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.

[Objective] To analyze the prevalence of human T-lymphocyte leukemia virus (HTLV) among blood donors in Guangzhou from 2016 to 2021, and provide a basis for blood collection and supply management in this region. [Methods] A total of 2 116 951 voluntary blood donors were screened for anti-HTLV by enzyme-linked immunosorbent assay (ELISA) from March 2016 to December 2021 in Guangzhou, and the reactive cases were further confirmed by Western blotting (WB). Qualitative data were analyzed by χ2 with spss19 software. The trend of the total positive rate of HTLV confirmation test by WB from 2016 to 2021 was analyzed with the Joinpoint software, and the annual percent change (APC) was used to determine whether the trend changes were statistically significant. [Results] From March 2016 to December 2021, the total positive rate for anti-HTLV by ELISA among voluntary blood donors in Guangzhou was 0.019 7% (416/ 2116 951), and the WB confirmed positive rate was 0.001 1% (23/2 116 951). The total positive rate of HTLV among individual voluntary blood donors in the six main districts (0.002 12%, 19/895 301) was higher than that among group voluntary blood donors (0.000 32%, 3/951 947) (P<0.05). There was no significant difference in the total positive rate of HTLV confirmation between the six main districts (0.001 19%) and the three non-main districts (0.000 37%) (P>0.05). The trend of the total positive rate of HTLV infection in the six main districts and the Guangzhou area(including the six main districts and three non-main districts) showed no significant increase or decrease. [Conclusion] The prevalence of HTLV among blood donors in Guangzhou remains at a low level.

ObjectiveTo establish the Shanghai twin birth cohort （STBC） and analyze the effects of genetic factors， shared environment， and non-shared environment interactions on birth health and growth and development of newborns. MethodsBased on the population-wide birth cohort in Shanghai， a comprehensive survey was conducted on the families with double and multiple babies born after January 1， 2015 to collect information on birth health， growth and development， and the family environment of the babies. ResultsBy December 31， 2021， a total of 7 195 pairs （14 405 cases） of twins were successfully included in the STBC survey. The average birth length of twins was 47.2 cm and average birth weight was 2 465.3 g. Heterozygous twins accounted for 69.05% and preterm babies accounted for 57.07%. The average age of the mothers of twins was 31.82 years， and the average age of the fathers was 33.87 years， with more than 80% of the parents having a college degree or above. 44.50% of the mothers used assisted reproductive technologies， 7.40% had illnesses during pregnancy， and 15.90% were exposed to passive smoking during pregnancy. During the survey period， the average monthly increase in the length of the twin infants was 2.09 cm， and the average monthly weight gain was 0.53 kg. ConclusionThe incidence of adverse outcomes such as maternal cesarean section rate， preterm birth， and low birth weight is higher in the twin birth population. Information on birth health as well as growth and development in childhood and adolescence in the twin birth population is collected based on STBC， which can provide a solid data foundation for studying children’s chronic non-communicable diseases， psychological and behavioral disorders and other complex health problems caused by the combined effects of genetics and the environment.

Objective To explore the prognostic value and immune infiltration landscape of anoikis-related long noncoding RNAs (arlncRNAs) in lung adenocarcinoma. Methods RNA-seq and clinical data of lung adenocarcinoma were downloaded from the TCGA database, and anoikis-related genes were obtained from the GeneCards and Harmonizome databases. Coexpression, differential, and WGCNA analyses were performed to screen differentially expressed arlncRNAs closely related to the occurrence of lung adenocarcinoma. A prognostic risk model was then constructed based on the arlncRNAs, and its predictive efficacy was further validated. Finally, consensus clustering was used to identify the molecular subtypes associated with anoikis in lung adenocarcinoma. Results Seven prognostic arlncRNAs were identified, and the prognostic risk models established based on them had AUC values of ROC curves greater than 0.7. Survival and immune infiltration analyses revealed that low-risk patients had high overall survival and immune infiltration, implying that they experienced good immune treatment effects. Drug sensitivity analysis showed that the high-risk patients were more sensitive to commonly used chemotherapeutic agents than the low-risk patients. According to the expression of model genes, subtypes C1 and C2 were identified through consensus clustering, and C1 showed a good prognosis. Conclusion The prognostic risk model based on the seven arlncRNAs can effectively predict the prognosis of lung adenocarcinoma patients. The results of immune-related and drug sensitivity analyses provide a reference for the precise individualized treatment of patients with lung adenocarcinoma.

Natural products are important sources for the discovery of anti-tumor drugs. Evodiamine is the main alkaloid component of the traditional Chinese herb Wu-Chu-Yu, and it has weak antitumor activity. In recent years, a number of highly active antitumor candidates have been discovered with a significant progress. This article reviews the research progress of evodiamine-based antitumor drug design strategies, in order to provide reference for the development of new drugs with natural products as leads.

Objective To investigate the in-hospital screening results of developmental dysplasia of the hip (DDH) in infants and young children in Ili area, and to analyze the risk factors affecting the occurrence of DDH. Methods According to the cluster sampling method 5 536 infants and young children who underwent DDH screening in the pediatric outpatient department and orthopedic outpatient department of our hospital from December 2019 to June 2022 were selected as the research objects. The children who met the diagnostic criteria of DDH were selected as the observation group (n=35), and 100 normal children were selected as the control group. Univariate and multivariate analysis were used to determine the independent risk factors affecting the occurrence of DDH in infants. Results Among the 39 cases were positive in primary screening, 35 cases were positive in secondary screening, and the positive rate was 6.32‰ . The results of single factor analysis showed that the proportion of women, second birth and above, caesarean section, breech delivery, family history, high altitude area, living environment room temperature < 18^°C, and leg binding when swaddling in the observation group was higher than that in the control group (P<0.05) . Logistic regression analysis showed that mode of production, region, room temperature of living environment and swaddling mode were independent risk factors for DDH in infants (P<0.05). Conclusion Caesarean section, high altitude area, living environment room temperature < 18^°C and leg binding in infants are related to the occurrence of DDH in infants, which can provide some reference for clinical screening, diagnosis and treatment.

Objective To explore the application value of ultrasonic measurement of optic nerve sheath diameter(ONSD)and cerebral blood flow parameters in intracranial hypertension caused by AIDS cryptococ-cal meningitis.Methods A total of 27 patients with cryptococcal meningitis diagnosed by Chongqing Public Health Medical Center from February to July,2022 were included.All patients were examined with ultrasound measurement of ONSD and ultrasound measurement of cerebral blood flow of intracranial middle cerebral ar-tery(MCA),including peak systolic velocity(PSV),end diastolic velocity(EDV),peak systolic velocity/end diastolic velocity(S/D)and resistance index(RI),and then lumbar puncture was performed and intracranial pressure(ICP)was recorded.The ICP≥200 mmH2O was defined as the ICP increased group,ICP＜200 mmH2O was defined as the ICP normal group,and 17 AIDS patients without complications were selected as the control group.The baseline data,ONSD and MCA cerebral blood flow parameters of the three groups were compared,and the statistically significant indexes were correlated with ICP,and the receiver operating charac-teristic(ROC)curve of the subjects was drawn to analyze the diagnostic efficacy of ONSD value in predicting intracranial hypertension caused by AIDS cryptococcal meningitis.Results There were no significant differ-ences in gender,age,systolic blood pressure or diastolic blood pressure among the ICP increased group,the ICP normal group and the control group(P＞0.05).There were no significant differences in PSV,EDV,S/D and RI among the three groups of MCA(P＞0.05),but there was significant difference in ONSD among the three groups(P＜0.05).There was a positive correlation between ICP and ONSD in the patients with AIDS cryptococcal meningitis(P＜0.01,r=0.736).The ROC curve analysis showed that when the ONSD cutoff value was 3.965 mm,it predicted the highest efficacy of intracranial high pressure in the patients with AIDS cryptococcal meningitis.The area under the ROC curve was 0.90(95％CI:0.714-1.000,P=0.001),the sensitivity was 90％,and the specificity was 100％.Conclusion Ultrasonic measurement of ONSD can effec-tively predict ICP in patients with AIDS cryptococcal meningitis and guide clinical decompression measures in time,which is worthy of clinical application.

BACKGROUND:For the replacement treatment of long-segment tracheal defects,although tissue engineering research has made some progress in recent years,it is still not perfect,and one of the biggest difficulties is that the hemodynamic reconstruction of the tracheal replacement cannot be achieved rapidly. OBJECTIVE:To preliminarily explore the potential of polycaprolactone scaffolds modified with exosome-loaded hydrogels to construct a rapidly vascularized tracheal substitute. METHODS:Exosomes were extracted from bone marrow mesenchymal stem cells of SD rats.After preparation of hyaluronic acid methacrylate solution,the exosome solution was mixed with hyaluronic acid methacrylate solution at a volume ratio of 1:1.Hyaluronic acid methacrylate hydrogels loaded with exosomes were prepared under ultraviolet irradiation for 5 minutes.The degradation of exosome-unloaded hydrogels and the controlled release of exosome-loaded hydrogels were detected.Polycaprolactone scaffolds were prepared by 3D printing.The pure hyaluronic acid methacrylate solution and the exosome-loaded hyaluronic acid methacrylate solution were respectively added to the surface of the scaffold.Hydrogel-modified scaffolds and exosome-modified scaffolds were obtained after ultraviolet irradiation.Thirty SD rats were randomly divided into three groups with 10 rats in each group and subcutaneously implanted with simple scaffolds,hydrogel-modified scaffolds and exosome-modified scaffolds,respectively.At 30 days after surgery,the scaffolds and surrounding tissues of each group were removed.Neovascularization was observed by hematoxylin-eosin staining and Masson staining and the expression of CD31 was detected by immunofluorescence. RESULTS AND CONCLUSION:(1)As time went by,the hydrogel degraded gradually,and the exosomes enclosed in the hydrogel were gradually released,which could be sustained for more than 30 days.The exosome release rate was faster than the degradation rate of the hydrogel itself,and nearly 20%of the exosomes were still not released after 30 days of soaking.(2)Under a scanning electron microscope,the surface of the simple polycaprolactone scaffold was rough.After hydrogel modification,a layer of gel was covered between the pores of the scaffold,and the scaffold surface became smooth and dense.(3)After 30 days of subcutaneous embedding,hematoxylin-eosin staining and Masson staining showed that more neovascularization was observed inside the scaffolds of the exosome-modified scaffold group compared with the hydrogel-modified scaffold group.The hydrogels on the scaffolds of the two groups were not completely degraded.Immunofluorescence staining showed that CD31 expression in the exosome-modified scaffold group was higher than that in the hydrogel-modified scaffold group(P<0.000 1).(4)These results indicate that hyaluronic acid methacrylate hydrogels can be used as controlled-release carriers for exosomes.The 3D-printed polycaprolactone scaffold modified by hyaluronic acid methacrylate hydrogel loaded with exosomes has good biocompatibility and has the potential to promote the formation of neovascularization.

Objective To clarify the expression and distribution of brain⁃derived neurotrophic factor (BDNF) in the cerebrum of plateau yaks and cattle, and to explore the relationship between BDNF function and the adaptability of altitude hypoxia. Methods Five yaks and five cattles were selected.The content and distribution of BDNF in frontal lobe, temporal lobe, parietal lobe, occipital lobe, cerebrum white matter and hippocampus of yak and cattle were analyzed by Real⁃time PCR, Western blotting and Immunohistochemistry. Results Real⁃time PCR result showed that BDNF mRNA expression in the cerebrum of yaks and cattles was highest in temporal cortex, followed by hippocampus, parietal cortex, occipital cortex and frontal cortex, and lowest in white matter. Western blotting results showed that the content of BDNF protein in the cerebrum of yaks was the highest in temporal cortex,followed by hippocampus. The content of BDNF protein in other tissues was parietal cortex, frontal cortex and cerebrum white matter, and the content of BDNF protein was the lowest in occipital cortex. The content of BDNF protein intlecerebrum of cattles was the highest in the temporal cortex, followed by the hippocampus. The content of BDNF protein in other tissues was parietal cortex, occipital cortex and frontal cortex in descending order, and the protein content in cerebrum white matter was the lowest. Immunohistochemical results showed that the positive expression of BDNF protein in the cerebrum of yaks and cattles was basically similar, mainly distributed in the granulosa cells and glial cells in the frontal cortex, temporal cortex, parietal cortex and occipital cortex, glial cells in cerebrum white matter, pyramidal cell layer and polyform cell layer in the hippocampus. There was the small amount of distribution in Martinotti cells and the molecular layer of hippocampus in the cerebral cortex. Conclusion BDNF mRNA and protein are distributed and expressed in different brain regions of yaks and cattles, but the expression level different, which is speculated to be closely related to the specific functions of different cerebrum regions. The expression level of the cerebrum of yak is higher than that of cattle except occipital cortex, suggesting that it is related to the altitude hypoxic environment. BDNF may play an important role in enhancing hypoxic tolerance and protecting internal environmental homeostasis in the process of animal adaptation to hypoxic environment.

ObjectiveTo investigate the possible mechanism of Guben Fangxiao Beverage （固本防哮饮） for the prevention and treatment of chronic airway inflammation during asthma remission. MethodsThirty-six female Balb/c mice were randomly divided into normal group， model group， low-， medium-， and high-dose of Guben Fangxiao Beverage group and montelukast sodium group， with 6 mice in each group. Except for the normal group， ovalbumin and respiratory syncytial virus were used in other groups to establish a mouse model of bronchial asthma in remission stage. After molding， the low-， medium-， and high-dose groups of Guben Fangxiao Beverage were respectively given 12， 24， and 36 g/（kg·d）， the montelukast sodium group was given montelukast sodium granule 2.6 mg/（kg·d）， and the mice in the normal group and model group were given 20 ml of double-distilled water， all by gavage， once a day for 28 days. The levels of interleukin 4 （IL-4） and interleukin 5 （IL-5） in the lung tissue of mice were detected； HE staining was used to observe the pathology of the lung tissue and to score the inflammation； DHE staining was used to observe the level of reactive oxygen species （ROS） in the lung tissue， and the activities of mitochondrial respiratory chain complexes Ⅰ， Ⅱ， Ⅲ， Ⅳ， and Ⅴ in the lung tissue were detected； the levels of serum superoxide dismutase （SOD）， catalase （CAT）， malondialdehyde （MDA） and adenosine triphosphate （ATP） were detected； the protein expression levels of phosphorylated adenosine monophosphate-activated protein kinase （p-AMPK）， nuclear factor erythroid 2-related factor 2 （Nrf2）， haem oxygenase 1 （HO-1） and cAMP responsive element binding protein （CREB） in the lung tissues of the model group were detected by Western blot. ResultsCompared with the normal group， the histopathological results of the lungs of mice in the model group showed an increase in inflammatory cells around the airways and an increase in inflammatory score； DHE staining showed an increase in the level of ROS， and an increase in the levels of IL-4 and IL-5 in the lung tissues； the levels of serum SOD， CAT， and ATP were reduced， and the level of MDA was elevated； the activities of the mitochondrial respiratory chain complexes Ⅰ， Ⅱ， Ⅲ， Ⅳ， and Ⅴ of the lung tissues were reduced， and the activities of p-AMPK， Nrf2， CREB protein expression decreased （P＜0.05）. Compared with the model group， the lung tissue inflammatory cells and inflammation scores of mice in each Guben Fangxiao Beverage dose group and montelukast sodium group were reduced； the levels of ROS， IL-4 and IL-5 in the lung tissue were reduced； the levels of CAT and ATP in the serum increased， and the content of MDA was reduced； and the activities of mitochondrial respiratory chain complexes Ⅰ and Ⅱ， as well as the expression of CREB protein， were elevated in the lung tissue （P＜0.05）. Compared with the high-dose group， the MDA level of the medium-dose Guben Fangxiao Beverage group decreased （P＜0.05）. The activity of mitochondrial respiratory chain complex V in the medium-dose group was higher than that in the montelukast sodium group， and the activity of mitochondrial respiratory chain complex Ⅳ in the medium- and high-dose groups was higher than that in the low-dose group （P＜0.05）. ConclusionGuben Fangxiao Beverage can inhibit oxidative stress and improve mitochondrial function to relieve chronic airway inflammation in bronchial asthma model mice during asthma remission， and its mechanism may be related to the activation of AMPK/Nrf2/HO-1 signaling pathway.