Background and purpose:For patients with human epidermal growth factor receptor 2(HER2)-positive metastatic breast cancer,trastuzumab treatment can prolong the overall survival and significantly improve the prognosis of patients.However,the reference original research trastuzumab(Herceptin?)is more expensive.Biosimilars have comparable efficacy and safety profiles while increasing patient access to treatment.This clinical trial aimed to evaluate the efficacy,pharmacokinetics,safety and immunogenicity of the trastuzumab biosimilar AK-HER2 compared to trastuzumab(Herceptin?)in patients with HER2-positive metastatic breast cancer.Methods:This multi-center,randomised,double-blind phase Ⅲ clinical trial was conducted in 43 subcenters in China.This study complied with the research protocol,the ethical principles stated in the Declaration of Helsinki and the quality management standards for drug clinical trials.It was approved by the hospital's medical ethics committee.The clinical trial registration agency is the State Food and Drug Administration(clinical trial approval number:2015L04224;clinical trial registration number:CTR20170516).Written informed consent was obtained from subjects before enrollment.Enrolled patients were randomly assigned to the AK-HER2 group and the control group,respectively receiving AK-HER2 or trastuzumab(initial loading dose 8 mg/kg,maintenance dose 6 mg/kg,every 3 weeks as a treatment cycle,total treatment time is 16 cycles)in combination with docetaxel(75 mg/m2,treatment duration is at least 9 cycles).The primary endpoint of this clinical trial was the objective response rate(ORR9)between the AK-HER2 group and the control group in the 9th cycle.Secondary efficacy endpoints included ORR16,disease control rate(DCR),clinical benefit rate(CBR),progression-free survival(PFS)and 1-year survival rate.In this study,100 subjects(AK-HER2 group to control group=1:1)were randomly selected for blood sample collection after the 6th cycle of medication,The collection time points were 45 minutes after infusion(the end of administration),4,8,24,72,120,168,336,and 504 hours after the end of administration.After collection,blood samples were analyzed by PK parameter set(PKPS).Other evaluation parameters included safety and immunogenicity assessment.Results:A total of 550 patients with HER2-positive metastatic breast cancer were enrolled in this clinical trial between Sep.2017 and Mar.2021.In the AK-HER2 group(n=237),129 subjects in the experimental group achieved complete response(CR)or partial response(PR),and the ORR9 was 54.4%.There were 134 subjects in the control group(n=241)who achieved CR or PR,and the ORR9 was 55.6%.The ORR9 ratio between the AK-HER2 group and the control group was 97.9%[90%confidence interval(CI):85.4%-112.2%,P=0.784],which was not statistically significant.In all secondary efficacy endpoints,no statistically significant differences were observed between the two groups.We conducted a mean ratio analysis of pharmacokinetics(PK)parameters between the AK-HER2 group and the control group,and the results suggested that the pharmacokinetic characteristics of the two drugs are similar.The incidence of treatment emergent adverse event(TEAE)leading to drug reduction or suspension during trastuzumab treatment was 3.6%(10 cases)in the AK-HER2 group and 8.1%(22 cases)in the control group.There was statistically significant difference between the two groups(P=0.027).The incidence rate was significantly lower in the AK-HER2 group than in the control group,and there was no statistically significant difference among the other groups.The differences in the positive rates of anti-drug antibodies(ADA)and neutralizing antibodies(NAB)between groups were of no statistical significance(P=0.385 and P=0.752).Conclusion:In patients with HER2-positive metastatic breast cancer,AK-HER2 was comparable to the trastuzumab(Herceptin?)in terms of drug efficacy,pharmacokinetics,safety and immunogenicity.

Objective To observe the value of quality control system based on artificial intelligence(AI)for improving imaging quality of chest CT.Methods Totally 1 726 CT images obtained from 415 patients were retrospectively collected,among which 1 414 images were used for convolutional neural network(CNN)training and the rest 312 images were used for validation.Precision,Recall,F1-Score,mean average precision(mAP)and intersection over union(IOU)of quality control system based on AI for chest CT scanning were calculated.Meanwhile,21 patients with unsatisfactory chest CT who would undergo re-examination were prospectively enrolled,and chest CT scanning with quality control system based on AI were performed.The results of 2 examinations were compared.Results Precision,Recall,F1-Score,mAP and IOU of quality control system based on AI for chest CT were all good.All 21 cases were diagnosed correctly with re-examination CT based on quality control system.Among 21 cases,the first CT misdiagnosed 19 cases,the displaying of the area,volume and display quality of pulmonary nodules were not significantly different,but the morphology,boundaries,spiny protrusions,vacuolar signs,inflatable bronchial signs of nodules as well as the thickened and twisted blood vessels were obviously different between 2 times examination.The first CT missed 1 case while correctly diagnosed 1 case.Conclusion The quality control system based on AI was helpful for improving imaging quality of chest CT and increasing diagnostic efficacy.

Objective:To explore potential predictors of refractory Mycoplasma pneumoniae pneumonia (RMPP) in early stage. Methods:The prospective multicenter study was conducted in Zhejiang, China from May 1 st, 2019 to January 31 st, 2020. A total of 1 428 patients with fever >48 hours to <120 hours were studied. Their clinical data and oral pharyngeal swab samples were collected; Mycoplasma pneumoniae DNA in pharyngeal swab specimens was detected. Patients with positive Mycoplasma pneumoniae DNA results underwent a series of tests, including chest X-ray, complete blood count, C-reactive protein, lactate dehydrogenase (LDH), and procalcitonin. According to the occurrence of RMPP, the patients were divided into two groups, RMPP group and general Mycoplasma pneumoniae pneumonia (GMPP) group. Measurement data between the 2 groups were compared using Mann-Whitney U test. Logistic regression analyses were used to examine the associations between clinical data and RMPP. Receiver operating characteristic (ROC) curves were used to analyse the power of the markers for predicting RMPP. Results:A total of 1 428 patients finished the study, with 801 boys and 627 girls, aged 4.3 (2.7, 6.3) years. Mycoplasma pneumoniae DNA was positive in 534 cases (37.4%), of whom 446 cases (83.5%) were diagnosed with Mycoplasma pneumoniae pneumonia, including 251 boys and 195 girls, aged 5.2 (3.3, 6.9) years. Macrolides-resistant variation was positive in 410 cases (91.9%). Fifty-five cases were with RMPP, 391 cases with GMPP. The peak body temperature before the first visit and LDH levels in RMPP patients were higher than that in GMPP patients (39.6 (39.1, 40.0) vs. 39.2 (38.9, 39.7) ℃, 333 (279, 392) vs. 311 (259, 359) U/L, both P<0.05). Logistic regression showed the prediction probability π=exp (-29.7+0.667×Peak body temperature (℃)+0.004×LDH (U/L))/(1+exp (-29.7+0.667×Peak body temperature (℃)+0.004 × LDH (U/L))), the cut-off value to predict RMPP was 0.12, with a consensus of probability forecast of 0.89, sensitivity of 0.89, and specificity of 0.67; and the area under ROC curve was 0.682 (95% CI 0.593-0.771, P<0.01). Conclusion:In MPP patients with fever over 48 to <120 hours, a prediction probability π of RMPP can be calculated based on the peak body temperature and LDH level before the first visit, which can facilitate early identification of RMPP.

Objective This study established a model of invasive Aspergillus niger lung disease in immunosuppressed rats to provide theoretical support for the pharmacodynamic evaluation of anti-invasive pulmonary aspergillosis drugs and mechanism studies.Methods Sixty SD rats were randomly divided into a normal control group;cyclophosphamide control group,and cyclophosphamide+fungal infection low,medium,and high dose groups,with 12 animals in each group.General clinical observations were performed daily,and the serum levels of immunoglobulin(Ig)G and IgM and galactomannan(GM)were detected by ELISA on the 3rd and 7th days of modeling.Simultaneously,the ratio of CD4+and CD8+cells,content of white blood cells(WBCs)and neutrophils(Neu)in peripheral blood,the Aspergillus niger load in alveolar lavage,and morphological changes to rat lung tissue were observed.Results Rats in the cyclophosphamide control and cyclophosphamide+fungal infection groups showed reduced voluntary activity and erect hair after modeling,and rats in the cyclophosphamide+fungal infection group also had shortness of breath and audible wet rhonchi in the lungs.Compared with the normal control group,rats in the cyclophosphamide control group showed significant reductions in the levels of CD4+,WBC,Neu,IgG,and IgM in the blood,and their proportion of CD8+cells was significantly higher(P＜0.05,P＜0.01).Compared with the cyclophosphamide control group,rats in the cyclophosphamide+fungal infection medium-and high-dose groups had significantly reduced blood levels of IgG,IgM,and CD4+cells(P＜0.05,P＜0.01);while the cyclophosphamide+fungal infection low-,medium-,and high-dose groups had significantly reduced blood levels of WBC and Neu(P＜0.05,P＜0.01).Additionally,rats in the cyclophosphamide+fungal infection medium-and high-dose groups had significantly increased blood CD8+cells(P＜0.05,P＜0.01),Blood GM levels and the alveolar lavage Aspergillus niger load were significantly increased in rats in the cyclophosphamide+fungal infection low-,medium-,and high-dose groups compared with the cyclophosphamide control group(P＜0.05,P＜0.01).The lung tissues of the cyclophosphamide+fungal infection low-,medium-,and high-dose groups showed mycelial distribution and destruction of alveolar epithelium,increase of bronchial epithelial cup cells in the alveoli,and infiltration of inflammatory cells,and the degree of lesions was positively correlated with the modeling dose.Conclusions In this study,we used Aspergillus niger combined with cyclophosphamide immunosuppressant to construct a model of invasive Aspergillus niger lung disease.The duration of the disease was positively correlated with the concentration of bacterial fluid and modeling time,confirming that cellular immunity plays an important role in the pathogenesis of the disease.At the same time,Ig can also affect the development of invasive pulmonary aspergillosis,and it is speculated that the pathogenesis may be related to the level of Ig produced by humoral immunity.

Objective:To observe the efficacy of cosmetic suturing techniques combined with topical recombinant human basic fibroblast growth factor (rh-bFGF) in repairing facial trauma.Methods:A prospective study was conducted on 140 patients with facial trauma admitted to the Department of Burn and Plastic Surgery, Northern Jiangsu People＇s Hospital from January to December 2022. Patients were divided into two groups based on different treatment methods using a random number table method: treatment group (70 cases), including 38 males and 32 females aged 3 to 54 (23.1±8.2) years, received cosmetic suturing techniques combined with topical rh-bFGF for wound repair; control group (70 cases), including 36 males and 34 females aged 2 to 49 (22.3±7.5) years, only received cosmetic suturing techniques for wound repair. Patients were followed up 2 weeks post-surgery to evaluate wound healing quality. Patient satisfaction was assessed using the visual analogue scale (VAS). Six months post-surgery, scar conditions were evaluated using the Vancouver scar scale (VSS).Results:In the treatment group, 65 cases were directly sutured, and 5 cases were repaired with skin flaps, with a first-class healing rate of 100% (70/70). In the control group, 66 cases were directly sutured, and 4 cases were repaired with skin flaps, with a first-class healing rate of 91.4% (64/70). The first-class healing rate in the treatment group was higher than that in the control group, with a statistically significant difference ( P=0.037). Two weeks post-surgery, the VAS score for surgical satisfaction in the treatment group was (1.13±0.52) scores, which was lower than that in the control group (2.56±1.32) scores, with a statistically significant difference ( P<0.001). Six months post-surgery, the VSS score for the treatment group was (2.49±1.27) scores, which was lower than that in the control group (4.67±1.93) scores, with a statistically significant difference ( P<0.001). Conclusions:In repairing facial trauma, the combination of cosmetic suturing techniques and topical rh-bFGF can improve wound healing quality, reduce wound scarring, and enhance patient satisfaction with surgery.

Objective:To assess the clinical effectiveness and safety of Omalizumab for treating pediatric allergic asthma in real world in China.Methods:The clinical data of children aged 6 to 11 years with allergic asthma who received Omalizumab treatment in 17 hospitals in China between July 6, 2018 and September 30, 2020 were retrospectively analyzed.Such information as the demographic characteristics, allergic history, family history, total immunoglobulin E (IgE) levels, specific IgE levels, skin prick test, exhaled nitric oxide (FeNO) levels, eosinophil (EOS) counts, and comorbidities at baseline were collected.Descriptive analysis of the Omalizumab treatment mode was made, and the difference in the first dose, injection frequency and course of treatment between the Omalizumab treatment mode and the mode recommended in the instruction was investigated.Global Evaluation of Treatment Effectiveness (GETE) analysis was made after Omalizumab treatment.The moderate-to-severe asthma exacerbation rate, inhaled corticosteroid (ICS) dose, lung functions were compared before and after Omalizumab treatment.Changes in the Childhood Asthma Control Test (C-ACT) and Pediatric Asthma Quality of Life Questionnaire (PAQLQ) results from baseline to 4, 8, 12, 16, 24, and 52 weeks after Omalizumab treatment were studied.The commodity improvement was assessed.The adverse event (AE) and serious adverse event (SAE) were analyzed for the evaluation of Omalizumab treatment safety.The difference in the annual rate of moderate-to-severe asthma exacerbation and ICS reduction was investigated by using t test.The significance level was set to 0.05.Other parameters were all subject to descriptive analysis.A total of 200 allergic asthma patients were enrolled, including 75.5% ( n=151) males and 24.5% ( n=49) females.The patients aged (8.20±1.81) years. Results:The median total IgE level of the 200 patients was 513.5 (24.4-11 600.0) IU/mL.Their median treatment time with Omalizumab was 112 (1-666) days.Their first dose of Omalizumab was 300 (150-600) mg.Of the 200 cases, 114 cases (57.0%) followed the first Omalizumab dosage recommended in the instruction.After 4-6 months of Omalizumab treatment, 88.5% of the patients enrolled ( n=117) responded to Omalizumab.After 4 weeks of treatment with Omalizumab, asthma was well-controlled, with an increased C-ACT score [from (22.70±3.70) points to (18.90±3.74) points at baseline]. Four-six months after Omalizumab administration, the annual rate of moderate-to-severe asthma exacerbation had a reduction of (2.00±5.68) per patient year( t=4.702 5, P<0.001), the median ICS daily dose was lowered [0 (0-240) μg vs. 160 (50-4 000) μg at baseline] ( P<0.001), the PAQLQ score was improved [(154.90±8.57) points vs. (122.80±27.15) points at baseline], and the forced expiratory volume in one second % predicted (FEV 1%pred) was increased [(92.80±10.50)% vs. (89.70±18.17)% at baseline]. In patients with available evaluations for comorbidities, including allergic rhinitis, atopic dermatitis or eczema, urticaria, allergic conjunctivitis and sinusitis, 92.8%-100.0% showed improved symptoms.A total of 124 AE were reported in 58 (29.0%) of the 200 patients, and the annual incidence was 0(0-15.1) per patient year.In 53 patients who suffered AE, 44 patients (83.0%) and 9 patients (17.0%) reported mild and moderate AE, respectively.No severe AE were observed in patients.The annual incidence of SAE was 0(0-1.9) per patient year.Most common drug-related AE were abdominal pain (2 patients, 1.0%) and fever (2 patients, 1.0%). No patient withdrew Omalizumab due to AE. Conclusions:Omalizumab shows good effectiveness and safety for the treatment of asthma in children.It can reduce the moderate-to-severe asthma exacerbation rate, reduce the ICS dose, improve asthma control levels, and improve lung functions and quality of life of patients.

Periarticular fracture of the shoulder is a common type of fractures in the elderly. Postoperative adverse events such as internal fixation failure, humeral head ischemic necrosis and upper limb dysfunction occur frequently, which seriously endangers the exercise and health of the elderly. Compared with the fracture with normal bone mass, the osteoporotic periarticular fracture of the shoulder is complicated with slow healing and poor rehabilitation, so the clinical management becomes more difficult. At present, there is no targeted guideline or consensus for this type of fracture in China. In such context, experts from Youth Osteoporosis Group of Chinese Orthopedic Association, Orthopedic Expert Committee of Geriatrics Branch of Chinese Association of Gerontology and Geriatrics, Osteoporosis Group of Youth Committee of Chinese Association of Orthopedic Surgeons and Osteoporosis Committee of Shanghai Association of Chinese Integrative Medicine developed the Chinese expert consensus on the diagnosis and treatment of osteoporotic periarticular fracture of the shoulder in the elderly ( version 2023). Nine recommendations were put forward from the aspects of diagnosis, treatment strategies and rehabilitation of osteoporotic periarticular fracture of the shoulder, hoping to promote the standardized, systematic and personalized diagnosis and treatment concept and improve functional outcomes and quality of life in elderly patients with osteoporotic periarticular fracture of the shoulder.

Objective:To investigate the inhibitory effect of deoxyribonuclease Ⅰ (DNaseⅠ) on Cutibacterium acnes biofilms. Methods:Cutibacterium acnes biofilms were constructed, and then were divided into 4 groups (negative control group, 5, 10 and 20 U/ml DNase Ⅰ groups) to be treated with DNase Ⅰ at different concentrations of 0, 5, 10 and 20 U/ml respectively. The biofilm viability was evaluated by tetrazolium salt colorimetric assay, the biofilm content was determined by crystal violet staining-based semi-quantitative analysis, the biofilm structure was observed by confocal laser scanning microscopy, and the live/dead bacteria ratio was calculated. One-way analysis of variance was used to analyze differences between groups. Results:After the treatment with DNase Ⅰ, the biofilm viability was significantly inhibited in the 5, 10 and 20 U/ml DNaseⅠ groups (1.882 ± 0.421, 1.653 ± 0.287, 1.473 ± 0.154, respectively) compared with the negative control group (2.668 ± 0.245), and the inhibitory effect was gradually enhanced with the increase in concentrations of DNase Ⅰ ( F = 9.68, P = 0.005). Crystal violet semi-quantitative analysis showed that the biofilm content was also significantly lower in the 5, 10 and 20 U/ml DNaseⅠ groups (1.039 ± 0.003, 0.489 ± 0.079, 0.147 ± 0.034, respectively) than in the negative control group (1.359 ± 0.071), and the higher the DNase Ⅰ concentration, the lower the biofilm content ( F = 174.40, P < 0.001). Confocal laser scanning microscopy showed that the biofilm structure was destroyed in the 5, 10 and 20 U/ml DNase Ⅰ groups compared with the negative control group, and the higher the DNase Ⅰ concentration, the more severe the destruction of biofilm structure. Additionally, the live/dead bacteria ratio was significantly lower in the 5, 10 and 20 U/ml DNaseⅠ groups (2.303 ± 0.457, 1.534 ± 0.526, 1.263 ± 0.354, respectively) than in the negative control group (4.475 ± 0.146), and the ratio decreased with the increase in concentrations of DNase Ⅰ ( F = 56.75, P < 0.000 1) . Conclusion:DNase Ⅰ had a destructive effect on the structure of Cutibacterium acnes biofilms, and could inhibit their viability.

Currently, cardiovascular disease has become a major threat to the health of Chinese residents, and prevention and control work is urgent. Self-determination theory is a widely applied theory of behavioral change, extensively used in the field of patient' rehabilitation. This article reviews the content, relevant theoretical models, motivation measurement methods, application status and influencing factors of self-determination theory in the rehabilitation of cardiovascular disease patients, so as to provide a basis for promoting the transition of cardiovascular disease patients to healthy lifestyles and maintaining healthy behavior.

The complexity of oral ulcerations poses considerable diagnostic and therapeutic challenges to oral specialists. The expert consensus was conducted to summarize the diagnostic work-up for difficult and complicated oral ulcers, based on factors such as detailed clinical medical history inquiry, histopathological examination, and ulceration-related systemic diseases screening. Not only it can provide a standardized procedure of oral ulceration, but also it can improve the diagnostic efficiency, in order to avoid misdiagnosis and missed diagnosis.
Consensus ; Humans ; Oral Ulcer/therapy*