Tripterygium wilfordii is a traditional Chinese medicinal herb belonging to the genus Tripterygium in the Celastraceae family， which has the effects of clearing heat and detoxifying， dispelling wind and dampness， and invigorating blood circulation to relieve pain， and is used to treat diseases such as rheumatoid arthritis， glomerulonephritis， nephrotic syndrome， lupus erythematosus， scabies， and stubborn tinea. Its chemical composition is diverse. Among them， triptolide（TP） is one of the main active and toxic components of T. wilfordii. It has significant biological activities such as anti-inflammation， anti-tumor， and immunosuppression. However， it causes serious adverse reactions such as liver and kidney function damage and reproductive system disorders. At the same time， TP has poor water solubility and low bioavailability， and the enhancement of bioavailability by increasing the dosage undoubtedly improves the exposure of the drug in non-target organs， leading to the occurrence of adverse reactions， and these largely limit the clinical application of TP. Based on this， this article extracted relevant data from the Web of Science， PubMed， and China National Knowledge Infrastructure（CNKI） databases， summarized the research on the adverse reactions of TP in recent years， and reviewed the progress of toxicity reduction research from the perspectives of structural modification， novel drug delivery systems， and compatibility. Structural modification can precisely alter the chemical structure of TP， reduce the activity of its toxic groups， and retain its biological activity while fundamentally reducing the occurrence of adverse reactions. New drug delivery systems can achieve targeted delivery of TP， increase its concentration in target organs， and reduce its exposure in non-target organs， thereby enhancing therapeutic efficacy and reducing adverse effects. In addition， the combination of TP with Chinese medicine compound， single-flavored Chinese medicine or monomer can reduce the adverse effects of TP and enhance the efficacy to different degrees， which is of clinical value. This paper systematically explains attenuation research from the above three perspectives， aiming to provide a theoretical basis for the full utilization of biological activity and drug development of TP.

Objective:To explore the incidence of sudden deafness accompanied with tinnitus, the selection of examination protocols and treatment, and to provide reference for the establishment of new guidelines for sudden deafness.Methods:CiteSpace software was used for analysis and data mining to analyze and summarize the computer-retrieved articles on diagnostic examination and treatment of sudden deafness accompanied with tinnitus collected from CNIC, Wanfang and Web of Science databases from 2011 to 2021.Results:A total of 207 randomized controlled studies were retrieved in this study, including 121 in Chinese and 86 in English. Finally, 74 Chinese literatures and 16 English literatures were included. Among the 74 valid Chinese literatures, 64 (86.5%) were accompanied with tinnitus, 58 (78.4%) with dizziness/vertigo, 25 (33.8%) with aural fullness, 10 (13.5%) with headache, 4 (5.4%) with insomnia, 4 (5.4%) with a mixture of dizziness and tinnitus, and 2 (2.7%) with vomiting. Among the 16 English literatures, 15 (93.8%) were accompanied with tinnitus, 12 (75.0%) with vertigo, 1 (6.3%) with aural fullness, and 1 (6.3%) with a mixture of various symptoms. Among the 64 Chinese articles mentioning tinnitus, only 9 mentioned tinnitus matching tests, and 1 mentioned that the treatment for tinnitus accompanying symptoms was sound therapy and psychological counseling. The incidence rates of tinnitus accompanying four different types of sudden deafness, from low to high, are as follows: low-to-mid frequency, 82.4%; mid-to-high frequency, 90.7%; complete deafness, 92.4%; and flat type, 92.8%.Conclusion:Tinnitus is the most common accompanying symptom of sudden deafness, and tinnitus matching test is an effective evaluation method. When establishing a scientific, comprehensive, and systematic diagnosis and treatment system or guidelines for sudden deafness, attention should be paid to the diagnosis and treatment of tinnitus symptoms and their adverse psychological reactions, in order to reduce the incidence of tinnitus patients in the later stage of recovery from sudden deafness.

Objective:To study the expression level of programmed death ligand 1 (PD-L1) in combined hepatocellular-cholangiocarcinoma (cHCC-CCA) and its correlation with the clinical characteristics and prognosis.Methods:The clinical data of 75 patients with cHCC-CCA undergoing surgery in Tianjin Medical University Cancer Institute and Hospital from January 2011 to December 2019, including 61 males and 14 females, with a median age of 55 years (36 to 77). Immunohistochemistry was conducted to determine the PD-L1 expression in tumor. The status of PD-L1 expression, clinicopathological data and prognosis of patients were analyzed.Results:In low-differentiated cHCC-CCA tissues, the proportion of PD-L1 expression (21.1%, 8/38) was higher than that in moderately to well-differentiated cHCC-CCA tissues (2.70%, 1/37, χ2=4.366, P=0.037). The median disease-free survival (DFS) and overall survival (OS)of PD-L1 positive patients were 12.3 and 15.1 months, respectively, lower than those of PD-L1 negative patients (14.4 and 23.3 months). The difference of DFS was statistically significant ( χ2=4.052, P=0.044). In multivariate analysis, major vascular invasion (DFS: HR=1.965, 95% CI: 1.119-3.450, P=0.019; OS: HR=1.781, 95% CI: 1.022-3.105, P=0.042) and lymph node metastasis (DFS: HR=2.451, 95% CI: 1.1033-5.814, P=0.042; OS: HR=2.652, 95% CI: 1.120-6.279, P=0.027) were identified as independent prognostic factors affecting DFS and OS. Conclusions:The proportion of PD-L1 positive is higher inthe low-differentiated cHCC-CCA tissue compared to that in moderately to well-differentiated cHCC-CCA. The major vascular invasion and lymph node metastasis are independent factors affecting the prognosis of patients with cHCC-CCA.

Objective:A two-dimensional (2D) in-house-built scintillator detection system (SDS) was utilized for quality assurance of the active spot scanning proton and heavy ion accelerator, aiming to establish a rapid detection method and provide reference for the quality of proton and heavy ion beam (spot position, spot size, virtual source-to-axis distance, profile depth dose distribution and beam range).Methods:The SDS consisted of a ceramic gadolinium-sulfoxylate phosphor-scintillating screen, a mirror and a commercial digital camera. The dose distribution image was obtained based on scintillator, mirror reflector and optical signal acquisition device to transform the proton and heavy ion beam into visible light through sulfur gadolinium oxide scintillator and collect visible light information to meet the clinical requirements for the quality of proton and heavy ion beam.Results:The deviation of spot position measured by multifilament proportional chamber and the SDS was less than 1mm. The differences of beam spot size measured by multifilament proportional chamber and the SDS were (1.40±0.59)mm for protons, and (0.5±0.08)mm for carbon ions. For 429.25MeV/u carbon, the virtual source-to-axis distance (V SAD) at the x-and y-axes was 751.8cm and 805.6cm. And difference between physical distance and virtual source-to-axis distance was less than 1%. The range of 287.5MeV/u carbon measured by SDS was 160mm. Conclusions:The in-house-built scintillator detector can measure beam spot position and size, virtual source, depth distribution curve and range, which can be used as an effective tool for quality assurance control of proton and heavy ion therapy.

Objective:To screen and analyze the prognostic protein biomarkers of DLBCL, and to explore their value in the prognostic evaluation.Methods:163 cases of confirmed DLBCLs from January 2011 to December 2016 were collected with their clinical, pathological and follow-up data, which were all from our hospital. The expression of protein markers were tested using immunohistochemical staining (IHC) . The immune phenotypes independent of the International Prognostic Index (IPI) that affect overall survival (OS) and progression-free survival (PFS) of DLBCL were explored by COX regression model, and the effect of their co-expression on the prognosis were also analyzed.Result:BCL6 negative (PFS: HR=1.652, 95% CI 1.030-2.649, P=0.037) , P53 positive (OS: HR=1.842, 95% CI 1.008-3.367, P=0.047) , and BCL2 strong positive expressions (S+) (OS: HR=2.102, 95% CI 1.249-3.537, P=0.005; PFS: HR=2.126, 95% CI 1.312-3.443, P=0.002) are adverse prognostic factors of DLBCL that are independent of IPI. BCL6 - (PFS: HR=2.042, 95% CI 1.021-4.081, P=0.043) , P53 + (OS: HR=3.069, 95% CI 1.244-7.569, P=0.015) and BCL2 S+ (OS: HR=2.433, 95% CI 1.165-5.082, P=0.018; PFS: HR=3.209, 95% CI 1.606-6.410, P=0.001) are adverse prognostic factors in the group of age≤60-year-old; in the group of IPI score 0-2, cases with BCL6 - (OS: HR=2.467, 95% CI 1.322-4.604, P=0.005; PFS: HR=2.248, 95% CI 1.275-3.965, P=0.005) and BCL2 S+ (PFS: HR=2.045, 95% CI 1.119-3.735, P=0.020) have worse prognosis. The co-expression of BCL6 - and BCL2 S+ has significant influence on prognosis of DLBCL ( P=0.005 and P<0.001) , in which BCL6 +/non-BCL2 S+ ( n=86) has the best prognosis[3-year-OS (71.6±4.9) %, 3-year-PFS (67.0±5.1) %], and BCL6 -/BCL2 S+ ( n=10) has the worst prognosis[3-year-OS (20.0±12.6) %, 3-year-PFS (10.0±9.5) %]; the co-expression of BCL6 - and P53 + has no significant influence on prognosis ( P=0.061 and P=0.089) , however, those cases with BCL6 +/P53 - ( n=98) often get better prognosis[3-year-OS (70.6±4.7) %, 3-year-PFS (64.6±4.9) %] than others; the co-expression of P53 + and BCL2 S+ has significant influence on prognosis of DLBCL ( P<0.001 and P<0.001) , and P53 +/BCL2 S+ ( n=5) has the worst prognosis (3-year-OS and 3-year-PFS are both 0) ; BCL2 S+ cases get shorter OS and PFS, regardless of the expression of BCL6 and P53. Conclusion:The expression and co-expression of BCL6 negative, P53 positive and BCL2 S+ have certain value in the prognostic evaluation of DLBCL, especially in the group of age≤60-year-old and IPI score 0-2.

Objective:To observe the changes of the expression level of long non-coding RNA (lncRNA) KCNQ1OT1 and microRNA (miR)-146a-3p in placenta tissues of preeclampsia (PE) patients, as well as their effect and mechanism on the biological functions of trophoblast cells.Methods:A total of 45 cases of hospitalized PE patients in Hainan General Hospital from July 2017 to July 2018 were selected as the PE group, 55 normal pregnant women during the same period were chosed as the control group. The expression level of KCNQ1OT1 mRNA and miR-146a-3p in the placenta tissues between two groups were detected by using quantitative real time (qRT)-PCR. Pearson′s test was furtherly analyzed the correlation between them. Human trophoblast cell line (HTR8/SVneo) were randomly divided into control and lipopolysaccharide (LPS) groups, and then LPS group were divide into four sub-groups,included LPS group, short hairpin RNA (sh)-KCNQ1OT1 (after silencing the expression of KCNQ1OT1), miR-146a-3p inhibitor and sh-KCNQ1OT1+miR-146a-3p inhibitor. The targeting relationship between KCNQ1OT1 and miR-146a-3p were predicted by bioinformatics software and confirmed by luciferase assay. The cell proliferation and invasion capacities were respectively detected by cell counting kit-8 (CCK-8) and transwell assay. The expression level of KCNQ1OT1 mRNA and miR-146a-3p were detected by qRT-PCR and the protein expression level of CXC chemokine ligand 12 （CXCL12） and CXC chemokine receptor type 4 (CXCR4) were tested by western blot.Results:(1) The mRNA expression level of KCNQ1OT1 in the placenta of PE group was lower than that of control group (0.23±0.03 vs 0.51±0.04, P<0.05), and the miR-146a-3p expression level was higher than that of the control group (0.49±0.03 vs 0.31±0.03, P<0.05), there were statistical significant differences between the two groups. (2) Luciferase assay showed that there was a targeting relationship between KCNQ1OT1 and mir-146a-3p. Compared with the control group, the mRNA expression level of KCNQ1OT1 in the LPS group were significantly decreased (0.91±0.03 vs 0.35±0.03, P<0.05), and the expression level of miR-146a-3p were significantly increased (0.22±0.03 vs 0.63±0.04, P<0.05). The cell proliferation, invasion and migration capacities and the protein expression of CXCL12 and CXCR4 significantly reduced in the LPS group compared with control group (all P<0.05). The mRNA expression level of KCNQ1OT1 (0.23±0.03) in the sh-KCNQ1OT1 group were further decreased, the expression of miR-146a-3p (0.85±0.03) were further increased, and the cell proliferation, invasion and migration capacities and the protein expression of CXCL12 and CXCR4 were all further reduced compared with control group，there were significant difference between two groups (all P<0.05). Comparing the miR-146a-3p inhibitor group, and sh-KCNQ1OT1+miR-146a-3p inhibitor group with the sh-KCNQ1OT1 group, respectively, the expression level of KCNQ1OT1 mRNA (0.78±0.04 vs 0.50±0.03) increased, and the expression level of miR-146a-3p (0.42±0.03 vs 0.46±0.03) decreased, the cell proliferation, invasion and migration capacities and the protein expression of CXCL12 and CXCR4 were all increased ,there were statistically significant differences (all P<0.05). Conclusion:KCNQ1OT1 could target the regulation of miR-146a-3p through CXCL12/CXCR4 pathway in the proliferation, invasion an migration of HTR8/SVneo cells, which may be involved in the pathogenesis of PE.

Objective To investigate neurosurgeons' knowledge,attitude and practice toward deceased organ donation and provide a reference to increase organ donation rate.Method In July 2015,150 questionnaires were issued to neurosurgeons from 36 hospitals in the Jilin province.Result 142 effective questionnaires were obtained.Neurosurgeons' knowledge toward deceased organdonation was relatively good in the whole.100％ (142/142) neurosurgeons were in favor of organ donation in public hospitals.95.8％ (136/142) neurosurgeons were willing to cooperate in organ donation and 100％ (142/142) approved legislation on brain death in China.97.2％ (138/142) were in favor of economic compensation for organ donor's family.100％ (142/142) neurosurgeons encountered to potential organ donors in the process of practice,but 71.8％ (102/142) prompted potential organ donors' families actively and initiatively to donate.Compared with physicians with junior titles,senior physicians had more active coordination donation behavior (x2 =12.133,P=0.002).The neurosurgeons,who had higher correct answer rate about the knowledge of organ donation,were more likely to take the initiative to coordinate organ donation (x2 =16.131,P＜0.001).Conclusion Professional training for neurosurgeon organ donation will contribute to promote potential organ donors in neurosurgery into actual organ donors.

OBJECTIVEInvestigate the best surgical resection of esophageal cancer by comparing the efficacy and safety between Ivor-Lewis esophagectomy and Sweet esophagectomy.

METHODSThe relevant literatures comparing Ivor-Lewis esophagectomy with Sweet esophagectomy were searched through PubMed, Embase, the Cochrane Library, Google scholar, CNKI, CBM, VIP, WanFang Data. RevMan 5.2 software was used for data analysis.

RESULTSA total of 4106 patients in 15 studies were reviewed and the data were pooled for analysis. Meta-analysis showed that, compared with the Sweet group, Ivor-Lewis operative time was significantly longer(pooled mean difference=57.40; 95%CI:42.43 to 72.38; P=0.000), operative bleeding was significantly higher(pooled mean difference=28.39, 95%CI:4.06 to 52.72, P=0.02); the number of lymph node dissection significantly more(pooled mean difference=4.19, 95%CI:3.06 to 5.32, P=0.000); No significant difference was present in hospital stay, vocal cord paralysis, chylous leakage, pulmonary complications, anastomotic leakage(all P>0.05). The 5-year survival between the two groups showed no significant difference(P=0.52).

CONCLUSIONSThe two kinds of operation have the same long term effect. Compared with Ivor-Lewis operation, Sweet operation is easier to perform, less time consuming and more tolerable. Ivor-Lewis operation can dissect more lymph nodes than Sweet operation, without increased complications.

Objective Investigate the best surgical resection of esophageal cancer by comparing the efficacy and safety between Ivor-Lewis esophagectomy and Sweet esophagectomy. Methods The relevant literatures comparing Ivor-Lewis esophagectomy with Sweet esophagectomy were searched through PubMed, Embase, the Cochrane Library, Google scholar, CNKI, CBM, VIP, WanFang Data. RevMan 5.2 software was used for data analysis. Results A total of 4106 patients in 15 studies were reviewed and the data were pooled for analysis. Meta-analysis showed that, compared with the Sweet group, Ivor-Lewis operative time was significantly longer (pooled mean difference=57.40; 95%CI:42.43 to 72.38;P=0.000), operative bleeding was significantly higher (pooled mean difference=28.39, 95%CI:4.06 to 52.72, P=0.02); the number of lymph node dissection significantly more (pooled mean difference=4.19, 95%CI:3.06 to 5.32, P=0.000); No significant difference was present in hospital stay, vocal cord paralysis, chylous leakage, pulmonary complications, anastomotic leakage (all P>0.05). The 5-year survival between the two groups showed no significant difference (P =0.52). Conclutions The two kinds of operation have the same long term effect. Compared with Ivor-Lewis operation, Sweet operation is easier to perform, less time consuming and more tolerable. Ivor-Lewis operation can dissect more lymph nodes than Sweet operation , without increased complications.

Objective Investigate the best surgical resection of esophageal cancer by comparing the efficacy and safety between Ivor-Lewis esophagectomy and Sweet esophagectomy. Methods The relevant literatures comparing Ivor-Lewis esophagectomy with Sweet esophagectomy were searched through PubMed, Embase, the Cochrane Library, Google scholar, CNKI, CBM, VIP, WanFang Data. RevMan 5.2 software was used for data analysis. Results A total of 4106 patients in 15 studies were reviewed and the data were pooled for analysis. Meta-analysis showed that, compared with the Sweet group, Ivor-Lewis operative time was significantly longer (pooled mean difference=57.40; 95%CI:42.43 to 72.38;P=0.000), operative bleeding was significantly higher (pooled mean difference=28.39, 95%CI:4.06 to 52.72, P=0.02); the number of lymph node dissection significantly more (pooled mean difference=4.19, 95%CI:3.06 to 5.32, P=0.000); No significant difference was present in hospital stay, vocal cord paralysis, chylous leakage, pulmonary complications, anastomotic leakage (all P>0.05). The 5-year survival between the two groups showed no significant difference (P =0.52). Conclutions The two kinds of operation have the same long term effect. Compared with Ivor-Lewis operation, Sweet operation is easier to perform, less time consuming and more tolerable. Ivor-Lewis operation can dissect more lymph nodes than Sweet operation , without increased complications.