Objective To study the cognitive impairment in SD rats after intermittent hypoxia (IH),and explore the relation of miR-26b up-regulated expression and neuron apoptosis in the hippocampus of SD rats after IH.Methods Eight-week-old male SD rats (n=20,each weighing approximately 300±10 g) were randomly divided into normal oxygen control group,IH 1-week group,IH 2-weeks group and IH 4-weeks group (n=5).Rats in the later three groups were given IH for different times,and rats in the normal oxygen control group were given normal oxygen.The spatial learning and memory abilities were detected by Morris Water Maze (MWM) in the normal oxygen control group and IH 4-weeks group.The levels of apoptosis proteins Caspase3 and Bax and anti-apoptosis protein Bcl-2 in the hippocampus of 4 groups were detected by Western blotting.The miR-26b expression level in the 4 groups was detected by real time-PCR.Results (1) The results of MWM revealed that the mean escape latency in the IH 4-weeks group was significantly prolonged as compared with that in the normal oxygen control group (P＜0.05);the time entering into the target quadrant in the IH 4-weeks group ([22.0±6.7] s) was significantly shorter than that in the normal oxygen control group ([39.8±8.8] s,P＜0.05).(2) Western blotting indicated that up-regulated expressions of apoptosis proteins Bax and Casepase3 and down-regulated expression of anti-apoptosis protein Bcl-2 in the IH 1-week group,IH 2-weeks group and IH 4-weeks group were noted as compared with those in the control group,with significant differences (P＜0.05);significantly higher apoptosis protein Bax and Casepase3 expressions in the IH 1-week group were noted as compared with those in the IH 2-weeks group and IH 4-weeks group (P＜0.05),while significantly decreased Bcl-2 expression in the IH 1-week group was noted as compared with that in the IH 2-weeks group and IH 4-weeks group (P＜0.05).(3) The results of real time-PCR revealed that the miR-26b expression level in the hippocampus was up-regulated in the IH 1-week group,IH 2-weeks group and IH 4-weeks group as compared with that in the control group,with significant differences (P＜0.05);miR-26b expression level in the IH 1-week group was significantly higher as compared with that in the IH 2-weeks group and IH 4-weeks group (P＜0.05).Conclusion The miR-26b up-regulated expression in the hippocampus might refer to Bax /Bcl-2-related mitochondrial apoptotic signaling pathway after IH brain injury;miR-26b could be a potential mean ofgene therapy after IH brain injury.

Objective:To understand residents' health status and disease characteristics by analyzing the disease spectrum and disease patterns of the entire population and elderly hospitalized patients in Tianjin between 2018 and 2020, thus providing scientific evidence for disease prevention and treatment.Methods:Information on the first page of inpatient medical records from 77 secondary or higher-level hospitals was provided by the Tianjin Health and Medical Big Data Platform.The codes of the International Classification of Diseases 10th revision(ICD-10)were used by the system for standardized diagnoses at hospital discharge.The disease spectrum of inpatients was analyzed based on the systems implicated by diseases.Age stratification was performed in examining changes in the orders of diseases across the spectrum.Results:Between 2018 and 2020, a total of 3 568 034 patients were discharged, with 1 204 733 in 2018, 1 372 747 in 2019, and 990 554 in 2020.Male patients accounted for 49.2%(1 756 867/3 568 034), elderly patients(65 years or older)accounted for 33.5%(1 194 189/3 568 034), and patients from tertiary hospitals accounted for 86.5%(3 085 482/3 568 034).According to the ICD-10, there were 19 categories of diseases when diagnoses at discharge were considered.Over the three-years period, the top ten diseases made up 81.1%(2 893 430/3 568 034)of all cases at discharge, with high consistency in their rankings(harmonic index value Wa=0.986, χ2=70.989, P<0.001).The circulatory system and the nervous system always occupied the top two positions, while the respiratory system decreased from third to seventh place in 2020.The rankings of factors affecting health and healthcare access increased.The circulatory system, nervous system, respiratory system, digestive system, and tumors consistently ranked among the top six categories in the disease spectrum of the elderly and the rankings of diseases related to the eye, ear, endocrine system, musculoskeletal system, and connective tissue system were also up compared to those of the entire population. Conclusions:Hospitalized patients are concentrated in tertiary hospitals, with a relatively high proportion of elderly patients.In the disease spectrum, circulatory system diseases, neurological system diseases, digestive system diseases, tumors, and respiratory system diseases have always been at the top of the list for medical treatment, both for the entire population and for elderly patients, with a significant decrease in the ranking of respiratory system diseases in 2020.The rankings of eye, ear, endocrine, musculoskeletal, and connective tissue diseases in elderly patients have increased compared to the entire population, indicating a need to step up the development of geriatric medicine and related specialties and the importance to promote the healthy China initiative and healthy aging.

Objective:To analyze the mechanism of Jindan Tablets, Xiaoyan Lidan Tablets and ursodeoxycholic acid in the treatment of gallstone and cholecystitis based on network pharmacology; To conduct a comparative analysis.Methods:The chemical components of Jindan Tablets, Xiaoyan Lidan Tablets and ursodeoxycholic acid and their drug targets were collected from Traditional Chinese Medicine Database and Analysis Platform (TCMSP). DAVID 6.8 database was used to search for the associated diseases of the drug targets. The disease targets of gallstone and cholecystitis were collected from GeneCards and other databases. The protein-protein interactions network was established based on the intersecting targets of three drugs and two diseases. KEGG enrichment analysis was performed based on the DAVID 6.8 database. Cytoscape 3.7.1 software was used to construct a complex network and topology analysis of component- target- disease between three drugs and diseases.Results:222 chemical components and 3 133 drug targets were collected for Jindan Tablets. 104 chemical components and 1 425 action targets were collected for Xiaoyan Lidan Tablets. 1 chemical component and 119 action targets were collected for ursodeoxycholic acid. The three drugs were associated with 31 diseases. 1 382 disease targets for gallstones and cholecystitis were collected. There were 237, 163 and 33 targets for gallstones and cholecystitis in the three drugs, of which 17 were shared by the three drugs and 20 were shared by Jindan Tablets and Xiaoyan Lidan Tablets. Based on the DAVID database, 113, 74 and 10 significant KEGG enrichment pathways were obtained for the three drugs respectively.Conclusions:The three drugs shared many targets and pathways in the treatment of gallstones and cholecystitis, which all had the function of regulating metabolism and inhibiting inflammatory response, while participating in apoptosis, oxidative stress and cancer pathology process. However, they had their own special effects, with Jindan Tablets favoring involving in the cancer process and inhibition of inflammation, and promoting angiogenesis. Xiaoyan Lidan Tablets and ursodeoxycholic acid focused on regulating cholesterol metabolism, and Xiaoyan Lidan Tablets also regulated steroid metabolism and inhibit inflammation, while ursodeoxycholic acid regulated bile acid metabolism.

Objective To investigate the changes of microglia cell phenotypes in the injured brains of rats following repetitive mild traumatic brain injury (rmTBI).Methods Sixty male SD rats were randomly divided into sham-operated group,injury of one-week group,injury of two-week group,injury of four-week group,and injury of six-week group (n=12).Rats in the injury groups were induced rmTBI models by controlled cortical impact (CCI),and rats in the sham-operated group were only performed bone window opening without hitting.Six rats from each group were sacrificed;immunofluorescent staining was used to detect the Iba-1 positive microglial cells in the injured cortex and changes ofmicroglia subsets in the injured brain after rmTBI were analyzed by flow cytometry.Results As compared with the sham-operated group,the injury of one-week group and injury of six-week group had significantly increased percentages of Iba-1 positive microglial cells in the injured cortex (19％ and 12％,P＜0.05).flow cytometry indicated that CD451ow/CD11b+ cells were the microglial cells,accountting for 90％ ofCD11b+ cells;as compared with the sham-operated group,the injury of one-week group,injury of two-week group,injury of four-week group,and injury of six-week group had significantly increased M1 type microglial cells (P＜0.06),with injury of six-week group enjoying the highest level;as compared with the sham-operated group,the injury of one-week group,injury of two-week group and injury of four-week group had significantly increased M2 type microglial cells (P＜0.06),with injury of two-week group enjoying the highest level.Conclusion Dynamic changes ofmicroglia subsets after rmTBI are noted,which reveals that different subsets of microglia phenotypes might play their unique roles in the acute or chronic phases after rmTBI.

The aim of the present study was to observe the activation of microglia in the prefrontal cortex of type 1 diabetes mellitus (T1DM) mice, and the expression of the marker genes of the disease-associated microglia (DAM) associated with neurodegenerative diseases. Sixty healthy adult male C57BL/6J mice were randomly divided into two groups, normal control (CON) group and T1DM group. Streptozocin (STZ) was injected intraperitoneally to induce T1DM mice. The spatial learning and memory function of mice was detected by Morris water maze at the 8th week after the successful model establishment. The number and activation of microglia in the prefrontal cortex of mice were detected by immunofluorescence staining and Western blot. Changes in the mRNA level of several DAM molecular markers were detected by RT-FQ-PCR. The results showed that, compared with CON mice, the fasting blood glucose of T1DM mice increased significantly, while the body weight of T1DM mice decreased remarkably (P < 0.05). The escape latency of water maze in T1DM mice was longer than that in CON mice (P < 0.05). Compared with CON group, the Iba1 protein expression and the number of microglia in prefrontal cortex of T1DM group increased significantly (P < 0.05). In addition, the mRNA levels of several DAM markers in prefrontal cortex of T1DM group were increased significantly (P < 0.05). These results suggest that the microglia are activated and transformed to DAM type in the prefrontal cortex of T1DM mice.
Animals ; Diabetes Mellitus, Experimental ; Diabetes Mellitus, Type 1 ; Hippocampus ; Male ; Mice ; Mice, Inbred C57BL ; Microglia ; Prefrontal Cortex

Chemokine 12 (CXCL12), also known as stromal cell derived factor-1 (SDF-1) and a member of the CXC chemokine subfamily, is ubiquitously expressed in many tissues and cell types. It interacts specifically with the ligand for the transmembrane G protein-coupled receptors CXCR4 and CXCR7. The CXCL12/CXCR4 axis takes part in a series of physiological, biochemical, and pathological process, such as inflammation and leukocyte trafficking, cancer-induced bone pain, and postsurgical pain, and also is a key factor in the cross-talking between tumor cells and their microenvironment. Aberrant overexpression of CXCR4 is critical for tumor survival, proliferation, angiogenesis, homing and metastasis. In this review, we summarized the role of CXCL12/CXCR4 in cancer, CXCR4 inhibitors under clinical study, and natural product CXCR4 antagonists. In conclusion, the CXCL12/CXCR4 signaling is important for tumor development and targeting the pathway might represent an effective approach to developing novel therapy in cancer treatment.
Animals ; Antineoplastic Agents ; chemical synthesis ; chemistry ; pharmacology ; Biological Products ; chemistry ; pharmacology ; Chemokine CXCL12 ; genetics ; metabolism ; Humans ; Molecular Targeted Therapy ; Neoplasms ; drug therapy ; genetics ; metabolism ; Receptors, CXCR4 ; antagonists & inhibitors ; genetics ; metabolism

Type 1 diabetes mellitus (T1DM)-induced cognitive dysfunction is common, but its underlying mechanisms are still poorly understood. In this study, we found that knockout of conventional protein kinase C (cPKC)γ significantly increased the phosphorylation of Tau at Ser214 and neurofibrillary tangles, but did not affect the activities of GSK-3β and PP2A in the hippocampal neurons of T1DM mice. cPKCγ deficiency significantly decreased the level of autophagy in the hippocampal neurons of T1DM mice. Activation of autophagy greatly alleviated the cognitive impairment induced by cPKCγ deficiency in T1DM mice. Moreover, cPKCγ deficiency reduced the AMPK phosphorylation levels and increased the phosphorylation levels of mTOR in vivo and in vitro. The high glucose-induced Tau phosphorylation at Ser214 was further increased by the autophagy inhibitor and was significantly decreased by an mTOR inhibitor. In conclusion, these results indicated that cPKCγ promotes autophagy through the AMPK/mTOR signaling pathway, thus reducing the level of phosphorylated Tau at Ser214 and neurofibrillary tangles.
AMP-Activated Protein Kinases/metabolism* ; Animals ; Autophagy ; Diabetes Mellitus, Type 1 ; Glucose ; Glycogen Synthase Kinase 3 beta/metabolism* ; Mice ; Phosphorylation ; Protein Kinase C/metabolism* ; TOR Serine-Threonine Kinases/metabolism* ; tau Proteins/metabolism*