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 any effect of a half palm ankle-foot orthosis and a hollow-heel ankle-foot orthosis on the gait of stroke survivors.Methods:The walking of twenty-five stroke survivors was quantified using a gait analysis system. They walked barefoot, wearing a half palm ankle-foot orthosis and wearing a hollow-heel ankle-foot orthosis. Walking speed, step frequency, duration of the swing phase on the healthy and affected sides, risk of falling and Timed Up and Go (TUG) test times were recorded and analyzed.Results:The average gait frequency when wearing the hollow-heel ankle-foot orthosis was significantly faster than that in the other two conditions. The gait asymmetry coefficient was significantly different when the subjects wore the hollow-heel ankle-foot orthosis compared with walking barefoot. Compared with being barefoot, the average TUG time was significantly shorter when wearing either orthosis and the risk of falling was significantly less. The fall risk was significantly lower when wearing the hollow-heel orthosis compared to the half palm orthosis.Conclusion:Wearing either ankle-foot orthosis can significantly correct the gait of stroke survivors and lower their risk of falling, with better effect when wearing the hollow-heel ankle-foot orthosis.

The ban on addition of antibiotics in animal feed in China has made the search for new antibiotics substitutes, e.g. bacteriocin, a hot topic in research. The present study successfully isolated an antibacterial substance producing strain of Bacillus sp. from alpaca feces by agar diffusion method, using Escherichia coli, Salmonella enterica, Staphylococcus aureus, Staphylococcus epidermidis, Micrococcus luteus and Listeria monocytogenes as indicator bacteria. The isolated strain was named as B. licheniformis SXAU06 based on colony morphology, Gram staining and 16S rRNA gene sequence. The antibacterial substance was isolated and purified through a series of procedures including (NH4)2SO4 precipitation, chloroform extraction, molecular interception and SDS-PAGE analysis. Bioinformatics analysis of the LC-MS/MS data indicated that the antibacterial substance was a bacteriocin-like substance (BLIS) with an approximate molecular weight of 14 kDa, and it was designated as BLIS_SXAU06. BLIS_SXAU06 exhibited high resistance to treatment of proteinase K, high temperature, high acidity and alkalinity. BLIS_SXAU06 was heterologously expressed in E. coli and the recombinant BLIS_SXAU06 exhibited effective antibacterial activity against S. aureus, S. epidermidis, M. luteus, and L. monocytogenes, showing potential to be investigated further.
Animals ; Anti-Bacterial Agents/pharmacology* ; Bacillus licheniformis ; Bacteriocins/pharmacology* ; China ; Chromatography, Liquid ; Escherichia coli/genetics* ; Listeria monocytogenes ; RNA, Ribosomal, 16S ; Staphylococcus aureus ; Tandem Mass Spectrometry

Objective:To explore the correlation between the number of sentinel regional lymph node (SALN) and non-sentinel regional lymph node (NSALN) metastasis in patients with early breast cancer after sentinel regional lymph node (SALN) biopsy.Methods:Retrospectively selected 400 female patients with early breast cancer who underwent SALN biopsy at the Department of Thyroid and Breast Surgery, Yijishan Hospital of Wannan Medical College from January 2016 to July 2021, and summarized and analyzed their clinical case data. The Chi-square test or Fisher exact probability method was used to compare the count data between groups. Perform single-factor analysis on the research indicators, then screen out indicators with statistically significant differences, then perform multi-factor Logistic regression analysis, draw a receiver operating characteristic curve, and combine the area under the curve to establish a predictive model.Results:SALN biopsy was performed in 400 patients with early breast cancer. A total of 1 504 lymph nodes were detected in 320 cases of total mastectomy, with an average of 4.7, 47 cases of macrometastasis, and 2 cases of postoperative macrometastasis. The false negative rate was 4.3%. Among 400 cases, 67 cases were positive for SALN, and the positive rate was 16.75% (67/400). The results of univariate analysis showed that the number of tumor thrombus in the vessel, the number of positive SALN and the metastasis of NSALN were closely related ( χ2=8.775, 16.53, P=0.003). The results of multivariate Logistic regression analysis showed that the number of tumor thrombi and SLN-positive ≥3 in the vessel were independent predictive risk factors for NSLN metastasis ( OR=16.149, 95% CI: 3.016-86.473, P<0.001; OR=31.76, 95% CI: 5.242-192.43, P<0.001). SALN positive was closely related to NSALN metastasis, but as the number of SALN detected increases (more than 6) and when only 1 to 2 SALN was positive, the probability of NSALN metastasis was significantly reduced ( P<0.05). Conclusions:The positive number of SALN and intravascular tumor thrombolus were closely related to NALN metastasis. SALN positive number ≥3 was the most important independent predictor of NSALN metastasis. The recurrence risk of sentinel lymph node can be reduced by increasing the number of SALN detected, when 1-2 positive sentinel lymph node are detected and the number of sentinel lymph node detected >6, axillary lymph node dissection can be exempted as appropriate.

From providing funds for the global fight against infectious diseases,to actively participating in global health security actions,to strengthening mutual cooperation in the field of health,and providing medical treatment,training and scholarships to countries in need,China's foreign aid on global poverty alleviation is increasingly diversified and expanding in scale.Indeed,China is playing an increasingly important leading role in the global health agenda.It is worth mentioning that over the years,artemisinin compound have saved millions of lives all over the world,especially in poverty-stricken areas.China's work mode of malaria elimination has also been written into WHO's technical documents and recommended to other countries.Since 2007,Chinese medical staff has carried out the Artemisinin Compound Malaria Control Project in Comoros,bringing Chinese prevention and treatment programs to the local area.By 2014,Comoros had achieved zero deaths from malaria,and the number of cases had dropped by 98％.Now,this program is also extended to Togo,another African country.This article preliminarily summarizes the malaria profile in Togo and introduces China-Togo Cooperative Artemisinin Malaria Control Demonstration Project to provide a reference for better anti-malaria assistance in Togo,and also shows one of the substantive actions of China's participation in global health governance,which contributes Chinese wisdom and offers Chinese solutions to global poverty alleviation.

Objective:To explore the value of chest low-dose CT (LDCT) in post-discharge follow-up assessments of patients with coronavirus disease 2019 (COVID-19).Methods:The chest CT findings of 58 patients with COVID-19 from March 17 to March 25, 2020 at Remin Hospital of Wuhan University were retrospectively analyzed. Two radiologists independently scored the subjective image quality on a 5-point Likert scale. The signal-to-noise ratio (SNR) and SD air of images and the CT radiation dose parameters were calculated, including the CT volume dose index (CTDI vol), dose length product (DLP), and effective radiation dose ( E). Results:The subjective image quality scores on CT images obtained before and after discharge by readers 1 and 2, were 4.45±0.22, 3.88±0.33 ( P>0.05) and 4.37±0.18, 3.91±0.35 ( P>0.05), respectively. The SNR and SD air in LDCT after discharge were 4.39±0.95 and 7.19±2.41, which were significantly lower than those in routine chest CT before discharge (5.14±1.06, Z=-5.551, P<0.001; 6.48±1.57, Z=-3.217, P<0.001). All of the obtained images were sufficient for diagnosis. The CTDI vol, DLP, and E in LDCT were significantly lower than those in routine CT [(2.41±0.09), (10.53±1.03)mGy, Z=-6.568, P<0.001; (88.03±5.33), (338.74±34.64)mGy·cm, Z=-6.624, P<0.001; and (1.23±0.17), (4.74±0.48)mSv, Z=-5.976, P<0.001]. Conclusions:Patients with COVID-19 can be followed up with low-dose chest CT after discharge.

Objective:To evaluate the modified efficacy of thoracic paravertebral block (TPVB) combined with general anesthesia in the patients undergoing laparoscopic radical nephrectomy.Methods:Eighty patients, aged 38-64 yr, with body mass index of 18-24 kg/m 2, of American Society of Anesthesiologists physical status Ⅰ or Ⅱ, scheduled for elective laparoscopic radical nephrectomy, were selected and randomly divided into 2 groups ( n=40 each) using a random number table method: general anesthesia group (group GA) and TPVB combined with general anesthesia group (group TPVB+ GA). A paravertebral catheter was placed at T 8 and T 10 under ultrasound guidance before induction of anesthesia, and 0.5% ropivacaine 10 ml was administered via the catheter in group TPVB+ GA.Anesthesia was induced with propofol, sufentanil, etomidate and rocuronium and maintained by intravenous infusion of propofol and remifentanil.Patient-controlled intravenous analgesia was performed with sufentanil, ketorolac tromethamine and tropisetron at the end of surgery.When postoperative visual analog scale score≥4, tramadol 50 mg was intravenously injected as rescue analgesic.Immediately before anesthesia induction (T 0), at 5 min after establishing pneumoperitoneum (T 1), at 2 h of pneumoperitoneum (T 2), and immediately after the end of pneumoperitoneum (T 3), and at 24 h after operation (T 4), venous blood samples were collected for determination of plasma norepinephrine concentrations (by enzyme-linked immunosorbent assay), plasma cortisol level (using radioimmunoassay), and blood glucose concentrations were measured.The intraoperative consumption of sufentanil and remifentanil was recorded.The intraoperative hypertension, hypotension, and bradycardia were recorded, and the nausea and vomiting, pruritus, and requirement for rescue analgesia occurred within 24 h after surgery were recorded. Results:Compared with group GA, the plasma concentrations of norepinephrine, cortisol and blood glucose were significantly decreased at T 1-4, the intraoperative consumption of sufentanil and remifentanil was reduced, and the postoperative requirement for rescue analgesia was decreased in group TPVB+ GA ( P<0.05). There was no significant difference in the incidence of intraoperative and postoperative adverse reactions between the two groups ( P>0.05). Conclusion:TPVB combined with general anesthesia is helpful in carrying out the anesthetic model of low-consumption opioids and is more helpful in inhibiting intraoperative and postoperative stress responses and postoperative pain responses than general anesthesia alone when used for laparoscopic radical nephrectomy.

Since December 2019, the corona virus disease 2019 (COVID-19) caused by the 2019 novel coronavirus (2019-nCoV) has been reported in Wuhan, Hubei Province. Almost 70% of patients susceptible to 2019-nCoV are over age of 50 years, with extremely large proportion of critical illness and death of the elderly patients. Meanwhile, the elderly patients are at high risk of osteoporotic fractures especially osteoporotic vertebral compression fractures (OVCF). During the prevention and control of COVID-19 epidemic, orthopedists are confronted with the following difficulties including how to screen and protect OVCF patients, how to accurately diagnose and assess the condition of OVCF patients with suspected or confirmed COVID-19, and how to develop reasonable treatment plans and comprehensive protective measures in emergency and outpatient clinics. In order to standardize the diagnosis and treatment of patients with OVCF diagnosed with COVID-19, the authors jointly develop this expert consensus. The consensus systematically recommends the standardized emergency and outpatient screening and confirmation procedures for OVCF patients with suspected or confirmed COVID-19 and protective measures for emergency and outpatient clinics. Moreover, the consensus describes the grading and classification of OVCF patients diagnosed with COVID-19 according to the severity of illness and recommends different treatment plans and corresponding protective measures based on the different types and epidemic prevention and control requirements.

Objective    To evaluate the efficacy and safety of modified maze Ⅳ (Cox-maze Ⅳ) in hypertrophic obstructive cardiomyopathy (HOCM) patients. Methods    From June 2016 to June 2019, 30 HOCM and persistent atrial fibrillation (pAF) patients received Cox-maze Ⅳ operation with modified extended Morrow operation, including 21 males and 9 females. The average age was 51.36±10.27 years and the average weight was 72.48±11.29 kg. All patients underwent left atrial appendectomy. Recurrence of AF, improvement of symptoms, cardiac function (NYHA) were assessed during follow-up. Results    There was no death during the perioperative period. Postoperative left ventricular outflow tract gradient was significantly decreased compared with that before operation (P<0.01), and all systolic anterior motion (SAM) signs disappeared after operation. Thirty patients were all effectively followed up for 3-40 (16.24±8.26) months. During the follow-up period, there was no death, and the cardiac function (NYHA) of all patients recovered to gradeⅠ-Ⅱ. At the end of follow-up, twenty-four patients (80.00%) maintained sinus rhythm, and twenty-seven patients (90.00%) maintained sinus rhythm after amiodarone conversion. Univariate analysis showed that the smoking history (P=0.04), left atrial diameter≥55 mm before operation (P=0.03), left atrial diameter≥50 mm after operation (P=0.02), postoperative tricuspid regurgitation (P=0.02) were closely related to postoperative AF recurrence. The increase of left atrial diameter after operation was an independent risk factor for AF recurrence (P=0.02). Conclusion    Morrow/Cox-maze Ⅳ procedure is safe and effective in treatment of patients with HOCM complicated with pAF, which helps to maintain postoperative sinus rhythm, and to improve the cardiac function. The increase of left atrial diameter after operation is an independent risk factor for AF recurrence.

Objective To evaluate the effect of sevoflurane preconditioning on high-mobility group box 1 protein ( HMGB1) ∕Toll-like receptor 4 ( TLR4) ∕nuclear factor kappa B ( NF-κB) signaling pathway during lung ischemia-reperfusion ( I∕R) in rats. Methods Thirty-six clean-grade healthy male Sprague-Dawley rats, aged 8-10 weeks, weighing 200-250 g, were divided into 3 groups ( n=12 each) using a random number table method: sham operation group ( group S) , lung I∕R group ( group I∕R) and sevoflu-rane preconditioning group ( group SP ) . The right pulmonary hilum was only isolated but not ligated in group S. Lung I∕R was induced by clamping the right pulmonary hilum for 60 min followed by 120 min of reperfusion in anesthetized rats in group I∕R. In group SP, 2. 1％ sevoflurane was inhaled for 30 min to per-form sevoflurane preconditioning, and the lung I∕R model was established at 10 min after the end of inhala-tion. The rats were sacrificed at 120 min of reperfusion, and the lungs were removed for examination of the pathological changes which were scored and for determination of wet to dry weight ratio ( W∕D ratio) , con-tent of tumor necrosis factor-alpha ( TNF-α) in lung tissues ( by enzyme-linked immunosorbent assay) and expression of HMGB1, TLR4 and NF-κB protein in lung tissues (by Western blot). Results Compared with group S, the pathological scores, W∕D ratio and content of TNF-α were significantly increased, and the expression of HMGB1, TLR4 and NF-κB was up-regulated in I∕R and SP groups ( P<0. 05) . Compared with group I∕R, the pathological scores, W∕D ratio and content of TNF-αwere significantly decreased, and the expression of HMGB1, TLR4 and NF-κB was down-regulated ( P<0. 05) , and the pathological changes of lung tissues were significantly attenuated in group SP . Conclusion Sevoflurane preconditioning reduces lung I∕R injury probably through inhibiting HMGB1∕TLR4∕NF-κB signaling pathway in rats.