Rubi Fructus has a long history of medicinal and edible use in China. It contains chemical components such as terpenes, flavonoids, phenolic acids, fatty acids, and alkaloids, and possesses various pharmacological activities, including antioxidant, anti-inflammatory, hypoglycemic, anti-tumor, anti-osteoporosis, and liver-protective effects. Rubi Fructus is widely applied in medical, health, and food fields. The quality of Rubi Fructus can directly affect the safety and effectiveness of clinical medication. Therefore, this article reviews the research progress on the chemical constituents and pharmacological effects of Rubi Fructus. Based on the concept of traditional Chinese medicine(TCM) quality markers(Q-markers), the article explores the screening and determination of Q-markers for Rubi Fructus from various aspects, including plant kinship, traditional efficacy, medicinal properties, measurability of chemical composition, different processing methods, producing areas, harvesting periods, and planting conditions. The components ellagic acid, kaempferol, quercetin, kaempferol-3-O-rutinoside, rutin, astragalin, tiliroside, and hyperoside are preliminarily proposed as Q-markers for Rubi Fructus, providing a reference for the quality control of Rubi Fructus.
Drugs, Chinese Herbal/pharmacology* ; Humans ; Rubus/chemistry* ; Fruit/chemistry* ; Quality Control ; Animals

Sodium-glucose co-transporter protein 2 inhibitor(SGLT2i)has steadily demonstrated benefits in the treatment of type 2 diabetes complicated with cardiovascular diseases based on evidence-based medicine,but its precise mechanism is yet unknown.We identified type 2 diabetes patients with HFpEF by searching PubMed,Web of Science,China knowledge network(CNKI),and other databases.We then summarized the pathological mechanism of HFpEF caused by type 2 diabetes.At the same time,to link to evidence-based medical,we explored the future of SGLT2i in clinical application.

Influenza imposes a significant disease burden on society and individuals annually, and influenza vaccination is considered a significant public health measure to prevent influenza and reduce influenza-related severe disease and death. The low influenza vaccination rate in China is partly due to certain factors affecting the willingness and behavior of individuals to receive them. Scientific research and targeted interventions on these factors can effectively improve the vaccination situation. Commonly used individual-level theoretical models for influenza vaccination behavior include the health belief model, protection motivation theory, and theory of planned behavior. This study reviews theoretical models commonly employed in researching influenza vaccination willingness and behavior. An overview of these practical applications and challenges models is presented to provide references for relevant research and intervention programs in China.

Objective:To investigate the effects of intra-articular injection of exosomes derived from dental pulp stem cells from hu-man exfoliated deciduous teeth(SHED-EXO)on subchondral bone homeostasis in rat temporomandibular joint osteoarthritis(TMJ OA)process.Methods:36 male SD rats were randomly divided into 3 groups(n=12):control(CON),sodium iodoacetate(MIA)-induced TMJ OA(MIA),and SHED-EXO injection into TMJ OA(SHED-EXO)groups.At 2 and 6 weeks post-treatment,Micro-CT,Double labeling,TRAP staining,and immunohistochemical staining were employed to detect osteoclasts and osteoblasts in the subchondral bone.Additionally,the mRNA expression levels of ADAMTs5,IL-1β,OCN and OPG/RANKL were analyzed by qRT-PCR.Results:The MIA group exhibited significant bone loss and an enlarged bone marrow cavity.In comparison with the CON group,BV/TV and Tb.Th were lower(P＜0.001),while BS/BV,Tb.Sp,and Tb.N were higher(P＜0.01).Additionally,the bone formation rate within 5 days was low-er than that of the control group(P＜0.001).When compared to the MIA group,the SHED-EXO group showed a significant increase in bone morphology and bone mass.BV/TV and Tb.Th were increased(P＜0.01),while BS/BV,Tb.Sp and Tb.N were decreased(P＜0.05).The bone formation rate was higher(P＜0.01).Compared with both the control and treatment groups,the MIA group exhibited a significant increase in the number of osteoclasts in the subchondral bone(P＜0.01),along with a notable decrease in H-type blood vessels and OCN-positive areas(P＜0.01).Conclusion:Intra-articular injection of SHED-EXO can reg-ulate condylar subchondral bone homeostasis in TMJ OA of rats by promoting osteogenesis and inhibiting osteoclasts.

Neurodegenerative diseases are a collective term for a large group of diseases caused by degenerative changes in nerve cells. Aging is the main risk factor for neurodegenerative diseases. The neurovascular unit(NVU) is the smallest functional unit of the brain, which regulates brain blood flow and maintains brain homeostasis. Accelerated aging of NVU cells directly impairs NVU function and leads to the occurrence of various neurodegenerative diseases. The intrinsic mechanisms of NVU cell aging are complex and involve oxidative stress damage, loss of protein homeostasis, DNA damage, mitochondrial dysfunction, immune inflammatory response, and impaired cellular autophagy. In recent years, studies have found that traditional Chinese medicine(TCM) can inhibit NVU aging through multiple pathways and targets, exerting a brain-protective effect. Therefore, this article aimed to provide a theoretical basis for further research on TCM inhibition of NVU cell aging and references for new drug development and clinical applications by reviewing its mechanisms of anti-aging, such as regulating relevant proteins, improving mitochondrial dysfunction, reducing DNA damage, lowering inflammatory response, antioxidant stress, and modulating cellular autophagy.
Humans ; Medicine, Chinese Traditional ; Neurodegenerative Diseases/drug therapy* ; Brain ; Aging ; Neurons ; Blood-Brain Barrier

Measurement bias (MB) has been described in causal structures but is still not entirely clear. In practice, the correctness of substitution estimate (SE) of effect is a prerequisite for causal inference, usually based on a bidirectionally non-differential misclassification between the measured exposure and the measured outcome. Based on a directed acyclic graph (DAG), this paper proposes a structure for the single-variable measure, where its MB is derived from the choice of an imperfect, "input/output device-like" measurement system. The MB of the SE is influenced both by the measurement system itself and by factors outside the measurement system: while the independence or dependence mechanism of the measurement system still ensures that the MB of the SE is bidirectionally non-differential; however, the misclassification can be bidirectionally non-differential, unidirectionally differential, or bidirectionally differential resulted from the factors outside the measurement system. In addition, reverse causality should be defined at the level of measurement, where measured exposures can influence measured outcomes and vice versa. Combined with temporal relationships, DAGs help elucidate MB's structures, mechanisms, and directionality.
Humans ; Confounding Factors, Epidemiologic ; Data Interpretation, Statistical ; Bias ; Causality

Objective: To investigate the clinical and pathologic characteristics of obese adults with nonalcoholic fatty liver disease (NAFLD) and to aid the diagnosis of nonalcoholic steatohepatitis (NASH). Methods: A total of 262 patients eligible for inclusion who received volume reduction metabolism surgery and liver biopsy in the First Affiliated Hospital of Nanjing Medical University from June 2018 to September 2019 were selected. HE staining, reticular fiber staining and Masson staining were performed. Statistical analysis was performed using SPSS 20.0. Results: The patients ranged in age from 18 to 66 years. Among the 262 cases, 65 cases (65/262, 24.8%) were male and 197 cases (197/262, 75.2%) were female. Sixty-one cases (61/262, 23.3%) were non-NAFLD, 201 cases (201/262, 76.7%) were NAFLD including 27 cases (27/201, 13.4%) of nonalcoholic fatty live (NAFL) and 174 cases (174/201, 86.6%) of NASH. The main lesions of NAFLD were in hepatic acinus zone 3. There were significant differences in age, alanine aminotransferase (ALT), glutamic oxaloacetic transaminase (AST), body mass index (BMI), fasting blood-glucose (FPG) and apolipoprotein A (APOA) levels among the non-NAFLD group, NAFL group and NASH group (P<0.05). Patients with BMI≥35 m/kg² combined with type 2 diabetes had a higher prevalence of NASH. Multiple logistic regression showed that ALT and APOA were independent predictors of NASH (P<0.001, OR=1.05, 95%CI: 1.020-1.082; P=0.027, OR=0.916, 95%CI: 0.878-0.941). Total cholesterol (CHO) and high-density lipoprotein (HDL) were independent predictors of lobular inflammation (P=0.043, 95%CI: 0.010-0.634; P=0.024, 95%CI:-3.068--0.216). AST and HDL were independent predictors of fibrosis stage (P=0.029, 95%CI: 0.001-0.021; P<0.001, 95%CI:-2.670--0.645). Conclusions: Biochemical indicators of NAFLD are closely related to its pathology. The histological lesions of NAFLD are mainly present in hepatic acinar area 3. The diagnosis of NASH is supported by extensive steatosis and high levels of CHO, ALT, AST and BMI, low levels of HDL and ApoA in biochemical markers, but pathological examination is still the gold standard for it.
Adult ; Humans ; Male ; Female ; Adolescent ; Young Adult ; Middle Aged ; Aged ; Non-alcoholic Fatty Liver Disease/pathology* ; Diabetes Mellitus, Type 2/pathology* ; Liver/pathology* ; Obesity/pathology* ; Apolipoproteins A

Objective:To analyze the epidemiological characteristics of indigenous 2019-nCoV infection in population under 18 years old in 31 provinces of China, and provide evidence for the prevention and control of COVID-19.Method:Demographic and epidemiologic information of children and adolescents with 2019-nCoV infection reported in China between April 29, 2020 and May 31, 2022 were collected from China's Disease Prevention and Control Information System. We analyzed the epidemiological characteristics of the 2019-nCoV infection in children and adolescents and compared the epidemiological characteristics of the cases at different epidemic stages.Result:A total of 63 916 indigenous 2019-nCoV infection cases in children and adolescents were reported in China from April 29, 2020 to May 31, 2022, in which 14 777 (23.12%) were confirmed cases and 49 139 (76.88%) were asymptomatic cases. An obvious incidence peak (40 864 cases) was observed in April, 2022, and two sub-peaks were observed in January, 2020 and January, 2021, respectively. The 2019-nCoV infection cases occurred in 187 cities above prefecture level in 30 provinces, the cases reported in Shanghai (41 562 cases), Changchun (5 753 cases) and Jilin (3 888 cases) accounted for 80.11% of the total cases (51 203/63 916). The proportion of the cases in males was 54.34%. The age of the cases, M ( Q1, Q3) was 10 (5, 14) years, and 57.73% of the cases were 6 - 15 years old. The cases in students accounted for the highest proportion (56.14%). The interval between illness onset and diagnosis of confirmed cases, M ( Q1, Q3) was 1 (0, 2) days. Among the 2019-nCoV infection cases in children and adolescents, 76.88% were asymptomatic, 21.78% were mild ones, 1.32% were moderately severe ones, 0.02% were severe ones, and there were no critical cases and deaths. Compared with other age groups, the proportion of severe or critical cases was higher in children aged <1 year (0.12%). The proportion of asymptomatic infections was highest in Omicron variant epidemic (78.43%). Conclusion:The 2019-nCoV infection cases in children and adolescents aged <18 years in 31 provinces in China were mainly primary and secondary school students aged 6-15 years. Most cases were asymptomatic and mild ones with low clinical severity. It is still necessary to strengthen the surveillance for 2019-nCoV infection in children and adolescents to improve the prevention and control of COVID-19 in school age children.

For a long time, the cultivation of medical students’ scientific research and innovation abilitymainly depends on scattered extracurricular scientific research activities. With limited students, unsystematic teaching and inadequate administrative guarantee, it often results in obvious weakness andinefficiency. Since 2002, the Biochemistry and Molecular Biology teaching team in Shantou UniversityMedical College has been working on a “3+X” model to nurture the scientific research and innovationability of medical students. Guided by the concepts of complementary development of science andeducation, student-centeredness, and Problem-based Learning, a model is established based on the‘HEART” professionalism courses and the academy culture specific to Shantou University. We also takefull advantage of the first-tier disciplines of biology, basic medicine and clinical medicine in ShantouUniversity and collaborate with other professional teaching teams. It is conceptualized in a framework thatembraces the comprehensive connotation of scientific research and innovation ability and adopts a corecurriculum system that runs through the 5-year medical undergraduate education. In this model, " 3" means " whole-person training", " whole-process training" and " omni-directional training" for medicalstudents; " X" refers to several confirmatory dimensions of the operational effectiveness of the " 3+X" model, including organizing medical students to participate in various forms of national college students’ innovative experimental research competitions, international college students’ academic seminars, writingand publishing academic papers by medical undergraduates as the first author, etc. The model proves tobe effective in cultivating the scientific research and innovation ability of medical students, hence settinga good example to solve the current problems in the cultivation of medical students’ scientific researchand innovation ability.

OBJECTIVE: To investigate the effect of suppressing high-mobility group box 1 (HMGB1) on neuronal autophagy and apoptosis in rats after intracerebral hemorrhage (ICH) in rats. METHODS: Rat models of ICH induced by intracerebral striatum injection of 0.2 U/mL collagenase Ⅳ were treated with 1 mg/kg anti-HMGB1 mAb or a control anti-IgG mAb injected via the tail immediately and at 6 h after the operation (n=5). The rats in the sham-operated group (with intracranial injection of 2 μL normal saline) and ICH model group (n=5) were treated with PBS in the same manner after the operation. The neurological deficits of the rats were evaluated using modified neurological severity score (mNSS). TUNEL staining was used to detect apoptosis of the striatal neurons, and the expressions of HMGB1, autophagy-related proteins (Beclin-1, LC3-Ⅱ and LC3-Ⅰ) and apoptosis-related proteins (Bcl-2, Bax and cleaved caspase-3) in the brain tissues surrounding the hematoma were detected using Western blotting. The expression of HMGB1 in the striatum was detected by immunohistochemistry, and serum level of HMGB1 was detected with ELISA. RESULTS: The rat models of ICH showed significantly increased mNSS (P < 0.05), which was markedly lowered after treatment with anti- HMGB1 mAb (P < 0.05). ICH caused a significant increase of apoptosis of the striatal neurons (P < 0.05), enhanced the expressions of beclin-1, LC3-Ⅱ, Bax and cleaved caspase-3 (P < 0.05), lowered the expressions of LC3-Ⅰ and Bcl-2 (P < 0.05), and increased the content of HMGB1 (P < 0.05). Treatment with anti-HMGB1 mAb obviously lowered the apoptosis rate of the striatal neurons (P < 0.05), decreased the expressions of Beclin-1, LC3-Ⅱ, Bax and cleaved caspase-3 (P < 0.05), increased the expressions of LC3-Ⅰ and Bcl-2 (P < 0.05), and reduced the content of HMGB1 in ICH rats (P < 0.05). CONCLUSION Down- regulation of HMGB1 by anti-HMGB1 improves neurological functions of rats after ICH possibly by inhibiting autophagy and apoptosis of the neurons.
Animals ; Apoptosis ; Apoptosis Regulatory Proteins/metabolism* ; Autophagy ; Beclin-1 ; Caspase 3/metabolism* ; Cerebral Hemorrhage/therapy* ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Rats ; Rats, Sprague-Dawley ; bcl-2-Associated X Protein/metabolism*