In RM group, manual ventilation mode was used, the pressure valve was adjusted to 30 cmH 2O, the pressure was increased to the maximum by rapid oxygenation, the breathing cuff was manually squeezed until the airway pressure achieved 30-35 mmHg, and 30 s later ventilation was performed with the original ventilation parameters, lasting for 30 s until the next lung recruitment.Peak airway pressure and mean airway pressure were recorded at 5 min after tracheal intubation (T 1), 20 min after pneumoperitoneum (T 2), immediately after pneumoperitoneum (T 3) and before extubation after surgery (T 4), and dynamic lung compliance was calculated.Blood gas analysis was performed at T 2 and T 4, and arterial partial pressure of oxygen and arterial partial pressure of carbon dioxide were recorded, oxygenation index, alveolar-arterial oxygen partial pressure difference and respiratory index were calculated.Lung ultrasonography scores were assessed before tracheal extubation (T 0) and at T 4 and 20 min after entering the postanesthesia care unit (T 5). The time of tracheal extubation and length of postoperative hospital stay were recorded.Hypoxemia in postanesthesia care unit and occurrence of pulmonary complications within 3 days after operation were recorded. Results:Compared with RM group, peak airway pressure and mean airway pressure were significantly decreased at T 2, 3, dynamic lung compliance was increased at T 2-4, arterial partial pressure of oxygen and oxygenation index were decreased , arterial partial pressure of carbon dioxide, alveolar-arterial oxygen partial pressure difference and respiratory index were increased at T 2 and T 4, lung ultrasonography scores were decreased at T 4 and T 5, and the incidence of postoperative hypoxemia was increased, and tracheal extubation time was prolonged in RM group ( P<0.05). Conclusions:Lung recruitment maneuver using incremental PEEP provides better efficacy than that using controlled lung expansion in infants undergoing laparoscopic surgery.

Diagnosis and treatment of genetically related urinary calculi / 中华泌尿外科杂志

In recent years, the incidence of single-gene nephrolithiasis has been increasing year by year. With the application of whole-genome analysis and whole-exome sequencing technology, the etiology of single-gene mutations leading to the development of urinary calculi has been extensively verified. Therefore, this article reviews the research on urinary calculi-related genetic diseases at home and abroad, and introduces transport proteins and channels; ions, protons and amino acids. The role of urinary calculi in the majority of clinicians realizes the significance of genetic testing in such diseases, thereby increasing the understanding of genetically related urinary calculi and improving the level of clinical diagnosis and treatment.