N-acetyl-p-aminophenol （APAP） is an antipyretic analgesic commonly used in clinical practice， and APAP overdose can cause severe liver injury and even death. In recent years， the incidence rate of APAP-induced liver injury （AILI） tends to increase， and it has become the second most common cause of liver transplantation worldwide. Autophagy is a highly conserved catabolic process that removes unwanted cytosolic proteins and organelles through lysosomal degradation to achieve the metabolic needs of cells themselves and the renewal of organelles. A large number of studies have shown that autophagy plays a key role in the pathophysiology of AILI， involving the mechanisms such as APAP protein conjugates， oxidative stress， JNK activation， mitochondrial dysfunction， inflammatory response and apoptosis. This article elaborates on the biological mechanism of autophagy in AILI， in order to provide a theoretical basis for the treatment of AILI and the development of autophagy regulators.

Autoimmune hepatitis(AIH)is a type of chronic hepatitis caused by the attack of hepatocytes by the autoimmune system,and with the prolongation of disease course,it may gradually progress to liver cirrhosis and even hepatocellular carcinoma.Although great achievements have been made in the understanding and treatment of AIH,its etiology and pathogenesis still remain unclear.T cells play a crucial role in the development and progression of AIH,and by focusing on follicular helper T cells,this article elaborates on the research advances in follicular helper T cells in AIH,in order to provide new ideas and strategies for the clinical treatment of AIH.

Autoimmune hepatitis(AIH)is chronic hepatitis caused by the attack of live cells by the immune system,and at present,the pathogenesis of AIH remains unclear.Inflammasomes are important components of innate immunity and are involved in a variety of pathophysiological processes.Studies have shown that inflammatory response associated with nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)plays an important role in the pathogenesis of AIH,which mainly mediates the release of proinflammatory factors and pyroptosis,thereby participating in the pathophysiological process of AIH.Therefore,the development and progression of AIH can be delayed by inhibiting the activation of NLRP3 inflammasomes,which provides new ideas for the prevention and treatment of AIH.

Objective:To explore the distribution and characteristics of microbiota in the lower reproductive tract of patients with cervical squamous cell carcinoma infected by human papilloma virus (HPV) 16 subtype.Methods:A prospective, cross-sectional study was conducted. A total of 6 patients with HPV16 single subtype positive cervical squamous cell carcinoma admitted to the Cancer Hospital of Chinese Academy of Medical Sciences from August 2019 to June 2020 were selected as cervical carcinoma group, and 6 healthy women who did not indicate abnormalities in thin-based layer cytology test (TCT) during the same period among the physical examination population and had HPV negative test result were selected as the healthy control group. A sterile cotton swab was used to collect secretions from the posterior cervical fornix in patients before antitumor treatment and healthy controls during physical examination. The high variable region of the 16S rRNA gene V1-V2 of the bacteria was amplified by using next generation sequencing (NGS), and then the distribution and characteristics of the bacteria were analyzed.Results:The age of cervical cancer group and the healthy control group was (51±8) years and (48±3) years, respectively, and the difference in age between the both groups was statistically significant ( t= 0.63, P= 0.540). The patients of both groups had reproductive history and no smoking experience. Alpha diversity analysis showed that compared with the healthy control group, the sobs ( t= 3.25, P= 0.009) and chao ( t= 2.91, P= 0.016) indexes were higher in cervical cancer group, and the differences were statistically significant. The shannon index was higher ( t= 2.07, P= 0.065) and simpson index was lower ( t= 1.74, P= 0.113) in cervical cancer group, while the difference was not statistically different. Data dimensionality reduction analysis in principal coordinate analysis (PCoA) based on bray-curtis distance showed that the difference in Beta diversity between the healthy control group and cervical cancer group was statistically significant ( R2= 0.154, P = 0.018). At the phylum level, the proportion of Firmicutes in cervical cancer group was lower than that in the healthy control group (30.21% vs. 68.28%), while the proportion of Bacteroidetes in cervical cancer group decreased slightly (6.87% vs. 8.11%); and the proportion of Actinobacteria (26.91% vs. 14.42%) and Proteobacteria (27.33% vs. 0.67%) had an increase in cervical cancer group. At the genus level, compared with the healthy control group, the proportion of Lactobacillus and Corynebacterium decreased in cervical cancer group, and loss of dominant flora could be detected; while Rhodococcus, Klebsiella and Aerococcus increased significantly in cervical cancer group. The bacteria species in cervical cancer group was increased compared with the healthy control group. Linear discriminant analysis (LDA) showed that Rhodococcus (LDA = 5.04), Klebsiella (LDA = 4.71), Enterobacter (LDA = 4.29), Ralstonia (LDA = 4.28), Ochrobactrum (LDA = 4.23) and Veillonella (LDA = 4.14) were the distinctive microbiota of cervical cancer group at the genus level. At the phylum level, Firmicutes (LDA = 5.23) in the healthy control group could be considered as a marker species. At the species level, the proportions of Rhodococcus ( P = 0.025), Ralstonia ( P = 0.045), Veillonella ( P = 0.044), Paraburkholderia ( P = 0.045), Pseudomonas ( P = 0.043) in cervical cancer group were increased compared with the healthy control group, and the differences were statistically significant. Conclusions:HPV16 single positive patients with cervical squamous cell carcinoma show the characteristics such as the increased diversity and richness of the lower reproductive tract microbiota compared with the healthy controls, while the abundance of Lactobacillus decreases. Rhodococcus and Klebsiella could serve as symbolic microbial in the lower reproductive tract. However, further studies still need to be verified.

Programmed death-1 and programmed death-ligand 1(PD-1/PD-L1)are regulatory immune checkpoint molecules that inhibit T cell activation and,therefore,play an important role in tumor immunotherapy.In recent years,increasing numbers of targeted therapeutic agents have been developed,but single immune checkpoint blockers cannot completely inhibit tumor occurrence,and tumor escape sporadically occurs.Consequently,combination therapy of targeted drugs is considered a useful method to inhibit tumorigenesis and tumor development.T cell immunoglobulin and immunoreceptor tyrosine-based inhibition motif(ITIM)domain(TIGIT)is an inhibitory type 1 poliovirus receptor that has recently been a hotspot of targeted drug therapy research.It has been shown that the combination therapy of TIGIT plus PD-1/PD-L1 can reduce tumor escape and inhibit tumorigenesis more effectively.Therefore,this review summarizes and discusses the progress on the dual blockade of TIGIT and PD-1/PD-L1 pathways in tumor immunotherapy to provide a theoretical basis for tumor im-munotherapy.

Objective:To explore the clinical manifestations and surgical outcomes of pediatric epilepsy patients with epileptic spasms (ES) as the main form of seizure, so as to analyze the correlative factors with prognosis and improve the understanding of the operation and preoperative positioning for such patients.Methods:The clinical data of patients with ES who underwent surgery therapy from June 2014 to December 2015 in Pediatric Epilepsy Center, Peking University First Hospital were collected and retrospectively analyzed.Demographic characteristics, seizure forms, etiology, electroencephalogram (EEG), cranial magnetic resonance imaging (MRI), operative methods, pathological findings as well as surgical outcomes evaluated by Engel classification during follow-up of the subjects were collected.Correlative factors with the prognosis were explored by comparing the data between patients with optimal outcome (Engel Ⅰ) and those with poor outcomes (Engel Ⅱ-Ⅳ).Results:A total of 25 pediatric patients were enrolled, including 16 males (64.0%) and 9 females (36.0%). The age of onset was (0.81±0.68) years, the age at operation was (2.98±1.63) years, and the course of disease was (2.17±1.48) years.Besides, 84.0% (21/25 cases) of the ES patients had multiple forms of seizures and partial seizure (19 cases) was the most common.MRI of the heads of all the children showed definite lesions, including 11 patients (44.0%) with lesions limited to one brain lobe and 14 patients (56.0%) involving multiple brain lobes or hemisphere.The most common etiology was focal cortical dysplasia (13 cases), followed by intracranial developmental tumors (3 cases). All patients underwent resection surgery, including resection of lesion (3 cases), single brain lobe resection (9 cases), multiple brain lobe dissection (3 cases) and hemisphere dissection (10 cases). During a follow-up period of 4.0 to 5.5 years, 1 patient was lost.Among the remaining 24 cases, 18 (75.0%) cases achieved good outcomes and wee classified as EngelⅠ, 2 cases (8.3%) and 4 cases(16.7%) were classified as Engel Ⅱand Ⅳ, respectively.The univariate comparison between the good epilepsy prognosis group and the poor epilepsy prognosis group showed that, patients whose EEG abnormalities are consistent with the anatomical lesions during the inter ictal tend to have good prognosis( P=0.006). Conclusions:(1) Optimal therapeutic effects were observed in ES patients with definite lesions treated by surgical therapy.(2) Interictal EEG consistent with the lesion side may suggest a good prognosis for surgical treatment.(3) Structural causes should be screened as soon as possible if a patient with ES is drug-refractory and presents clues of focal origin.

Based on the heart rate monitor front end AD8232 chips and Zigbee system solutions CC2530 single chip, the wireless ECG monitor has been realized in order to implement the acquisition, processing and wireless transmission of electrocardiogram signal. Meanwhile, the real-time heart rate has been calculated and wirelessly transmitted. The wireless ECG monitor is characterized by low power consumption, small size and simple operation. It can be seen from the experimental results that the wireless ECG monitor designed in this paper can successfully obtain favorable ECG data and real-time heart rate data and display it.
Electrocardiography ; Equipment Design ; Heart Rate ; Monitoring, Physiologic ; Signal Processing, Computer-Assisted ; Wireless Technology

Objective To analyze clinical efficacy of artificial prosthesis in giant cell tumor in distal femur,and to investigate risk factors affecting prosthesis failure and functional outcomes.Methods 42 patients with giant cell tumor of bone in distal femur,who had undergo prosthesis replacement from January 2002 to May 2015,were enrolled in this study.There were 24 males and 18 females,with an average age of 38.53± 12.87 years.There were 28 primary patients and 14 relapsed patients,including 11 cases of recurrence once and 3 cases of twice.Three-dimensional finite element model was used to analyze the effect of different angles of deviation of the spinal needle on the deformation of the bone wall.The correlations between the factors such as age,sex,occupation,prosthesis type,and other factors on prosthesis loosening were compared.Biomechanical effect of lower limbs caused by prosthesis offset angle was analyzed through gait analysis.Analyzed the effects of primary tumor or recurrence,prosthesis service status,and length of surgical osteotomy on joint function.Results A total of 42 patients were followed up by 20-158 months,with an average of 68.7 months.The 3 year survival rate of prosthesis was 83.33％ for 3 years and 57.14％ for 5 years.The major reason of prosthesis failure was loose (18/42,42.8％).X-ray films showed 19 cases of prosthetic intramedullary nail and sagittal bias of medullary force line angle ＞ 3° in the first follow-up.Osteotomy length (OR=0.132,P=0.0027) and offset angle of needle (OR=25.000,P=0.000) were significantly correlated to prosthesis loose.A length more than 12 cm and angle more than 3° were easier to result in prosthesis loose.There were no significant correlation between prosthesis failure and patients age,gender,occupation and prosthesis type.Gait analysis shows that the unsuitable bias angle of the prosthesis can significantly change the joint force of the prosthesis.The average score of MSTS 93 function evaluation was 25.43±4.256,excellent in 33 cases,good in 7 cases and poor in 2 cases.Function of patients with primary GCT were better than that of recurrent ones.Patients with one 1 times recurrence were better than that of recurrence twice (P=0.003).Patients without prosthesis loosening and revision were better than that with loosening (P=0.001).Patients with an osteotomy length less than 12 cm had a poorer function than that with more than 12 cm (P=0.002).Conclusion The main factors affecting distal femoral prosthesis replacement therapy of GCT is loosening,which was caused by broach and medullary cavity mismatch,osteotomy length,prosthesis rotation,prosthesis position.The function of the prosthesis is mainly affected by operation times,prosthesis status,osteotomy length and low patella.

BACKGROUND:As the sensitivity, clarity and accuracy of traditional ultrasound contrast agents are easy to be affected by objective factors, it is difficult to achieve diagnose and therapy simultaneously. Carbon nano tubes (CNTs) possess a specific reticular, hol ow and tubular structure and the potential to enhance the ultrasound imaging. The functional CNTs obtained through non-covalent adsorption, covalent bonding and internal embedding hold a good biocompatibility and high drug loading efficiency. So the drug loaded CNTs are added into the microbubble to synthesize a multi-functional ultrasound contrast agent. OBJECTIVE:To prepare the span-poly(ethylene glycol) (span-PEG) ultrasound contrast agent microbubble combined with folate-CNTs-paclitaxel (FA-CNTs-PTX) and to investigate its appearance, particle size as wel as loading efficiency of CNTs and PTX. METHODS:Firstly, the span-PEG microbubble was prepared using the acoustic cavitation method and its preparation process was optimized through the orthogonal experiment. Then the FA-CNTs-PTX compound was synthesized by the electrostatic self-assembly andπ-πadsorption principle. In the end, the span-PEG ultrasound contrast agent microbubble combined with FA-CNTs-PTX was obtained by loading the FA-CNTs-PTX into the span-PEG microbubble. The appearance of the composite microbubble were observed using scanning and transmission electron microscopes, the distribution and average particle size were detected by laser particle size analyzer, and the loading efficiency of CNTs and PTX was measured through ultraviolet spectroscopy. RESULTS AND CONCLUSION:The composite microbubble had a smooth surface and the average particle size was 442 nm. The loading efficiency of CNTs and PTX in the composite microbubble was 1.69%and 47.9%, respectively. To conclude, the FA-CNTs-PTX targeting drug delivery system is successful y loaded into the span-PEG microbubble. The composite microbubble is a hol ow sphere that has uniform nanoscaled particle size distributions, which is expected to become an ideal ultrasound contrast agent involved in angiography and targeting therapy.

We determined molecular characteristics of Listeria monocytogenes foodborne isolates in Hangzhou and investigated the characterization of local strains.Multi-locus sequence typing(MLST) and pulsed-field gel electrophoresis(PFGE) were applied to identify molecular types of Listeria monocytogenes isolates.Results showed that a total of 133 strains of 6 serotypes were divided into 19 MLST types including a new type ST767.ST9 and ST121 were the major ST types.There were 33 and 45 PFGE patterns characterized by AscⅠ and ApaⅠ.The molecular types of Listeria monocytogenes strains were widely distributed in Hangzhou.It is indicated that the major clusters were Lineage Ⅰ and Lineage Ⅱ which will cause listeriosis.The contamination of Listeria monocytogenes in food is serious in Hangzhou and the surveillance and management should be strengthened to prevent the food borne diseases.