ObjectiveTo investigate the status of overlapping hepatitis B virus （HBV） infection in patients with chronic hepatitis C virus （HCV） infection and the serological characteristics of such patients. MethodsA total of 8 637 patients with HCV infection who were hospitalized from January 1， 2010 to December 31， 2020 and had complete data of HBV serological markers were enrolled， and the composition ratio of patients with overlapping HBV serological markers was analyzed among the patients with HCV infection. The patients were divided into groups based on age and year of birth， and serological characteristics were analyzed， and the distribution of HBV-related serological characteristics were analyzed across different HCV genotypes. ResultsThe patients with HCV/HBV overlapping infection accounted for 5.85%， and the patients with previous HBV infection accounted for 48.10%； the patients with protective immunity against HBV accounted for 14.67%， while the patients with a lack of protective immunity against HBV accounted for 31.39%. The patients were divided into groups based on age： in the 0 — 17 years group， the patients with protective immunity against HBV accounted for 61.41% （304 patients）； the 18 — 44 years group was mainly composed of patients with previous HBV infection （698 patients， 37.31%）， the 45 — 59 years group was predominantly composed of patients with previous HBV infection （1 945 patients， 50.38%）， and the ≥60 years group was also predominantly composed of patients with previous HBV infection （1 486 patients， 61.66%）. The patients were divided into groups based on the year of birth： in the pre-1992 group， the patients with previous HBV infection accounted for 51.63% （4 112 patients）； in the 1992 — 2005 group， the patients with protective immunity against HBV accounted for 54.72% （168 patients）； in the post-2005 group， the patients with protective immunity against HBV accounted for 64.38% （235 patients）. In this study， 6 301 patients underwent HCV genotype testing： the patients with genotype 1b accounted for the highest proportion of 51.71% （3 258 patients）， followed by those with genotype 2a （1 769 patients， 28.07%）， genotype 3b （63 patients， 1.00%）， genotype 3a （10 patients， 0.16%）， genotype 4 （21 patients， 0.33%）， and genotype 6a （5 patients， 0.08%）. ConclusionWith the implementation of hepatitis B planned vaccination program in China， there has been a significant reduction in the proportion of patients with previous HBV infection among the patients with HCV/HBV overlapping infection， but there is still a relatively high proportion of patients with a lack of protective immunity against HBV.

Alzheimer’s disease (AD) is a central neurodegenerative disease characterized by progressive cognitive decline and memory impairment in clinical. Currently, there are no effective treatments for AD. In recent years, a variety of therapeutic approaches from different perspectives have been explored to treat AD. Although the drug therapies targeted at the clearance of amyloid β-protein (Aβ) had made a breakthrough in clinical trials, there were associated with adverse events. Neuroinflammation plays a crucial role in the onset and progression of AD. Continuous neuroinflammatory was considered to be the third major pathological feature of AD, which could promote the formation of extracellular amyloid plaques and intracellular neurofibrillary tangles. At the same time, these toxic substances could accelerate the development of neuroinflammation, form a vicious cycle, and exacerbate disease progression. Reducing neuroinflammation could break the feedback loop pattern between neuroinflammation, Aβ plaque deposition and Tau tangles, which might be an effective therapeutic strategy for treating AD. Traditional Chinese herbs such as Polygonum multiflorum and Curcuma were utilized in the treatment of AD due to their ability to mitigate neuroinflammation. Non-steroidal anti-inflammatory drugs such as ibuprofen and indomethacin had been shown to reduce the level of inflammasomes in the body, and taking these drugs was associated with a low incidence of AD. Biosynthetic nanomaterials loaded with oxytocin were demonstrated to have the capability to anti-inflammatory and penetrate the blood-brain barrier effectively, and they played an anti-inflammatory role via sustained-releasing oxytocin in the brain. Transplantation of mesenchymal stem cells could reduce neuroinflammation and inhibit the activation of microglia. The secretion of mesenchymal stem cells could not only improve neuroinflammation, but also exert a multi-target comprehensive therapeutic effect, making it potentially more suitable for the treatment of AD. Enhancing the level of TREM2 in microglial cells using gene editing technologies, or application of TREM2 antibodies such as Ab-T1, hT2AB could improve microglial cell function and reduce the level of neuroinflammation, which might be a potential treatment for AD. Probiotic therapy, fecal flora transplantation, antibiotic therapy, and dietary intervention could reshape the composition of the gut microbiota and alleviate neuroinflammation through the gut-brain axis. However, the drugs of sodium oligomannose remain controversial. Both exercise intervention and electromagnetic intervention had the potential to attenuate neuroinflammation, thereby delaying AD process. This article focuses on the role of drug therapy, gene therapy, stem cell therapy, gut microbiota therapy, exercise intervention, and brain stimulation in improving neuroinflammation in recent years, aiming to provide a novel insight for the treatment of AD by intervening neuroinflammation in the future.

Serine protease inhibitor Kazal-type (SPINK) is a skin keratinizing protease inhibitor, which was initially found in animal serum and is widely present in plants, animals, bacteria, and viruses, and they act as key regulators of skin keratinizing proteases and are involved in the regulation of keratinocyte proliferation and inflammation, primarily through the inhibition of deregulated tissue kinin-releasing enzymes (KLKs) in skin response. This process plays a crucial role in alleviating various skin problems caused by hyperkeratinization and inflammation, and can greatly improve the overall condition of the skin. Specifically, the different members of the SPINK family, such as SPINK5, SPINK6, SPINK7, and SPINK9, each have unique biological functions and mechanisms of action. The existence of these members demonstrates the diversity and complexity of skin health and disease. First, SPINK5 mutations are closely associated with the development of various skin diseases, such as Netherton’s syndrome and atopic dermatitis, and SPINK5 is able to inhibit the activation of the STAT3 signaling pathway, thereby effectively preventing the metastasis of melanoma cells, which is important in preventing the invasion and migration of malignant tumors. Secondly, SPINK6 is mainly distributed in the epidermis and contains lysine and glutamate residues, which can act as a substrate for epidermal transglutaminase to maintain the normal structure and function of the skin. In addition, SPINK6 can activate the intracellular ERK1/2 and AKT signaling pathways through the activation of epidermal growth factor receptor and protease receptor-2 (EphA2), which can promote the migration of melanoma cells, and SPINK6 further deepens its role in stimulating the migration of malignant tumor cells by inhibiting the activation of STAT3 signaling pathway. This process further deepens its potential impact in stimulating tumor invasive migration. Furthermore, SPINK7 plays a role in the pathology of some inflammatory skin diseases, and is likely to be an important factor contributing to the exacerbation of skin diseases by promoting aberrant proliferation of keratinocytes and local inflammatory responses. Finally, SPINK9 can induce cell migration and promote skin wound healing by activating purinergic receptor 2 (P2R) to induce phosphorylation of epidermal growth factor and further activating the downstream ERK1/2 signaling pathway. In addition, SPINK9 also plays an antimicrobial role, preventing the interference of some pathogenic microorganisms. Taken as a whole, some members of the SPINK family may be potential targets for the treatment of dermatological disorders by regulating multiple biological processes such as keratinization metabolism and immuno-inflammatory processes in the skin. The development of drugs such as small molecule inhibitors and monoclonal antibodies has great potential for the treatment of dermatologic diseases, and future research on SPINK will help to gain a deeper understanding of the physiopathologic processes of the skin. Through its functions and regulatory mechanisms, the formation and maintenance of the skin barrier and the occurrence and development of inflammatory responses can be better understood, which will provide novel ideas and methods for the prevention and treatment of skin diseases.

ObjectiveTo explore the therapeutic effect of Xuebijing injection （XBJ） on severe acute pancreatitis induced acute lung injury （SAP-ALI） by regulating formyl peptide receptors （FPRs）/nucleotide-binding oligomerization domain-like receptor 3 （NLRP3） inflammatory pathway. MethodsSixty rats were randomly divided into a sham group， a SAP-ALI model group， low-， medium-， and high-dose XBJ groups （4， 8， and 12 mL·kg^-1）， and a positive drug （BOC2， 0.2 mg·kg^-1） group. For the sham group， the pancreas of rats was only gently flipped after laparotomy， and then the abdomen was closed， while for the remaining five groups， SAP-ALI rat models were established by retrograde injection of 5% sodium taurocholate （Na-Tc） via the biliopancreatic duct. XBJ and BOC2 were administered via intraperitoneal injection once daily for 3 d prior to modeling and 0.5 h after modeling. Blood was collected from the abdominal aorta 6 h after the completion of modeling， and the expression of interleukin （IL）-1β， IL-6， and tumor necrosis factor-α （TNF-α） in plasma was measured by enzyme-linked immunosorbent assay （ELISA）. The amount of ascites was measured， and the dry-wet weight ratios of pancreatic and lung tissue were determined. Pancreatic and lung tissue was taken for hematoxylin-eosin （HE） staining to observe pathological changes and then scored. The protein expression levels of FPR1， FPR2， and NLRP3 in lung tissue were detected by the immunohistochemical method. Western blot was used to detect the expression of FPR1， FPR2， and NLRP3 in lung tissue. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of FPR1， FPR2， and NLRP3 in lung tissue. ResultsCompared with the sham group， the SAP-ALI model group showed significantly decreased dry-wet weight ratio of lung tissue （P<0.01）， serious pathological changes of lung tissue， a significantly increased pathological score （P<0.01）， and significantly increased protein and mRNA expression levels of FPR1， FPR2， and NLRP3 in lung tissue （P<0.01）. After BOC2 intervention， the above detection indicators were significantly reversed （P<0.01）. After treatment with XBJ， the groups of different XBJ doses achieved results consistent with BOC2 intervention. ConclusionXBJ can effectively improve the inflammatory response of the lungs in SAP-ALI rats and reduce damage. The mechanism may be related to inhibiting the expression of FPRs and NLRP3 in lung tissue， which thereby reduces IL-1β and simultaneously antagonize the release of inflammatory factors IL-6 and TNF-α.

ObjectiveTo evaluate the effects of Tongnaoyin on the blood-brain barrier status and neurological impairment in acute ischemic stroke （AIS） patients with the syndrome of phlegm-stasis blocking collaterals by dynamic contrast-enhanced magnetic resonance imaging （DCE-MRI）. MethodsA total of 63 patients diagnosed with AIS in the Jiangsu Province Hospital of Chinese Medicine from October 2022 to December 2023 were enrolled in this study. According to random number table method，the patients were assigned into a control group （32 cases） and an observation group （31 cases）. The control group received conventional Western medical treatment，and the observation group took 200 mL Tongnaoyin after meals，twice a day from day 2 of admission on the basis of the treatment in the control group. After 7 days of treatment，the patients were examined by DCE-MRI. The baseline data for two groups of patients before treatment were compared. The National Institute of Health Stroke Scale （NIHSS） score and modified Rankin Scale （mRS） score were recorded before treatment and after 90 days of treatment for both groups. The rKtrans，rKep，and rVe values were obtained from the region of interest （ROI） of the infarct zone/mirror area and compared between the two groups. ResultsThere was no significant difference in the NIHSS or mRS score between the two groups before treatment. After 90 days of treatment，the NIHSS and mRS scores declined in both groups，and the observation group had lower scores than the control group （P<0.05）. After treatment，the rKtrans and rVe in the observation group were lower than those in the control group （P<0.01）. ConclusionCompared with conventional Western medical treatment alone，conventional Western medical treatment combined with Tongnaoyin accelerates the repair of the blood-brain barrier in AIS patients，thereby ameliorating neurological impairment after AIS to improve the prognosis.

The Expert Consensus on Clinical Application of Qinbaohong Zhike Oral Liquid in Treatment of Acute Bronchitis and Acute Attack of Chronic Bronchitis （GS/CACM 337-2023） was released by the China Association of Chinese Medicine on December 13^th， 2023. This expert consensus was developed by experts in methodology， pharmacy， and Chinese medicine in strict accordance with the development requirements of the China Association of Chinese Medicine （CACM） and based on the latest medical evidence and the clinical medication experience of well-known experts in the fields of respiratory medicine （pulmonary diseases） and pediatrics. This expert consensus defines the application of Qinbaohong Zhike oral liquid in the treatment of cough and excessive sputum caused by phlegm-heat obstructing lung， acute bronchitis， and acute attack of chronic bronchitis from the aspects of applicable populations， efficacy evaluation， usage， dosage， drug combination， and safety. It is expected to guide the rational drug use in medical and health institutions， give full play to the unique value of Qinbaohong Zhike oral liquid， and vigorously promote the inheritance and innovation of Chinese patent medicines.

BACKGROUND:In recent years,with the rapid development of biomedicine,the study of brain aging and exosomes has attracted more and more attention,but there is no bibliometrics analysis in this field. OBJECTIVE:To objectively analyze domestic and foreign literature on brain aging and exosomes in the past 15 years,to summarize the research status,hot spots,and development trends in this field. METHODS:Using the core database of Web of Science as a search platform,we downloaded the literature on brain aging and exosomes published from the establishment of the database to December 28,2022,and analyzed the data from the aspects of country or region,institution,author,keywords,and co-cited literature using CiteSpace 6.1.R6 visualization software. RESULTS AND CONCLUSION:A total of 1 045 research articles were included,and the number of publications on brain aging and exosomes research both domestically and internationally was showing an increasing trend year by year.The United States ranked first with 429 papers,and China ranked second with 277 papers.Louisiana State University ranked first with 16 articles.Professor Lukiw Walter J from Louisiana State University in the United States was the author with the highest number of publications,and Professor Bartel DP from the Massachusetts Institute of Technology was the author with the most citations.The most prolific Journal was the International Journal of Molecular Sciences.Alzheimer's disease,microRNA,gene expression,extracellular vesicles,exosomes,oxidative stress,and biomarkers are the most relevant terms.According to the research on hot topics,biomarkers have become a new research hotspot.The above results indicate that the research on brain aging and exosomes has gradually increased in the past 15 years.The research direction has gradually shifted from the initial exploration of the expression of miRNAs in central nervous system diseases related to brain aging to the search for biomarkers that can identify and diagnose neurodegenerative diseases.The study of exocrine miRNAs to protect central nervous system from damage has emerged as promising therapeutic strategy.

BACKGROUND:Previous studies by our research group discovered that Jiawei Xiaoyao San has a significant anti-liver cancer effect,but the specific mechanism of action was unclear. OBJECTIVE:To investigate the regulatory effects of the traditional Chinese medicine formula Jiawei Xiaoyao San on the levels of miRNAs in plasma exosomes of rats with diethylnitrosamine chronically induced primary liver cancer,based on high-throughput sequencing combined with bioinformatics. METHODS:SD rats were randomly divided into a blank control group,a liver cancer model group,and a Jiawei Xiaoyao San treatment group.Liver cancer models were induced by continuous administration of diethylnitrosamine for 12 weeks.Starting from the 17th week,rats in the Jiawei Xiaoyao San treatment group were administered Jiawei Xiaoyao San once daily until the end of the 20th week,while rats in the blank control and liver cancer model groups were given an equivalent volume of saline.Anti-hepatocellular carcinoma effects were validated by assessing the morphological structure of rat liver tissues,along with the expression of the hepatocellular carcinoma markers,Glypican-3 protein and serum alpha-fetoprotein.Plasma exosomes from each group of rats were isolated using ultracentrifugation.High-throughput sequencing technology was used to screen for differentially expressed miRNAs in rat plasma exosomes.Bioinformatics was used to predict the potential biomarkers through which Jiawei Xiaoyao San exerts its anti-liver cancer effects via liver cancer-derived exosomal miRNAs,followed by functional analysis. RESULTS AND CONCLUSION:(1)Jiawei Xiaoyao San significantly improved the morphological structure of liver tissues in a rat model of liver cancer.Compared with the liver cancer model group,the expression of liver cancer markers Glypican-3 protein and serum alpha-fetoprotein was significantly reduced in the Jiawei Xiaoyao San treatment group.(2)Bioinformatics analysis showed that in the Jiawei Xiaoyao San group,upregulated miR-223-3p in the liver cancer model group had target binding sites with genes E2F1 and NCOA1,which were closely related to liver cancer survival and prognosis.Therefore,Jiawei Xiaoyao San has a therapeutic effect on liver cancer,possibly by targeting negative regulation of NCOA1/E2F1 through liver cancer plasma-derived exosomal miR-223-3p,thereby playing anti-liver cancer effect.

Objective: To explore the association between CDKAL1 rs35261542, FAIM2 rs 3205718, and VGLL4 rs 2574704 polymorphisms with childhood obesity and related metabolic phenotypes to provide evidence for personalized prevention and management strategies. Methods: Based on the 2023 Long term Nutritional Health Effects of Early Childhood Nutrition Package Intervention project, the study enrolled 1 078 children aged 5-7 years from four counties in Henan (Songxian and Ruyang countries) and Guizhou (Guiding and Fuquan countries) provinces. Using BMI Z scores, 87 overweight and obese(OVOB) children were selected and matched by sex, age, and BMI Z score with 117 normal weight controls. Participants were further stratified into four metabolic phenotype groups: metabolically healthy normal weight (MHNW, n =51), metabolically unhealthy normal weight (MUNW, n =66), metabolically healthy obesity (MHO, n =31) and metabolically unhealthy obesity (MUO, n =56) based on four conventional cardiometabolic risk factor (CR) criteria. Data were collected through questionnaires, anthropometric measurements, serum biochemical tests, and KASP genotyping. The distribution of three genetic polymorphisms ( CDKAL1 rs35261542, FAIM2 rs3205718, VGLL4 rs 2574704) across metabolic subgroups was analyzed. Multivariate Logistic regression models assessed associations between these polymorphisms and obesity/metabolic phenotypes. Results: Multivariate Logistic regression analysis showed that Homozygous mutant AA genotype of CDKAL1 rs 35261542 was positively associated with OVOB( OR =3.63), MHO ( OR =11.04), MUO ( OR = 4.88 ) ( P <0.05). Homozygous TT genotype of FAIM2 rs 3205718 increased OVOB risk ( OR =4.44, P <0.05) but showed no association with metabolic phenotypes ( P >0.05). Homozygous mutant TT of VGLL4 rs 2574704 reduced the risks of MHO and MUO ( OR = 0.30, 0.24， P <0.05). Cumulative genetic effects analysis demonstrated carriers of 1 or 2 risk genotypes of rs 35261542 and rs 3205718 had progressively higher OVOB risk ( OR =2.53, 20.79), and the combination of rs 35261542 and rs 2574704 increased risks for both MHO ( OR =8.50) and MUO ( OR =5.00) ( P <0.05). Conclusions The AA genotype of rs 35261542 ( CDKAL1 ) positively correlates with childhood obesity and metabolic abnormalities. The TT genotype of rs 3205718 ( FAIM 2) increases obesity risk but not metabolic phenotypes. The TT genotype of rs 2574704 ( VGLL 4) shows protective effects against metabolic dysfunction. Risk genotypes exhibit dosedependent cumulative effects on obesity and metabolic outcomes.

[摘 要] 目的：评估放疗作为原位疫苗的联合治疗模式在晚期软组织肉瘤（STS）患者中的有效性和安全性。方法：回顾性分析2020年12月至2024年9月期间在南京大学医学院附属鼓楼医院肿瘤中心接受联合治疗模式的12例晚期STS患者的临床资料。12例患者均接受了联合治疗。放疗主要以大分割为主。靶向治疗：安罗替尼10例、阿帕替尼2例。免疫治疗以PD-1抗体为主。主要研究终点为疾病控制率（DCR），次要研究终点为客观有效率（ORR）及安全性。结果：接受联合治疗的12例STS患者中有0例CR，4例PR，7例SD，1例PD。ORR为33%，DCR为91.7%，其中靶病灶的DCR为100%。12例患者中，9例出现Ⅰ~Ⅱ级不良反应。最常发生的血液学不良反应是贫血（6例）、肝功能检查结果异常（3例）。最常发生的非血液学不良反应是尿蛋白（5例）、高血压（4例）、甲状腺功能异常（3例）、厌食（3例）、恶心呕吐（2例）；仅2例发生Ⅲ级血液毒性，有1例发生Ⅲ级气胸。结论：放疗作为原位疫苗的联合治疗模式在晚期STS患者中展现出较高的DCR，且未出现严重不良反应。该联合治疗模式具有良好的有效性与安全性。