Objective To study the effects of Gouteng Jiangya Jieyu Prescription(Uncariae Ramulus cum Uncis,Gastrodiae Rhizoma,Pheretima,Puerariae Lobatae Radix,Salviae Miltiorrhizae Radix et Rhizoma,etc.)on learning and memory ability,hippocampal inflammatory response and autophagy-related protein expression in rats with hypertension complicated with depression(HD).Methods Thirty spontaneously hypertensive rats(SHR)were randomly divided into model group,positive control group(Levamlodipine Besylate 0.45 mg·kg-1+Fluoxetine Hydrochloride 1.80 mg·kg-1)and Gouteng Jiangya Jieyu Prescription high-,medium-and low-dose groups(25.38,12.69,6.34 g·kg-1).Another 6 SD rats were used as blank control group.The SHR rats were intervened by chronic mild unpredictable stress combined with solitary rearing to replicate the HD rat model.At the same time,intragastric administration was given once a day for 6 weeks.The systolic blood pressure and diastolic blood pressure of rat tail artery were measured by non-invasive sphygmomanometer.The learning and memory ability of rats was detected by Morris water maze test.The ultrastructure of hippocampal neurons was observed by transmission electron microscope.The contents of interleukin-1β(IL-1β),IL-18 and IL-10 in hippocampus were detected by ELISA.The expression of autophagy-related proteins Beclin1 and Bcl-2 in hippocampus was detected by immunohistochemistry.The expression of autophagy-related proteins LC3Ⅰ and LC3Ⅱ in hippocampus was detected by Western Blot.Results Compared with the blank control group,the SBP and DBP of the rats in the model group were significantly increased from week 1-6(P＜0.01).The escape latency was significantly prolonged on the third and fourth day(P＜0.01).The first time of crossing the platform was significantly prolonged(P＜0.01),the times of crossing the platform area was significantly reduced(P＜0.05),and the retention time of the platform area was significantly shortened(P＜0.01).The neuronal cell body was obviously swollen,the ridge was destroyed,the nucleus was shrunk,and a large number of autophagosomes appeared;the contents of IL-1β and IL-18 in hippocampus were significantly increased(P＜0.01).The ratio of LC3Ⅱ/LC3Ⅰ protein expression and the expression of Beclin1 protein in hippocampus were significantly up-regulated(P＜0.05,P＜0.01),and the expression of Bcl-2 protein was significantly down-regulated(P＜0.01).Compared with the model group,the SBP of rats in the low-dose group of Gouteng Jiangya Jieyu Prescription was significantly decreased at the weeks 1,3,4,5,6(P＜0.01),and the DBP was significantly decreased at weeks 1,3,4,5(P＜0.05,P＜0.01).The SBP of the rats in the medium-dose group of Gouteng Jiangya Jieyu Prescription was significantly decreased at weeks 1,5,6(P＜0.01),and the DBP was significantly decreased at week 4(P＜0.05).The SBP of rats in the high-dose group of Gouteng Jiangya Jieyu Prescription was significantly decreased in the first week(P＜0.01).The escape latency of rats in the high-and medium-dose groups of Gouteng Jiangya Jieyu Prescription was significantly shortened on the third day(P＜0.05),and the escape latency of rats in the high-and low-dose groups of Gouteng Jiangya Jieyu Prescription was significantly shortened on the fourth day(P＜0.05).The first crossing platform time of rats in the high-,medium-and low-dose groups of Gouteng Jiangya Jieyu Prescription was significantly shortened(P＜0.01).The times of rats crossing the platform area in the medium-and low-dose groups of Gouteng Jiangya Jieyu Prescription were significantly increased(P＜0.05),and the retention time in the platform area was significantly prolonged(P＜0.05).In the administration group,the degree of hippocampal neuron damage was reduced,the nuclear shrinkage was significantly improved,and the autophagosomes were reduced.The contents of pro-inflammatory factors IL-1β and IL-18 in the hippocampus of rats in the high-and medium-dose groups of Gouteng Jiangya Jieyu Prescription were significantly decreased(P＜0.05,P＜0.01).The content of anti-inflammatory factor IL-10 in the hippocampus of rats in the high-dose group of Gouteng Jiangya Jieyu Prescription was significantly increased(P＜0.01).The protein expression ratio of LC3Ⅱ/LC3Ⅰ in hippocampus of high-,medium-and low-dose groups of Gouteng Jiangya Jieyu Prescription was significantly down-regulated(P＜0.01),and the expression of Bcl-2 protein was significantly up-regulated(P＜0.01).The expression of Beclin1 protein in the hippocampus of the high-and medium-dose groups of Gouteng Jiangya Jieyu Prescription was significantly down-regulated(P＜0.05,P＜0.01).Conclusion Gouteng Jiangya Jieyu Prescription can reduce the tail arterial pressure of HD rats,improve their learning and memory ability,and alleviate hippocampal neuronal damage.The mechanism may be related to reducing the release of inflammatory factors,increasing the level of anti-inflammatory factors,and regulating the expression of hippocampal autophagy-related proteins LC3Ⅱ/LC3Ⅰ,Beclin1 and Bcl-2.

AIM: To explore retinal microvascular changes in migraine patients using meta-analysis.METHODS: The National Library of Medicine PubMed, Embase, and Cochrane Library were searched to find relevant studies, and the search period was from the creation of database to June 2023. Two investigators independently screened the literatures, extracted data, and evaluated the quality of included studies using the NOS scale. STATA15.0 was used for Meta-analysis and publication bias evaluation, sensitivity analysis was performed for results with large heterogeneity, and the funnel plot and Egger were used to assess the publication bias of the literature.RESULTS:A total of 12 studies, including 217 patients(252 eyes)with migraine with aura(MA), 283 patients(388 eyes)with migraine without aura(MO), and 374 healthy individuals(479 eyes), were included in this Meta-analysis. Several optical coherence tomography angiography(OCTA)indicators, including foveal avascular zone(FAZ)macular or optic disc perfusion density were compared and analyzed. The Meta-analysis results showed that compared with healthy controls, patients with MA had a significant increase in FAZ area and perimeter, a significant decrease in perfusion density of the macular deep capillary plexus(mDCP)except for the fovea, and a significant decrease in perfusion density of the radial peripapillary capillaries(RPC)around the optic disc; the FAZ parameters were significantly increased in MO, while the differences in perfusion density of the macular superficial capillary plexus(mSCP), mDCP and RPC were not statistically significant, except for the perfusion density in the parafovea mDCP.CONCLUSIONS: Both MA and MO patients had an enlarged FAZ area, patients with MA had a significant decrease in mDCP perfusion density, and migraine patients had some degree of retinal ischemia.

OBJECTIVE To study the protective effects of Dachengqi decoction （DCQD） on intestinal septic mice， and to explore the possible mechanisms from the Toll-like receptor 4（TLR4）/myeloid differentiation factor 88（MyD88） signaling pathway. METHODS The SPF male C57BL/6J mice were randomly divided into Sham group， Sham+DCQD-H group， model （CLP） group， DCQD-L group， DCQD-H group and Positive group. The model of intestinal sepsis was established by cecal ligation and puncture in CLP group， DCQD-L group， DCQD-H group and Positive group. Three days before the operation and seven days after the operation， DCQD-L group and DCQD-H group were given DCQD intragastrically at 4， 8 g/kg （calculated by crude drug）， respectively. Positive group was given ulinastatin intraperitoneally 2 h before operation and 7 d after the operation （at 50 000 U/kg）. In Sham group and Sham+DCQD-H group， only cecum of mice was exposed without ligation and puncture. Sham+DCQD- H group was given DCQD intragastrically （8 g/kg，calculated by crude drug） 3 days before the operation and 7 days after the operation. Both the Sham group and CLP group were given normal saline 0.2 mL intragstrically and intraperitoneally each day， for 10 consecutive days. After the operation， the severity of sepsis was assessed， and the 7 d survival rate of mice was assessed. One hour after the last medication， the levels of tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） in serum and ileum of mice were determined； the pathological and morphological changes of mice’s liver， lung， kidney and ileum were observed； mRNA expressions of the TLR4 and MyD88 in ileum were tested. RESULTS Compared with CLP group， sepsis score， the levels of TNF-α and IL-6 in serum and ileum （except for IL-6 in ileum of DCQD-L group）， damage score of the liver， lung， kidney and ileum， mRNA expressions of TLR4 and MyD88 in ileum were all decreased significantly in DCQD-L group and DCQD-H group （P＜0.05 or P＜0.01）， while 7 d survival rate （except for DCQD-L group） was increased significantly （P＜0.05）. The damage to liver tissue in mice was significantly improved， and inflammation infiltration and apoptosis were reduced； lung tissue damage had been alleviated， with varying degrees of improvement in alveolar atrophy， bleeding and edema； the renal tissue damage was improved and weakened dilation of renal tubular lumen was weakened； the damage and edema of ileal tissue were significantly improved. CONCLUSIONS DCQD may exert a protective role on intestinal septic model mice. The mechanism may be related to the inhibition of systemic inflammation， the reduction of multiple organ damage， and down-regulation of TLR4/MyD88 signaling pathway.

Objective:To analyze the distribution characteristics of special types of diabetes in China, in order to provide a theoretical basis for the diagnosis and treatment of special types of diabetes.Methods:Pubmed, CNKI, and WanFang Data were searched for the case reports and clinical studies of special types of diabetes in China from 2011 to 2021. After independent literature screening by 2 researchers according to the inclusion and exclusion criteria, diseases and the number of corresponding cases included were extracted for statistics. The etiological composition and disease characteristics of three subtypes of special type diabetes were analyzed.Results:A total of 613 articles(7 377 patients)were included and roughly divided into eight subtypes of special type diabetes according to etiological classification for disease composition analysis. The results by ratio in descending order were as follows: mono-genetic gene defects in islet β-cell function, pancreatogenic diabetes, diabetes induced by drugs or chemicals, endocrine disease, mono-genetic gene defects in insulin action, other genetic syndromes associated with diabetes, infection, and uncommon immune-mediated diabetes. The disease composition of the three subtypes of special types of diabetes that we focused on were mono-genetic gene defects in islet β-cell function(50.21%), pancreatogenic diabetes(35.65%), and mono-genetic gene defects in insulin action(1.56%). The composition analysis of the special types of diabetes in each subtype showed that neonatal diabetes mellitus(NDM, n=1 749, 23.71%)and maturity onset diabetes in young(MODY, n=1 554, 21.07%)accounted for the largest proportions. According to the composition analysis of each subtype of MODY patients, the top three subtypes were MODY2(50.89%), MODY3(16.03%), and MODYX(8.91%). In addition, taking MODY as an example, patients with de novo mutations(DNMs)and(or)new mutation sites were summarized and analyzed. The results revealed 31 MODY patients with DNMs(1.99%) and 339 MODY patients with new mutation sites(21.81%). Conclusions:According to the literature analysis, NDM and MODY represent the largest proportion of patients with special type diabetes in China. MODY2 patients make up the largest proportion of MODY patients. In addition, diabetic patients carrying DNMs and(or)new mutation sites should be taken seriously.

Objective:To investigate the protective mechanism of remote ischemic preconditioning (RIPC) on cerebral ischemia-reperfusion (I/R) injury in rats.Methods:Forty-eight SD rats were randomly divided into sham operation group, RIPC group, I/R group, RIPC+I/R group, and compound C group ( n=9 in each group). The neurological function score, cerebral infarction volume (TCC staining) and neuronal apoptosis rate (TUNEL staining) were measured. The activity of superoxide dismutase (SOD) 2 and malondialdehyde level in homogenate of brain tissue were detected. Expression levels of AMP-activated protein kinase (AMPK)/peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α signaling pathway-related proteins in brain tissue were detected by Western blot. Results:The neurological deficit score, cerebral infarction volume and neuron apoptosis rate in the I/R group were significantly higher than those in the sham operation group (all P<0.05). Compared with the I/R group, the neurological deficit score, cerebral infarction volume and neuron apoptosis rate in the RIPC+I/R group were significantly decreased (all P<0.05). Compared with the RIPC+I/R group, the neurological deficit score, cerebral infarction volume and neuron apoptosis rate in the compound C group were significantly increased (all P<0.05). Compared with the sham operation group, the SOD activity in the I/R group was significantly decreased, and the malondialdehyde content was significantly increased (all P<0.05). Compared with the I/R group, the SOD activity in the RIPC+I/R group was significantly increased, and the malondialdehyde content was significantly decreased (all P<0.05). Compared with the RIPC+I/R group, the SOD activity in the compound C group was significantly decreased, and the malondialdehyde content was significantly increased (all P<0.05). Compared with the sham operation group, the expressions of AMPK, p-AMPK, PGC-1α, nuclear respiratory factor (NRF)-1, mitochondrial transcription factor A (TFAM), SOD2, uncoupling protein 2 (UCP2), cytochrome C (CytC), and apoptosis-inducing factor (AIF) in the brain tissue of the I/R group were significantly increased (all P<0.05). Compared with the I/R group, the expressions of AMPK, p-AMPK, PGC-1α, NRF-1, TFAM, SOD2 and UCP2 in the ischemic brain tissue of the RIPC+I/R group were significantly increased, while the expressions of CytC and AIF were significantly decreased (all P<0.05). Compared with the RIPC+I/R group, the expressions of AMPK, p-AMPK, PGC-1α, NRF-1, TFAM, SOD2 and UCP2 in the brain tissue of the compound C group were significantly decreased, while the expressions of CytC and AIF were significantly increased (all P<0.05). Conclusions:RIPC has a protective effect on I/R injury. Its mechanism may be associated with the activation of AMPK/PGC-1α signaling pathway and maintaining mitochondrial biogenesis.

Objective : To compare the effect of BoneCeramic and Bio-OSS on osteogenic after PAOO and bone marrow stromal osteogenic differentiation in rats. Methods: 36 8-week-old SD rats were enrolled and divided into 3 groups: corticotomy group(CO group);corticotomy+Bio-Oss implantation group(BO group);corticotomy+BoneCeramic implantation group(BC group).Immediately, a standard orthodontic spring(50 N/kg) was activated to pull the right upper first molars toward midrange movement.At 28,60 days after activation, 6 rats were randomly selected from each group and sacrificed.The mesial movement distance, palatal alveolar bone height loss(ABHL) and bone volume fraction(BVF) of the first molars were measured by micro-CT.The Results : There was no difference in tooth movement between the three groups; The ABHL value of the control group was higher than that of the experimental group at 28 and 60 days, and the BVF value was lower than that of the two groups.Meanwhile, the ABHL value of the BO group was higher than that of the BC group at 60 days, and the BVF value was lower than that of the BC group.CCK-8 showed that the two materials did not inhibit the growth of BMSCs.SEM showed that BMSCs were more distributed on the surface of BoneCeramic material.Quantitative ALP detection showed that BMSCs exhibited higher ALP activity on the surface of BoneCaremic material, and mRNA expressions of RUNX-2,OPN and OCN were higher. Conclusion BoneCeramic is more beneficial to osteogenesis after PAOO and osteogenic differentiation of BMSCs in SD rats.

Congenital generalized lipodystrophy type 1 (CGL1) is an autosomal recessive genetic disease caused by mutations in AGPAT2 gene. The main clinical mainifestations include body subcutaneous fat loss, muscle hypertrophy, obvious subcutaneous veins, pseudoacromegaly, hirsutism, and acanthosis nigricans. What′s more, CGL1 is always accompanied by metabolic diseases. Therefore, it is easily misdiagnosed as metabolic syndrome, type 2 diabetes, polycystic ovary syndrome, acromegaly, or Cushing′s syndrome. Meanwhile, it is difficult to distinguish it from partial lipoatrophy syndrome. In this article, we present clinical and molecular characteristics of a patient with CGL1 and review mutations reported in literature to replenish current knowledge about this orphan disease.

Objective:To investigate the effect of Guilu Erxian Jiao (GEJ) on the negative feedback function of hypothalamic-pituitary-adrenal (HPA) axis and its possible mechanism in rats with post-traumatic stress disorder(PTSD).Methods:The PTSD rat model was established using single prolonged stress (SPS). Ninety six SD rats were randomly divided into control group (control), model group (SPS), GEJ group (GEJ) and paroxetine group (PRX) according to the random number table with 24 rats in each group. Except the control group, the rats in the other groups were constructed using the PTSD model. On the 8th day after the establishment of the model, the rats of the GEJ group (3.6 g/kg) and the PRX group (10 mg/kg) were respectively given the drug by gavage for 21 days. The rats in control group and SPS group were given the same amount of distilled water once a day for 21 days. After continuous administration for 21 days, 12 rats were randomly selected from each group for the dexamethasone suppression test (DST), then 6 rats were selected for the RT-PCR, and the remaining 6 rats were used for immunohistochemistry. The contents of plasma adrenocorticotrophic hormone (ACTH) were measured by Elisa. The expression levels of glucocorticoid receptor (GR), mineralocorticoid receptor (MR), adrenocorticotropic hormone releasing factor Ⅰ receptor (CRF1R) and adrenocorticotropic hormone releasing factor Ⅱ receptor (CRF2R) were detected by RT-PCR and immunohistochemistry.Results:(1) In DST, plasma ACTH level in SPS group was significantly lower than that in control group((145.89±19.41)μg/L, (203.59±35.78)μg/L, t=3.16, P<0.01), and that in the PRX group and GEJ group were significantly higher than that in SPS group((218.47±37.55)μg/L, t=3.98, P<0.01; (205.33±66.54)μg/L, t=3.26, P<0.01). (2) RT-PCR results showed that, in hippocampus, the GR mRNA and MR mRNA expressions in SPS group were significantly higher than those in control group((1.29±0.02), (1.00±0.06), t=6.88, P<0.01; (1.38±0.02), (1.00±0.05), t=7.97, P<0.01), and that in the GEJ group significantly decreased comparing to SPS group((0.96±0.07), t=7.87, P<0.01; (0.86±0.13), t=11.03, P<0.01). (3) Immunohistochemical results showed that, in hippocampus, the positive cell expressions of GR and MR in the SPS group were significantly higher than those in control group((84.33±12.82), (69.33±8.19), t=2.50, P<0.05; (77.33±6.65), (56.33±11.79), t=2.25, P<0.05), and that in the GEJ group significantly were lower than SPS group((68.33±4.55), t=2.67, P<0.05; (59.50±4.18), t=2.25, P<0.05). In amygdala, the positive cells expression of GR, MR and CRF1R in the SPS group significantly decreased compared with the control group((62.67±6.89), (77.17±10.70), t=3.10, P<0.05; (60.50±11.66), (91.83±15.63), t=3.43, P<0.05; (54.50±19.96), (88.17±22.43), t=2.31, P<0.05); and that in GEJ group significantly increased compared with the SPS group((74.33±5.85), t=2.11, P<0.05; (83.67±12.55), t=2.53, P<0.05; (88.67±16.28), t=2.35, P<0.05). Conclusion:GEJ can inhibit the enhanced HPA axis negative feedback function induced by SPS, which may be related to regulating expression of GR, MR and CRF1R in the hippocampus and amygdala.

Objective To investigate the clinical therapeutic effect of citicoline sodium combined with Shenxiong glucose in the treatment of senile hypertensive cerebral infarction in the elders.Methods 80 elderly patients with senile hypertensive cerebral infarctiontreated in our hospital were selected and randomly divided into the single treatment group and the combination treatment group,40 cases in each group.Both groups received the routine treatment.The single treatment group additionally received Shenxiong glucose injection (100 ml/d),while patients in the combination treatment group additionally received Shenqiong glucose injection combined with citicoline sodium intravenous infusion therapy (0.5 g/d),both groups were treated for 2 weeks.The levels of serum inflammatory factors,the neurological deficit score,the cognitive function score were compared and analyzed before and after treatment between two groups.Results After systemic treatment,the blood pressure and blood lipid levels of two groups were significantly improved,but there was no significant difference between the two groups (P ＞ 0.05);The serum levels of interleukin (IL)-6,IL-8 and tumor necrosis factor-α (TNF-α) of the combination treatment group improved more significantly (P ≤0.05).After treatment,the oxidative stress indexes were significantly improved in the two groups (P ≤ 0.05).The content of malondialdehyde (MDA) was decreased,while the superoxide dismutase (SOD) activity and nitric oxide (NO) content were increased significantly (P ≤ 0.05);and the improvement degree in the combination treatment group was better than in the single treatment group (P ≤0.05).The degree of improvement in the Modified Edinburgh-Scandinavia Stroke Scale (MESSS) and Hasegawa Dementia Scale (HDS) scores of the combination treatment group was more significant than those in the single treatment group (P ≤ 0.05).The total effective rate of the combination treatment group was 92.5％,which was significantly higher than that of the single group (75.0％),with statistically significant difference (P ≤ 0.05).No obvious adverse reactions happened in two groups during treatment.Conclusions Combination of citicoline sodium and shenxiang glucose on the basis of routine treatment can significantly reduce oxidative stress and inflammation levels,promote the recovery of neurological and cognitive functions,and improve the clinical efficacy and safety.It is worth popularizing and applying in the clinical treatment of senile hypertensive cerebral infarction.

AIM: To investigate the effects of transient receptor potential channel 6 (TRPC6) on the proliferation of rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) induced by IL-1β.METHODS: The mRNA expression of TRPC6 in synovial tissues from RA or OA patients was studied by RT-qPCR.RA-FLS were cultured by enzyme digestion and tissue adhesion methods.The method of flow cytometry was applied to identify the RA-FLS.RA-FLS were treated with different concentrations (0, 0.25, 0.5, 1, 2, 4, 8 and 16 μg/L) of IL-1β for 36 h.The cell viability was examined by CCK-8 assay.RA-FLS were incubated with IL-1β (16 μg/L) for different time (12, 24, 36, 48, 60 and 72 h), and the cell viability was measured by CCK-8 assay.The interference efficiency of TRPC6-siRNA was determined by RT-qPCR and Western blotting.After incubation in the presence or absence of IL-1β medium, the cell viability, the percentage of EdU-positive cells and the percentage of (G2/M+S) phase were measured by CCK-8 assay, EdU labeling assay and flow cytometry, respectively.RESULTS: The mRNA expression of TRPC6 was found in synovial tissue with higher levels in RA patients than that in OA patients.TRPC6-siRNA significantly decreased the mRNA and protein expression of TRPC6 (P<0.05).When RA-FLS were treated with IL-1β, the proliferation of RA-FLS was increased (P<0.05).The differences of the cell viability, the percentage of EdU-positive cells and the (G2/M+S) phase percentage between TRPC6-siRNA group and blank control group or NC-siRNA group were significant, in the presence of IL-1β (P<0.05).However, they were not significant in the absence of IL-1β.CONCLUSION: TRPC6 is involved in the proliferation of RA-FLS induced by IL-1β.Silencing of TRPC6 gene inhibits the growth of RA-FLS induced by IL-1β.