ObjectiveTo investigate the characteristics of mitochondrial translational initiation factor 2 （MTIF2） gene methylation and its association with the development and progression of hepatocellular carcinoma （HCC）. MethodsMethSurv and EWAS Data Hub were used to perform the standardized analysis and the cluster analysis of MTIF2 methylation samples， including survival curve analysis， methylation signature analysis， the association of tumor signaling pathways， and a comparative analysis based on pan-cancer database. The independent-samples t test was used for comparison between two groups； a one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test was used for further comparison between two groups. The Cox proportional hazards model was used to perform the univariate and multivariate survival analyses of methylation level at the CpG site. The Kaplan-Meier method was used to investigate the survival differences between the patients with low methylation level and those with high methylation level， and the Log-likelihood ratio method was used for survival difference analysis. ResultsGlobal clustering of MTIF2 methylation showed that there was no significant difference in MTIF2 gene methylation level between different races， ethnicities， BMI levels， and ages. The Kaplan-Meier survival curve analysis showed that the patients with N-Shore hypermethylation of the MTIF2 gene had a significantly better prognosis than those with hypomethylation （hazard ratio ［HR］=0.492， P<0.001）， while there was no significant difference in survival rate between the patients with different CpG island and S-Shore methylation levels （P>0.05）. The methylation profile of the MTIF2 gene based on different ages， sexes， BMI levels， races， ethnicities， and clinical stages showed that the N-Shore and CpG island methylation levels of the MTIF2 gene decreased with the increase in age， and the Caucasian population had significantly lower N-Shore methylation levels of the MTIF2 gene than the Asian population （P<0.05）； the patients with clinical stage Ⅳ had significantly lower N-Shore and CpG island methylation levels of the MTIF2 gene than those with stage Ⅰ/Ⅱ （P<0.05）. Clinical validation showed that the patients with stage Ⅲ/Ⅳ HCC had a significantly lower methylation level of the MTIF2 gene than those with stage Ⅰ/Ⅱ HCC and the normal population （P<0.05）. ConclusionN-Shore hypomethylation of the MTIF2 gene is a risk factor for the development and progression of HCC.

Diffuse large B-cell lymphoma （DLBCL） is a highly heterogeneous disease. Although standard first-line regimens can cure ＞50% of patients， approximately one-third of them develop relapsed/refractory DLBCL （r/r DLBCL）. Consequently， immunotherapy targeting molecular abnormalities has become pivotal for managing r/r DLBCL. The results of this review show that with advances in understanding DLBCL pathogenesis and the tumor immune microenvironment， antibody-based therapies have evolved rapidly， progressing from monoclonal antibodies （e.g.， rituximab， tafasitamab） to bispecific antibodies（e.g.， odronextamab，glofitamab， epcoritamab） and antibody-drug conjugate （e.g.， polatuzumab vedotin， loncastuximab tesirine）. These engineered agents enhance immune cytotoxicity and tumor-specific targeting， providing novel therapeutic options for r/r DLBCL patients.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

African swine fever(ASF)is an acute and highly pathogenic hemorrhagic disease of pigs,causing huge economic losses to pig industry.In order to quantitatively detect clinical samples of ASF and inactivated ASFV antigens,the IgG of ASF positive serum was used as capture anti-body and the HRP-labeled p72 monoclonal antibody was used as detecting antibody.The standard curve was drawn with the cell-cultured ASFV,and a sandwich ELISA detection of antigen was es-tablished.The specificity,sensitivity and stability of the method were evaluated.The effects of dif-ferent inactivation methods and adjuvant addition on antigen detection were further evaluated.The results showed that the minimum detection limits of the recombinant protein and the ASFV were 0.1 mg/L and 103.7 TCID50/mL,respectively.There was no cross-reaction with five common porcine pathogenic viruses,and the coefficient variations between batches was less than 10％.The total co-incidence rate with real-time fluorescence quantitative PCR was 92％(23/25).The sensitivity of antigen detection was significantly reduced when antigen was treated by BEI inactivation,and the detection results were severely interfered by aluminum adjuvant and nano-adjuvant.In summary,the sandwich ELISA antigen detection method established is specific,sensitive,and repeatable,with a good consistency to the qPCR method,which provides an effective clinical diagnostic meth-od for ASFV antigen.

Metastasis of colorectal cancer is the primary cause of progression and mortality.Although surgical resection is the preferred method for liver metastasis of colorectal cancer,liver transplantation,as a treatment approach,has attracted widespread attention for patients with unresectable colorectal cancer liver metastases.Recently,an increasing number of clinical trials have focused on the indications for liver transplantation in the treatment of unresectable colorectal cancer liver metastases.Therefore,we systematically summarize the progress of liver transplantation in the application of unresectable colorectal cancer liver metastasis from the aspects of indications,contraindications and advantages over traditional treatment methods.

Objective:To combine ultrasound and clinical characteristics for predicting the treatment time of strontium 90( 90Sr) radioisotope applicator therapy for pathological scars when the therapeutic effect meets the clinical effective criteria. Methods:From September 2022 to October 2023, 48 patients (90 lesions) with pathological scars who underwent 90Sr radioisotope applicator therapy at the Department of Nuclear Medicine, Nanfang Hospital, Southern Medical University were prospectively collected. The clinically effective criteria of 90Sr radioisotope applicator therapy for pathological scars were defined as a reduction of the superficial height of the scar higher than 50%. All lesions were divided into short period treatment group (2 months, 38 lesions) and long period treatment group (>2 months, 52 lesions) according to the duration of treatment when the therapeutic effect met the clinical criteria. Univariate comparative analyses of ultrasound and clinical characteristics between the two groups were performed. The statistically significant variates were used to build a multivariate logistic regression model for analyzing the independent predictors of the treatment time of 90Sr radioisotope applicator therapy for pathological scars. Results:Family history, blood flow signal, disease duration, age, and scar Young′s modulus were independent predictors of the effective treatment time of 90Sr radioisotope applicator therapy for pathological scars (all P<0.05). By using the selected variables, a predictive model was developed, area under the ROC curve (AUC) were 0.886 (95% CI=0.817-0.955, P<0.001), and the calibration curve showed that the model was well calibrated(χ 2=5.668, P=0.684). Conclusions:The multivariate logistic regression model with family history, blood flow signal, disease duration, age, and scar Young′s modulus could be used to predict the treatment time of 90Sr radioisotope applicator therapy for pathologic scars, which can help to guide the design of treatment plan, reduce unnecessary radiation damage, and improve patient compliance.

Alzheimer's disease （AD） is a neurodegenerative disease often characterized by cognitive impairment in clinical practice. The main pathogenesis includes β amyloid protein （Aβ） excessive deposition， neuroinflammatory response， Tau protein hyperphosphorylation， and other factors， and currently only a few chemical drugs have been approved for clinical treatment of AD. The mechanism of action is relatively single， so it is imperative to find new treatment strategies. Traditional Chinese medicine theory believes that the loss of nourishment in the brain and marrow， as well as the loss of vital energy， is the internal mechanisms underlying the occurrence and development of AD， which runs through the entire treatment process. The pathogenesis of AD is closely related to the inflammasome signaling pathway of nucleotide binding oligomerization domain-like receptor protein 3 （NLRP3）. Activating the NLRP3 signaling pathway increases neuroinflammatory response， intervenes in microglial polarization， and regulates Aβ sedimentation， cellular autophagy， brain homeostasis， etc. This article takes the NLRP3 signaling pathway as the starting point to sort out and summarize the upstream and downstream targets under the AD mechanism in the past five years， as well as the research on the NLRP3 signal pathway targets with the participation of the relevant traditional Chinese medicine compounds， such as Danggui Shaoyaosan， modified Shuyu Wan， Qingxin Kaiqiao prescription， Kaixin San， Jiedu Yizhi prescription， and modified Buwang San， traditional Chinese medicine monomer extracts， such as silibinin， Lycium barbarum polysaccharides， liquiritigenin， salidroside， baicalin， cinnamaldehyde， betaine， acacetin， and Hericium erinaceus， and acupuncture and moxibustion. It also reviews the latest achievements in the prevention and treatment of AD. This study provides ideas and directions for in-depth research on the prevention and treatment of cognitive dysfunction related diseases with traditional Chinese medicine.

Objective To explore the effect of histologic chorioamnionitis(HCA)on clinical outcomes of preterm infants with a gestational age<34 weeks.Methods This retrospective study enrolled 497 cases of premature infants with a gestational age<34 weeks and their mothers who were hospitalized in the Qingdao Women and Children's Hospital from January 2019 to December 2022.According to whether the pathology of placenta was diagnosed as HCA or not,patients were divided into the HCA group(257 cases)and the control group(240 cases).The propensity score matching analysis was performed at a ratio of 1︰1.Ten items were matched,including gestational age,birth weight,gender,cesarean section,gestational diabetes mellitus,gestational hypertension,placental abruption,premature rupture of membranes,use of antenatal glucocorticoids and assisted reproductive technology.The differences of major complications and survival rate were compared between the two groups.Results A total of 156 pairs premature infants were successfully matched.Before matching,the incidences of early-onset sepsis(EOS)and bronchopulmonary dysplasia(BPD)were higher in the HCA group than those of the control group(26.1%vs.7.5%,45.1%vs.25.8%,P＜0.01).The incidence of EOS was higher in the HCA group than that of the control group after matching(24.4%vs.7.7%,P＜0.01),and the incidence of neonatal respiratory distress syndrome(NRDS)was significantly lower in the HCA group than that in the control group after matching(34.0%vs.46.8%,P＜0.05).There were no significant differences in survival rate and the incidences of other complications between the two groups before and after matching(P>0.05).Conclusion Preterm infants exposed to HCA have a higher risk of EOS and a lower risk of NRDS after propensity score matching.HCA has no significant effect on survival rate and other complications of premature infants.

BACKGROUND:Pretreatment with moxibustion is a preventive treatment in traditional Chinese medicine.Pretreatment with moxibustion at the onset of prodromal symptoms can significantly reduce the symptoms and delay the onset of many diseases,but the exact mechanism remains to be studied. OBJECTIVE:To investigate the mechanism of SIRT1/FoxO3 pathway in moxibustion pretreatment to ameliorate oxidative stress injury in cerebral ischemia-reperfusion model rats. METHODS:Forty-eight Sprague-Dawley rats were randomly divided into sham-operated group,model group,moxibustion pretreatment group,and moxibustion pretreatment+EX527(SIRT1 inhibitor)group,with 12 rats in each group.The moxibustion pretreatment group was given moxibustion with seed-sized moxa cone at Baihui,Dazhui,and Zusanli before modeling,three moxa-cones per acupoint,once a day for 7 days.In the model group,moxibustion pretreatment group and moxibustion pretreatment+EX527 group,the rat model of middle cerebral artery occlusion was made by suturing of the middle cerebral artery 30 minutes after the last moxibustion.After 2 hours of cerebral ischemia,the middle artery suture was removed and the rats were reperfused for 12 hours.In the sham-operated group,only the common carotid artery,internal carotid artery,and external carotid artery were dissected without suturing the middle cerebral artery.In the moxibustion pretreatment+EX527 group,EX527(15 mg/kg)was given intraperitoneally 30 minutes before each moxibustion.After 12 hours of reperfusion,the rats were scored for neurological deficits,and the cerebral infarct volume was calculated by 2,3,5-triphenyltetrazolium chloride staining method.The levels of oxidative stress factors in the infarcted tissues were detected by the kit method,and western-blot method was used to detect the expression levels of SIRT1,FoxO3,p-FoxO3 and brain-derived neurotrophic factor in the ischemic area of the cerebral cortex. RESULTS AND CONCLUSION:After 12 hours of reperfusion,the neurobehavioral score in the model group was significantly higher than that in the sham-operated group(P＜0.01),while the score in the moxibustion pretreatment group was significantly lower than that in the model group(P＜0.01)and moxibustion pretreatment+EX527 group(P＜0.05).There were no obvious infarct foci in the brain tissue of the sham-operated rats,but obvious ischemic foci were observed in the right side of the brain tissue of the rats in the model group(P＜0.01).The right infarct volume in the moxibustion pretreatment group was significantly reduced compared with the model group(P＜0.01),while the right infarct volume in the moxibustion pretreatment+EX527 group was significantly enlarged compared with the moxibustion pretreatment group.After 12 hours of reperfusion,the level of malondialdehyde was significantly elevated(P＜0.01)and the expression of superoxide dismutase was significantly decreased(P＜0.01)in the model group compared with the sham-operated group.The levels of malondialdehyde was significantly decreased(P＜0.01,P＜0.05)and the expression of superoxide dismutase was significantly increased(P＜0.01,P＜0.05)in the moxibustion pretreatment group compared with the model group and the moxibustion pretreatment+EX527 group.Western blot results showed that the expression levels of SIRT1,FoxO3,p-FoxO3,and brain-derived neurotrophic factor proteins were significantly higher in the model group compared with the sham-operated group(P＜0.01);compared with the model group,the expression levels of SIRT1,FoxO3,and brain-derived neurotrophic factor were significantly higher in the moxibustion pretreatment group(P＜0.01),and p-FoxO3 expression was significantly lower(P＜0.01);compared with the moxibustion pretreatment+EX527 group,the expression levels of SIRT1,FoxO3,and brain-derived neurotrophic factor were elevated in the moxibustion pretreatment group(P＜0.05),and no statistically significant difference was found in the p-FoxO3 expression(P＞0.05).To conclude,moxibustion pretreatment can significantly improve neurological function in rats after cerebral ischemia-reperfusion,and the mechanism may be related to the activation of SIRT1/FoxO3 pathway to reduce oxidative stress injury in the rat model of cerebral ischemia-reperfusion.

BACKGROUND:It was found that moxibustion can inhibit the inflammatory factors in the serum of rats with cerebral ischemia/reperfusion injury,resist oxidative stress,inhibit cell apoptosis,and effectively reduce cerebral ischemia/reperfusion injury. OBJECTIVE:To observe the effects of different moxibustion intervention time on the expression levels of nucleotide binding oligomerization domain-like protein 3 inflammasome(NLRP3),cysteine aspartase(caspase-1),apoptosis-related speck-like protein,exfoliatin-D protein,interleukin-1β and interleukin-18 in rats with cerebral ischemia/reperfusion injury,and to explore its action mechanism. METHODS:SD rats were randomly divided into sham operation group(n=9)and operation group(n=36).The model of focal cerebral ischemia/reperfusion injury was established by middle cerebral artery occlusion in the operation group.After successful modeling,the rats in the operation group were further divided into model group,moxibustion 10-minute group,moxibustion 15-minute group and moxibustion 30-minute group,with 9 rats in each group.Rats in the moxibustion 10-minute,15-minute and 30-minute groups were given moxibustion at"Baihui,Dazhui and Zusanli",respectively,once a day for a total of 7 days.The neurological deficits of rats were evaluated by LONGA method.The cerebral infarction was observed by 2,3,5-triphenyltetrazolium chloride staining.The pathological changes of brain tissue were observed by hematoxylin-eosin staining.The contents of interleukin-1β and interleukin-18 in serum of rats in each group were detected by ELISA.Immunohistochemistry and western blot assay were used to detect the expression levels of NLRP3,caspase-1,apoptosis-related spot-like protein and gasdermin D in the ischemic cortex of rats in each group. RESULTS AND CONCLUSION:Compared with the sham operation group,the neurological deficit score of the model group was significantly increased(P<0.01).Compared with the model group,the neurological deficit score of the moxibustion groups was significantly reduced(P<0.01).Compared with the sham operation group,the infarct volume of the model group was significantly increased(P<0.01).Compared with the model group,the infarct volume of the moxibustion groups was significantly reduced(P<0.01);the infarct volume of the rats was smallest in the moxibustion 30-minute group(P<0.05).Compared with the model group,the contents of inflammatory factors interleukin-1β and interleukin-18 in the serum of rats in the moxibustion groups were decreased(P<0.01).Compared with the moxibustion 10-minute group,the contents of inflammatory factors in the serum of rats in the moxibustion 30-minute group were significantly decreased(P<0.05).Compared with the model group,the expression of NLRP3,apoptosis-related spot-like protein,Caspase-1 and gasdermin D protein in the ischemic cortex of the moxibustion groups was significantly decreased(P<0.01).Compared with the moxibustion 10-minute and 15-minute groups,the expression of protein in the moxibustion 30-minute group was significantly decreased(P<0.05).It is concluded that moxibustion at Baihui,Dazhui and Zusanli can reduce cerebral ischemia/reperfusion injury,among which moxibustion for 30 minutes has the best effect,and its mechanism may be related to the inhibition of pyroptosis mediated by NLRP3/Caspase-1 pathway.