Pegylated interferon α-2b （PEG-IFN-α-2b） is currently a first-line drug for the treatment of chronic hepatitis B virus infection and is widely used in clinical practice. This drug has multiple effects of inhibiting viral replication， regulating immunity， and improving liver function， and some patients can achieve clinical cure. However， it often causes various adverse reactions during treatment， which are important factors for compromising treatment compliance and efficacy. This article systematically reviews the adverse reactions and their mechanisms during PEG-IFN-α-2b therapy for chronic hepatitis B， including influenza-like symptoms， peripheral blood cytopenia， thyroid dysfunction， and neuropsychiatric symptoms， and it also summarizes the monitoring and management strategies for these adverse reactions， in order to provide evidence-based guidance for clinical decision-making and emphasize the importance of individualized treatment.

Objective:To investigate the effects of lipopolysaccharide (LPS)-activated stimulator of interferon genes (STING) signaling on the biological behavior of periodontal ligament cells and its mechanism of action.Methods:Human periodontal ligament cells (hPDLC) were divided into the PBS group and the LPS group by stimulated with phosphate-buffered saline (PBS) and LPS derived from Porphyromonas gingivalis (ATCC 33277) for 12 hours, respectively. The intracellular distribution of 8-hydroxydeoxyguanosine (8-OHdG), a marker of DNA damage, and the activation level of STING signaling were detected by immunofluorescence. The source of intracellular double-stranded DNA was detected by live-cell probes. The levels of osteogenic-related proteins, such as special protein 7 (SP7), bone morphogenetic protein 2 (BMP2), cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS), and STING were detected by Western blotting. The cell supernatants of the PBS group and the LPS group were collected, and the levels of inflammatory cytokines, such as interleukin (IL)-1β, IL-6, and interferon (IFN)-β, were detected by double-antibody sandwich enzyme-linked immunosorbent assay (ELISA). A total of 12 cgas knockout mice and 12 littermate wild-type mice were constructed. The maxillary second molars of the mice were ligated with silk or sham surgery, respectively. After 7 days of modeling, the mice were divided into littermate control sham surgery group, littermate control periodontitis group, cgas knockout sham surgery group, and cgas knockout periodontitis group, with 6 mice in each group. Micro-CT was used to collect image data, and three-dimensional reconstructions were performed on the maxillary samples of each group. The distance from the cemento-enamel junction to the alveolar bone crest (CEJ-ABC), bone volume fraction (BV/TV), and bone mineral density (BMD) in the model area were statistically analyzed using CTAn and CTVOX software. Frozen sectioning was used to obtain sections of the maxillary molars of each group of mice, and the signal intensities of cGAS and STING proteins were detected by immunofluorescence. Results:Immunofluorescence results showed that the fluorescence signal intensity of 8-OHdG outside the nucleus in the LPS group (4.09±0.24) was significantly higher than that in the PBS group (1.00±0.10) ( t=20.33, P<0.001). The co-localization signal of mitochondrial marker TOM20 and 8-OHdG (8.56±0.53) were significantly higher than that of PBS group (1.00±0.09) ( t=24.37, P<0.001). Live cell DNA probe detection showed that the signal intensity of double-stranded DNA in LPS group (3.23±0.12) was significantly stronger than that in PBS group (1.00±0.17) ( t=18.30, P<0.001). Immunofluorescence demonstrated a significant increase in STING expression in hPDLC of the LPS group ( t=6.42, P<0.001), and it was colocalized with the Golgi marker GM130. ELISA results showed that the abundance of IL-6, IFN-β, and IL-1β in the supernatant of the LPS group were higher than those of the PBS group ( t=12.44, t=11.38, t=9.48, all P<0.001). Animal experiments confirmed that compared with the sham operation group [(207.61±38.09) and (238.97±45.90) μm], the CEJ-ABC in the periodontitis group [(420.31±35.32) and (405.16±35.51) μm] were increased ( P<0.01), while the CEJ-ABC in the cgas knockout periodontitis group [(295.11±35.43) and (309.15±32.22) μm] were significantly lower than those in the control periodontitis group of the same litter ( P<0.01). Compared with the sham operation group (45.84±6.41), the STING fluorescence signal in the periodontitis group (152.44±6.86) was significantly increased ( P<0.001). Compared with the control periodontitis group of the same litter, the STING signal in the cgas knockout periodontitis group was significantly reduced (88.31±9.70) ( P<0.001). Conclusions:LPS stimulation can activate the STING signal by generating mitochondrial-derived double-stranded DNA, stimulating hPDLC to secrete inflammatory cytokines and impairing osteogenic differentiation potential. Suppressing STING activation in animal models can reduce bone destruction in periodontitis.

Objective:To investigate the effects of lipopolysaccharide (LPS)-activated stimulator of interferon genes (STING) signaling on the biological behavior of periodontal ligament cells and its mechanism of action.Methods:Human periodontal ligament cells (hPDLC) were divided into the PBS group and the LPS group by stimulated with phosphate-buffered saline (PBS) and LPS derived from Porphyromonas gingivalis (ATCC 33277) for 12 hours, respectively. The intracellular distribution of 8-hydroxydeoxyguanosine (8-OHdG), a marker of DNA damage, and the activation level of STING signaling were detected by immunofluorescence. The source of intracellular double-stranded DNA was detected by live-cell probes. The levels of osteogenic-related proteins, such as special protein 7 (SP7), bone morphogenetic protein 2 (BMP2), cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS), and STING were detected by Western blotting. The cell supernatants of the PBS group and the LPS group were collected, and the levels of inflammatory cytokines, such as interleukin (IL)-1β, IL-6, and interferon (IFN)-β, were detected by double-antibody sandwich enzyme-linked immunosorbent assay (ELISA). A total of 12 cgas knockout mice and 12 littermate wild-type mice were constructed. The maxillary second molars of the mice were ligated with silk or sham surgery, respectively. After 7 days of modeling, the mice were divided into littermate control sham surgery group, littermate control periodontitis group, cgas knockout sham surgery group, and cgas knockout periodontitis group, with 6 mice in each group. Micro-CT was used to collect image data, and three-dimensional reconstructions were performed on the maxillary samples of each group. The distance from the cemento-enamel junction to the alveolar bone crest (CEJ-ABC), bone volume fraction (BV/TV), and bone mineral density (BMD) in the model area were statistically analyzed using CTAn and CTVOX software. Frozen sectioning was used to obtain sections of the maxillary molars of each group of mice, and the signal intensities of cGAS and STING proteins were detected by immunofluorescence. Results:Immunofluorescence results showed that the fluorescence signal intensity of 8-OHdG outside the nucleus in the LPS group (4.09±0.24) was significantly higher than that in the PBS group (1.00±0.10) ( t=20.33, P<0.001). The co-localization signal of mitochondrial marker TOM20 and 8-OHdG (8.56±0.53) were significantly higher than that of PBS group (1.00±0.09) ( t=24.37, P<0.001). Live cell DNA probe detection showed that the signal intensity of double-stranded DNA in LPS group (3.23±0.12) was significantly stronger than that in PBS group (1.00±0.17) ( t=18.30, P<0.001). Immunofluorescence demonstrated a significant increase in STING expression in hPDLC of the LPS group ( t=6.42, P<0.001), and it was colocalized with the Golgi marker GM130. ELISA results showed that the abundance of IL-6, IFN-β, and IL-1β in the supernatant of the LPS group were higher than those of the PBS group ( t=12.44, t=11.38, t=9.48, all P<0.001). Animal experiments confirmed that compared with the sham operation group [(207.61±38.09) and (238.97±45.90) μm], the CEJ-ABC in the periodontitis group [(420.31±35.32) and (405.16±35.51) μm] were increased ( P<0.01), while the CEJ-ABC in the cgas knockout periodontitis group [(295.11±35.43) and (309.15±32.22) μm] were significantly lower than those in the control periodontitis group of the same litter ( P<0.01). Compared with the sham operation group (45.84±6.41), the STING fluorescence signal in the periodontitis group (152.44±6.86) was significantly increased ( P<0.001). Compared with the control periodontitis group of the same litter, the STING signal in the cgas knockout periodontitis group was significantly reduced (88.31±9.70) ( P<0.001). Conclusions:LPS stimulation can activate the STING signal by generating mitochondrial-derived double-stranded DNA, stimulating hPDLC to secrete inflammatory cytokines and impairing osteogenic differentiation potential. Suppressing STING activation in animal models can reduce bone destruction in periodontitis.

Objective:To conduct a series case study on hospitalized anthrax cases in five hospitals in North China, to share clinical experiences in the diagnosis and treatment of cutaneous and pulmonary anthrax.Methods:A retrospective, multicenter cohort study was conducted on the anthrax patients admitted to five hospitals in North China from August 2018 to March 2022. Forty patients were divided into severe and mild groups. The clinical features, treatment and prognosis of the patients were collected and analysed. Statistical evaluations included independent sample t test, Mann-Whitney U test, and chi-square test. Results:Among the 40 patients with anthrax, 10(25.0%) were severely ill and 30(75.0%) were mildly ill. According to the sites of infection, 40 patients were classified as 39 cutaneous anthrax cases (one case had secondary pulmonary anthrax) and one pulmonary anthrax case. The rates of chills and fever, lymphadenopathy, liver dysfunction and hypoalbuminemia in the severe group were all higher than those in the mild group, with statistically significant differences ( χ2=5.71, 6.54, 4.68 and 9.22, respectively, all P<0.05). The peripheral white blood cell count, neutrophil count, neutrophil/lymphocyte ratio and C-reactive protein were (11.8±4.9)×10 9/L, (9.5±5.1)×10 9/L, 8.6±7.3, 27.9(8.6, 167.7) mg/L, respectively, which were all higher than those in mild disease group ((7.5±2.4)×10 9/L, (5.0±2.1)×10 9/L, 3.2±2.3, 3.5(1.2, 14.7) mg/L), with statistically significant differences ( t=2.66, t=2.71, t=2.32 and Z=-3.01, respectively, all P<0.05). The albumin level in the severe group was (35.5±8.1) g/L, which was lower than that of the mild group ((43.7±3.2) g/L), and the difference was statistically significant ( t=-3.13, P=0.011). The severe cases were more likely to have skin lesions greater than four centimetre in diameter, multiple, vesicular, or edematous, with a significant difference ( χ2=6.01, P=0.014). Among 39 patients with cutaneous anthrax, 28(71.8%) in the mild group were treated with penicillin alone, and nine (23.1%) in the severe group were treated with penicillin, ofloxacin, piperacillin/tazobactam combined with one of linezolid, doxycycline, or clindamycin for anti-infection treatment. The two patients with pulmonary anthrax were treated with closed thoracic drainage for pleural effusion and pneumothorax, and were treated with two bactericidal and one protein synthesis inhibitor antibiotics. All 40 anthrax patients were cured and discharged from hospital. Conclusions:Patients with mild cutaneous anthrax can generally be treated with single penicillin, and patients with severe cutaneous anthrax and pulmonary anthrax should be treated with combined antibiotics.

Aim To investigate the serum levels of thrombin-antithrombin complex(TAT),tissue type plas-minogen activator-inhibitor complex(t-PAIC)and thrombomodulin(TM)in patients with intracranial atherosclerotic steno-sis(ICAS),and their correlations with the degree of stenosis.Methods A total of 196 ICAS patients(ICAS group)who underwent treatment in Cangzhou People's Hospital from January 2021 to February 2023 were enrolled as research sub-jects.Based on the degree of vascular stenosis,they were separated into three groups:mild group(n=78),moderate group(n.=64),and severe group(n=54).A group of 196 healthy outpatient with similar clinical basic data to ICAS patients was selected as controls.The serum levels of TAT,t-PAIC,and TM in each group were compared;Spearman method was applied to analyze the correlation between serum levels of TAT,t-PAIC,TM and stenosis severity in ICAS pa-tients;Multivariate Logistic regression was applied to analyze the influencing factors of severe stenosis in ICAS patients;ROC curve was applied to analyze the predictive value of serum TAT,t-PAIC,TM and total cholesterol(TC)levels for se-vere stenosis in ICAS patients.Results Compared with the control group,the serum levels of TAT,t-PAIC,and TM were significantly increased in the ICAS group(P＜0.05);the levels of serum TAT,t-PAIC,TM,and TC in the mild,moderate,and severe groups increased accordingly(P＜0.05).Spearman analysis showed that the serum levels of TAT,t-PAIC,and TM in ICAS patients were positively correlated with the degree of stenosis(r=0.574,0.695,0.628;all P＜0.05).Multivariate Logistic regression analysis showed that TAT,t-PAIC,TM,and TC were independent risk factors for severe stenosis in ICAS patients(P＜0.05).The ROC curve showed that the AUC of severe stenosis in ICAS patients predicted by combination of TAT,t-PAIC,TM,and TC was 0.927,with a sensitivity of 83.33％and a specificity of 86.62％,which was superior to the independent prediction of TAT,t-PAIC,TM and TC(Zcombined detection-TAT=4.617,Zcombined deteetion-t-PAIC=4.024,Zcombined detection-TM=4.004,Zcombined detection-TC=7.078,all P=0.000).Conclusion The ser-um levels of TAT,t-PAIC,and TM in the ICAS group were significantly increased,and were positively correlated with the severity of stenosis.The combination of the three and TC has a high predictive value for the occurrence of severe stenosis in ICAS patients.

Objective:To analyze the clinical features of an outbreak of extensive drug resistant typhoid fever, and to provide experience for the diagnosis and treatment of drug resistant typhoid fever.Methods:Seven patients with confirmed diagnosis of extensive drug resistant typhoid fever who visited Beijing You′an Hospital, Capital Medical University, from January 27 to February 15, 2022 were included. The clinical characteristics, drug sensitivity tests, consultation and treatment history and prognosis of the patients were analyzed through descriptive study.Results:Of the seven extensive drug resistant typhoid fever patients, three were male and four were female, one of whom was pregnant (at 32-week gestation), aged (29.8±6.8) years, with a range of 22 to 42 years. There were seven cases with fever, and the course of fever ranged from six to 20 days. There were five cases with diarrhea and lack of typhoid-specific manifestations such as rose spot, apathetic facial expression and relatively slow pulse. Four cases were complicated with intestinal bleeding and six cases developed liver function injury. Six cases had loss or decrease in eosinophil ratio and two cases had decreased white blood cell count. The results of drug susceptibility tests showed that seven strains of Salmonella typhi were resistant to chloramphenicol, ampicillin, sulfamethoxazole-trimethoprim, quinolones, ceftriaxone, cefepime, ceftazidime, cefuroxime, and sensitive to carbapenem antibiotics, tigecycline and piperacillin/tazobactam. All seven cases had a history of antimicrobial use before admission. One case was administered with intravenous ceftizoxime for seven days after admission. After discharge, cefixime was administered orally for seven days. Six patients were given intravenous piperacillin sodium/tazobactam sodium for 14 days. All blood/fecal cultures were negative and the patients were cured and discharged. During the follow-up, one patient developed splenic abscess. All the seven patients were residents of the same apartment in Beijing City, and there were water cuts and turbid odors in the incubation period, which were considered as typhoid fever outbreak caused by waterborne transmission. Conclusions:With the use of antimicrobial agents, the typical clinical manifestations of typhoid fever are absent, and the drug resistance rates to quinolone and third-generation cephalosporins increase. Appropriate antimicrobial agents should be selected and the anti-infection course should be prolonged.

The hemodynamics of children with congenital heart disease (CHD) often changes during the perioperative period. Unfortunately, the evaluation of cardiac function in children with CHD is mainly focused on the left ventricle. With the further understanding of cardiac hemodynamics, the monitoring of RV function has gradually become an important part of cardiac intensive care department. We totally searched five databases including Pubmed, Embase, Cochrane, Wanfang Med, as well as China National Knowledge Infrastructure (CNKI) and reviewed the clinical research progress of the application of TAPSE in the evaluation of RV systolic function in children with CHD to provide a theoretical basic for the monitoring of RV function before and after operation in children with CHD.

Background As emerging environmental contaminants with ecological risks, flame retardants (FRs) exhibit obvious toxicity and persistence. In recent years, as FRs have been widely detected in indoor environments and human samples, the human health risks after FRs exposure are of great concern. Objective To systematically understand the topic evolution, research status, progress, and development trends on the toxicity and health effects of FRs on humans worldwide. Methods We retrieved the literature regarding toxicity of FRs and their effects on human health through the Web of Science database from 2000 to 2020, screened and processed the literature using Endnote software, and analyzed annual publications, important citations, and authors. CiteSpace and VOSviewer were employed to draw co-citation network, keyword co-occurrence network, and keyword clustering map for bibliometric visualization analysis. Results From 2000 to 2020, 472 international papers on toxic effects and human health impacts of FRs were published. In terms of publication years, FRs-related research was mainly divided into three stages: the infancy and exploration stage (2001—2006), when the research on the toxic effects of FRs was just starting; the growth stage (2007—2015), when the risk assessments of FRs on human health were conducted; and the acceleration stage (2016—), when the studies have shifted to the mechanism of FRs damage to human health. In this field, China published the largest number of published articles in the world (177 papers), but the intermediary centrality (reflecting academic influence) was only 0.19, far lower than that of European and American countries such as the Netherlands (0.78), Britain (0.51), and Germany (0.44). Among the top 10 research institutions in terms of the number of articles published, the Chinese Academy of Sciences topped the list with 49 articles. Van der Veen and other researchers had a strong influence on the research of the toxic effects of phosphorous FRs since their papers published in 2012 were cited 1319 times and in the most prominent node in the literature co-citation network. The high-frequency keywords in the literature on the human health effects of FRs were polybrominated diphenyl ethers (217 times), brominated FRs (166 times), toxicity (147 times), FRs (102 times), exposure, polychlorinated biphenyls, in vitro experiment, plasticizer, etc. Through keyword clustering and co-occurrence analyses, it was found that current research is systematically exploring the toxic mechanism of FRs from a perspective integrating pollution source-exposure route-final receptor of pollutants, and is evaluating the environmental health risks via different exposure routes. The visualized bibliometric analysis findings suggested that future studies understand the underlying mechanisms of various cell damage caused by FRs toxicity, identify the key factors of change and their relationships, aiming to provide a scientific basis for targeted prevention of health effects of FRs. Conclusion The research hotspots on the toxic effects of FRs and their effects on human health have changed over time, and the breadth and depth have been increasing. The toxic effects of brominated/phosphorus FRs have always been the mainstream direction in this field. Further studies will focus on the molecular mechanisms of human toxicity after FRs exposure.

With the continuous development of gene therapy, more new technologies have been found and gradually applied in the basic research and clinical treatment of various diseases. In the field of AIDS treatment, gene therapy shows obvious advantages over traditional antiretroviral therapy. In recent years, short hairpin RNA (shRNA), clustered regulatory interspaced short palindrome repeat (CRISPR), transcription activator-like effector nucleases (TALEN), and zinc finger nucleases (ZFN) have been applied in AIDS treatment and have fruitful results. This paper reviews the major breakthroughs in this field since the emergence of gene therapy and the latest research achievements and their progress, with a view to providing a useful reference on a wider range of gene therapy application.