The dynamic tracking of antibody‒drug conjugates (ADCs) in serum is crucial. However, a versatile bioanalytical platform is lacking due to serious matrix interferences, the heterogeneity and complex biotransformation of ADCs, and the recognition deficiencies of traditional affinity technologies. To overcome this, a multiepitope recognition technology (MERT) was developed by simultaneously immobilizing CDR and non-CDR ligands onto MOF@AuNPs. MERT's excellent specificity, ultrahigh ligand density, and potential synergistic recognition ability enable it to target the different key regions of ADCs to overcome the deficiencies of traditional technologies. The binding capacity of MERT for antibodies is ten to hundred times higher than that of the mono-epitope or Fc-specific affinity technologies. Since MERT can efficiently capture target ADCs from serum, a novel bioanalytical platform based on MERT and RPLC‒QTOF-MS has been developed to monitor the dynamic changes of ADCs in serum, including the fast changes of drug-to-antibody ratio from 3.67 to 0.22, the loss of payloads (maytansinol), and the unexpected hydrolysis of the succinimide ring of the linker, which will contribute to clarify the fate of ADCs and provide a theoretical basis for future design. In summary, the MERT-based versatile platform will open a new avenue for in-depth studies of ADCs in biological fluids.

Dynamic tracking analysis of monoclonal antibodies (mAbs) biotransformation in vivo is crucial, as certain modifications could inactivate the protein and reduce drug efficacy. However, a particular challenge (i.e. immune recognition deficiencies) in biotransformation studies may arise when modifications occur at the paratope recognized by the antigen. To address this limitation, a multi-epitope affinity technology utilizing the metal organic framework (MOF)@Au@peptide@aptamer composite material was proposed and developed by simultaneously immobilizing complementarity determining region (CDR) mimotope peptide (HH24) and non-CDR mimotope aptamer (CH1S-6T) onto the surface of MOF@Au nanocomposite. Comparative studies demonstrated that MOF@Au@peptide@aptamer exhibited significantly enhanced enrichment capabilities for trastuzumab variants in comparison to mono-epitope affinity technology. Moreover, the higher deamidation ratio for LC-Asn-30 and isomerization ratio for HC-Asn-55 can only be monitored by the novel bioanalytical platform based on MOF@Au@peptide@aptamer and liquid chromatography-quadrupole time of flight-mass spectrometry (LC-QTOF-MS). Therefore, multi-epitope affinity technology could effectively overcome the biases of traditional affinity materials for key sites modification analysis of mAb. Particularly, the novel bioanalytical platform can be successfully used for the tracking analysis of trastuzumab modifications in different biological fluids. Compared to the spiked phosphate buffer (PB) model, faster modification trends were monitored in the spiked serum and patients' sera due to the catalytic effect of plasma proteins and relevant proteases. Differences in peptide modification levels of trastuzumab in patients' sera were also monitored. In summary, the novel bioanalytical platform based on the multi-epitope affinity technology holds great potentials for in vivo biotransformation analysis of mAb, contributing to improved understanding and paving the way for future research and clinical applications.

Objective    To review and analyze the treatment of chylothorax after video-assisted thoracoscopic lung cancer surgery and to discuss the best clinical treatment methods and effects. Methods    A total of 400 patients diagnosed with chylothorax at the Department of Thoracic Surgery, West China Hospital, Sichuan University from January 2012 to January 2020 were continuously collected. According to the inclusion and exclusion criteria, 37 patients were finally included. There were 20 males and 17 females with an average age of 55.55±10.49 years. Chylothorax was diagnosed primarily by triglyceride levels (above 110 mg/dL) or the Sudan triple stain test. Treatment included surgical and non-surgical treatment. The overall incidence, high risk factors and treatment methods of chylothorax after radical thoracoscopic surgery for lung cancer were analyzed. According to the treatment methods, the patients were divided into a surgical treatment group and a non-surgical treatment group. The average daily drainage volume and average hospital stay of the patients between the two groups were analyzed. Results    Included patients accounted for 0.3% (37/12 515) of lung cancer thoracoscopic surgery in our hospital during the same period. The incidence of postoperative chylothorax in patients with right lung surgery (0.2%, 29/12 515) was higher than that of patients with left lung surgery (0.1%, 8/12 515). Of 37 patients with chylothorax after lung cancer surgery, 32 patients were in the non-surgical treatment group (86.5%, 32/37), and the rate was higher compared with the surgical treatment group (13.5%, 5/37, P=0.000). The average daily drainage in the surgical treatment group was 777 mL more than that in the non-surgical treatment group (95%CI 588.58 to 965.55, P<0.001). The total drainage volume of the surgical treatment group was more than that of the non-surgical treatment group (8 609.2卤4 680.3 mL vs. 4 911.2卤3 925.5 mL, P=0.055). The postoperative hospital stay and total hospital stay in the surgical treatment group were shorter than those in the non-surgical treatment group (P=0.162, P=0.118). The tube indwelling time (8.2卤2.7 d) was shorter than that of the non-surgical treatment group (12.3卤6.8 d, P=0.204). Conclusion 聽 聽The treatment of chylothorax after radical resection of VATS lung cancer is still mainly non-surgical treatment. Surgical treatment should be initiated as early as possible when the drainage volume is too large 72 hours after chylothorax surgery after radical resection of VATS lung cancer.

Objective:To understand the sales characteristics and salt iodine content in urban and rural salt market of Guizhou Province.Methods:In accordance with the "Guizhou Province 2020 Iodine Deficiency Disorders Monitoring Field Technical Guidance Work Program", 14 counties (cities, districts) from 88 counties (cities, districts) of 9 cities (states) in Guizhou Province were selected in August 2020. Each county (city, district) selected the urban area and a representative township, and at least 2 supermarkets were selected from the urban area, and 5 supermarkets or retail stores from the townships as the investigation sites, to collect the label information of all commercially available salt within the scope of investigation. At the same time, salt samples were collected after excluding the same brand, variety, and specification, and salt iodine was detected by redox titration.Results:A total of 107 labels of commercially available salt were collected, involving 21 brands, of which Biyuan brand had the largest number (53 samples, 49.5%) and the widest sales range, involving 12 counties (cities, districts). Salt producing areas came from 13 provinces, and the salt produced in Sichuan Province was the most widely distributed in the surveyed area (36 samples), followed by Chongqing Municipality (17 samples) and Hubei Province (16 samples). There were 19 brands (75 samples) and 7 brands (32 samples) of salt sold in urban and rural areas, respectively, and the main brand was Biyuan, accounting for 38.7% (29/75) and 75.0% (24/32), respectively. There were 8 brands (27 samples) and 16 brands (80 samples) of salt sold in retail stores and supermarkets, respectively, and the main brand was Biyuan, accounting for 66.7% (18/27) and 43.8% (35/80), respectively. Among 107 salt samples, it was found that the labeled iodine content did not meet the Guizhou Province salt iodization implementation standard (21 - 39 mg/kg), and only 39 samples (36.4%) had electronic anti-counterfeiting traceability codes on their labels. After excluding the same brand, variety, and specification, the median salt iodine of the 51 salt samples was 23.6 mg/kg, ranging from 19.2 to 38.1 mg/kg, and 21 - 39 mg/kg accounted for 96.1% (49/51).Conclusions:There are many salt brands sold in urban and rural areas in Guizhou Province, and the electronic traceability platform needs to be improved. Salt iodine is mainly distributed in the low-value area of the standard range, which brings potential risks to the sustainable and effective prevention and control of iodine deficiency disorders.

Developmental exposure to bisphenol A (BPA), an endocrine-disrupting contaminant, impairs cognitive function in both animals and humans. However, whether BPA affects the development of primary sensory systems, which are the first to mature in the cortex, remains largely unclear. Using the rat as a model, we aimed to record the physiological and structural changes in the primary auditory cortex (A1) following lactational BPA exposure and their possible effects on behavioral outcomes. We found that BPA-exposed rats showed significant behavioral impairments when performing a sound temporal rate discrimination test. A significant alteration in spectral and temporal processing was also recorded in their A1, manifested as degraded frequency selectivity and diminished stimulus rate-following by neurons. These post-exposure effects were accompanied by changes in the density and maturity of dendritic spines in A1. Our findings demonstrated developmental impacts of BPA on auditory cortical processing and auditory-related discrimination, particularly in the temporal domain. Thus, the health implications for humans associated with early exposure to endocrine disruptors such as BPA merit more careful examination.
Humans ; Rats ; Animals ; Benzhydryl Compounds/toxicity* ; Phenols/toxicity* ; Auditory Perception/physiology* ; Neurons/physiology*

Objective:To understand the salt sales situation and salt iodine content in the market of Guizhou Province 3 years after the system reform of salt industry.Methods:From August to October 2020, in 9 cities (prefectures) of Guizhou Province, 2 counties (cities and districts) were selected from each city (prefecture), 1 urban area and 1 township were selected from each county (city and district), 1 large supermarket and 1 farmers' market were selected in the urban area, and 1 small supermarkets or convenience stores were selected in the township, to check the varieties, place of origin and iodine content label on the package of salt sold, and different brands of salt were collected and sent to the provincial and county salt iodine laboratories. The iodine content was determined and analyzed.Results:A total of 18 large supermarkets, 18 farmers' markets and 18 small supermarkets or convenience stores were investigated, and 70 salt samples of 23 brands, 3 types and origin from 11 provinces were collected. Among them, there were 56 samples with iodine content of 21 - 39 mg/kg on the package. The iodine content range of provincial detection was 19.23 - 37.41 mg/kg (two of them were lower than 21.0 mg/kg), and the median was 25.75 mg/kg. There were 12 samples of two iodine contents (18 - 33 and 21 - 39 mg/kg) marked on the package, and the salt iodine range of provincial detection was 23.52 - 32.90 mg/kg, with a median of 26.55 mg/kg. One sample was marked with 18 - 33 mg/kg, and the iodine content of provincial detection was 25.20 mg/kg; the iodine content of 1 sample of non-iodized salt was not detected. According to the actual test value, iodine contents of 68 samples were within the range of packaging marks, accounting for 97.14% of the total. Taking the provincial test results as a standard, the absolute value of the relative deviation of the provincial and county test results was 0 - 27.45%, the average deviation was 7.65%, and the coincidence rate was 91.43% (66/70). The county test results were acceptable.Conclusions:After the system reform of salt industry, there are many kinds of salt which come from many provinces, and more than 97% of the salt iodine content which is within the standard range of salt concentration in Guizhou Province.

Objective:To analyze the distribution and drug resistance of wound pathogenic microorganisms in outpatients of wound healing center so as to provide a basis for the standardized construction of wound healing centers.Methods:A retrospective case series study was used to analyzed the data of 365 outpatients treated at Ruijin Hospital, Shanghai Jiaotong University School of Medicine from December 2017 to October 2019. There were 220 males and 145 females, aged (58.8±18.9)years (range, 18-98 years). The patients included 92 first-visit patients and 273 re-visit patients. The culture results (positive rate of pathogenic microorganisms, bacterial species, bacterial distribution) and drug sensitivity results of the wound secretions were compared and analyzed.Results:(1) Among 365 samples of wound secretions, 198 patients were positive for pathogenic microorganisms with a positive rate of 54.3%. A total of 107 strains (51.0%) of Gram-positive bacteria were detected, mainly Staphylococcus aureus (70 strains, 33.3%); 95 strains (45.2%) of Gram-negative bacteria were detected, mainly Escherichia coli (20 strains, 9.5%), followed by Pseudomonas aeruginosa (17 strains, 8.1%); 8 strains (3.8%) of fungi were detected. (2) A total of 26 (28.3%) first-visit patients were positive for pathogenic microorganisms, and 172 (63.0%) re-visit patients were positive for pathogenic microorganisms. The rate of positive microorganism detection had significant differences between first-visit and re-visit patients ( P<0.05). (3) A total of 29 strains were detected in first-visit patients, including 16 strains (55.2%) of Gram-positive bacteria, 11 strains (37.9%) of Gram-negative bacteria and 2 strains (6.9%) of fungi. A total of 181 strains were detected in re-visit patients, including 91 strains (50.3%) of Gram-positive bacteria, 84 strains (46.4%) of Gram-negative bacteria and 6 strains (3.3%) of fungi. The microbial distribution was significantly different between first-visit and re-visit patients ( P<0.05). (4) Compared with first-visit patients, the resistance of Staphylococcus aureus isolated from the re-visit patients to spenicillin, oxacillin, ciprofloxacin, tetracycline, clindamycin, moxifloxacin, erythromycin, and levofloxacin were increased variably. No vancomycin-resistant Staphylococcus aureus was detected, indicating that the staphylococcus aureus presented in the wound was highly sensitive to vancomycin. Conclusions:Staphylococcus aureus is the most common microorganism in wound secretions in outpatients of wound healing center. The rate of positive pathogenic microorganisms in wound secretions of re-visit patients is significantly higher than that of first-visit patients, and the distribution of pathogenic microorganisms of first-visited and revisited patients differs significantly. The Staphylococcus aureus detected in re-visit patients has a higher resistance to common antibiotics compared with first-visit patients. It is suggested that timely detection of pathogenic microorganisms in outpatients and effective control and supervision of outpatient infections are important contents that cannot be ignored in the construction of wound healing center.

Objective:To preliminarily investigate the efficacy and safety of bevacizumab plus neoadjuvant chemotherapy combined with concurrent chemoradiotherapy in the treatment of locally advanced giant cervical cancer (LACC).Methods:Twenty-four patients with LACC who were treated with bevacizumab combined with neoadjuvant chemotherapy were assigned into the study group, and 30 patients receiving neoadjuvant chemotherapy in phase Ⅱ clinical trial (ChiCTR-TRC-11001832) were allocated in the control group. The survival rate was calculated by the Kaplan- Meier method, and the significance of differences between the variables was determined by the log-rank test. Results:The tumor volumes were (1.64±23.15) cm 3 and (12.83±15.08)( P=0.037), and the complete remission (CR) rates were calculated as 45.8% and 13.3%( P=0.004) in the study and control groups after neoadjuvant chemotherapy. The tumor volumes were (0±1.5) cm 3 and (1.00±10.63) cm 3( P=0.022) and the CR rates were 70% and 50%( P=0.009) in the study and control groups before afterloading treatment. The median follow-up was 24.6(9.3-101.7) months. The 1-and 2-year overall survival rates were 96%, 96% and 90%, 71%( P=0.110), the recurrence-free survival rates was 96%, 96% and 97%, 89%( P=0.512), and the distant metastasis-free survival rates were 96%, 88% and 83%, 80%( P=0.297) in the study and control groups, respectively. Adverse reactions were acceptable in both groups. Conclusion:Bevacizumab combined with neoadjuvant chemotherapy can significantly reduce the tumor volume, improve the tumor CR rate and yield tolerable adverse reactions.

Background and aim:Real-world data on the effectiveness and safety of treatment with the direct-acting antiviral agent-based regimen are limited on the Chinese mainland.The aim of this study was to conduct a multicenter,prospective,real-world study of ombitasvir/paritaprevir/ritonavir(OBT/PTV/r)combined with dasabuvir(DSV)in hepatitis C virus(HCV)genotype 1b-infected non-cirrhotic or compensated cirrhotic Chinese adult patients. Materials and methods:Genotype 1b-infected patients were enrolled at eight sites in China.Patients received 25/150/100 mg of OBT/PTV/r once daily combined with 250 mg of DSV twice daily for 8 weeks or 12 weeks.Sustained virological response at 12 weeks post-treatment(SVR12)and the incidence of adverse events were assessed.We have also evaluated the effect of intensive questioning of patients who were overdue for SVR12 testing.Intention-to-treat(1TT)and modified 1TT(mITT)populations were used in the analysis. Results:One hundred forty patients were included,among whom 90.0％(126/140)were newly diag-nosed,9.3％(13/140)had compensated cirrhosis,92.9％(130/140)received 12 weeks of treatment,and 7.1％(10/140)received 8 weeks of treatment.In the mITT population,the virological response rate at week 4 was 96.4％(108/112),and at the end of treatment was 100％(102/102).Among these patients,139 patients completed 12 weeks of treatment,and 73 patients were followed-up.All followed-up patients achieved SVR12.There was no adverse event-related discontinuation.Serious adverse events during treatment were reported in two(1.4％)patients,and none were considered to be drug-related.Sixty-six(47.1％)patients did not return to receive the HCV RNA test at 12 weeks post-treatment. Conclusions:The rate of SVR12 was consistent with Phase Ⅲ clinical studies.OBT/PTV/r combined with DSV showed effectiveness in Chinese adult patients,and both tolerability and safety profile were favorable.However,patient compliance should be further improved in the real world.

Objective To evaluate the diagnostic efficacy of Kwak and ACR( 2017 ) thyroid imaging reporting and data systems ( T I‐RADS ) for thyroid nodules . Methods Cases of thyroid nodule who underwent surgery from January 2015 to M arch 2018 in 15 hospitals in Sichuan province were collected and the ultrasonographic features of thyroid nodules were retrospectively analyzed by trained senior ultrasound physicians using Kwak and ACR T I‐RADS classification methods . Totally ,12 712 thyroid nodules were observed ,7 023 thyroid nodules in 7 023 cases with complete ultrasound and surgical and pathological data were eventually enrolled in the study . T hyroid nodules with solid ,hypoechoic or very hypoechoic ,tall/wide ratio ≥ 1 , margin ill‐defined and microcalcification were classified as malignant signs of ultrasound . M alignant percentage was calculated and diagnostic tests were performed . Results ① T here was a statistical difference between the benign and malignant nodules in the two types of T I‐RADS classification ( P＜0 .01) . ② T he area under ROC curve of Kwak and ACR in the diagnosis of malignant nodules were 0 .89 and 0 .84 ,respectively . T he Youden index of Kwak and ACR were 0 .66 and 0 .57 ,respectively . ③Taking Kwak T I4B and ACR T R4 as critical points for malignancy ,the sensitivity ,specificity ,positive predictive value and negative predictive value of Kwak T I 4B were 75 .0% ,90 .9% ,83 .2% ,and 85 .9% , respectively . T he accuracy of Kwak T I4B was 84 .9% ; T he sensitivity ,specificity ,positive predictive value and negative predictive value of ACR T R4 were 88 .2% ,68 .9% ,62 .9% ,and 90 .8% ,respectively . T he accuracy of ACR T R4 was 76 .2% . T he Kappa value of Kwak TI4B and ACR T R4 was 0 .52 . T he χ2 value of Kwak T I4B and ACR T R4 was 2 174 .6 ( P ＜ 0 .01 ) . Conclusions T he diagnostic values of two T I‐RADS classification methods for thyroid malignant nodules are high . T he overall efficiency of Kwak T I‐RADS classification method is better than that of ACR TI‐RADS classification method .