Cancer cell membrane (CCM) derived nanotechnology functionalizes nanoparticles (NPs) to recognize homologous cells, exhibiting translational potential in accurate tumor therapy. However, these nanoplatforms are majorly generated from fixed cell lines and are typically evaluated in cell line-derived subcutaneous-xenografts (CDX), ignoring the tumor heterogeneity and differentiation from inter- and intra- individuals and microenvironments between heterotopic- and orthotopic-tumors, limiting the therapeutic efficiency of such nanoplatforms. Herein, various biomimetic nanoplatforms (CCM-modified gold@Carbon, i.e., Au@C-CCM) were fabricated by coating CCMs of head and neck squamous cell carcinoma (HNSCC) cell lines and patient-derived cells on the surface of Au@C NP. The generated Au@C-CCMs were evaluated on corresponding CDX, tongue orthotopic xenograft (TOX), immune-competent primary and distant tumor models, and patient-derived xenograft (PDX) models. The Au@C-CCM generates a photothermal conversion efficiency up to 44.2% for primary HNSCC therapy and induced immunotherapy to inhibit metastasis via photothermal therapy-induced immunogenic cell death. The homologous CCM endowed the nanoplatforms with optimal targeting properties for the highest therapeutic efficiency, far above those with mismatched CCMs, resulting in distinct tumor ablation and tumor growth inhibition in all four models. This work reinforces the feasibility of biomimetic NPs combining modular designed CMs and functional cores for customized treatment of HNSCC, can be further extended to other malignant tumors therapy.
Animals ; Humans ; Squamous Cell Carcinoma of Head and Neck/therapy* ; Heterografts ; Photothermal Therapy ; Biomimetics ; Disease Models, Animal ; Head and Neck Neoplasms/therapy* ; Cell Line, Tumor ; Tumor Microenvironment

Matrix protein p17 is a structural protein of human immunodeficiency virus（HIV）. It not only plays a key role in multiple stages of HIV life cycle，but also is closely associated with HIV-related lymphoma，neurocognitive impairment and breast cancer. This article reviews the role of matrix protein p17 in HIV infection and HIV-related diseases.

Objective:To understand the pathogen infection and epidemiological characteristics of children with diarrhea in Tianjin.Methods:Stool samples from 1 466 children with diarrhea in Tianjin Children's Hospital from August 2017 to July 2018 were collected, and all samples were tested for five intestinal-related pathogens (norovirus, rotavirus, Clostridium difficile toxin, adenovirus, and astrovirus). Results:Among the 1 466 samples, 627 samples were positive for nucleic acid detection of intestinal pathogens, with a positive rate of 42.8%. The detection rate of norovirus was the highest (26.3%), followed by rotavirus (15.3%), Clostridium difficile toxin (4.6%), adenovirus (4.1%), and astrovirus (1.84%). The infection has obvious seasonality. The positive detection rates of the five pathogens were similar among children of different sexes, and only the positive detection rates of norovirus and rotavirus were statistically significant among different ages ( P<0.05). There were 110 cases of mixed infection, and the mixed infection of norovirus and rotavirus was the most common, with a total of 37 cases. Conclusions:The pathogen spectrum of infant infectious diarrhea in Tianjin is complex and diverse, and the main pathogens are norovirus and rotavirus.

Objective:To investigate the molecular epidemiological characteristics of norovirus (NoV) in hospitalized children with sporadic acute gastroenteritis in Tianjin in 2019.Methods:Fecal specimens and clinical data were collected from 3 116 hospitalized children with sporadic acute gastroenteritis possibly caused by viral infection in Tianjin Children′ Hospital between January and December, 2019. Real-time quantitative PCR was used to detect NoV. Partial sequences of RNA-dependent RNA polymerase (RdRp) and capsid genes of NoV were amplified by RT-PCR. Sequence alignment and phylogenetic analysis were performed for further analysis.Results:Among the 3 116 specimens, 809 (26.0%) were positive for NoV. There were significant differences in NoV detection rate between different age groups ( P=0.000), and the highest NoV detection rate (31.6%) was observed in the age group of 7-12 months. Moreover, the detection rate of NoV varied with seasons ( P=0.000), and the NoV detection rate was highest in winter (39.0%). Based on the sequence analysis of RdRp and capsid genes, 286 identified NoV strains belonged to six genotypes, which were GⅡ.P12-GⅡ.3, GⅡ.P16-GⅡ.2, GⅡ.P17-GⅡ.17, GⅡ.Pe-GⅡ.2, GⅡ.Pe-GⅡ.3 and GⅡ.Pe-GⅡ.4. The predominant genotype was GⅡ.Pe-GⅡ.4 Sydney 2012 (61.2%), followed by GⅡ.P12-GⅡ.3 (33.6%, 96/286), GⅡ.Pe-GⅡ.3 (2.4%, 7/286), GⅡ.P16-GⅡ.2 (2.1%, 6/286), GⅡ.Pe-GⅡ.2 (0.3%, 1/286) and GⅡ.P17-GⅡ.17 (0.3%, 1/286). Patients carrying the NoV of GⅡ.Pe-GⅡ.4 Sydney 2012 genotype were likely to suffer from vomiting than those positive for NoV of GⅡ.P12-GⅡ.3 genotype. Conclusions:NoV was an important pathogen causing acute gastroenteritis in children. GⅡ.Pe-GⅡ.4 Sydney 2012 and GⅡ.P12-GⅡ.3 were the major genotypes of NoV in hospitalized children with sporadic acute gastroenteritis in Tianjin in 2019.

Objective:To investigate the prevalence and clinical characteristics of Mycoplasma pneumoniae( Mp) genotypes and subtypes in children in Tianjin. Methods:Children with pneumonia admitted to Tianjin Children′s Hospital from December 2017 to December 2019 were selected as the research objects. Bronchoalveolar lavage fluid was collected by fiberoptic bronchoscopy. The positive samples were detected by real-time fluorescent quantitative PCR and Mp culture. PCR-restriction fragment length polymorphism(RFLP) and multiple variable number tandem repeats were used for genotyping. Detailed clinical and laboratory data were collected for all cases. Results:The results of RFLP showed that there were 138 cases (78.9%) of typeⅠand 37 cases (21.1%) of type Ⅱ; 37 cases of type M3-5-6-2, including six subtypes B, G, M, S, V and Y; 138 cases of M4-5-7-2 were detected, including seven subtypes of E, J, P, U, X, Z and a. In M3-5-6-2 type, there were 1 case of P1-Ⅰtype (2.7%), 36 cases of P1-Ⅱtype (97.3%), 137 cases of P1-Ⅰ type (99.2%) and 1 case of P1-Ⅱ type (0.7%) in M4-5-7-2 type. There was no significant difference in genotype distribution among different age groups. There were statistical differences in the distribution of four seasons among the 13 genotypes of B, G, M, S, V, Y and E, J, P, U, X, Z, a. All Mp infected children had symptoms of fever and cough. The hospitalization time, fever duration, high fever (>39℃), cough duration, skin changes, digestive system symptoms and liver function injury rate of P1-Ⅰ/M4-5-7-2 pneumonia children were higher than those of P1-Ⅱ/M3-5-6-2 pneumonia children, but the difference was not statistically significant. The WBC count of P1-Ⅱ/M3-5-6-2 types was higher than that of typeⅠand M4-5-7-2; the LDH of P1-Ⅰ/M4-5-7-2 was higher than that of Ⅱ and M3-5-6-2, with statistical difference. There was no significant difference in the incidence of inflammatory consolidation, atelectasis, pleural thickening and pleural effusion among different genotypes. Conclusions:Mp infection in children with pneumonia in Tianjin is mainly P1-Ⅰ/ M4-5-7-2, and P1-Ⅱ is on the rise. P1-Ⅰ and M4-5-7-2 were associated with fever and severe symptoms.

Objective:To evaluate the prevalence of human rhinovirus (HRV) infection in hospitalized children in Tianjin and investigate the clinical impact of HRV infections.Methods:From July 2017 to December 2019, 2 945 nasopharyngeal secretion specimens were screened for HRV using polymerase chain reaction (PCR). VP4/VP2 sequences of HRV were further characterized. The clinical characteristics of the HRV infection were analyzed. The detection results of HRV for different groups and different months were compared using SPSS 19.0.Results:HRV-positive specimens accounted for 8.15% (240/2 945), of which 74.78% (86/115) were diagnosed with pneumonia, 40.83%(98/240) had co-infections with other common pathogens. HRV infections could be detected throughout the year with peaks in spring (11.00%, 66/660) and autumn (9.29%, 81/872). The positive rate of HRV was 4.14%(29/700) in winter. By VP4/VP2 sequence analysis, HRV-A was the most frequently detected strain(50.00%, 78/156), followed by HRV-C (41.67%, 65/156).46.15% (30/65) of HRV-C infections occurred in October and November. There were several different HRV-A types and HRV-C types. The most commonly detected HRV-A types were A12(11.54%, 9/78), A49(6.41%, 5/78), A22, A101, and A66(5.13%, 4/78), etc. The most common HRV-C types were C2(20.00%, 13/65), C22(9.23%, 6/65), C26, C43, C54 and C53(4.62%,3/65). Patients with HRV-A infections are more likely to show fever symptoms than HRV-C (χ2=5.411, P<0.05). No significant difference in other symptoms were found between the two types. Conclusions:HRV was a commonly detected virus among infants and had a clear seasonal distribution. It′s also possible for the HRV patients to have co-infections with other pathogens.HRV showed high genetic diversity.

Objective:To explore the effects of maternal pre-pregnancy body mass index (BMI) and gestational weight gain and its subtypes on the risk of preeclampsia.Methods:Pregnant women delivered in the Department of Obstetrics and Gynecology of the First Affiliated Hospital of Shanxi Medical University from March 2012 to September 2016 were selected as the research subjects. According to the inclusion and exclusion criteria, 9 274 pregnant women were included. 901 preeclampsia pregnant women were selected as the case group, and 8 373 non-preeclampsia pregnant women were selected as the control group. General demographic characteristics, pre-pregnancy weight, height, lifestyle during pregnancy, reproductive history, and disease history of pregnant women were collected, and pre-pregnancy BMI and gestational weight gain were calculated. Unconditional logistic regression was used to analyze the relationship between pre-pregnancy BMI and weight gain during pregnancy and PE and its clinical subtypes.Results:Among the 901 preeclampsia after inclusion and exclusion, 401 cases were diagnosed as early-onset PE (EOPE), 500 cases were late-onset PE (LOPE), 178 cases were Mild PE (MPE), and 723 cases were severe PE (SPE). There were statistically significant differences between PE and non-PE pregnant women in terms of maternal age, residence, parity, family history of gestational diabetes and hypertension ( P<0.05). After adjusting for the above factors, the logistic regression analysis results showed that pre-pregnancy BMI<18.5 kg/m 2 and inadequate gestational weight gain were protective factors for PE ( OR=0.74, 95% CI: 0.56-0.98; OR=0.78, 95% CI: 0.62-0.99), while pre-pregnancy BMI≥24.0 kg/m 2 and excessive gestational weight gain were risk factors for PE ( OR=1.82, 95% CI: 1.54-2.14; OR=1.82, 95% CI: 1.54-2.15). After subtype analysis on PE, the results showed that pre-pregnancy BMI<18.5 kg/m 2 was a protective factor for EOPE and MPE ( OR=0.52, 95% CI: 0.32-0.83; OR=0.47, 95% CI: 0.23-0.97), while pre-pregnancy BMI≥24.0 kg/m 2 and excessive gestational weight gain were risk factors for clinical subtypes of PE. After stratification according to pre-pregnancy BMI, excessive gestational weight gain was the risk factor for PE ( OR=1.86, 95% CI: 1.51-2.30; OR=1.90, 95% CI: 1.39-2.60) in pregnant women 18.5 kg/m 2≤BMI<24.0 kg/m 2 and ≥24.0 kg/m 2. Inadequate gestational weight gain ( OR=0.55, 95% CI: 0.34-0.89) was a protective factor for PE in pregnant women with pre-pregnancy BMI≥24.0 kg/m 2. Excessive gestational weight gain ( OR=4.05, 95% CI: 1.20-13.69) was a risk factor for EOPE in pregnant women with pre-pregnancy BMI<18.5 kg/m 2. Excessive gestational weight gain was a risk factor for the clinical subtype of PE in pregnant women 18.5 kg/m 2≤BMI<24.0 kg/m 2 before pregnancy. Inadequate gestational weight gain was a protective factor for EOPE and MPE ( OR=0.39, 95% CI: 0.19-0.80; OR=0.29, 95% CI: 0.11-0.77) in pregnant women with pre-pregnancy BMI≥24.0 kg/m 2. Excessive weight gain was a risk factor for EOPE, LOPE and SPE ( OR=1.60, 95% CI: 1.06-2.42; OR=2.20, 95% CI: 1.44-3.37; OR=2.28, 95% CI: 1.58-3.29). Conclusions:Pre-pregnancy BMI and gestational weight gain affect the risk of preeclampsia and its clinical subtypes. In contrast, the influence of gestational weight gain on preeclampsia varies among different pre-pregnancy BMI groups. Therefore, it is recommended to pay attention to the changes in pre-pregnancy BMI and gestational weight gain simultaneously to reduce preeclampsia.

Objective:To analyze the pathogenic bacteria and epidemiological characteristics in children with respiratory tract infection in Tianjin area.Methods:Retrospective case analysis was performed on 2 392 hospitalized children in the wards of respiratory diseases, intensive care unit and special care ward of Tianjin Children′s Hospital from June 2018 to May 2019. Thirteen pathogenic bacteria in deep sputum and bronchoalveolar lavage fluid samples were detected by loop-mediated isothermal amplification. The laboratory data and clinical characteristics of the infected children were analyzed, and the comparison between groups was performed by t test or χ 2 test. Results:Among 2 392 cases, 1 407 were males and 985 females. There was no significant difference in the detection rate between males and females (72.5% (1 020/1 407) vs.74.2% (731/985), χ 2=0.87, P=0.35). A total of 1 751 strains and 12 kinds of positive respiratory pathogens were detected, with a detection rate of 73.2%. Among them, 913 (38.2%) strains were Mycoplasma pneumoniae (MP), 514 (21.5%) were Streptococcus pneumoniae (Sp), 381 (15.9%) were Methicillin-resistant Staphylococcus aureus (MRSA) and 279 (11.7%) were Hemophilus influenzae (Hi). There was significant difference in the detection rate of pathogens among different age groups (χ2=83.67, P<0.01). The positive rate of alveolar lavage fluid group was higher than that of deep sputum fluid group [81.6% (614/752) vs. 69.3% (1 137/1 640), χ 2=39.89, P<0.01]. The length of hospital stay of children infected with different pathogens was significantly different (all P<0.01). There was significant difference in duration of fever among children infected with different pathogens (χ2=228.69,103.56, 3.96, 27.38,24.50,41.66, all P<0.05). There were 63 (7.7%) cases of atelectasis, 260 (31.9%) cases of pleurisy and 120 (14.7%) cases of pleural effusion in MP children. Children with Sma were most likely to involve the heart system (2/9), and children with Eco infection had a higher incidence of complications such as those of blood (3/19), urinary (2/19), digestive systems(4/19), systemic inflammatory response syndrome and sepsis (1/19). Conclusions:The main bacterial pathogens of respiratory tract infection in children in Tianjin were MP, Sp, MRSA and Hi. It is suggested that clinicians should not only pay attention to the respiratory symptoms of children, but also pay attention to the complications caused by bacterial pathogen infection, so as to prevent the deterioration of the disease and improve the prognosis.

SARS-CoV-2 has caused tens of thousands of infections and more than one thousand deaths. There are currently no registered therapies for treating coronavirus infections. Because of time consuming process of new drug development, drug repositioning may be the only solution to the epidemic of sudden infectious diseases. We systematically analyzed all the proteins encoded by SARS-CoV-2 genes, compared them with proteins from other coronaviruses, predicted their structures, and built 19 structures that could be done by homology modeling. By performing target-based virtual ligand screening, a total of 21 targets (including two human targets) were screened against compound libraries including ZINC drug database and our own database of natural products. Structure and screening results of important targets such as 3-chymotrypsin-like protease (3CLpro), Spike, RNA-dependent RNA polymerase (RdRp), and papain like protease (PLpro) were discussed in detail. In addition, a database of 78 commonly used anti-viral drugs including those currently on the market and undergoing clinical trials for SARS-CoV-2 was constructed. Possible targets of these compounds and potential drugs acting on a certain target were predicted. This study will provide new lead compounds and targets for further and studies of SARS-CoV-2, new insights for those drugs currently ongoing clinical studies, and also possible new strategies for drug repositioning to treat SARS-CoV-2 infections.