Herpes simplex viruses type 1(HSV1)is among the most ubiquitous human pathogens that cause a wide variety of disease states.The latent infection of the central nervous system and sporadically reactivation is the central part of HSV1 pathogenesis,which also brings challenges to antiviral therapies.At present,the mechanism of establishing,maintaining and reactivation of HSV1 has not been fully clarified,whereas it has been generally accepted that the epigenetic regulation may play an important role.Accumulating researches have also indicated that the lytic and latent viral genomes exhibit the different chromatin structures,and the accumulation of diverse post-translational modifies the histones endow viral genes with transcriptional activation or repression features.In addition,the latency-associate transcripts of virus may also participate in the genome epigenetic modification.In this review,we summarize the research progress of epigenetic regulation of HSV1 and highlight the critical role of chromatin remodeling in HSV1 lytic proliferation and establishment of latent infection.

BACKGROUND:The activation of NOD-like receptor thermal protein domain associated protein 3(NLRP3)inflammasome has been found to be an important factor in the pathogenesis of gouty arthritis,and the activation of NLPR3 inflammasome can be effectively inhibited by regulating the PTEN-induced kinas 1(PINK1)/Parkin signaling pathway. OBJECTIVE:To investigate the effect of Duhuo Jisheng Decoction on the PINK1/Parkin/NLRP3 signaling pathway. METHODS:(1)Animal experiment:Male Sprague-Dawley rats were randomly divided into control group,model group,positive control group(Qiushuixian tablets 0.3 mg/kg),and low-,medium-,and high-dose Duhuo Jisheng Decoction groups(6.9,13.8,and 27.6 g/kg,respectively).A rat gouty arthritis model was constructed by injecting monosodium urate crystal suspension into the right hind ankle joint cavity of rats in all the groups except for the control group.(2)Cell experiment:Human monocytes(THP-1)were divided into blank control group,model group,Duhuo Jisheng Decoction-containing serum group,and PINK1 siRNA+Duhuo Jisheng Decoction-containing serum group.The cells in each group except the blank control group were stimulated with sodium urate to establish an in vitro gouty arthritis model.(3)The swelling degree,joint circumference,gait score,joint inflammation index and degree of pathological grading in the ankle joints of rats were observed.Enzyme-linked immunosorbent assay was used to detect the levels of uric acid,C-reactive protein,NLRP3,and interleukin 1β.Immunoblotting assay was used to detect the levels of proteins related to the PINK1/Parkin/NLRP3 pathway.Tetramethyl azolidine blue assay was used to detect cell activity.Immunofluorescent double staining was performed to detect the level of mitophagy.Immunofluorescence was used to detect the expression of NLRP3 and interleukin 1β. RESULTS AND CONCLUSION:(1)Compared with the control group,rats in the model group showed elevated ankle swelling and ankle circumference at 6-48 hours(P<0.05),elevated gait scores and joint inflammation indexes at 24 and 48 hours(P<0.05),elevated serum uric acid and C-reactive protein levels,degree of pathological classification,expression of PINK1,Parkin,and NLRP3 proteins,and interleukin 1β level in synovial tissues(P<0.05).Compared with the model group,the protein expression levels of PINK1 and Parkin in all the Duhuo Jisheng Decoction groups were elevated,while the levels of the other indexes were decreased(P<0.05).(2)Compared with the model group,NLRP3 activity,interleukin 1β level and mitochondrial outer membrane translocator protein 20 protein level in the Duhuo Jisheng Decoction-containing serum group were decreased(P<0.05),while the proliferation inhibition rate,PINK1,Parkin and LC3B protein level were increased(P<0.05).Compared with the model group,the mitochondrial autophagy level of cells in the Duhuo Jisheng Decoction-containing serum group was elevated(P<0.05),while NLRP3 and interleukin 1β protein levels were decreased(P<0.05).(3)Compared with the Duhuo Jisheng Decoction-containing serum group,the mitochondrial autophagy level of cells in the PINK1 siRNA+Duhuo Jisheng Decoction-containing serum group was decreased(P<0.05),and the expression levels of NLRP3 and interleukin 1β were elevated(P<0.05).To conclude,Duhuo Jisheng Decoction inhibits the activation of NLRP3 inflammasome by regulating the PINK1/Parkin signaling pathway, thereby exerting a therapeutic effect on gouty arthritis.

BACKGROUND:The distribution of the necrotic area plays an important role in hip preservation treatment.At present,there are few studies on whether the difference in the three-dimensional spatial distribution of osteonecrosis of the femoral head affects the clinical outcome of fibular support. OBJECTIVE:To explore the relationship between the spatial distribution and clinical outcome at the sites of osteonecrosis of the femoral head and fibular support using CT three-dimensional reconstruction so as to provide a basis for optimizing the applicable conditions of fibular support and improving the hip preservation effect of fibular support. METHODS:Eighty patients with osteonecrosis of the femoral head who were treated with fibular support for hip preservation from January 2010 to January 2021 were selected as the study subjects according to the inclusion criteria.They were followed up for at least 2 years.According to the clinical outcome,the patients were divided into the successful hip preservation group(n=55)and the failure hip preservation group(n=25).3D reconstruction was performed according to the preoperative and postoperative CT images of the patients.According to the three-column theory,the femoral head was divided into outer nine areas,middle nine areas and inner nine areas(L1-9,C1-9,and M1-9)to explore the spatial distribution of necrotic area of the femoral head and fibular support area and its relationship with clinical outcome. RESULTS AND CONCLUSION:(1)Before operation,the necrotic area of the femoral head was mainly distributed in L1,L2,L4,L5,C1,C2,C4,and C5(the upper and middle part of the anterior part of the outer ninth area and the middle part of the middle ninth area).After operation,the fibular support area was mainly distributed in L5,L6,C5,and C6(the middle and lower part of the outer ninth area and the middle and lower part of the middle ninth area).(2)There were significant differences in the distribution of osteonecrosis of the femoral head between the successful hip preservation group and the failure hip preservation group in L8(the posterior middle part of the outer ninth area),C3(the anterior lower part of the middle ninth area),C6(the lower middle part of the middle part of the inner ninth area)and M2(the anterior middle part of the inner ninth area)(P<0.05).There was a significant difference in the distribution of fibular support in L5 and L6(middle and lower part of outer nine)(P<0.05).Among them,the L8 region could be used as an independent predictor of hip preservation failure in fibular support surgery.The area under the curve of the L8 single factor prediction model was 0.698[95%CI(0.575,0.822)];the sensitivity was 76%,and the specificity was 63.6%.(3)It turns out,when the necrotic area involves L8,C3,C6,and M2,especially L8,the failure of fibular support may increase,and when the fibular support involves L5 and L6,the effect of hip preservation is often not ideal.

BACKGROUND:Bone has bioelectric effects.However,bone defects can lead to loss of endogenous bioelectricity in bone.The implantation of bone tissue engineering scaffolds with bioelectric effect into bone defects will replenish the missing electrical signals and accelerate the repair of bone defects. OBJECTIVE:To introduce the bioelectric effect of bone tissue and expound the repair effect of electrical stimulation on bone defects,summarize the research progress of bioelectric effect applied to bone tissue engineering,in order to provide new ideas for the research of bone tissue engineering. METHODS:Relevant articles were searched on CNKI,WanFang,PubMed,Web of Science and ScienceDirect databases,using"bioelectrical effect,bioelectrical materials,electrical stimulation,bone tissue engineering,bone scaffold,bone defect,bone repair,osteogenesis"as the English and Chinese search terms.Finally,87 articles were included for analysis. RESULTS AND CONCLUSION:(1)Bioelectrical effect combined with ex vivo electrical stimulation to design bone tissue engineering scaffolds is an ideal and feasible approach,and the main materials involved include metallic materials,graphene materials,natural bio-derived materials,and synthetic biomaterial.At present,the most widely used conductive material is graphene material,which benefits from its super conductivity,large specific surface area,good biocompatibility with cells and bones,and excellent mechanical properties.(2)Graphene materials are mainly introduced into the scaffold as modified materials to enhance the conductivity of the overall scaffold,while its large surface area and rich functional groups can promote the loading and release of bioactive substances.(3)However,there are still some major challenges to overcome for bioelectrically effective bone tissue engineering scaffolds:not only electrical conductivity but also the overall performance of the bracket needs to be considered;lack of uniform,standardized preparation of bioelectrically effective bone tissue engineering scaffolds;extracorporeal electrical stimulation intervention systems are not yet mature enough;lack of individualized guidance on stent selection to enable the selection and design of the most appropriate stent for patients with different pathologies.(4)When designing conductive scaffolds,researchers have to deeply consider the comprehensive effects of the scaffolds,such as biocompatibility,mechanical properties,and biodegradability.This combination of properties can be achieved by combining multiple materials.(5)Beyond that,clinical translation should be the ultimate consideration for conductive stent design.On the basis of evaluating the safe current threshold for electrical stimulation to act on the human body and facilitate the repair of bone defects,animal experiments as well as basic experiments are designed and then applied to the clinic to achieve the ultimate goal of applying bioelectrical effect bone tissue engineering scaffolds in the clinic.

Objective:To understand the loss to follow-up of children born to pregnant women with HIV infection (HIV-exposed children) and analyze its influencing factors in China in 2019.Methods:The data were collected from the follow-up records of pregnant women with HIV infection and their children reported by the national "Management Information System for the Prevention of HIV, syphilis and Hepatitis B Mother-to-Child Transmission" in 2019. HIV-exposed children were defined as those who were not followed up after birth or who were not followed up at 18 months of age and who were not followed up at 21 months of age. The univariate and multivariate influencing factors of loss to follow-up of children born to HIV-infected pregnant women were analyzed by χ2 test and logistic regression model. SPSS 25.0 software was used for statistical analysis. Results:The number of HIV-infected pregnant women was 5 039, the number of live-born children was 5 035, the number of loss to follow-up children within 18 months of age was 283, and the loss to follow-up rate children was 5.62%(283/5 035). The results of multivariate logistic regression analysis showed that the rate of loss to follow-up of exposed children born to pregnant women who worked as farmers (animal husbandry and fishery) (a OR=0.34, 95% CI: 0.22-0.53), unmarried (a OR=0.47, 95% CI: 0.24-0.93), first marriage (a OR=0.38, 95% CI: 0.22-0.67), remarriage (a OR=0.36, 95% CI: 0.20-0.67) and cohabiting (a OR=0.47, 95% CI: 0.23-0.97), and knew they had HIV infection before this pregnancy (a OR=0.53, 95% CI: 0.40-0.70) was lower. Han nationality (a OR=1.52, 95% CI: 1.09-2.13), primary school (a OR=2.06, 95% CI: 1.10-3.89) and junior middle school (a OR=1.81, 95% CI: 1.03-3.17) educational level, non-use of antiviral drugs (a OR=6.21, 95% CI: 4.32-8.93) and delivery in township (street) level midwifery institutions (a OR=5.72, 95% CI: 1.61-20.27) had higher rates of loss to follow-up among infants born to HIV-infected pregnant women. Conclusions:HIV-exposed children still have a specific rate of loss to follow-up in China in 2019. In order to further reduce the rate of loss to follow-up, it is of great significance to improve the detection rate of HIV before pregnancy and the rate of antiviral drugs used in pregnant women with HIV infection, which is of great significance for the effective implementation of comprehensive intervention measures of prevention of mother-to-child transmission of HIV.

Objective:To explored the correlation between anxiety and depression and cerebral small vessel disease(CSVD)in the elderly patients with type 2 diabetes mellitus(T2DM), and analyzed the influencing factors of anxiety and depression.Methods:Clinical data of 101 elderly T2DM inpatients admitted to the Department of Endocrinology, the Second Affiliated Hospital of Fujian Medical University from July 2020 to December 2021 were retrospectively analyzed, and clinical features, laboratory tests and examination data were collected.The Hamilton Depression Scale and the Hamilton Anxiety Scale were used for assessment, with a cut-off value of 14 points for anxiety and 8 points for depression.Brain scans were performed using 3.0T magnetic resonance scanner, including T1WI sequence, T2WI sequence, 3D-FLAIR sequence, SWI sequence.According to the total MRI load scoring standard of CSVD proposed by Staals, MRI imaging changes of CSVD, namely lacunar foci(LIs), cerebral microhemorrhage(CMBs), perivascular space(PVSs), and white matter high signal(WMHs), were analyzed and scored respectively.Load score ≥1 was defined as CSVD group.According to the above criteria, the enrolled patients were divided into depression group and anxiety group, and the clinical characteristics, biochemical test data and MRI imaging characteristics of CSVD between the two groups were analyzed by single factor analysis, and then Spearman correlation analysis was used to analyze the related factors of the elderly T2DM with anxiety and depression.Binary logistic analysis was used to analyze the risk factors of depression and anxiety in the elderly patients with T2DM.Results:Compared with the non-depressed group, the elderly T2DM patients with depression were older, more female, and the incidence of WMHs and DWMHs was higher( P<0.05).Compared with the non-anxious group, the incidence of WMHs and DWMHs in the elderly T2DM patients with anxiety group was higher( P<0.05).Spearman correlation analysis showed that age( r=0.224, P=0.024), WMHs( r=0.231, P=0.020), PWMHs( r=0.201, P=0.044), DWMHs( r=0.274, P=0.006)was positively correlated with depression in the elderly T2DM, while gender( r=-0.225, P=0.024)、ALT( r=-0.208, P=0.037)、AST( r=-0.204, P=0.041)was negatively correlated with depression in the elderly T2DM.WMHs( r=0.213, P=0.033)and DWMHs( r=0.270, P=0.006)were positively correlated with anxiety in the elderly T2DM.Binary logistic regression analysis showed that gender( OR=0.359, 95% CI: 0.130-0.990, P=0.048), DWMHs(OR=4.373, 95% CI: 1.290-14.828, P=0.018)were the influencing factors for the elderly T2DM patients with depression, and DWMHs( OR=5.000, 95% CI: 1.444-17.317, P=0.011)was the influencing factors for the elderly T2DM patients with anxiety. Conclusions:DWMHs is closely related to the onset of depression and anxiety in the elderly T2DM patients, suggesting that CSVD may be involved in the development of depression and anxiety in the elderly T2DM patients.

Nicotinamide mononucleotide (NMN) is one of the key precursors of coenzyme Ⅰ (NAD⁺). NMN exists widely in a variety of organisms, and β isomer is its active form. Studies have shown that β-NMN plays a key role in a variety of physiological and metabolic processes. As a potential active substance in anti-aging and improving degenerative and metabolic diseases, the application value of β-NMN has been deeply explored, and it is imminent to achieve large-scale production. Biosynthesis has become the preferred method to synthesize β-NMN because of its high stereoselectivity, mild reaction conditions, and fewer by-products. This paper reviews the physiological activity, chemical synthesis as well as biosynthesis of β-NMN, highlighting the metabolic pathways involved in biosynthesis. This review aims to explore the potential of improving the production strategy of β-NMN by using synthetic biology and provide a theoretical basis for the research of metabolic pathways as well as efficient production of β-NMN.
Nicotinamide Mononucleotide/metabolism* ; NAD/metabolism*

Objective:To analyze the construction and operation of the 19th Hangzhou Asian Games designated hospitals, and to discuss the medical emergency security work of large-scale sports events, so as to provide references for the planning of designated hospitals in future large-scale sports events.Methods:Retrospective analysis was made on the establishment principles, requirements, selection of medical support personnel, and training exercises of the designated hospitals, focusing on the key links such as organizational system, staffing, designated areas, and drug management.Results:Total of 40 designated hospitals have successfully completed the task of medical security by rebuilding the medical security area of the Asian Games, elevating the process, equipping facilities, and strengthening staff training. During the Asian Games, 349 people were transferred to designated hospitals by ambulance, 54 people were hospitalized, 19 people underwent surgery, and 1022 people went to designated hospitals by themselves.Conclusion:The construction of the designated hospitals during the 19th Hangzhou Asian Games was of high quality, efficient and smooth operation. It is suggested that efforts should be made in the reconstruction of the medical security area for the Asian Games to be "relatively independent". The treatment process of self-visiting patients should be fully considered and the flat urgent emergency response mechanism needs to be established.

Objective:To investigate the value of fractional exhaled nitric oxide (FeNO) combined with small airway function test to replace bronchial provocation test and induced sputum test in differentiating cough variant asthma (CVA) from eosinophilic bronchitis (EB).Methods:The clinical data of 105 patients with chronic cough admitted to The Third People's Hospital of Hubei, Jianghan University from January 2018 to December 2021 were retrospectively analyzed. These patients consisted of 40 patients with CVA (CVA group), 25 patients with EB (EB group), and 40 patients with other chronic coughs (other chronic cough group). FeNO and lung function were compared between groups. The value of FeNO, small airway function, and their combination in differentiating CVA from EB were analyzed using the receiver operating characteristic curves.Results:FeNO level was the highest in the CVA group [33.0 (30.0, 37.8) ppb], followed by the EB group [28.0 (25.5, 32.0) ppb], and the lowest in other chronic cough group [13.0 (11.0, 15.0) ppb]. There was significant difference in FeNO level between groups ( H value = 79.00, P < 0.05). There were no significant differences in forced vital capacity (FVC), forced expiratory volume in 1 second (FEV 1), FEV 1/FVC, peak expiratory flow (PEF) between groups (all P > 0.05). Maximal mid-expiratory flow (MMEF) [74 (66.0, 77.4) in the CVA group, 80 (79.0, 83.3) in the EB group, 88.0 (86.4, 90.0) in other chronic coughs group], FEF25 (%) [70.0 (60.3, 75.1) in the CVA group, 78.0 (74.1, 85.0) in the EB group, 81.7 (78.9, 86.3) in other chronic coughs group], FEF50 (%) [75.2 (67.1, 80.8) in the CVA group, 80.6 (75.7, 85.9) in the EB group, 89.4 (87.0, 90.5) in other chronic coughs group], FEF75 (%) [76.4 (68.7, 85.8) in the CVA group, 80.9 (77.4, 89.7) in the EB group, 90.8 (87.2, 94.2) in other chronic coughs group] were significantly lower in the CVA group than those in other chronic coughs group. With the exception of FEF25 (%), MMEF (%), FEF50 (%), and FEF75 (%) were significantly lower in the EB group compared with other chronic coughs group. MMEF (%) and FEF25 (%) in the CVA group were significantly lower compared with the EB group. There were significant differences in MMEF (%), FEF50 (%), and FEF75 (%) between groups ( H = 62.82, 47.04, 47.41, 49.11, all P < 0.01). There were significant differences in FEF50 (%) and FEF75 (%) between CVA and EB groups (both P > 0.05). In binary logistic regression equation, FeNO and MMEF (%) were important indexes to distinguish CVA from EB ( P < 0.05). Bronchial provocation test and induced sputum test were used as the gold standard to distinguish CVA from EB. When FeNO and MMEF (%) were used separately to distinguish CVA from EB, the optimal threshold value was 30.0 ppb and 77.7 respectively, the area under the receiver operating characteristic curve was 0.77 and 0.82 respectively, the diagnostic sensitivity was 70% and 77.5% respectively, and the diagnostic specificity was 72% and 88% respectively. When FeNO and MMEF (%) were used in combination to distinguish CVA from EB, the area under the receiver operating characteristic curve was 0.89, and the diagnostic sensitivity and specificity was 75% and 96% respectively. Conclusion:FeNO and MMEF (%) can be used to distinguish CVA from EB. FeNO combined with MMEF (%) has a higher value in distinguishing CVA from EB than FeNO and MMEF alone.

Objective:To investigate the clinical difference between primary suture and T tube drainage in laparoscopic choledocholithotomy.Methods:The clinical data of 124 patients treated by laparoscopic choledocholithotomy in Suzhou Municipal Hospital from December 2018 to February 2020 were retrospectively studied. The patients were divided into the primary suture group (71 cases) and the T tube drainage group (53 cases) according to the different surgical methods, and the differences in the relevant treatment indicators were compared between the two groups.Results:There were no statistically significant differences between the two groups in gender, hypertension, diabetes mellitus, preoperative aspartate aminotransferase, preoperative alanine aminotransferase, preoperative total bilirubin, preoperative common bile duct diameter, postoperative length of stay, total cost of hospitalization, postoperative exhaust time, or postoperative biliary leakage, et al. Compared with the T tube drainage group, the primary suture group had more single choledocholithiasis before operation (33 cases vs. 15 cases), shorter operation time: (100.14 ± 38.90) h vs. (140.45 ± 54.17) h, less intraoperative bleeding: (35.70 ± 30.17) ml vs. (49.53 ± 34.58) ml, and later extraction time of Winslow hole drainage tube after operation: (7.15 ± 2.61) d vs. (5.45 ± 3.35) d, and the differences were statistically significant ( P<0.05). Conclusions:Under the condition of strictly controlling the indications of primary suture and being operated by general surgeons who can skillfully operate laparoscope and choledochoscope, laparoscopic choledocholithotomy for primary suture has better curative effect than T tube drainage, and has higher clinical application value.