Objective:To discuss the effects of superelastic nickel-titanium archwires(SENT)and heat-activated nickel-titanium archwires(HANT)on the initial alignment efficiency of mandibular anterior teeth and pain levels of the patients with extraction orthodontic treatment and non-extraction orthodontic treatment by using low-friction self-ligating brackets,and to provide the basis for the selection of the most suitable archwire in orthodontic clinical practice.Methods:Eighty patients underwent fixed orthodontic treatment with self-ligating brackets were randomly assigned to SENT or HANT subgroups,and there were 40 patients in extraction orthodontic treatment group and 40 patients in non-extraction orthodontic treatment group.A single operator fully engaged a 0.014-inch straight archwire into the brackets.The patients,operators,and data measurers were all blinded;the initial clinical alignment efficiency of the archwires of the patients in various groups was observed,and the Little's index was calculated;the visual analog scale(VAS)scores and pain perception of the patients in various groups were recorded 4 h after initial bonding of the appliances and every day before breakfast during the first week of orthodontic treatment;multivariate regression analysis was performed for the initial Little's index,gender,and age,and the influence factors of pain in the patients was analyzed.Results:There were no significant differences in age,gender,and initial Little's index among the patients in extraction group and non-extraction group(P＞0.05).Compared with before treatment,the Little's indexes of the patients in both HANT and SENT subgroups in non-extraction orthedontic treatment group were decreased 4 weeks after treatment,but the difference between groups was not significant(P＞0.05).Compared with SENT subgroup in non-extraction orthodontic treatment group,the Little's index of the patients in HANT subgroup was decreased(P＜0.05).In extraction orthodontic treatment group,there were no significant differences in Little's indexes of the patients between the HANT and SENT subgroups before and after treatment(P＞0.05).The pain perception peaked on the first day after initial bonding and gradually decreased to baseline levels.The patients in SENT and HANT subgroups in both extraction and non-extraction orthodontic treatment groups showed the similar patterns of pain change.There were no significant differences in the average VAS scores and maximum pain intensity scores between the patients in SENT and HANT subgroups at different time points(P＞0.05).The type of archwire had no significant effect on the degree of pain,while time significantly affected the degree of pain.The multivariate regression analysis results showed a significant correlation between initial Little's index and maximum VAS scores of the patients in extraction orthodontic treatment group(b=0.359,P=0.033).Gender and age did not affect the degree of pain of the patients in either group.Conclusion:When applying low-friction self-ligating brackets for orthodontic treatment,the initial alignment efficiency with 0.014-inch HANT archwires is superior to 0.014-inch SENT archwires in non-extraction treatment group,while both archwires show the same efficiency in extraction patients.SENT and HANT archwires do not affect the initial degrees of pain of the orthodontic patients.

Lenvatinib mesylate is an oral receptor tyrosine kinase inhibitor against targets of vascular endothelial growth factor receptors 1-3, fibroblast growth factor receptors 1-4, platelet-derived growth factor receptor α, stem cell growth factor receptor, and rearranged during transfection, et al. Lenvatinib has been approved by the National Medical Products Administration of China on September 4,2018, for the first-line treatment of patients with unresectable hepatocellular carcinoma who have not received systematic treatment before. Up to February 2023, Lenvatinib has been listed in China for more than 4 years, accumulating a series of post-marketing clinical research evidences. Based on the clinical practice before and after the launch of lenvatinib and referring to the clinical experience of other anti-angiogenesis inhibitors, domestic multidisciplinary experts and scholars adopt the Delphi method to formulate the Chinese Expert Guidance on Overall Application of Lenvatinib in Hepatocellular Carcinoma after repeated discussions and revisions, in order to provide reference for reasonable and effective clinical application of lenvatinib for clinicians.

Lenvatinib mesylate is an oral receptor tyrosine kinase inhibitor against targets of vascular endothelial growth factor receptors 1-3, fibroblast growth factor receptors 1-4, platelet-derived growth factor receptor α, stem cell growth factor receptor, and rearranged during transfection, et al. Lenvatinib has been approved by the National Medical Products Administration of China on September 4, 2018, for the first-line treatment of patients with unresectable hepatocellular carcinoma who have not received systematic treatment before. Up to February 2023, Lenvatinib has been listed in China for more than 4 years, accumulating a series of post-marketing clinical research evidences. Based on the clinical practice before and after the launch of lenvatinib and referring to the clinical experience of other anti-angiogenesis inhibitors, domestic multidisciplinary experts and scholars adopt the Delphi method to formulate the Chinese Expert Guidance on Overall Application of Lenvatinib in Hepatocellular Carcinoma after repeated discussions and revisions, in order to provide reference for reasonable and effective clinical application of lenvatinib for clinicians.

Objective:To study the clinical efficacy of ultrasound-guided radiofrequency acupotomy in early and middle-stage knee osteoarthritis (KOA).Methods:A total of 62 patients with KOA were enrolled and then randomly divided into the radiofrequency acupuncture group and the control group. The two groups were treated with radiofrequency acupotomy and conventional acupotomy under ultrasound guidance, respectively. The treatments were conducted once a week, twice in total. The Western Ontario and McMaster Universities Arthritis Index (WOMAC) of all the patients was evaluated before the treatment as well as the day, 2 weeks, and 1 month after the treatment.Results:Before the treatment, the differences between the two groups in gender, age, body mass index (BMI), WOMAC pain score, WOMAC stiffness score, WOMAC function score, and WOMAC total score were not statistically significant (all P>0.05), indicating the two groups were comparable. On the day, 2 weeks, and 1 month after the treatment, the above WOMAC scores of the two groups were lower than those before the treatment, and the differences were statistically significant (all P<0.01). The WOMAC scores of the radiofrequency acupotomy group were lower than those of the control group at the same period, and the differences were statistically significant (all P<0.05). Conclusions:For patients with early and middle-stage KOA, ultrasound-guided radiofrequency acupotomy therapy has proven clinical efficacy in relieving pain and improving knee joint function.

The pandemic of Corona Virus Disease 2019 (COVID-19) continues, which shows the concentrated or sporadic cases in multiple places. Current COVID situation is still complex. During the COVID-19, routine diagnosis and treatment of liver cancer patients has been affected in different degrees. Under the premise of following the treatment guidelines, how to reduce the risk of infection of patients and medical staff, utilize limited medical resources to maximally ensure anti-tumor treatment and related emergency treatment, and help patients get through the epidemic period is a problem for liver oncologists. Thus, experts of liver cancer treatment related disciplines of Zhongshan Hospital, Fudan University have written the Expert guidance on overall management of liver cancer during the COVID-19, which aims to provide references for liver oncolo-gists to conduct clinical work safely and effectively under the epidemic prevention and control, and to help patients fight against the epidemic smoothly.

Objective:To compare the histologic features of immune-mediated hepatitis (IMH) due to immune checkpoint inhibitors (ICIs) monotherapy and combined ICIs anti-angiogenesis tyrosine kinases (TKIs) targeted therapy.Methods:Twenty-one IMH patients who had liver biopsy during ICIs treatment in Zhongshan Hospital of Fudan University from 2015 to 2019 were included. Among them, ten were treated with ICIs monotherapy, and 11 were treated with combined ICIs and anti-angiogenesis targeted therapy. The histologic features of IMH were assessed by HE staining and PD-L1/2 was evaluated by immunohistochemical staining.Results:Patients treated with monotherapy ICIs presented with different levels of lobular hepatitis and portal inflammation. Besides, there were also cholangitis, endothelialitis, Kupffer cells activation and peliosisi hepatitis. Eight cases (8/10) showed mild and two cases (2/10) showed moderate hepatic injury. As for patients receiving combined ICIs and TKIs therapy, the extent of IMH was more severe, with four cases (4/11) showing moderate-severe liver injury, with confluent or bridging necrosis, portal inflammation, cholangitis, interface hepatitis. Among these, one patient developed acute severe hepatitis with massive hepatocyte necrosis and died of multisystem dysfunction. In those cases with severe liver injury, many CD8 positive lymphocytes aggregated in the portal area and hepatic sinusoid, and PD-L1 was expressed in many endothelial cells. There were both 2 cases of death in ICIs monotherapy and combination therapy group. Among the latter group, 1 patient developed acute severe hepatitis with massive hepatocyte necrosis and died of multisystem dysfunction.Conclusion:Compared with ICIs monotherapy, combined ICIs and anti-angiogenesis targeted TKIs therapy may cause overlapping hepatic injury, leading to severe IMH.

Objective To analyze the colistin heteroresistance in Pseudomonas aeruginosa strains and their in vitro susceptibility to antibiotics used in combination.Methods Two hundred and ninety-seven carbapenem-resistant Pseudomonas aeruginosa strains were selected for this study.Broth microdilution method was used to determine the minimum inhibitory concentrations of colistin and other antimicrobials against the Pseudomonas aeruginosa strains.The colistin heterogeneity of 20 colistin sensitive strains was analyzed by using population analysis profiles.The time-kill curves of 3 randomly selected colistin heteroresistant strains were used to determine the bacteriostatic activity of colistin.Chequer-board method was used to measure the combination efficacy of colistin with other antimicrobials including imipenem,meropenem,biapenem,ceftazidime,levofloxcin,piperacillin/tazobactam and cefoperazone/sulbactam.Results The colistin sensitive Pseudomonas aeruginosa strains accounted for 99.66％ of the 297 isolates.Population analysis profiles displayed that 35％ of the 20 isolates were colistin heteroresistant and 20％ of the 20 isolates were heterogeneous.It showed that when colistin was used in combination with other drugs,they mainly had synergistic and additive effects on heteroresistant isolates,but additive and indifferent effects on non-heterogeneous isolates.Conclusion Multidrug resistant Pseudomonas aeruginosa strains were highly susceptible to colistin,but heteroresistant and heterogeneous strains were common.The efficacy of colistin against heteroresistant isolates could be enhanced by using in combination with other drugs.

Objective: To explore the clinical significance of transcription factor Sp1 expression in hepatocellular carcinoma (HCC) and association between Sp1 expression and survival in HCC patients. Methods:With the use of immunoreactivity, Sp1 expres-sion and its correlation with other clinicopathological characteristics were examined in a tissue microarray that contains samples from 98 HCC patients. Results:HCC tissues expressed markedly higher levels of Sp1 than did adjacent normal liver tissues. Sp1 expression was closely associated with microvascular invasion, which suggests that HCC with more microvascular invasion is prone to have in-creased Sp1 expression. Overexpression of Sp1 correlates with significantly shorter overall survival and higher recurrence rates in HCC patients after curative resection. Conclusion:Transcription factor Sp1 may be an independent prognostic factor for both overall surviv-al and cumulative recurrence rate.

Objective:To establish an improved model of mouse partial hepatectomy for study on liver regeneration .Methods :Healthy 8~10 week old male C57BL/6 mice were anesthetized by intraperitoneal injection .Then ,common hepatic pedicle of left lateral lobe of liver and middle lobe of liver was wrapped around with 6-0 proline suture .6-0 proline was fixed on the sur-face of right middle lobe of liver ,which was 0 .2 cm away from the hepatic pedicle .Hepatic pedicle was ligated and left lateral lobe and middle lobe of liver were resected 0 .2 cm away from ligature .The postoperative survival rate and the situation of liver weight vecovery at 3rd day ,7th day ,and 14th day after the operation were observed .Results:An improved mouse model of partial hepatectomy ,of which left lateral lobe of liver and middle lobe of liver were resected ,was established .The weight of removed liver accounted for 66 .7% of total liver and the survival rate of mice was 100% .After liver resection ,the compensa-tory regeneration of remaining liver achieved 58 .2% of the total liver weight at the 3rd day ,78 .0% at the 7th day ,and 93 .2%at the 14th day after the operation .Conclusions :An improved mouse model of partial hepatectomy was successfully established for study on liver regeneration ,which has advantages such as simplicity ,operability and high success rate .

Objective:To evaluate the effect of interferon-αon the expression and activity of transcription factor specificity pro-tein 1(Sp1) in hepatocarcinoma cells .Methods :The effect of interferon-αon the expression and phosphorylation level of Sp1 in hepatocarcinoma cell line M HCC97H were detected by Western blotting .The effect of interferon-α on the activity of Sp1 was analyzed by electrophoretic mobility shift assay (EMSA) .Results :Interferon-α significantly reduced the expression and phos-phorylation level of Sp1 ,and the reducement on phosphorylation was more distinct .Interferon-α also inhibited the activity of Sp1 significantly .Conclusions :Interferon-αinhibits the activity of Sp1 by down regulating the expression and phosphorylation level of Sp1 .Sp1 may be an optional predictor of clinical efficacy of interferon-αon hepatocarcinoma .