Anti-inflammatory Mechanism of Modified Erchentang on Chronic Obstructive Pulmonary Disease Through Jagged1/Notch1/Hes1 Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo observe the effect of modified Erchentang on the expression of key molecules in the Jagged1/Notch1/Hes1 signaling pathway in lung tissues of rats with chronic obstructive pulmonary disease （COPD） and explore its anti-inflammatory effect and molecular mechanism on COPD through the Jagged1/Notch1/Hes1 signaling pathway. MethodSixty SD rats were randomly divided into normal group， model group， low-， medium-， and high-dose modified Erchentang groups （5， 10， 20 g·kg-1）， and γ-secretase inhibitor DAPT group （0.02 g·kg-1）， with 10 rats in each group. The COPD model was induced in rats by cigarette smoking combined with intratracheal instillation of lipopolysaccharide （LPS）. Rats were treated with corresponding drugs by gavage， while those in the normal group and the model group were treated with the same amount of normal saline by gavage. The serum levels of Notch1， soluble intercellular adhesion molecule-1 （sICAM-1）， activated leukocyte cell adhesion molecule （ALCAM）， and soluble vascular adhesion molecule-1 （sVCAM-1） were detected by enzyme-linked immunosorbent assay （ELISA）. The mRNA expression of Jagged1， Notch1， and Hes1 was detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The protein expression of Jagged1， Notch1， Notch1 intracellular domain （NICD1）， and Hes1 in lung tissues of rats was detected by immunohistochemistry （IHC）. ResultCompared with the normal group， the model group showed increased serum content of Notch1， sICAM-1， ALCAM， and sVCAM-1 （P<0.01）， increased mRNA expression of Jagged1， Notch1， and Hes1 in lung tissues （P<0.01）， and increased protein expression of Jagged1， Notch1， NICD1， and Hes1 （P<0.01）. Compared with the model group， the medium- and high-dose modified Erchentang groups and the DAPT group showed decreased serum content of Notch1， sICAM-1， ALCAM， and sVCAM-1 （P<0.05， P<0.05）， down-regulated mRNA expression of Jagged1， Notch1， and Hes1 （P<0.05， P<0.01）， and reduced protein expression of Jagged1， Notch1， NICD1， and Hes1（P<0.05， P<0.01）. ConclusionModified Erchentang may inhibit the inflammatory response in the lung of COPD rats， and its mechanism may be related to the resistance of inflammatory injury in the lung by decreasing the mRNA expression of Jagged1， Notch1， and Hes1 and inhibiting the release of Notch1， sICAM-1， ALCAM， and sVCAM-1.

Distribution and drug resistance of pathogenic bacteria for infection after liver transplantation / 临床肝胆病杂志

Objective To investigate the distribution and drug resistance of pathogenic bacteria for infection after liver transplantation, and to provide a scientific basis for the rational clinical application of antibiotics. Methods The pathogenic bacteria isolated from the specimens of 904 patients with infection after liver transplantation in The Affiliated Hospital of Qingdao University from March 2014 to December 2021 were analyzed in terms of distribution and drug resistance. WHONET 5.6 software was used to perform a statistical analysis of strains and bacterial resistance rate, and Excel was used to analyze the sources of specimens, composition ratios, and distribution of pathogenic bacteria. Results A total of 2 208 non-repetitive pathogenic bacteria were isolated, mainly from the specimens of respiratory tract (31.25%), bile (22.28%), ascites (13.18%), blood (8.38%), and drainage fluid (4.62%). The top 10 pathogenic bacteria were Klebsiella pneumoniae subspecies (10.69%), Enterococcus faecium (10.42%), Escherichia coli (8.24%), Pseudomonas aeruginosa (8.24%), Staphylococcus epidermidis (8.06%), Acinetobacter baumannii (7.93%), Stenotrophomonas maltophilia (6.61%), Enterobacter cloacae (3.22%), Staphylococcus haemolyticus (3.08%), and Staphylococcus aureus (2.94%), accounting for 69.43% of the total pathogenic bacteria. Pseudomonas aeruginosa, Stenotrophomonas maltophilia, Klebsiella pneumoniae subspecies, and Acinetobacter baumannii were the main pathogenic bacteria isolated from respiratory tract specimens; Enterococcus faecium was the main pathogenic bacterium isolated from bile, ascites, and drainage fluid specimens; Escherichia coli , Staphylococcus epidermidis , and Klebsiella pneumoniae subspecies were the main pathogenic bacteria isolated from blood specimens. Drug sensitivity data showed that Enterobacterales bacteria had a relatively high resistance rate to cephalosporins and fluoroquinolones and a resistance rate of 50% to macrolides, fluoroquinolones, sulfonamides, and lincomycin, and a small part of these strains were resistant to linezolid and quinupristin/dalfopristin (< 3%), with no Staphylococcus epidermidis strains resistant to tigecycline and vancomycin. A total of 287 drug-resistant strains were monitored, accounting for 13%, among which there were 128 carbapenem-resistant Acinetobacter baumannii strains, 88 carbapenem-resistant Pseudomonas aeruginosa strains, 26 carbapenem-resistant Klebsiella pneumoniae subspecies strains, 11 carbapenem-resistant Escherichia coli strains, 23 methicillin-resistant Staphylococcus aureus strains, and 11 vancomycin-resistant Enterococcus strains. The carbapenem-resistant Klebsiella pneumoniae subspecies strains mainly produced serine carbapenemase, and the carbapenem-resistant Escherichia coli strains mainly produced metal β-lactamase. Conclusion Gram-negative bacteria are the main pathogenic bacteria for infection after liver transplantation, and there are differences in the distribution of pathogenic bacteria between different types of specimens. The resistance rate of some strains tend to increase, and therefore, it is necessary to strengthen the management of nosocomial infection and antibiotics.

Efficacy of human umbilical cord mesenchymal stem cells via different transplantation approaches in treatment of rats with liver cirrhosis / 临床肝胆病杂志

ObjectiveTo investigate the therapeutic effect of the frozen and fresh preparations of human umbilical cord mesenchymal stem cells （hUC-MSC） on a rat model of liver cirrhosis after transplantation via the portal vein or the caudal vein. MethodsA total of 70 specific pathogen-free healthy male Sprague-Dawley rats were randomly divided into normal group （13 rats fed with ordinary tap water and rat food） and liver cirrhosis model group （57 rats given subcutaneous multi-point injection of mixed carbon tetrachloride/olive oil solution）. At week 8， the growth of rats was observed for both groups， and 3 rats were selected from each group for histopathological examination to confirm the formation of liver cirrhosis. A total of 50 rats were selected from the liver cirrhosis model and were divided into model group， portal vein group+fresh cell preparation group， portal vein+frozen cell preparation group， caudal vein+fresh cell preparation group， and caudal vein+frozen cell preparation group using a random number table， with 10 rats in each group. Fresh or frozen hUC-MSC were transplanted via the portal vein or the caudal vein， and after 4 weeks of administration， the different groups were compared in terms of the changes in liver function parameters and liver fibrosis degree. Continuous data were expressed as mean±standard deviation， and the independent-samples t test was used for comparison between two groups； a one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsAt week 8 of modeling， the model group showed the formation of pseudolobules of different sizes in the liver and met the diagnostic criteria for liver cirrhosis， with significant increases in the levels of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， total bilirubin （TBil）， and alkaline phosphatase （ALP） compared with the normal group （all P<0.001）， suggesting that the rat model of liver cirrhosis was established successfully. There were significant differences in the levels of ALT， AST， TBil， and ALP between the five groups （F=232.00， 177.10， 112.30， 121.70， all P<0.001）. Further comparison between two groups showed that the model group had significantly higher levels of ALT， AST， TBil， and ALP than the normal group （all P<0.01）， and the portal vein group+fresh cell preparation group， the portal vein+frozen cell preparation group， the caudal vein+fresh cell preparation group， and the caudal vein+frozen cell preparation group had significantly lower levels of ALT， AST， TBil， and ALP than the model group （all P<0.01）. ConclusionThere are significant improvements in liver function and liver fibrosis degree in a rat model of liver cirrhosis at week 4 after the transplantation of hUC-MSC， and frozen or fresh cell preparation and different transplantation approaches have no significant influence on treatment outcome.

Clinical Effect of Shugan Hewei Prescription Combined with Vonoprazan on Refractory Gastroesophageal Reflux Disease Due to Qi Depression and Phlegm Obstruction / 中国实验方剂学杂志

ObjectiveTo evaluate the clinical efficacy and adverse effects of Shugan Hewei prescription combined with vonoprazan in the treatment of refractory gastroesophageal reflux disease （RGERD） due to qi depression and phlegm obstruction. MethodEighty RGERD patients who met the inclusion criteria underwent 24-hour pH impedance and high-resolution esophageal manometry and electronic gastroscopy. The 80 patients were randomly assigned to an observation group （Shugan Hewei prescription， one bag each time， twice a day + vonoprazan， 20 mg each time， once a day） and a control group （vonoprazan， 20 mg each time， once a day） by the random number table method. The treatment in both groups lasted for 4 weeks. The clinical efficacy was examined. The scores of TCM symptoms （pharyngeal discomforts such as phlegm obstruction， retrosternal discomfort， and belching）， somatic symptoms， quality of life， and improvement of esophageal mucosa under gastroscopy were observed in both groups before treatment and after treatment for 2 and 4 weeks. ResultSeventy-five patients completed the trial were included in this study， including 38 patients in the observation group and 37 patients in the control group. The total response rate in the observation group was 89.47%（34/38）， which was higher than that （62.16%，23/37） in the control group （χ2=13.014， P<0.01）. After treatment， the scores of esophageal mucous membrane， reflux disease symptoms， TCM symptoms， gastroesophageal reflux disease health-related quality of life scale （GERD-HRQL）， and somatic self-rating scale （SSS） decreased in both groups（P<0.05）. Moreover， the observation group outperformed the control group in alleviating heartburn， acid reflux， throat discomforts， midnight coughing， nausea and dry vomiting， mucousy mouth， and insomnia in the patients with GERD （P<0.05，P<0.01）. However， the two groups showed no statistically significant differences in the improvement of esophageal mucosa after treatment. ConclusionThe combination of Shugan Hewei prescription with vonoprazan was superior to vonoprazan alone in treating RGERD regarding clinical symptoms， physical signs， quality of life， and somatic symptoms， without causing obvious adverse effects.

Effect of peroxisome proliferator-activated receptor γ on skin physiological and pathological processes / 中华皮肤科杂志

Peroxisome proliferator-activated receptors (PPARs) are widely involved in lipid metabolism, glucose metabolism, cell growth and differentiation, and inflammation in the human body. PPARγ agonists can inhibit skin inflammatory response, protect epidermal barrier function, and repair skin injury. This review summarizes various roles of PPARγ in skin biology, and discusses its function in skin diseases, such as psoriasis and skin tumors.

Comparison of efficacy of femoral tunnel creation with figure-of-four position and traditional knee hyperflexed position for arthroscopic anterior cruciate ligament reconstruction using tendon autograft / 中华创伤杂志

Objective:To compare the efficacy of arthroscopic anterior cruciate ligament reconstruction using tendon autograft with figure-of-four position and traditional knee hyperflexed position for femoral tunnel creation.Methods:A retrospective case series study was conducted to analyze the clinical data of 46 patients with ACL injury admitted to Second Affiliated Hospital of Harbin Medical University from August 2019 to October 2019, including 26 males and 20 females; aged 24-40 years [(31.1±7.5)years]. All patients underwent arthroscopic ACL reconstruction using tendon autograft. The femoral tunnel was created with figure-of-four position in 21 patients (figure-of-four position group) and with traditional knee hyperflexed position in 25 patients (knee hyperflexed position group). The operation time was compared between the two groups. The center position, length and angle of femoral tunnel were evaluated and measured by three dimensional CT reconstruction and Bernard quadrant method at 8 weeks postoperatively. The knee function was assessed by knee Lysholm score preoperatively, at 8 weeks and at 1 year postoperatively. Complications were observed as well.Results:All patients were followed up for 2-20 months [(15.3±2.1)months]. The operation time was (28.5±2.6)minutes in figure-of-four position group, significantly less than (39.5±2.4)minutes in knee hyperflexed position group ( P<0.05). The tunnel center position was located at (27.1±1.4)% and (25.1±2.6)% within the Bernard quadrant in figure-of-four position group, similar with (28.1±2.8)% and (26.1±3.1)% in knee hyperflexed position group (all P>0.05). Total tunnel length and thick tunnel length were (42.1±2.4)mm and (34.1±2.4)mm in figure-of-four position group, significantly longer than (38.2±2.5)mm and (31.1±2.7)mm in knee hyperflexed position group (all P<0.05). The coronal plane angle of the tunnel was (41.1±2.4)° in figure-of-four position group, significantly smaller than (47.5±2.6)° in knee hyperflexed position group ( P<0.05). The sagittal plane angle of the tunnel was (42.1±1.4)° in figure-of-four position group, significantly greater than (37.1±1.8)° in knee hyperflexed position group ( P<0.05). Figure-of-four position group showed the knee Lysholm score of (53.4±5.2)points preoperatively, (97.1±1.4)points at 8 weeks postoperatively and (98.3±2.3)points at 1 year postoperatively. Knee hyperflexed position group showed the knee Lysholm score of (54.3±7.4)points preoperatively, (97.1±1.6)points at 8 weeks postoperatively and (98.1±1.3)points at 1 year postoperatively. The knee Lysholm score did not differ significantly between the two groups (all P>0.05), but the knee function was significantly improved in both groups when compared with that before the operation (all P<0.05). There were 1 patient with femoral tunnel fracture, one with injury to the medial condylar cartilage and one with injury to the posterior root of lateral meniscus in knee hyperflexed position group, while no above-mentioned complications occurred in figure-of-four position group ( P<0.05). Conclusion:Arthroscopic ACL reconstruction using tendon autograft with femoral tunnel creation through figure-of-four position and traditional knee hyperflexed position can both contribute knee functional recovery, but the figure-of-four position has the advantages of short operation time, accurate tunnel positioning, favorable length and angle of the tunnel and less complications.

Clinical characteristics and prognosis of RUNX1-RUNX1T1 fusion gene-positive with ASXL2 gene mutations in acute myeloid leukemia / 白血病·淋巴瘤

Objective:To investigate the clinical characteristics and prognosis of patients with RUNX1-RUNX1T1 fusion gene-positive acute myeloid leukemia (AML) with ASXL2 gene mutation.Methods:The clinical data of 145 newly diagnosed RUNX1-RUNX1T1 fusion gene-positive AML patients treated at the Second Hospital Center of Shanxi Medical University from October 2010 to March 2021 were retrospectively analyzed. Sanger sequencing was used to detect the gene mutation. According to the presence or absence of ASXL2 gene mutation, the patients were divided into mutation group and non-mutation group. The clinical characteristics, gene mutations and prognosis were compared among the two groups.Results:Among 145 AML patients with positive RUNX1-RUNX1T1 fusion gene, we identified recurrent mutations of c-kit, ASXL2, N/KRAS, FLT3, ASXL1, TET2, NPM1 and DNMT3A genes, with mutation rates of 40.7% (59/145), 20.7% (30/145), 15.9% (23/145), 12.4% (18/145), 11.7% (17/145), 11.0% (16/145), 5.5% (8/145), and 2.1% (3/145), respectively. A total of 18 mutation sites were detected in 30 patients with ASXL2 gene mutations including 5 point mutations and 13 frameshift mutations, which mainly occured in the exons 12 and 13. Lactate dehydrogenase (LDH) at initial diagnosis of 30 AML patients with ASXL2 mutation was lower than that of those with ASXL2 non-mutation ( Z = 2.34, P = 0.020), while prothrombin time (PT) of AML patients with ASXL2 mutation was longer than that of those with ASXL2 non-mutation ( Z = 1.99, P = 0.047). A total of 21 (21/30, 70%) patients simultaneously had other gene mutations. The incidence of RAS mutations in patients with ASXL2 mutation was higher than that those with ASXL2 non-mutation, and the difference was statistically significant [30.0% (9/30) vs. 12.1% (14/115), χ2 = 4.41, P = 0.036]. There were no statistically significant differences in complete remission rate [86.7% (26/30) vs. 74.8% (86/115)] and recurrence rate [43.3% (13/30) vs.31.3% (36/115)] of patients with ASXL2 mutation and ASXL2 non-mutation ( χ2 = 0.39, P = 0.534; χ2 = 0.54, P = 0.432). The median overall survival (OS) time was 26 months (1-135 months) and 30 months (1-120 months), respectively in patients with ASXL2 mutation and ASXL2 non-mutation; the median disease-free survival (DFS) time was 14 months (0-60 months) and 13 months (0-94 months), respectively in patients with ASXL2 mutation and ASXL2 non-mutation; and the differences in OS and DFS were not statistically significant of both groups ( χ2 = 0.05, P = 0.822; χ2 = 0.34, P = 0.562). Compared with ASXL1 mutant patients, cases with ASXL2 mutation had higher OS and DFS rates, and the differences were statistically significant ( P = 0.003, P = 0.007). The differences in OS and DFS between patients with ASXL2 mutations and those with positive mutations of c-kit, RAS, FLT3, TET2, NPM1, DNMT3A were not statistically significant (all P > 0.05). Conclusions:RUNX1-RUNX1T1 positive AML patients with ASXL2 mutation tend to have low LDH and high PT, and often coexist with RAS mutations, and their prognosis is better than that in patients with ASXL1 positive mutation.

Clinical efficacy of hepatic artery chemoembolization combined with systemic treatment in the treatment of recurrent hepatocellular carcinoma with abdominal lymph node metastasis / 中华消化外科杂志

In China, patients with hepatocellular carcinoma (HCC) are usually with late stage and long medical history when diagnosed, resulting in a lower 5-year survival rate. For advanced HCC, guidelines from different countries have different indications for local treatment. The applica-tion of hepatic artery chemoembolization has brought new treatment opportunities to patients with advanced HCC. Due to tumor heterogeneity, the response to immunotherapy is different in patients with intrahepatic recurrent lesions and extrahepatic metastatic lesions of primary hepatic carcinoma. Therefore, hepatic artery chemoembolization combined with systemic treatment is beneficial to prolong the survival of patients. The authors introduce the clinical experience of a patient with recurrent advanced HCC combined with abdominal lymph node metastasis who was treated with hepatic artery chemoembolization combined with atezolizumab plus bevacizumab. The results show that tumor is controlled in a short period with a good clinical effect.

Protective effects of valproic acid on cardiac and cerebral injury in rats subjected to severe scalding combined with seawater immersion injury with delayed fluid replacement / 中国药房

OBJECTIVE To study the protective effects o f valproic acid on cardiac and cerebral injury in rats subjected to severe scalding combined with seawater immersion injury with delayed fluid replacement. METHODS The rats were divided into scalding+delayed fluid replacement group （group S ），scalding+seawater immersion+delayed fluid replacement group （group SS ）， scalding+seawater immersion+valproic acid+delayed fluid replacement group （group SSV ）according to random number table ，with 60 rats in each group. All groups were subjected to 35％total body surface area third-degree full-thickness scalding with boiled water. Group SS and group SSV were immersed in artificial ；seawater（30 min）immediately after scalding ，and group SSV was subcutaneously injected with valproic acid 300 mg/kg immediately after out of water. Sodium lactate Ringer ’s 0314-2279277。E-mail：125467374@qq.com injection was injected intravenously within 30 minutes according to 1/2 Parkland formula at 2 h after scalding in each group for delayed fluid replacement. The death time of rats was recorded ，and the average survival time and 24 h survival rate of rats in each group were calculat ed. Mean arterial pressure （MAP），heart rate （HR），respiration rate （RR），rectal temperature （RT），arterial blood pH ，arterial partial pressure of oxygen （PaO2），arterial blood partial pressure of carbon dioxide （PaCO2），HCO3－，creatine kinase MB isoenzyme （CK-MB）and neuron specific enolase （NSE）were detected before scalding ，at 0，2，5 h after scalding. The pathological changes of cardiac and cerebral tissue were observed. RESULTS The 24 h survival rate of group SS （55％）was significantly lower than that of group S （90％）， while that of group SSV （75％）was increased significantly ，compared with group SS （P＜0.05）. Compared with group S ，the levels of MAP ，RT，HR，pH，PaO2 and HCO 3－ in group SS were significantly lowered ，while the levels of CK-MB and NSE were increased significantly at 0，2，5 h after scalding ；the levels of PaCO 2 were increased significantly at 2，5 h after scalding ， while the levels of RR were decreased significantly at 0，2 h after scalding （P＜0.05）. Compared with group SS ，the levels of MAP，RT，HR，pH，PaO2 and HCO 3－ in group SSV were significantly increased ，while the levels of PaCO 2，CK-MB and NSE were decreased significantly at 2，5 h after scalding ；the level of RR was increased significantly at 2 h after scalding （P＜0.05）. At 2，5 h after scalding ，cardiac and cerebral injury of rats in group SS were aggravated significantly than that in group S ；cardiac and cerebral injury of rats in group SSV were relieved significantly than that in group SS. CONCLUSIONS After severe scalding combined seawater immersion injury ，hypodermic injection of sodium valproate could protect cardiac and cerebral function of rats ， improve vital signs and blood gas index ，prolong survival time and improve survival rate in rats.

Clinical analysis of breast reconstruction with single-port inflatable endoscopic prepectoral prosthesis implantation / 国际外科学杂志

Objective:To investigate the surgical method and clinical application value of single-port inflatable endoscopic prepectoralis prosthesis implantation for breast reconstruction (external prosthesis wrapping Off-Label).Methods:From September 2021 to February 2022, 7 breast cancer patients who underwent single-port inflatable endoscopic prepectoralis prosthesis implantation breast reconstruction (Off-Label) in Beijing Friendship Hospital, Capital Medical University were retrospectively analyzed. Statistical analysis of surgical complications, postoperative movement deformities, postoperative chest wall pain, postoperative quality of life and satisfaction scores of patients were conducted.Results:All 7 patients successfully completed the operation. There were no complications such as postoperative bleeding, infection, ischemic necrosis of nipple-areola complex or skin flap, postoperative movement deformity, postoperative chest wall pain, capsular contracture, prosthesis exposure or removal. The BREAST-Q scale was used to evaluate the quality of life and satisfaction after breast reconstruction. Postoperative breast satisfaction (55-100 points), chest wall status (52-89 points), and social psychological status (62-100 points) can be compared High rating.Conclusion:The single-port inflatable endoscopic prepectoral prosthesis implantation breast reconstruction (Off-Label) can achieve better radical effect and cosmetic effect through a shorter operation time, and the postoperative quality of life and satisfaction of patients are higher.

HBcAg-specific Th9 cells in patients with HBV infection / 中华微生物学和免疫学杂志

Objective:To investigate the changes of non-specific and HBV core antigen (HBcAg)-specific Th9 cells, and intereleukin-9 (IL-9) in HBV-infected patients, and to assess the influence of Th9 cells on CD8 + T cell function. Methods:Twelve patients with acute hepatitis B (AHB) and 58 with chronic hepatitis B (CHB), who were hospitalized in the First Affiliated Hospital of Xinxiang Medical University between January 2018 and January 2019, were enrolled in this study. Twenty healthy subjects negative for HBsAg were selected as controls. Peripheral blood mononuclear cells (PBMCs) and plasma samples were isolated. Non-specific Th9 cells (CD3 + CD4 + IL-9 + ) and HBcAg-specific Th9 cells were analyzed by flow cytometry. Plasma IL-9 level was measured by enzyme linked immunosorbent assay. CHB patients received tenofovir disoproxil fumarate (TDF) antiviral therapy. The changes of non-specific Th9 cells, HBcAg-specific Th9 cells and plasma IL-9 level were assessed 48 weeks after TDF therapy. CD4 + CCR4 -CCR6 -CXCR3 -(Th9) cells and CD8 + T cells were isolated from 12 HLA-A2 restricted CHB patients and co-cultured with HepG2.2.15 cells with the presence of anti-IL-9 neutralizing antibody. The percentage of dead HepG2.2.15 cells and the levels of IFN-γ and TNF-α were detected. Student′s t test, one-way analysis of variance or SNK- q test was used for statistical comparison between groups. Results:There were no significant differences in non-specific Th9 cells or plasma IL-9 level among AHB patients, CHB patients and healthy controls ( P>0.05). HBcAg-specific Th9 cells was down-regulated in CHB patients when compared with AHB patients [(2.49±0.61)% vs (3.19±0.62)%, P<0.001]. The percentage of HBcAg-specific Th9 cells was negatively correlated with HBV DNA ( r=-0.385, P=0.003), but not correlated with ALT ( P>0.05) in CHB patients. TDF therapy for 48 weeks remarkably elevated the HBcAg-specific Th9 cells [(2.94±0.48)%, P<0.001], however, did not affect non-specific Th9 cells or plasma IL-9 level ( P>0.05) in CHB patients. The cytotoxicity of HBcAg-specific Th9 cells was low in CHB patients. However, HBcAg-specific Th9 cells could induce enhanced cytotoxicity of CD8 + T cells to HepG2.2.15 cells, which manifested as increased percentage of dead HepG2.2.15 cells and higher levels of IFN-γ and TNF-α. Anti-IL-9 neutralizing antibody reduced the enhancement of CD8 + T cell cytotoxicity by HBcAg-specific Th9 cells ( P<0.001). Conclusions:Chronic HBV infection might suppress the level and function of HBcAg-specific Th9 cells, resulting in persistent infection.

Systematic evaluation of the relationship between tumor-infiltrating lymphocytes and prognosis of triple negative breast cancer / 国际外科学杂志

Objective:To investigate the prognostic value of tumor infiltrating lymphocytes (TILs) and their phenotypes, CD4 + TILs, CD8 + TILs and FOXP3 + TILs, in short-term prognosis (PCR) and long-term prognosis (DFS, OS) of triple negative breast cancer (TNBC), and to provide theoretical support for the immunotherapy of TNBC. Methods:A systematic surch of PubMed, Medline, Embase, Web of Science, CBM, CNKI was conducted to identified eligible articles. All prospective trials and observational controlled trials published before August 2020 were retrieved.The two authors independently evaluated the quality of the included literature, extracted the data, and conducted systematic evaluation and analysis using RevMan5.3 software.Results:A total of 48 literatures were included.Every 10% increase in TILs and TILs expression in the high-expression group predicted a higher PCR, OR were 1.81 (95% CI: 1.44-2.28) and 1.09 (95% CI: 1.02-1.15). For longer survival, the HR for DFS and OS were 0.99 (95% CI: 0.98-0.99) and 0.90 (95% CI: 0.86-0.94), 0.87 (95% CI: 0.79-0.96) and 0.88 (95% CI: 0.83-0.92). Phenotypic CD4 + TILs, CD8 + TILs, and FOXP3 + TILs did not show statistically significant differences in PCR among patients, but in long-term prognosis, higher infiltration predicted longer survival, with HR for DFS of 0.54 (95% CI: 0.36-0.80), 0.46(95% CI: 0.33-0.64) and 0.45(95% CI: 0.31-0.68). HR of OS were 0.49 (95% CI: 0.32-0.76), 0.59 (95% CI: 0.54-0.66) and 0.44 (95% CI: 0.27-0.71). Conclusion:The infiltration degree of TILs and the increase of TILs expression by 10% can be used as a prognostic index of TNBC.High levels of phenotypic infiltration of CD4 + TILs, CD8 + TILs, and FOXP3 + TILs predicted better long-term survival, but there was no statistically significant difference in short-term survival.

Construction and application value of CT-based radiomics model for predicting recurrence of early-stage hepatocellular carcinoma after resection / 中华消化外科杂志

Objective:To construct a computed tomography (CT)-based radiomics model for predicting tumor recurrence of early-stage hepatocellular carcinoma (HCC) after resection, and explore its application value.Methods:The retrospective cohort study was conducted. The clinicopathological data of 243 patients with early-stage HCC who underwent hepatectomy in 2 medical centers between January 2009 and December 2016 were collected, including 165 in the First Affiliated Hospital of Nanjing Medical University and 78 in the Wuxi People′s Hospital. There were 182 males and 61 females, aged from 30 to 86 years, with a median age of 57 years. According to the random numbers showed in the computer, 243 patients were randomly assigned into training dataset consisting of 162 patients and test dataset consisting of 81 patients, with a ratio of 2∶1. Using radiomics technique, a total of 3 384 radiomics features were extracted from the tumor and its periphery at arterial-phase and portal-phase images of CT scan. In the training dataset, a radiomics signature was constructed and predicted its performance after dimension reduction of stable features by using aggregated feature selection algorithms [feature ranking via maximal relevance and minimal redundancy (MRMR) combined with random survival forest (RSF) + LASSO-COX regression analysis]. Risk factors for tumor recurrence were selected using the univariate COX regression analysis, and two radiomics models including radiomics 1 (preoperative) and radiomics 2 (postoperative) were constructed and predicted their performance using backward stepwise multivariate COX regression analysis. The two models were validated in the training and test dataset. Observation indicators: (1) follow-up; (2) construction of HCC recurrence-related radiomics signature for early-stage HCC after resection; (3) prediction performance of HCC recurrence-related radiomics signature for early-stage HCC after resection; (4) construction of HCC recurrence-related radiomics prediction model for early-stage HCC after resection; (5) validation of HCC recurrence-related radiomics prediction model for early-stage HCC after resection; (6) comparison of the prediction performance of radiomics model with that of other clinical statistical models and current HCC staging systems; (7) stratification analysis of postoperative recurrence risk based on radiomics models for early-stage HCC after resection. Patients were followed up using outpatient examination or telephone interview once every 3 months within the first 2 years and once every 6 months after 2 years. The follow-up included collection of medical history, laboratory examination, and abdominal ultrasound examination. Contrast-enhanced CT or magnetic resonance imaging (MRI) examination was performed once every 6 months, and they were performed in advance on patients who had suspected recurrence based on laboratory examination or abdominal ultrasound for further diagnosis. Follow-up was up to January 2019. The endpoint was time to recurrence, which was from the date of surgery to the date of first detected disease recurrence or metastasis. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed by the t test. Measurement data with skewed distribution were described as M (range), and comparison between groups was analyzed by the Mann-Whitney U test. Count data were described as absolute numbesr or percentages, and comparison between groups was analyzed using the chi-square test. The survival curve and survival rate were respectively drawn and calculated by the Kaplan-Meier method, and the survival analysis was performed using the Log-rank test. Serum alpha-fetoprotein level was analyzed after the natural logarithm transformation. X-tile software was used to select the optimal cut-point for continuous markers. Results:(1) Follow-up: all the 243 HCC patients received follow-up. Patients in the training dataset were followed up for 4.2-109.2 months, with a median follow-up time of 51.6 months. Patients in the test dataset were followed up for 12.7-107.6 months, with a median follow-up time of 73.2 months. The 2-, 5-year disease-free survival rates were 77.8% and 53.1% of the training dataset respectively, versus 86.4% and 61.7% of the test dataset. There was no significant difference in terms of disease-free survival between two datasets ( χ2=1.773, P>0.05). (2) Construction of HCC recurrence-related radiomics signature for early-stage HCC after resection: of the 3 384 radiomics features, 2 426 radiomics features with high stability were selected for analysis. There were 37 radiomics features identified after combining the top 20 radiomics features ranked by MRMR and RSF algorithms. LASSO-COX regression algorithm further reduced their dimensionality to retain 7 radiomics features and construct a radiomics signature. The indicators including region, scanning phase, and weighting coefficient of above mentioned seven features were Feature 1 (peritumoral, arterial phase, 0.041), Feature 2 (peritumoral, arterial phase, -0.103), Feature 3 (peritumoral, arterial phase, -0.259), Feature 4 (intratumoral, arterial phase, 0.211), Feature 5 (peritumoral, portal venous phase, -0.170), Feature 6 (intratumoral, portal venous phase, 0.130), and Feature 7 (intratumoral, portal venous phase, 0.090), respectively. Radiomics signature score=0.041×Feature 1-0.103×Feature 2-0.259×Feature 3+ 0.211×Feature 4-0.170×Feature 5+ 0.130×Feature 6+ 0.090×Feature 7. (3) Prediction performance of HCC recurrence-related radiomics signature for early-stage HCC after resection: the radiomics signature showed favorable prediction performance in both training and test datasets, with respective C-index of 0.648 [95% confidence interval ( CI): 0.583-0.713] and 0.669 (95% CI: 0.587-0.750). (4) Construction of HCC recurrence-related radiomics prediction model for early-stage HCC after resection: results of univariate analysis showed that ln(serum alpha-fetoprotein), liver cirrhosis, tumor margin status, arterial peritumoral enhancement, intratumoral necrosis, radiomics signature, satellite nodules, and microvascular invasion were related factors for tumor recurrence after resection of early-stage HCC ( hazard ratio=1.202, 1.776, 1.889, 2.957, 1.713, 4.237, 4.364, 4.258, 95% CI: 1.083-1.333, 1.068-2.953, 1.181-3.024, 1.462-5.981, 1.076-2.728, 2.593-6.923, 2.468-7.717, 2.427-7.468, P<0.05 ). Results of multivariate analysis showed that the radiomics model 1 (preoperative) consisted of ln(serum alpha-fetoprotein), tumor margin status, and radiomics signature ( hazard ratio=1.145, 1.838, 3.525, 95% CI: 1.029-1.273, 1.143-2.955, 2.172-5.720, P<0.05); the radiomics model 2 (postoperative) consisted of ln(serum alpha-fetoprotein), radiomics signature, microvascular invasion, and satellite nodules ( hazard ratio=1.123, 2.386, 3.456, 3.481, 95% CI: 1.005-1.254, 1.501-3.795, 1.863-6.410, 1.891-6.408, P<0.05). Risk prediction formulas: radiomics model 1 = 0.135×ln(serum alpha-fetoprotein)+ 0.608×tumor margin status (0: smooth; 1: non-smooth)+ 1.260×radiomics signature; radiomics model 2 = 0.116×ln(serum alpha-fetoprotein)+ 0.870×radiomics signature + 1.240×microvascular invasion (0: absent; 1: present)+ 1.247×satellite nodules (0: absent; 1: present). (5) Validation of HCC recurrence-related radiomics prediction model for early-stage HCC after resection: in both training and test datasets, radiomics model 1 provided good prediction performance, with respective C-index of 0.716 (95% CI: 0.662-0.770) and 0.724 (95% CI: 0.642-0.806), while radiomics model 2 provided better prediction performance, with respective C-index of 0.765 (95% CI: 0.712-0.818) and 0.741 (95% CI: 0.662-0.820). Calibration curves demonstrated good agreement between model-predicted probabilities and observed outcomes. (6) Comparison of the prediction performance of radiomics model with that of other clinical statistical models and current HCC staging systems: in the training dataset, the prediction performance of radiomics model 1 for tumor recurrence after resection of early-stage HCC was significantly different from that of ERASL model (preoperative), Barcelona clinic liver cancer (BCLC) staging, Hong Kong liver cancer (HKLC) staging, and cancer of the liver Italian program (CLIP) classification (C-index=0.562, 0.484, 0.520, 0.622, 95% CI: 0.490-0.634, 0.311-0.658, 0.301-0.740, 0.509-0.736, P<0.05); the prediction performance of radiomics model 2 for tumor recurrence after resection of early-stage HCC was significantly different from that of ERASL model (postoperative), Korean model, and the eighth edition TNM staging (C-index=0.601, 0.523, 0.513, 95% CI: 0.524-0.677, 0.449-0.596, 0.273-0.753, P<0.05). In the test dataset, the prediction performance of radiomics model 1 for tumor recurrence after resection of early-stage HCC was significantly different from that of ERASL model (preoperative), BCLC staging, HKLC staging, CLIP classification (C-index=0.540, 0.473, 0.504, 0.545, 95% CI: 0.442-0.638, 0.252-0.693, 0.252-0.757, 0.361-0.730, P<0.05); the prediction performance of radiomics model 2 for tumor recurrence after resection of early-stage HCC was significantly different from that of ERASL model (postoperative), Korean model, and the eighth edition TNM staging (C-index=0.562, 0.513, 0.521, 95% CI: 0.451-0.672, 0.399-0.626, 0.251-0.791, P<0.05). (7) Stratification analysis of postoperative recurrence risk based on radiomics models for tumor recurrence after resection of early-stage HCC: according to the analysis of X-tile, the score of radiomics model 1 < 1.4 (corresponding to total points < 62.0 in nomogram) was classified into low-risk group while the score of radiomics model 1 ≥ 1.4 (corresponding to total points ≥ 62.0 in nomogram) was classified into high-risk group. The score of radiomics model 2 < 1.7 (corresponding to total points < 88.0 in nomogram) was classified into low-risk group while the score of radiomics model 2 ≥ 1.7 (corresponding to total points ≥ 88.0 in nomogram) was classified into high-risk group. In the training dataset, the 2- and 5-year recurrence rates were 14.1%, 35.3% for low-risk patients and 63.0%, 100.0% for high-risk patients, which were predicted by radiomics model 1. There were significant differences between the two groups ( χ2= 70.381, P<0.05). The 2- and 5-year recurrence rates were 12.9%, 38.2% for low-risk patients and 81.8%, 100.0% for high-risk patients, which were predicted by radiomics model 2. There were significant differences between the two groups ( χ2= 98.613, P<0.05). In the test dataset, the 2- and 5-year recurrence rates were 5.6%, 29.3% for low-risk patients and 70.0%, 100.0% for high-risk patients, which were predicted by radiomics model 1. There were significant differences between the two groups ( χ2= 64.453, P<0.05). Ther 2- and 5-year recurrence rates were 5.7%, 28.1% for low-risk patients and 63.6%, 100.0% for high-risk patients, which were predicted by radiomics model 2. There were significant differences between the two groups ( χ2= 58.032, P<0.05). Conclusions:The 7-feature-based radiomics signature is built by selection of CT radiomics features in this study, and then HCC recurrence-related radiomics prediction model for early-stage HCC after resection is constructed. The proposed radiomics models can complement the existing clinical-radiological-pathological prognostic sources, accurately and individually predict tumor recurrence risk preoperatively and postoperatively, which facilitate clinical decision-support for patients with early-stage HCC.

Progress of chimeric antigen receptor T-cell therapy in treatment of hematological malignancies / 白血病·淋巴瘤

Chimeric antigen receptor T-cell (CAR-T) therapy is effective in treating lymphoma and leukemia. A large number of basic and clinical studies have led to the rapid development of CAR-T therapy. This paper reviews the concept of CAR-T therapy, the application of CAR-T in hematologic diseases, and the problems and solutions of CAR-T.

Review of cognitive enhancement techniques based on the combination of cognitive training and transcranial direct current stimulation / 生物医学工程学杂志

Cognitive enhancement refers to the technology of enhancing or expanding the cognitive and emotional abilities of people without psychosis based on relevant knowledge of neurobiology. The common methods of cognitive enhancement include transcranial direct current stimulation (tDCS) and cognitive training (CT). tDCS takes effect quickly, with a short effective time, while CT takes longer to work, requiring several weeks of training, with a longer effective time. In recent years, some researchers have begun to use the method of tDCS combined with CT to regulate the cognitive function. This paper will sort out and summarize this topic from five aspects: perception, attention, working memory, decision-making and other cognitive abilities. Finally, the application prospect and challenges of technology are prospected.

Clinical efficacy of liver resection for colorectal liver metastasis in the elderly and prognosis factor analysis / 中华老年医学杂志

Objective:To investigate the clinical efficacy of liver resection for colorectal liver metastases(CRLM)in elderly patients and to analyze factors influencing prognosis.Methods:Clinicopathological and follow-up data of 476 CRLM patients undergone liver resection at our department between January 2000 and August 2016 were retrospectively analyzed.Patients were divided into two groups according their ages: the elderly group(n=112, aged 65 years or older)and the young and middle-aged group(n=364, aged less than 65 years). The safety of the surgical treatment and long-term survival were compared between the two groups.Results:The overall postoperative complication rate was 30.3%.There was no significant difference in postoperative complication rates between the elderly group and the young and middle-aged group(32.1% vs. 29.7%, P=0.618). The mortality within 90 days after surgery was 0.9% in the elderly group and 0.5% in the young and middle-aged group( P=0.688). The 5-year survival rates after surgery were similar between the elderly group and the young and middle-aged group(42.4% vs.44.3%, P=0.672). Multivariate analysis revealed that clinical risk score(CRS)≥3 and RAS mutation were independent risk factors for prognosis. Conclusions:Liver resection is safe in carefully selected elderly CRLM patients and can achieve good long-term outcomes.The CRS and RAS genotype can help predict prognosis in elderly CRLM patients.

Prognosis and risk factors after surgical treatment for colorectal cancer liver metastases / 中华肝胆外科杂志

Objective:To study the impact of surgical treatment on long-term survival in patients with colorectal cancer liver metastases, and to identify the associated risk factors.Methods:The clinical, pathological, and follow-up data were prospectively collected from 781 consecutive patients who underwent hepatic resection for colorectal liver metastases at Hepatopancreatobiliary Surgery Department Ⅰ, Peking Cancer Hospital from Jan 2000 to Nov 2018. There were 497 males and 284 females. The average age was 56.7 years (range 19 to 83 years). The tumor recurrence and survival outcomes on follow-up were analyzed. Survival curves were plotted using the Kplan-Meier mothod. Parametric survival analysis was used to identify predictors of cancer-specific survival.Results:The 1-, 3-, 5- and 10-year overall survival rates were 91.6%, 57.3%, 45.2% and 27.6%, respectively. The median survival was 46 months. The 1-, 3-, 5- and 10-year disease-free survival rates were 45.3%, 26.0%, 22.9%, and 19.5%, respectively. The median disease-free survival was 11 months. On multivariate analysis, 5 risk factors were found to be independent predictors of poor survival: RAS/BRAF gene mutation ( HR=1.650, 95% CI: 1.302-2.089), right-sided colonic primary ( HR=1.361, 95% CI: 1.151-1.667), node-positive primary ( HR=1.660, 95% CI: 1.284-2.146), largest hepatic tumor ≥3 cm ( HR=1.473, 95% CI: 1.157-1.874), and extrahepatic disease ( HR=1.610, 95% CI: 1.294-2.003). Conclusion:Surgery is the key to long-term survival for patients with liver metastases from colorectal cancer. Right colonic primary, RAS/BRAF gene mutation, primary lymph node metastasis, hepatic metastasis with a maximum diameter ≥3 cm and extrahepatic metastasis were factors associated with poor prognosis.

Predictors of early recurrence and long-term survival in patients after resection for colorectal cancer liver metastases with a low-risk on clinical risk score / 中华肝胆外科杂志

Objective:To study the related factors of early recurrence and long-term survival after hepatectomy for patients with colorectal cancer liver metastases (CRLM) with a low-risk on clinical risk score (CRS).Methods:The clinicopathological data of 983 consecutive patients with CRLM who underwent liver resection at Department of Hepatopanereatobiliary Surgery Ⅰ, Peking University Cancer Hospital & Institute between January 2000 and November 2018 were studied retrospectively. A total of 420 patients with a CRS of 0-2 met the inclusion criteria of this study. There were 272 males and 148 females, aged from 21 to 83 years, with a median age 59 years. Univariate and multivariate logistic regression analyses were performed to identify the related factors associated with early recurrence. Survival curves were generated by the Kaplan-Meier method and compared by the log-rank test.Results:Of 420 patients, 272(64.8%) patients developed recurrence, with 163 patients developing early recurrence. Multivariate analysis revealed synchronous liver metastasis ( OR=1.587, 95% CI: 1.021-2.467), number of liver metastases ≥3( OR=1.904, 95% CI: 1.091-3.324) and RAS mutation ( OR=1.774, 95% CI: 1.157-2.270) were independent risk factors of early recurrence. The 5-year overall survival of patients with early recurrence was significantly lower than those with non-early recurrence (33.4% vs 71.1%, P<0.05). For the 163 patients with early recurrence, 41(25.2%) underwent repeat liver resection. When compared with the remaining 122(74.8%) patients who underwent non-resectional treatment, these 41 patients had a significantly higher 5-year overall survival rate (63.5% vs 21.1%, P<0.05). Conclusions:In patients with colorectal cancer liver metastases with a low risk on CRS, the independent risk factors for early recurrence were synchronous liver metastasis, number of liver metastases ≥3, and RAS mutation. Re-resection of early recurrent disease achieved better survival outcomes.

Clinical effects and mechanism of treating extensive deep burns by stage-Ⅱ Meek skin grafting on adipose tissue after tangential excision / 中华烧伤杂志

Objective@#To observe the clinical effects of stage-Ⅱ Meek skin grafting on adipose tissue after tangential excision in patients with extensive deep burns, and to explore the functional mechanism.@*Methods@#The medical records of 26 extensively burned patients who met the inclusion criteria and were admitted to the Department of Burns and Plastic Surgery of the Fourth Medical Center of PLA General Hospital from May 2015 to December 2017 were retrospectively analyzed. According to the treatment methods, 14 patients were enrolled in stage-Ⅰ skin grafting group (10 males and 4 females, aged 27 to 75 years), and 12 patients were enrolled in stage-Ⅱ skin grafting group (10 males and 2 females, aged 31 to 76 years). Patients in the 2 groups all underwent debridement of tangential excision, and their healthy adipose tissue was preserved. Meek skin grafting was performed just after tangential excision in patients in stage-Ⅰ skin grafting group. In patients in stage-Ⅱ skin grafting group, porcine acellular dermal matrix (ADM) was applied to cover the wound after tangential excision, and 3 days later, it was removed and Meek skin grafting was performed. The times of complement skin grafting and the wound basic healing time of patients in the 2 groups were observed and recorded. In the stage-Ⅱ skin grafting group, the adipose tissue of patients were taken from the wound center immediately after tangential excision and immediately after the removal of porcine ADM, for the observation of structure of the fault surface of adipose tissue through hematoxylin and eosin staining and microvessel density (MVD) through immunohistochemical staining. Data were processed with independent sample t test and Fisher′s exact probability test.@*Results@#(1) The times of complement skin grafting of patients in stage-Ⅱ skin grafting group was (1.83±0.17) times, which was obviously less than (3.36±0.63) times in stage-Ⅰ skin grafting group (t=2.19, P<0.05). The wound basic healing time of patients in stage-Ⅱ skin grafting group was (35.1±2.3) d, which was obviously shorter than (48.8±4.9) d in stage-Ⅰ skin grafting group (t=2.27, P<0.05). (2) Immediately after tangential excision, the intercellular substance was few between the adipose cells in adipose tissue of patients in stage-Ⅱ skin grafting group. Immediately after the removal of porcine ADM, there was regenerated granulation tissue in the intercellular space of adipose cells of adipose tissue of patients in stage-Ⅱ skin grafting group. Immediately after tangential excision, the MVD of adipose tissue of patients in stage-Ⅱ skin grafting group was 20.2±1.3 under per 400-time field, which was obviously less than 32.2±1.9 under per 400-time field immediately after the removal of porcine ADM (t=-5.38, P<0.01).@*Conclusions@#Meek skin grafting on the adipose tissue in stage-Ⅱ surgery after tangential excision could reduce the times of complement skin grafting and shorten wound healing time of patients with extensive deep burns. The mechanism may be related to the improvement of the recipient condition of adipose tissue.

Perioperative airway management in patients undergoing bronchoscopic treatment of tracheal stenosis / 中华麻醉学杂志

Data of patients underwent bronchoscopic treatment of tracheal stenosis from May 2011 to April 2016 were collected.Patients were questioned about the medical history before operation,and the airway was fully evaluated.The laryngeal mask was used for the patients with upper 1/3 tracheal stenosis and subglottic stenosis,and endotracheal intubation was applied for the other patients.Patients with severe tracheal stenosis received extracorporeal membrane oxygenation (ECMO)-assisted ventilation.The tracheal tube or laryngeal mask was removed immediately when patients were awake and spontaneous breathing and swallowing reflex recovered after operation,and oxygen was inhaled by mask.A total of 189 patients were included in this study,93 patients received endotracheal intubation,and 91 patients were ventilated via the laryngeal mask,and 5 patients underwent ECMO-assisted ventilation.Forty-four patients adopted the method of preserving spontaneous breathing,and the other 145 patients did not.There were 165 patients in whom the endotracheal tube or laryngeal mask was removed immediately after they were awake,and the remaining 24 cases were sent to the intensive care unit with the endotracheal tube.For the patients with tracheal stenosis,preoperative interview and airway assessment are especially important,and appropriate airway management strategies should be developed;vital signs should be closely observed during operation,and the proper ventilation mode is selected,and ECMO-assisted ventilation could be considered for the patients with severe tracheal stenosis;the timing of removal of the endotracheal tube or laryngeal mask should be seized after operation.