OBJECTIVE To evaluate the efficacy and safety of tyrosine kinase inhibitors （TKI） in the treatment of HER2- positive breast cancer in order to provide evidence-based evidence for clinical medication. METHODS Retrieved from CNKI， Wanfang database， VIP， PubMed， Cochrane Library， Embase and Web of Science， randomized controlled trial （RCT） about TKI （trial group） versus drugs excluding TKI （control group） in the treatment of HER2-positive breast cancer were collected from the establishment of the database to April 2023. Meta-analysis and sensitivity analysis were performed by using RevMan 5.4.1 and Stata 17 software. RESULTS Total of 24 RCT studies were included， involving 15 538 HER2-positive breast cancer patients. The meta- analysis results showed that compared with the control group， the progression-free survival （PFS） [HR＝0.91， 95%CI （0.80， 1.02）， P＝0.12]， overall survival （OS） [HR＝0.95， 95%CI （0.89， 1.01）， P＝0.11]， objective response rate （ORR） [OR＝1.21， 95%CI （0.86， 1.69）， P＝0.27]， and pathological complete response rate （pCR） [OR＝1.44， 95%CI （0.91， 2.27）， P＝0.12] had no statistically significant difference in the trial group； among the 3/4 grade ADRs， the trial group had a higher incidence of anemia [OR＝1.77， 95%CI （1.16，2.70）， P＝0.008]， rash [OR＝11.26， 95%CI （7.32，17.31）， P＜0.000 01]， paronychia [OR＝8.67， 95%CI（1.62，46.53）， P＝0.01]， diarrhea [OR＝10.17， 95%CI（5.03，20.58）， P＜0.000 01]， oral mucositis inflammation [OR＝ 9.34， 95%CI （3.13， 27.83）， P＜0.000 1]， elevated aspartate aminotransferase [OR＝2.09， 95%CI （1.13，3.84）， P＝0.02]， and hypokalemia [OR＝2.37， 95%CI （1.31，4.30）， P＝0.005] than that of the control group. Subgroup analysis results showed that compared with the placebo group， TKI could improve OS and ORR （P＜0.05）， while compared with trastuzumab， TKI had no advantage in PFS， OS， ORR， and pCR， and TKI combined with trastuzumab could significantly improve PFS， OS， ORR， and pCR compared with the trastuzumab group （P＜ 0.05）. Sensitivity analysis suggested that the results were relatively robust and the risk of publication bias was low. CONCLUSIONS Compared with trastuzumab， TKI has no advantages in PFS， OS， ORR and pCR in the treatment of HER2- positive breast cancer， but TKI combined with trastuzumab can significantly improve PFS， OS， ORR and pCR； TKI can increase the risk of grade 3/4 anemia， rash， paronychia， diarrhea， oral mucositis， elevated aspartate aminotransferase， and hypokalemia.

Tumor-associated macrophage(TAM)play a crucial role in the immune microenvironment of lung can-cer.Through changes in their phenotype and phagocytic functions,TAM contribute to the initiation and progression of lung cancer.By promoting the formation of an immune-suppressive microenvironment and accelerating the growth of abnormal tumor vasculature,TAM facilitate the invasion and metastasis of lung cancer.Macrophages can polarize into different subtypes with distinct functions and characteristics in response to various stimuli,categorized as anti-tumor M1 and pro-tumor M2 types.In tumor tissues,TAM typically polarize into the alternatively activated M2 phenotype,exhibiting inhibitory effects on tumor immunity.This article reviews the role of anti-angiogenic drugs in modulating TAM phenotypes,highlighting their po-tential to reprogram M2-type TAM into an anti-tumor M1 phenotype.Additionally,the functional alterations of TAM play a significant role in anti-angiogenic therapy and immunotherapy strategies.In summary,the regulation of TAM polarization and function opens up new avenues for lung cancer treatment and may serve as a novel target for modulating the immune microen-vironment of tumors.

Objective:To construct a program for improving care ability of caregivers for children with home enteral tube feeding (HETF) based on timing theory, and explore its preliminary effects.Methods:Based on the framework of timing theory and literature review, intervention measures to improve the care ability of caregivers for children with HETF were extracted and summarized to form a preliminary program draft. Fourteen caregivers with experience in caring for children with HETF were subjected to qualitative interviews to supplement the content of the program, and the program was revised through expert meetings to form the final draft. Non-synchronous control method was adopted, and 89 children with HETF and 89 caregivers of them admitted to the Children's Hospital of Fudan University from March 2022 to February 2023 were continuously included as study subjects. The children and their caregivers included from March to August 2022 were in control group ( n=42), and the children and their caregivers included from September 2022 to February 2023 were in intervention group ( n=47), and the plan was preliminarily applied. Family Caregiver Task Inventory (FCTI) was used to evaluate the impact of the program on improving caregiver care ability. Age specific body weight z-values, height specific body weight z-values, and complications were used to evaluate the impact of the program on the growth and development of children and the incidence of tube feeding complications. The data was collected at the time of enrollment and one, two, and three months after discharge. Results:There were 66 children who completed the whole study, including 33 children in the control group and the intervention group, and 33 caregivers in each group. The application results showed that the total score of FCTI in the intervention group decreased from (25.91±2.94) at enrollment to (5.85±2.60) at three months after discharge, while the total score of FCTI in the control group decreased from (26.12±4.34) at enrollment to (12.52±3.60) at three months after discharge, and the total score of FCTI in both groups decreased over time. At one, two, and three months after discharge, the total FCTI score of the intervention group was lower than that of the control group, and the difference was statistically significant ( P<0.05). At three months after discharge, the incidence of complications in children with HETF in the intervention group was lower than that in the control group with a statistical difference ( P<0.05) . Conclusions:The program for improving care ability of caregivers for children with HETF based on timing theory is scientific and provides basis for the management of home tube feeding of children.

Objective:To describe the implementation status of home enteral nutrition (HEN) in pediatric patients, providing reference for the management of HEN in pediatric patients.Methods:This study was a cross-sectional study. From March 2020 to May 2021, convenience sampling was used to select 161 pediatric patients who were discharged from the Children's Hospital of Fudan University and underwent HEN as participants. The survey questionnaire was designed to collect clinical data based on the research purpose.Results:Among the 161 pediatric patients who underwent HEN, congenital malformations, digestive system diseases, neurological diseases, malignant tumors, and respiratory system diseases accounted for 38.5% (62/161), 21.7% (35/161), 19.3% (31/161), 11.2% (18/161), and 9.3% (15/161), respectively. A total of 120 pediatric patients were followed up and recorded with nutritional supplements, 49 pediatric patients received whole protein nutritional supplements, 19 received amino acid nutritional supplements, 16 received whole protein nutritional supplements with homemade homogenization, 15 received short peptide nutritional supplements, seven received breast milk with whole protein nutritional supplements, five received homemade homogenization, five received animal milk, two received breast milk, and two received amino acid nutritional supplements with homemade homogenization. A total of 118 pediatric patients were followed up with tube feeding, including 107 cases using intermittent feeding, nine cases using continuous feeding, and two cases using intermittent combined continuous feeding. There were 46 children with tube slippage, nine cases of vomiting, six cases of tube blockage, three cases of abdominal pain and bloating, two cases of diarrhea, one case of nasal redness, one case of aspiration pneumonia, and one case of exudation around the stoma. After a short-term HEN, 74 cases continued to receive tube feeding, 49 cases were successfully removed from the tube and switched to oral feeding, three cases were switched to tube and oral combined feeding, five cases died due to severe illness.Conclusions:Pediatric patients undergoing HEN have a wide range of diseases and a high incidence of tube slippage. Education should be provided to family caregivers to enhance their ability to identify and handle complications, as well as to make correct choices in feeding formulations and methods. We should also establish a sound follow-up system, closely monitor the nutritional status of pediatric patients, and actively assist in preventing complications.

OBJECTIVE To evaluate the efficacy and safety of antibody-drug conjugates （ADC） in the treatment of breast cancer， so as to provide an evidence-based reference for clinical medication. METHODS Retrieved from CNKI， Wanfang database， VIP， PubMed， the Cochrane Library， Embase， and Web of Science， randomized controlled trials （RCTs） about trastuzumab emtansine， trastuzumab deruxtecan and sacituzumab govitecan （trial group） versus chemotherapy or other anti-tumor drugs （control group）， were collected during the inception to April 2023. After screening the literature， extracting data， and evaluating the quality of the literature， a meta-analysis was conducted by using RevMan 5.4.1 software. RESULTS A total of 8 RCTs were included， with a total of 5 577 patients. The results of the meta-analysis showed that the progression-free survival （PFS） [HR＝0.76， 95%CI （0.69， 0.83）， P＜0.000 01]， overall survival （OS） [HR＝0.87， 95%CI （0.81， 0.93）， P＜0.000 1]， and clinical benefit rate （CBR） [OR＝2.70， 95%CI （1.15， 6.33）， P＝0.02] of the trial group were significantly higher than control group. There was no statistically significant difference in objective response rate （ORR） between the two groups [OR＝2.34， 95%CI （0.59， 9.33）， P＝0.23]. The results of subgroup analysis showed that the PFS of HER2-positive patients and HER2-negative patients， and the OS of HER2-positive patients in the trial group were significantly higher than control group （P＜0.05）. The incidence of anemia and increase of aspartic acid transaminase （AST） in the trial group was significantly higher than control group （P＜0.05）. The results of sensitivity analysis showed that the results obtained with PFS， OS， and ORR as indicators were relatively robust， while the results obtained with CBR as indicators lacked robustness. CONCLUSIONS ADC drugs have significant effects on breast cancer， but will increase the risk of anemia and elevated AST.

Objective:To investigate the efficacy of different preferred thrombectomy strategies for embolic acute vertebrobasilar artery occlusion (AVBAO).Methods:Forty-four patients with embolic AVBAO who underwent endovascular treatment in Department of Neurology, Nanyang Central Hospital from January 2019 to June 2021 were included in the study. Patients were divided into stent-retriever thrombectomy group ( n=27) and aspiration thrombectomy group ( n=17) according to different preferred thrombectomy strategies. Modified Rankin scale (mRS) was used to evaluate the prognoses of these patients 90 d after surgery; the differences of clinical data, surgery-related characteristics, prognoses and complications between the two groups were compared. Results:There was no significant difference between the 2 groups in terms of time from onset to puncture, sites of target vessel occlusion, proportion of patients accepted intraoperative remedial measures, and successful recirculation rate of target vessels ( P>0.05). Compared with the aspiration thrombectomy group, the stent-retriever thrombectomy group had significantly decreased utilization rate of middle catheters, significantly increased retrieval attempts in thrombectomy, statistically lower re-recanalization rate of first-time thrombectomy on the target vessels, significantly longer time from puncture to re-recanalization, and significantly higher incidence of new embolism ( P<0.05). There was no significant difference between the 2 groups in incidences of vascular rupture and postoperative spontaneous intracerebral hemorrhage (sICH), and good prognosis rate 90 d after surgery ( P>0.05). Conclusion:For embolic AVBAO patients, similar recanalization and short-term good prognosis can be obtained by aspiration thrombectomy to those by stent-retriever thrombectomy; besides that, aspiration thrombectomy has advantages as shorter recanalization time, less new embolic complications and higher re-recanalization rate of first-time thrombectomy.

Objective:To analyze the characteristics of clinical and laboratory indexes in patients with liver disease with positive anti-liver cytosol antibody type 1 (anti-LC1), in order to provide references for clinical and differential diagnosis.Methods:The clinical data of 23 832 inpatients and outpatients with positive anti-LC1 autoantibodies detected in routine autoantibody test from January 2010 to January 2020 were retrospectively analyzed, and their clinical and laboratory indexes were compared. Western blotting was used to detect anti-LC1, anti-soluble liver antigen antibody (anti-SLA), anti-glycoprotein 210 antibodies and anti-nucleosome 100 antibodies. Indirect immunofluorescence assay was used to detect anti-nuclear antibody (ANA), anti-mitochondrial antibody, anti-Smooth muscle antibody (ASMA), anti-liver and kidney microsomal antibody (anti-LKM) and other autoantibodies. Normally distributed measurement data between the two groups were compared by independent-sample t-test, and the multiple groups comparison were compared by one-way analysis of variance. Non-normally distributed measurement data were compared by non-parametric rank sum test.Results:38 anti-LC1 positive patients were detected in 23832 autoantibody tests. The age of initial diagnosis ranged from 11.0 to 84.0 (50.6 ± 16.0) years. There were 8 males (21.1%) and 30 females (78.9%). A total of 31 cases (81.6%) were positive for anti-LC1 and ANA, and the dominant karyotype was speckled pattern, accounting for 54.8%. Five cases (13.2%) were positive for ASMA, and no simultaneous positive with anti-LKM or anti-SLA. Among the 38 anti-LC1 positive patients, 9 were diagnosed with autoimmune hepatitis (AIH), 6 with possible AIH, 6 with primary biliary cholangitis (PBC), 8 with hepatitis B, 2 with hepatitis C, 1 with alcoholic liver disease, 2 with non-alcoholic fatty liver disease, 1 with drug-induced liver injury, 1 with hepatolenticular degeneration, and 2 with tumor. Confirmed and probable AIH cases accounted for 39.5% (15/38) of anti-LC1 positive cases. Among anti-LC1 positive patients, 47.4% (18/38) had entered the stage of liver cirrhosis. AIH group globulin level was higher than HBV group ( P = 0.006) and other disease groups ( P = 0.001). AIH group IgG level was higher than PBC group ( P = 0.027), HBV group ( P = 0.009) and other disease groups ( P = 0.004). the of the PBC group IgM level was higher than AIH group ( P = 0.003), HBV group ( P = 0.003) and other disease groups ( P = 0.006). Conclusion:Anti-LC1 is not only detected in AIH, but also observed in patients with primary biliary cholangitis, hepatitis B and C, alcoholic and non-alcoholic liver disease, drug-induced liver injury, hereditary metabolic liver disease and tumor. In addition, it is mainly female gender dominance and nearly half of ANA-positive young, middle-aged and elderly patients develop liver cirrhosis. For the diagnosis of type 2 autoimmune hepatitis, whether anti-LC1 is a specific antibody needs further research, but if AIH is highly suspected, this antibody can be used as a substitute.

Objective: To understand the characteristics and clinical significance of anti-soluble liver antigen antibody (anti-SLA) in patients with liver diseases. Methods: Serum samples from seventy-seven patients with anti-SLA were collected from Beijing You'An Hospital during the period between January 2010 and December 2018. Anti-SLA, anti-liver cytosol type 1 antibody (anti-LC1), anti-glycoprotein 210 antibody(anti-gp210) and anti-nuclear body protein sp100 antibody(anti-sp100) were detected by immunoblotting; indirect immunofluorescence assay used for detecting anti-nuclear antibody (ANA), anti-mitochondrial antibody (AMA), anti-smooth muscle antibody (SMA), and anti-liver kidney microsome antibody (anti-LKM). One-way analysis of variance was used to compare the ages of different anti-SLA groups. The non-parametric rank sum test was used to compare the liver function indexes and immunoglobulins in different intensity groups of anti-SLA. P<0.05 was considered statistically significant. Further comparisons were made between the two groups, the correction level α′=0.008 3, P<0.008 3 was considered statistically significant. Results: The average age of 77 anti-SLA positive patients was (52.50±1.25) years old, 70 females (90.9%) and 7 males (9.1%). 80.5% of anti-SLA-positive patients (62/77 cases) were strongly positive at the time of initial diagnosis (+++ to ++++).The Alanine aminotransferase (ALT) level in the SLA++ group was higher than that in the SLA++++ group (232.7 U/L vs 65.6 U/L,χ²=7.751,P=0.005) and the immunoglobulin M(IgM) level in the SLA+++ group was lower than that in the SLA++++ group (1 270 mg/L vs 2 270 mg/L,χ²=8.337,P=0.004).There was no significant difference in age, other liver function and immunological indicators among the different groups.Seventy cases (90.9%) were both anti-SLA and ANA positive, 13 cases (16.9%) were positive with SMA, and none positive with anti-LKM and anti-LC1. Among anti-SLA positive patients, 58 cases were diagnosed with autoimmune hepatitis (AIH), 12 were AIH/primary biliary cholangitis (PBC) overlap syndrome (OS), 2 were drug-induced liver injury, 2 were chronic hepatitis B, and 3 were hepatitis A, hepatitis E and acquired immune deficiency syndrome (AIDS) with liver injury, respectively.Cases of AIH and AIH/PBC OS accounted for 90.9% (70/77 cases) of anti-SLA-positive patients, and 5 of 7 patients diagnosed with non-AIH (and OS) had elevated IgG, showing AIH feature.92.3% (12/13 cases) of anti-SLA with high titers of AMA were diagnosed as AIH/PBC overlap syndrome. Of the 77 anti-SLA-positive patients, 28 (36.4%) had advanced or end-stage liver disease, including decompensated cirrhosis (22 cases), chronic acute liver failure (4 cases), and liver transplantation (1 case) and death from liver failure (1 case). Conclusions Anti-SLA has high diagnostic specificity for AIH;anti-SLA positive in patients with PBC should be an important biomarker for the diagnosis of AIH/PBC overlap syndrome.

Objective: To explore clinical features and severity of chronic graft- versus- host disease (cGVHD) after chemotherapy plus donor lymphocyte infusion (Chemo-DLI) in a consecutive cohort of acute leukemia patients who were minimal residual disease (MRD) positive after allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: The global scoring system proposed by National Institutes of Health (NIH) Consensus Conference was used to identify the characteristics and severity of cGVHD in patients who MRD positive after Chemo-DLI. Results: 54 (59.3%) patients were diagnosed with cGVHD after Chemo-DLI, with the median time of onset of 70 (13-504) days. There were 6 cases (6.6%) of mild cGVHD, 21 cases (23.1%) of moderate cGVHD and 27 cases (29.7%) of severe cGVHD.The 5-year cumulative incidence of relapse after Chemo-DLI was 61.9% (95%CI 45.3%-78.5%) , 15.1% (95%CI 1.1%-29.1%) , and 26.6% (95%CI 9.2%-44.0%) (χ²=18.901, P<0.001) in non-cGVHD, mild to moderate cGVHD, and severe cGVHD groups, respectively. The 5-year cumulative incidence of relapse after Chemo-DLI was 61.9% (95%CI 45.3%-78.5%) , 19.9% (95%CI 8.1%-31.7%) , and 28.6% (95%CI 0.0%-65.0%) (χ²=18.307, P<0.001) in non-cGVHD, classical cGVHD, and overlap syndrome groups, respectively. cGVHD was not associated with non-relapse morality after Chemo-DLI. Probabilities of 5-year leukemia-free survival (LFS) after Chemo-DLI were 24.0% (95%CI 9.1%-38.9%) , 77.2% (95%CI 60.8%-93.6%) , and 64.9% (95%CI 45.7%-84.1%) (χ²=24.447, P<0.001) in non-cGVHD, mild to moderate cGVHD, and severe cGVHD groups, respectively. Probabilities of 5-year LFS after Chemo-DLI were 24.0% (95%CI 9.1%-38.9%) , 75.5% (95%CI 62.7%-88.3%) , and 42.9% (95%CI 1.8%-84.0%) (χ²=25.665, P<0.001) in non-cGVHD, classical cGVHD, and overlap syndrome groups, respectively. Probabilities of 5-year overall survival (OS) after Chemo-DLI were 50.0% (95%CI 31.1%-68.9%) , 87.9% (95%CI 74.7%-100.0%) , and 71.0% (95%CI 52.0%-90.0%) (χ²=9.517, P=0.009) in non-cGVHD, mild to moderate cGVHD, and severe cGVHD groups, respectively. Probabilities of 5-year OS after Chemo-DLI were 50.0% (95%CI 31.1%-68.9%) , 83.9% (95%CI 72.8%-95.0%) , and 51.4% (95%CI 6.2%-96.6%) (χ²=10.673, P=0.005) in non-cGVHD, classical cGVHD, and overlap syndrome groups, respectively. In multivariate analysis, patients receiving allo-HSCT in first complete remission stage and classical cGVHD after Chemo-DLI were associated with lower relapse risk and better survival. Conclusions These findings highlight the close relation between cGVHD and the graft-versus-leukemia effect in patients who were MRD positive and received Chemo-DLI after allo-HSCT. However, overlap syndrome could not improve the clinical outcomes of these patients.

OBJECTIVETo explore the differential characteristics of the AMA-M2 autoantibody in patients with primary biliary cirrhosis (PBC) and non-PBC patients.

METHODSPatients with abnormal liver function at the Capital Medical University affiliated to Beijing You-an Hospital were enrolled in this study between January 2011 and December 2013. Serum levels of ANA, AMA and AMA-M2 were detected by indirect fluorescence assay and enzyme-linked immunosorbent assay. The patients' clinical data was obtained for retrospective analysis. Statistical analyses were performed using the SPSS 16.0 software. Enumeration data have been presented as numbers and percentages, and were analyzed using the chi-square test and one-way ANOVA test.

RESULTSOf the 5315 patients with abnormal liver function, 15.3% (811/5315) were AMA-M2 positive patients; among those 811 patients, 78.4% (636) had PBC, 4.4% (36) had PBC overlapping with autoimmune hepatitis (AIH), 4.4% (36) had drug-induced liver injury, 6.5% (53) had hepatitis B, 3.3% (27) had hepatitis C, 0.6% (5) had hepatitis E, 0.9% (7) had alcoholic liver disease, 0.5% (4) had non-alcoholic fatty liver, 0.8% (6) had primary hepatic carcinoma, and 0.1% (1) had infectious mononucleosis. Serum AMA-M2 level was significantly higher in the PBC patients (vs. other groups, P less than 0.001) with the exception of the patients with PBC/AIH overlap syndrome. Among the 811 patients with AMA-M2 positivity, 88.5% (718) showed AMA positivity and 91.1% (739) showed ANA positivity. Serum alanine transferase (ALT) and aspartate transferase (AST) levels were significantly higher in the drag-induced liver injury patients (527.74+/-684.65 U/L, 490.60+/-716.89 U/L) and the hepatitis E patients (1015.94 ± 165.55 U/L, 665.4 ± 297.14 U/L) than in the PBC patients (96.02 ± 115.56 U/L, 94.82 ± 83.32 U/L) (ALT: F =8.041, P < 0.001, P < 0.001; AST: F =8.066, P < 0.001, P < 0.001). Serum alkaline phosphatase (ALP; 265.16 ± 179.08 U/L) and glutamyl transferase (GGT; 332.02 ± 279.29 U/L) were significantly higher in the PBC patients than in the hepatitis B patients (135.35 ± 123.17 U/L, 140.27 ± 229.24 U/L) and the hepatitis C patients (85.65 ± 27.77 U/L, 92.70 ± 125.72 U/L) (ALP: F=3.911, P =0.01, P=0.001; GGT: F=4.081, P <0.001, P < 0.001). The serum IgM level was significantly higher in the PBC patients (4.60 ± 2.67 g/L) than in the patients with drug-induced liver injury (1.76 ± 1.15 g/L), hepatitis B (2.02 ± 1.41 g/L), hepatitis C (1.48 ± 0.92 g/L), hepatitis E (1.40 ± 0.68 g/L), alcoholic liver disease (1.57 ± 1.07 g/L), non-alcoholic fatty liver (1.05 ± 0.72 g/L), and primary hepatic carcinoma (2.64 ± 2.26 g/L) (F=16.83, P < 0.001, P < 0.001, Probability value < 0.001, Probability value < 0.05, Probability value < 0.01, Probability value < 0.05 respectively).

CONCLUSIONAlthough detection of serum AMA-M2 is an important feature of PBC diagnostic testing,there is a high ratio of serum AMA-M2 detected in patients with drug-induced liver injury, hepatitis B, C and E, alcoholic liver disease, non-alcoholic fatty liver,and primary hepatic carcinoma. The AMA-M2 positive non-PBC patients still require close observation to watch for future development of PBC.

Autoantibodies ; Beijing ; Carcinoma, Hepatocellular ; Chemical and Drug Induced Liver Injury ; Enzyme-Linked Immunosorbent Assay ; Hepatitis B ; Hepatitis C ; Hepatitis, Autoimmune ; Humans ; Liver Cirrhosis, Biliary ; Liver Diseases, Alcoholic ; Liver Function Tests ; Liver Neoplasms ; Retrospective Studies