With the development of small-molecule immunotherapy drugs, its combination with the programmed cell death ligand 1/programmed cell death protein 1 (PD-L1/PD-1) antibodies would provide a new opportunity for cancer treatment. Therefore, targeting PD-L1/PD-1 axis by small-molecule drug is an attractive approach to enhance antitumor immunity and considered as the next generation of tumor immunotherapy. In the present study, we investigated the anti-tumor role of salvianolic acid B (SAB) by regulating the PD-L1 level in tumors. Changes of total PD-L1 and membrane PD-L1 levels were determined by Western blot, flow cytometry and PD-1/PD-L1 interaction assays. The expression of mRNA level of PD-L1 was detected by real-time PCR. The cytotoxicity of activated peripheral blood mononuclear cell (PBMC) cells toward co-cultured tumor cells was measured by cell impedance assay and crystal violet experiment. Surface plasma resonance technique was used to analyze the direct interaction between SAB and ubiquitin carboxyl-terminal hydrolase 2 (USP2). The antitumor effect of SAB in vivo was examined by C57BL/6 mice bearing MC38 xenograft tumor (all animal experiments were conducted in accordance with the Animal Ethics Committee of the Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences). Western blot and flow cytometry assay showed that SAB can significantly downregulate the abundance of PD-L1 in RKO and PC3 cells in dose- and time-dependent manner. PD-1/PD-L1 binding assay revealed that SAB reduces the binding of tumor cells to recombinant PD-1 protein. Mechanism studies revealed that SAB can bind directly to USP2 protein and inhibit its activity, thus promote the ubiquitin-proteasome pathway degradation of PD-L1 proteins. In addition, Cell impedance and crystal violet staining indicated that SAB enhances the killing activity of co-cultured PBMC cells toward tumor cells. MC38 tumor transplanted mouse experiments revealed that SAB treatment displayed significant suppression in the growth of MC38 tumor xenografts in C57BL/6 mice with an inhibition rate of 63.2% at 20 mg·kg^-1. Our results demonstrate that SAB exerts its anti-tumor activity by direct binding and inhibiting the activity of USP2 and reducing the PD-L1 level. Our study provides an important material basis and scientific basis for the potential application of SAB in tumor immunotherapy drug targeting USP2-PD-L1 axis.

Objective To investigate the effect of microtubule binding protein STOP on myelin formation of oligodendrocyte in BTBR mice spectrum disorder in vitro, a highly purified primary culture method of oligodendrocyte precursor cells from cerebral cortex of BTBR mice was established. Establishment of a highly efficient transfection method for overexpression of STOP gene in oligodendrocyte precursor cells of BTBR mice cerebral cortex using lentiviral vector. Methods BTBR mice were used as experimental objects, 6-10 suckling mice were taken each time, repeat 3 times independently. The single cell suspension was prepared by trypsin digestion, and the primary oligodendrocyte precursor cells were obtained by immunomagnetic bead cell sorting method . After 5 days of culture, the cell purity was identified by oligodendrocyte precursor cell marker staining. The primary cultured oligodendrocyte precursor cells were transfected with STOP gene vector constructed in the early stage of the project group. 72-96 hours after transfection, the fluorescence staining of oligodendrocyte precursor cells was observed under fluorescence microscope, and the transfection rate and cell survival rate were calculated. Results The oligodendrocyte precursor cells of BTBR mice extracted by immunomagnetic beads sorting method basically adhered to the wall completely after 48 hours, and the cells had strong ability of proliferation. On the fifth da)' of culture, the purity of the cells was more than 95% identified by immunofluorescence. A lentivirus transfection method for primary oligodendrocyte precursor cells of BTBR mice with high transfection efficiency was established. The fluorescence expression of the cells was obvious after being photographed by high connotation microscope, the lentivirus transfection rate of oligodendrocyte precursor cells was increased to 60%-70%. Conclusion The primaiy oligodendrocyte precursor cells of BTBR mouse cerebral cortex with high purity were successfull)' isolated and cultured. A method for lentivirus infection of primaiy oligodendrocyte precursor cells in the cerebral cortex of BTBR mice is successfully established.

We aimed to evaluate the effectiveness and safety of single-course initial regimens in patients with low-risk gestational trophoblastic neoplasia (GTN). In this trial (NCT01823315), 276 patients were analyzed. Patients were allocated to three initiated regimens: single-course methotrexate (MTX), single-course MTX + dactinomycin (ACTD), and multi-course MTX (control arm). The primary endpoint was the complete remission (CR) rate by initial drug(s). The primary CR rate was 64.4% with multi-course MTX in the control arm. For the single-course MTX arm, the CR rate was 35.8% by one course; it increased to 59.3% after subsequent multi-course MTX, with non-inferiority to the control (difference -5.1%,95% confidence interval (CI) -19.4% to 9.2%, P = 0.014). After further treatment with multi-course ACTD, the CR rate (93.3%) was similar to that of the control (95.2%, P = 0.577). For the single-course MTX + ACTD arm, the CR rate was 46.7% by one course, which increased to 89.1% after subsequent multi-course, with non-inferiority (difference 24.7%, 95% CI 12.8%-36.6%, P < 0.001) to the control. It was similar to the CR rate by MTX and further ACTD in the control arm (89.1% vs. 95.2%, P =0.135). Four patients experienced recurrence, with no death, during the 2-year follow-up. We demonstrated that chemotherapy initiation with single-course MTX may be an alternative regimen for patients with low-risk GTN.
Antineoplastic Combined Chemotherapy Protocols/adverse effects* ; Dactinomycin/adverse effects* ; Female ; Gestational Trophoblastic Disease/drug therapy* ; Humans ; Methotrexate/therapeutic use* ; Pregnancy ; Retrospective Studies

Objective    To investigate the prognosis and risk factors of mild to moderate or moderate atrioventricular valve regurgitation (AVVR) after Fontan operation. Methods    A total of 34 patients with mild to moderate or moderate AVVR who accepted Fontan operation and atrioventricular valve (AVV) repair between 2004 and 2018 in our center were selected as an AVV repair group. The patients in the same period were matched as a control group by the ratio of 1 : 1-2. Finally 99 patients were included into this study, including 64 males and 35 females, with an average age of 63.4±36.3 months and weight of 17.3±6.7 kg. Grades of AVVR decreased more than 1 was defined as significant improvement. Endpoints of the study were death, Fontan takedown, AVV replacement. Risk factors including Fontan procedures, AVV repair procedures, cardiac anatomy were analyzed. Results    Patients were followed up for 1.5 (0.3-4.0) years. Overall mortality was 15.2%. Most (82.4%) of AVV repair group accepted single AVV repair procedure while partial annuloplasty was the most common (52.9%). With the extension of follow-up, the degree of AVVR in the whole group showed a gradually increasing trend (r=0.352, P=0.000). Mild to moderate AVVR improved spontaneously after Fontan operation, while moderate AVVR did not. AVV repair could improve the degree of AVVR after moderate regurgitation, without increasing the surgical mortality, and regurgitation significantly decreased in 8.8% patients. AVV repair was not effective for mild to moderate AVVR and would increase surgical mortality. Conclusion    AVV function shows a gradual downward trend after Fontan operation. AVV repair is effective for moderate AVVR, does not increase mortality, but the degree of improvement is limited. AVV repair is not effective for mild to moderate AVVR and increases surgical mortality.

Objective: To explore the association between drinking behavior and self injury behavior in adolescents. Methods: A total of 9 247 students from 4 middle schools were investigated. Drinking behavior and self injury behavior were collected from questionnaire survey. Univariate and multivariate Logistic regression analysis were used to analyze the relationship between drinking behavior and self injury behavior. Results: Among the 9 247 middle school students, 52.8% reported ever drinking, 24.9% reported drinking behavior in the past 30 days, and 14.6% reported been drunk in the past year. The average age of drinking for the first time was 12.47±3.05. About 47.2% of the participants had self injury behavior. Male with younger drinking age ( OR =1.52), had been drunken ( OR =1.35) and frequent drinking ( OR =1.54) increased the incidence of self injury. Female reported drinking at younger age ( OR =1.69), had been drunk ( OR =1.82) and lived in cities and towns ( OR =1.20) had a higher risk of self injury. Conclusion Drinking at younger age, heavy and frequent drinking are associated with higher risk of self injury in adolescents in sex specific fashion.

Malocclusion is one of the three most common oral diseases reported by World Health Organization(WHO). In China, its incidence rate is rising. Malocclusion seriously affects the dental and maxillofacial function, facial appearance and growth development of nearly 260 million children in China, and what is more, it affects their physical and mental health development. Malocclusion occurrence is related to genetic and environmental factors. Early treatment of malocclusion can create a good dental and maxillofacial development environment, correct abnormal growth and control the adverse effects of abnormal genetic factors. It can effectively reduce the prevalence of children's malocclusion and enhance their physical and mental health. This is an urgent need from the economic perspective of our society, so it has great practical and social significance. Experts from the project group "standard diagnose and treatment protocols for early orthodontic intervention of malocclusions of children" which initiated by China National Health Institute of Hospital Administration wrote the "China Experts' Consensus on Preventive and Interceptive Orthodontic Treatments of Malocclusions of Children", which aims to guide and popularize the clinical practice, improve the clinical theory and practice level, and accelerate the disciplinary development of early treatment of children's malocclusion in China. The consensus elaborates the harmfulness of malocclusion and the necessity of early treatment, and brings up the principles and fundamental contents. Based on the law of dental and maxillofacial development, this paper puts forward the guiding suggestions of preventive and interceptive treatments in different stages of dental development ranging from fetus to early permanent dentition. It is a systematic project to promote and standardize the early treatment of malocclusion. Through scientific and comprehensive stratified clinical practice and professional training, the clinical system of early treatment of malocclusion in China will eventually be perfected, so as to comprehensively care for children's dental and maxillofacial health, and improve their oral and physical health in China.
Child ; China/epidemiology* ; Consensus ; Dental Care ; Humans ; Malocclusion/prevention & control* ; Orthodontics, Interceptive

The outbreak of novel coronavirus pneumonia (NCP) has become the most severe public health issue at the moment, threatening people′s lives. Pediatricians in Shanghai have recently launched a discussion on the focused questions of NCP, including the incidence situation, epidemiological features, essentials of early screening, treatment and nosocomial infection prevention of children′s novel coronavirus infection (2019-nCoV), and further put forward the experts proposal upon the patterns of disease occurrence, development, diagnosis and control, for the reference of frontline pediatricians.

BACKGROUND: Penehyclidine is a newly developed anticholinergic agent. We aimed to investigate the role of penehyclidine in acute organophosphorus pesticide poisoning (OP) patients. METHODS: We searched the Pubmed, Cochrane library, EMBASE, Chinese National Knowledge Infrastructure (CNKI), Chinese Biomedical literature (CBM) and Wanfang databases. Randomized controlled trials (RCTs) recruiting acute OP patients were identified for meta-analysis. Main outcomesincluded cure rate, mortality rate, time to atropinization, time to 60% normal acetylcholinesterase (AchE) level, rate of intermediate syndrome (IMS) and rate of adverse drug reactions (ADR). RESULTS: Sixteen RCTs involving 1,334 patients were identified. Compared with the atropine-or penehyclidine-alone groups, atropine combined with penehyclidine significantly increased the cure rate (penehyclidine+atropine vs. atropine, 0.97 vs. 0.86, RR 1.13, 95% CI [1.07–1.19]; penehyclidine+atropine vs. penehyclidine, 0.93 vs. 0.80, RR 1.08, 95% CI [1.01–1.15]) and reduced the mortality rate (penehyclidine+atropine vs. atropine, 0.015 vs. 0.11, RR 0.17, 95% CI [0.06–0.49]; penehyclidine+atropine vs. penehyclidine, 0.13 vs. 0.08, RR 0.23, 95% CI [0.04–1.28]). Atropine combined with penehyclidine in OP patients also helped reduce the time to atropinization and AchE recovery, the rate of IMS and the rate of ADR. Compared with a single dose of atropine, a single dose of penehyclidine also significantly elevated the cure rate, reduced times to atropinization, AchE recovery, and rate of IMS. CONCLUSION Atropine combined with penehyclidine benefits OP patients by enhancing the cure rate, mortality rate, time to atropinization, AchE recovery, IMS rate, total ADR and duration of hospitalization. Penehyclidine combined with atropine is likely a better initial therapy for OP patients than atropine alone.

Thoracic aortic dissection (TAD) is one of the most lethal aortic diseases due to its acute onset, rapid progress, and high rate of aortic rupture. The pathogenesis of TAD is not completely understood. In this mini-review, we introduce three emerging experimental mouse TAD models using β-aminopropionitrile (BAPN) alone, BAPN for a prolonged duration (four weeks) and then with added infusion of angiotensin II (AngII), or co-administration of BAPN and AngII chronically. We aim to provide insights into appropriate application of these three mouse models, thereby enhancing the understanding of the molecular mechanisms of TAD.
Aminopropionitrile/toxicity* ; Aortic Dissection/pathology* ; Angiotensin II/toxicity* ; Animals ; Aortic Aneurysm, Thoracic/pathology* ; Disease Models, Animal ; Male ; Mice ; Mice, Inbred C57BL

Objective: To study the clinicopathological features of invasive lobular carcinoma (ILC) of the breast with extracellular mucin and outcomes of patients. Method: Clinicopathological features and clinical follow-up (39-123 months and a median follow-up of 55 months) of seven ILC with extracellular mucin were obtained. Hematoxylin-and-eosin (H&E) and immunohistochemistry (IHC) stained sections were reviewed, and fluorescence in situ hybridization (FISH) assay was performed for tumors with HER2 IHC 2+. Patient prognosis was analyzed and literatures related to ILC with extracellular mucin were reviewed. Results: All seven patients were female, aged from 43 to 73 years (median age, 55 years). The tumors ranged in size from 1 to 5 cm (median size 2 cm). All seven cases were of histological grade 2. Most areas of the tumors presented with the morphology of classic ILC, and variable amount of extracellular mucin were observed focally. In six cases, part of the tumor cells contained intracellular mucin, and the nucleus were pushed to one side of the cells, creating the impression of signet-ring cells. Two patients had lymph node metastases at diagnosis, and developed liver and bone metastases at 38th and 48th month, respectively, after surgery, and died at 48th and 123th month, respectively. While the other five patients, except one lost to follow-up, had been disease-free during the follow-up period. IHC results showed estrogen receptor (ER) and progesterone receptor (PR) positivity in 7/7 and 6/7 cases, respectively. Tumors of six patients were HER2 IHC 0/1+. The remaining one was HER2 IHC 2+, while FISH assay revealed HER2 gene amplification in that tumor. The proportion of cases with HER2-positivity was 1/7. The proliferation index Ki-67 ranged from less than 5% to 30%, and Ki-67 less than or equal to 10% were in 5/7 cases. According to the 2013 St. Gallen International Expert Consensus on breast cancer, all tumors were of luminal types; of those, two were luminal A and five were luminal B. Conclusions ILC with extracellular mucin tends to occur in women over 50 years old. All tumors in the study are grade 2 classic ILC, with signet-ring cells as a common feature. All seven tumors are classified as luminal types, with luminal B as the main molecular subtype.