Purpose: This study aims to evaluate the efficacy and safety of a new combination treatment of vinorelbine and pyrotinib in human epidermal growth factor receptor 2 (HER2)–positive metastatic breast cancer (MBC) and provide higher level evidence for clinical practice. Materials and Methods: This was a prospective, single-arm, phase 2 trial conducted at three institutions in China. Patients with HER2-positive MBC, who had previously been treated with trastuzumab plus a taxane or trastuzumab plus pertuzumab combined with a chemotherapeutic agent, were enrolled between March 2020 and December 2021. All patients received pyrotinib 400 mg orally once daily plus vinorelbine 25 mg/m2 intravenously or 60-80 mg/m2 orally on day 1 and day 8 of 21-day cycle. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included the objective response rate (ORR), disease control rate (DCR), overall survival, and safety. Results: A total of 39 patients were enrolled. All patients had been pretreated with trastuzumab and 23.1% (n=9) of them had accepted trastuzumab plus pertuzumab. The median follow-up time was 16.3 months (95% confidence interval [CI], 5.3 to 27.2), and the median PFS was 6.4 months (95% CI, 4.0 to 8.8). The ORR was 43.6% (95% CI, 27.8% to 60.4%) and the DCR was 84.6% (95% CI, 69.5% to 94.1%). The median PFS of patients with versus without prior pertuzumab treatment was 4.6 and 8.3 months (p=0.017). The most common grade 3/4 adverse events were diarrhea (28.2%), neutrophil count decreased (15.4%), white blood cell count decreased (7.7%), vomiting (5.1%), and anemia (2.6%). Conclusion Pyrotinib plus vinorelbine showed promising efficacy and tolerable toxicity as second-line treatment in patients with HER2-positive MBC.

Objective:To explore the feasibility of deep learning technology for renal artery recognition in retroperitoneal laparoscopic renal surgery videos.Methods:From January 2020 to July 2021, the video data of 87 cases of laparoscopic retroperitoneal nephrectomy, including radical nephrectomy, partial nephrectomy, and hemiurorectomy, were retrospectively analyzed. Two urological surgeons screened video clips containing renal arteries. After frame extraction, annotation, review, and proofreading, the labeled targets were divided into training set and test set by the random number table in a ratio of 4∶1. The training set was used to train the neural network model. The test set was used to test the ability of the neural network to identify the renal artery in scenes with different difficulties, which was uniformly transmitted to the YOLOv3 convolutional neural network model for training. According to the opinion of two senior doctors, the test set was divided into high, medium, and low discrimination of renal artery and surrounding tissue. High identification means a clean renal artery and a large exposed area. For middle recognition degree, the renal artery had a certain degree of blood immersion, and the exposed area was medium. Low identification means that the exposed area of the renal artery was small, often located at the edge of the lens, and the blood immersion was severe, which may lead to lens blurring. In the surgical video, the annotator annotated the renal artery truth box frame by frame. After normalization and preprocessing, all images were input into the neural network model for training. The neural network output the renal artery prediction box, and if the overlap ratio (IOU) with the true value box was higher than the set threshold, it was judged that the prediction was correct. The neural network test results of the test set were recorded, and the sensitivity and accuracy were calculated according to IOU.Results:In the training set, 1 149 targets of 13 videos had high recognition degree, 1 891 targets of 17 videos had medium recognition degree, and 349 targets of 18 videos had low recognition degree. In the test set, 267 targets in 9 videos had high recognition degree, 519 targets in 11 videos had medium recognition degree, and 349 targets in 18 videos had low recognition degree. When the IOU threshold was 0.1, the sensitivity and accuracy were 52.78% and 82.50%, respectively. When the IOU threshold was 0.5, the sensitivity and accuracy were 37.80% and 59.10%, respectively. When the IOU threshold was 0.1, the sensitivity and accuracy of high, medium and low recognition groups were 89.14% and 87.82%, 45.86% and 78.03%, 32.95%, and 76.67%, respectively. The frame rate of the YOLOv3 algorithm in real-time surgery video was ≥15 frames/second. The false detection rate and missed detection rate of neural network for renal artery identification in laparoscopic renal surgery video were 47.22% and 17.49%, respectively (IOU=0.1). The leading causes of false detection were similar tissue and reflective light. The main reasons for missed detection were image blurring, blood dipping, dark light, fascia interference, or instrument occlusion, etc.Conclusions:Deep learning-based renal artery recognition technology is feasible. It may assist the surgeon in quickly identifying and protecting the renal artery during the operation and improving the safety of surgery.

Objective:To evaluate the cost effectiveness of primary prophylaxis (PP) with pegylated recombinant human granulocyte colony stimulating factor (PEG-rhG-CSF), PP with recombinant human granulocyte colony stimulating factor (rhG-CSF) and no prophylaxis in women with early-stage breast cancer in China.Methods:Two phase Markov models were constructed for a hypothetical cohort of patients aged 45 with stage Ⅱ breast cancer. The first phase modelled costs and outcomes of 4 cycles docetaxel combined with cyclophosphamide [TC×4, febrile neutropenia (FN) risk>20%] chemotherapy, which assumptions based on literature reviews, including FN rates [base-case (deterministic sensitivity analysis range), 0.29 (0.24-0.35)] and related events [FN case-fatality, 3.4 (2.7-4.1)]. Second phase modelled the long term survival which was link with the relative dose intensity (RDI) [mortality hazard ratio ( HR) of RDI < 85% vs ≥85%, 1.45 (1.00-2.32)]. Clinical effectiveness, therapeutic costs, and economic utilities were estimated from peer-reviewed publications and expert opinions in case of unavailability of published evidences. Results:Compared to rhG-CSF PP and no prophylaxis, the cost of PEG-rhG-CSF PP increased to 5 208.19 RMB and 5 222.73 RMB, respectively. The quality-adjusted life-years (QALYs) enhanced to 0.066 and 0.297, respectively. Accordingly, the incremental cost effectiveness ratios (ICERs) are 79 146.3 RMB and 17 558.77 RMB per QALY, which were both below the willingness to pay (WTP) threshold of three times GDP per capita (18, 000 RMB) recommended by the WHO. Sensitivity analysis suggested that the more clinically effective the primary prophylaxis with PEG-rhG-CSF is, the more cost-effective primary prophylaxis with PEG-rhG-CSF will be. And the lower the mortality HR of RDI<85% vs ≥85% is, the more cost-effective primary prophylaxis with PEG-rhG-CSF will be. Conclusion:Although the cost of PP PEG-rhG-CSF is higher, considering the additional benefits, the administrating of PP PEG-rhG-CSF is likely to be a cost-effective alternative to PP rhG-CSF and no prophylaxis in patients with early stage breast cancer whose FN risks are more than 20% in China.

Objective:To evaluate the cost effectiveness of primary prophylaxis (PP) with pegylated recombinant human granulocyte colony stimulating factor (PEG-rhG-CSF), PP with recombinant human granulocyte colony stimulating factor (rhG-CSF) and no prophylaxis in women with early-stage breast cancer in China.Methods:Two phase Markov models were constructed for a hypothetical cohort of patients aged 45 with stage Ⅱ breast cancer. The first phase modelled costs and outcomes of 4 cycles docetaxel combined with cyclophosphamide [TC×4, febrile neutropenia (FN) risk>20%] chemotherapy, which assumptions based on literature reviews, including FN rates [base-case (deterministic sensitivity analysis range), 0.29 (0.24-0.35)] and related events [FN case-fatality, 3.4 (2.7-4.1)]. Second phase modelled the long term survival which was link with the relative dose intensity (RDI) [mortality hazard ratio ( HR) of RDI < 85% vs ≥85%, 1.45 (1.00-2.32)]. Clinical effectiveness, therapeutic costs, and economic utilities were estimated from peer-reviewed publications and expert opinions in case of unavailability of published evidences. Results:Compared to rhG-CSF PP and no prophylaxis, the cost of PEG-rhG-CSF PP increased to 5 208.19 RMB and 5 222.73 RMB, respectively. The quality-adjusted life-years (QALYs) enhanced to 0.066 and 0.297, respectively. Accordingly, the incremental cost effectiveness ratios (ICERs) are 79 146.3 RMB and 17 558.77 RMB per QALY, which were both below the willingness to pay (WTP) threshold of three times GDP per capita (18, 000 RMB) recommended by the WHO. Sensitivity analysis suggested that the more clinically effective the primary prophylaxis with PEG-rhG-CSF is, the more cost-effective primary prophylaxis with PEG-rhG-CSF will be. And the lower the mortality HR of RDI<85% vs ≥85% is, the more cost-effective primary prophylaxis with PEG-rhG-CSF will be. Conclusion:Although the cost of PP PEG-rhG-CSF is higher, considering the additional benefits, the administrating of PP PEG-rhG-CSF is likely to be a cost-effective alternative to PP rhG-CSF and no prophylaxis in patients with early stage breast cancer whose FN risks are more than 20% in China.

Objective To investigate the clinical effect of paclitaxel coated balloon in the treatment of symptomatic lower extremity arteriosclerosis obliterans.Methods From January 2016 to April 2017,64 patients with symptomatic lower limb arteriosclerosis obliterans ( ASO ) of femoral and popliteal artery stenosis admitted to Chongming Branch Xinhua Hospital affiliated to Shanghai Jiaotong University School of Medicine were selected as the research subjects.According to the principle of randomization, they were divided into two groups, 32 cases in each group.In the drug?coated group, ordinary balloon was pre?expanded,and then paclitaxel drug?coated balloon was used to expand.If there were still retraction and stenosis of diseased vessels, which affected the blood flow of lower limbs, remedial stents were implanted.Bare stent group used a slightly smaller balloon to pre?expand superficial femoral artery and then release the stent.After one year follow?up, the changes of ankle?brachial index ( ABI), restenosis rate of target lesion vessels, Rutherford grading changes, clinical drive target vessel revascularization rate, perioperative period,death rate of patients during follow?up period, amputation rate and complication rate were observed.Results There were no amputations or deaths in the whole group during the perioperative period and follow?up.The incidence of complications in the drug?coated group was 3.1%( 1／32 ), significantly lower than that in the bare stent group 18.8%( 6／32) ( χ2 ＝4.010, P＝ 0.045).Before treatment,the ABI of patients in drug?coated group and bare stent group at 6 months and 12 months after treatment were significantly different ( Finter?group ＝ 7.028, Pinter?group ＝ 0.024, Fintra?group ＝ 219.028, Pintra?group＝0.000,Finteraction＝350.028,Pinteraction＝0.000),and ABI of the two groups at 12 months after treatment were (0.73± 0.11) and ( 0.68 ± 0.09),respectively, the difference was statistically significant ( t＝1.990, P＝0.025).Six months after operation, the restenosis rates of target lesions in the two groups were 9.4%(3／32) and 15.6%(5／32), respectively, with no significant difference ( χ2 ＝0.571, P＝0.450); The restenosis rate of bare stent group was 37.5%(12／32) 12 months after operation,which was significantly higher than that of drug?coated group by 15.6%(5／32) (χ2＝3.925,P＝0.048).Clinical observation results showed that 12 months after operation,the target?lesion revascularization (TLR) of the drug?coated group was 3.1%(1／32) and that of the bare stent group was 9.4%(3／32),with no significant difference.Rutherford grading was improved in both groups(χ2＝1.067,P＞0.05). Conclusion Paclitaxel drug?coated balloon is safe and effective in the treatment of symptomatic lower limb arteriosclerosis obliterans,which is worthy of clinical application.

Objective: To evaluate the disinfection efficacy of peracetic acid disinfectant (type Ⅲ ) on gastrointestinal endoscopy. Methods: Endoscopes were disinfected respectively by 2% glutaraldehyde (GA group) and peracetic acid disinfectant (type Ⅲ ) (PAA group) according to the process by the 2016 version of "Regulation for cleaning and disinfection technique of flexible endoscope" , and then samples were collected through biopsy channel at the specified steps. The bacterial count and pathogenic bacteria of these samples were detected. Hepatitis B virus surface antigen (HBsAg), hepatitis C virus (HCV) antibody and Treponemia pallidum antibody (TP-Ab) were detected by chemiluminesent microparticle immunoassay (CMIA) in the PAA group. The PAA group were continuously sampled for 5 days. Results: A total of 56 gastroscopes and 16 colonoscopes were disinfected in the GA group, and 46 gastroscopes and 15 colonoscopes were disinfected in the PAA group. Compared with pre-disinfection, the bacterial count was both significantly reduced in the two groups after disinfection (P<0.05). The qualified rate of gastroscopes disinfection and total qualified rate of the PAA group were higher than those of the GA group [the qualified rate of gastroscopes: 97.83% (45/46) VS 92.86% (52/56), P>0.05; total qualified rate: 98.36% (60/61) VS 94.44% (68/72), P>0.05]. The qualified rate of colonoscopes in the two groups were both 100.00% (15/15, 16/16). After disinfecting by peracetic acid disinfectant (Type Ⅲ), HBsAg, anti-HCV and TP-Ab were negative. There were no significant differences on colonies number at different steps in a 5-day continuous sampling (P>0.05). Conclusion Peracetic acid disinfectant (type Ⅲ) can provide a satisfied disinfectant effect, and be applied in clinic to meet the requests of high-level disinfection for gastrointestinal endoscopy.

OBJECTIVETo explore the correlation between 13q33-q34 microdeletion and clinical phenotype.

METHODSRoutine chromosomal banding was performed to analyze the karyotype, while array-based comparative genomic hybridization (aCGH array) and single nucleotide polymorphism array(SNP array) were employed to investigate the genome copy number variations.

RESULTSThe karyotype of patient 1 was 46, XY, 9qh+,13qs. Patient 2 showed 46, XX, der (13). Patient 3 showed 46, XX, r(13) (p11.2q32) [43]/45, XX, 13[4]/46, XX, r(13;13) [2]/47, XX, 2r(13;13) [1]. Patient 4 did not undergo chromosome karyotyping analysis. Array analysis showed that four patients have different microdeletions in 13q33-34 region and had common features of 13q33-q34deletion including intellectual disability, facial dysmorphism, microcephaly, hypotonia, low birth weight and genital abnormality.

CONCLUSIONThe severity of phenotypes showed no correlation with the size of deletion in 13q33-q34. The lower percentage of patients with congenital heart disease suggested a complex pathogenesis of such disease. EFNB2, LIG4 and SOX1 in 13q33-34 region are promising candidates for mental retardation. LIG4 was also a likely candidate for microcephaly.

Child, Preschool ; Chromosome Banding ; methods ; Chromosome Deletion ; Chromosomes, Human, Pair 13 ; genetics ; Female ; Genetic Testing ; methods ; Humans ; Infant ; Intellectual Disability ; genetics ; Male

BACKGROUND: The animals commonly used to induce experimental allergic encephalomyelitis (EAE) in oversea laboratory are rodentia animals such as Lewis rats. But in China we are short of Lewis rats. The un-susceptive animal Wistar rats are inexpensive and plentiful. The adding of pertussis toxin may induce EAE successfully in EAE un-susceptive Wistar rats.OBJECTIVE: To investigate the influence of pertussis toxin injected atdifferent sites in inducing EAE model in un-susceptive Wistar rats.DESIGN: A randomized control animal experiment.SETTING: Institute of Brain Science, Shanxi Datong University.MATERIALS: The study was performed in the Institute of Brain Science of Shanxi Datong University from March to October in 2003. Fifty-eight und adjuvant (CFA) group (n=10).METHODS: Besides routine immunization, each rat in the foot dorsum EAE group and intraperitoneal EAE group was administrated with 005 mL pertussis toxin (containing 5.0×1010 thalli), which were given intraperitoneally and subcutaneously on one hind foot respectively, and the antigen in the CFA group was replaced by CFA.cidence rate and tine of atta ck: In the foot dorsum EAE group, the incidence of EAE was 87.5% (21/24), and the time of attack was at (10.25 ±1.67) days after immunization, which were significantly different from those in the intraperitoneal EAE group [35.7% (9/24), (14.8±l.79) days, P sum EAE group, the change of body mass was (-16.00±7.30) g and the symptomscpre was 3.4±0.7, and those in the intraperitoneal EAE group Therewere no or little infiltration of inflammatory cells in the encephalon and spinal cord of CFA rats. In the EAE rats, there were inflammatory cells infiltrated in the boundary of white matter and gray matter of lumbar intumescence, spinal pia mater, spinal parenehyma, and the boundary of cerebral cortex and medulla, even deep medulla, meninges and around lateral ventricle. There were also mild inflammations in the cerebellum,brainstem and optic chiasma, which were concordant with the observed asynchronism, tic, etc. Hematoxylin and eosin (HE) staining displayed that the infiltrated mononuclear cells assembled in perivascular spaces, which were identified by morphological criteria as lymphocyte and macrophages.Forming typical muff-like changes, the inflammation was less severe in intraperitoneal EAE group than in subcutaneous foot dorsum EAE group.CONCLUSION: The EAE model induced in Wistar rats by Pertussis toxin administered subcutaneously on foot dorsum has the representative course of diseases, pathology change and clinical manifestation and the incidence of diseases is high and the cost is low. So it is a more ideal EAE model inducing method.

China ; Humans ; Neurology ; Pediatrics

BACKGROUNDTo explore the clinical and pathological characteristics and pathogenesis of autoimmunohepatitis (AIH).

METHODSThe serum and liver biopsy specimens and clinical data of 26 cases with patients with AIH were analyzed and scored according to the criteria of International autoimmune hepatitis (IAIHG, 1999). The changes of dendritic cells (DC) in the liver tissues were observed with a panel of DC markers (CD-80/B7-1, CD-86/B7-2, CD-1a and HLA-DR) and immunohistochemistry, and the activation of hepatic stellate cells (HSC) and the expression of TGF-alpha were also detected. Liver tissue specimens from 10 patients with chronic viral hepatitis B and C respectively and 5 normal liver specimens were chosen as controls.

RESULTSMean aggregate scores of 26 AIH cases, including 21 cases of type B (80.8%) and 5 cases of type C (19.2%), which were 18.6 +/- 1.4 and 19.1 +/- 2.1 respectively. There were significant differences between the type B and type C in the average age levels of serum ALT and AST, and alpha-Glo (P <0.001 or P< 0.01 or P <0.05). Histological features of all the AIH liver tissues showed the lesions of chronic active hepatitis such as interface hepatitis/piecemeal necrosis (100%), obvious lobular inflammation (type B 95.2%, type C 100%), bridging necrosis (57.1% type B, 80.0% type C, P<0.05), rosetting of liver cells (71.4% type B, 100% type C, P<0.01), central lobular confluent necrosis (33.3% type B, 80.0% type C, P<0.001), predominant plasmacytic infiltration (type B 95.2%, type C 20.0%, P<0.001). The rates of increased and concentrated DC in the portal and lobular areas, especially in the active lesions in type B and type C AIH were 85.7% (18/21) and 5/5 respectively. It was found that DC and lymphocytes surrounded the hepatocytes which partly expressed HLA-DR antigen, while there were no or a few HLA-DR positive hepatocytes in controls. Meanwhile, the number of alpha-SMA positive HSC and the expression of TGF- were obviously increased in AIH liver tissues.

CONCLUSIONSSeveral clinical and pathological features of AIH were identified in this study. As an antigen-presenting cell, DC might play an important role in the pathogenesis of AIH. In China, sub-type B of AIH might be more frequent than sub-type C and there were differences in clinical aspects, serology and pathology between the two types.

Adolescent ; Adult ; Child ; Dendritic Cells ; immunology ; Female ; Hepatitis, Autoimmune ; blood ; pathology ; Humans ; Liver ; pathology ; Male ; Middle Aged