Objective To investigate the effect of angiotensinogen (AGT), angiotensin-converting enzyme (ACE) and AngII receptor (ATR) gene polymorphisms combined with climatic factors on the incidence of essential hypertension (EH) in Tibetan population in Gannan area. Methods A follow-up study was conducted to select 671 Tibetan people in Gannan area who were physically examined in April 2019 at the Health Management Center of the Second Hospital of Lanzhou University and agreed to be enrolled as a fixed cohort, and the blood pressure values of the enrolled subjects were measured after 3.5 years of follow-up, and a total of 501 cases were obtained. At the same time, the peripheral blood of all subjects was collected and the polymorphisms of AGT, ACE and ATR genes were detected by gene chip technology, and the possible interactions were analyzed by logistic regression model, fork generation method and multifactor-dimensionality reduction (MDR). Results Sunshine time was a protective factor for the incidence of hypertension in the Tibetan population of Gannan (OR=0.781), while relative humidity (OR=1.182), air pressure (OR=1.338) and temperature (OR=1.449) were the risk factors for the incidence of hypertension. According to the results of partial correlation analysis, temperature had no effect on the incidence of hypertension after controlling air pressure. There was an additive interaction between high air pressure and the polymorphisms of rs699 (OR=1.650, 95%CI: 1.293-2.399, P<0.001) and rs5049 (OR=1.711, 95%CI: 1.337-4.920, P<0.001) genes of AGT gene; there was a multiplicative interaction between relative humidity and rs699 (OR=0.472, 95%CI: 0.120-0.783, P<0.05);there was a multiplicative interactions between the altitude ≥ 3000m and rs699 (OR=1.503, 95%CI: 1.220-3.174, P<0.01), rs5049 (OR=1.673, 95%CI: 1.380-3.961, P<0.001) or rs2148582 (OR=0.519, 95%CI: 0.284-0.716, P<0.05).However, there was no interaction between climatic factors and ACE or ATR gene polymorphisms on the incidence of hypertension. Conclusion Climatic factors and altitude ≥3 000 m are closely related to the incidence of hypertension in the Tibetan population of Gannan area, and the interaction between AGT gene polymorphisms and climatic factors affects the incidence of hypertension in the population of this area.

OBJECTIVES: To explore the mechanism of Shuangshu Decoction (SSD) for inhibiting growth of gastric cancer xenografts in nude mice. METHODS: Network pharmacology analysis was conducted to identify the common targets of SSD and gastric cancer cell ferroptosis, and bioinformatics analysis and molecular docking were used to validate the core targets. In the cell experiment, AGS cells were treated with SSD-medicated serum, Fer-1 (a ferroptosis inhibitor), or both, and the changes in cell viability, ferroptosis markers (ROS, Fe²⁺ and GSH), expressions of P53, SLC7A11 and GPX4, and mitochondrial morphology were examined. In a nude mouse model bearing gastric cancer xenografts, the effects of gavage with SSD, intraperitoneal injection of Fer-1, or their combination on tumor volume/weight, histopathology, and expressions of P53, SLC7A11 and GPX4 levels were evaluated. RESULTS: The active components in SSD (quercetin and wogonin) showed strong binding affinities to P53. In AGS cells, SSD treatment dose-dependently inhibited cell proliferation, increased ROS and Fe²⁺ levels, upregulated P53 expression, and downregulated the expressions of SLC7A11 and GPX4, but these effects were effectively attenuated by Fer-1 treatment. SSD also induced mitochondrial shrinkage and increased the membrane density, which were alleviated by Fer-1. In the tumor-bearing mouse models, gavage with SSD significantly reduced tumor size and weight, caused tumor cell necrosis, upregulated P53 and downregulated SLC7A11 and GPX4 expression in the tumor tissue, and these effects were obviously mitigated by Fer-1 treatment. CONCLUSIONS SSD inhibits gastric cancer growth in nude mice by inducing cell ferroptosis via the P53/SLC7A11/GPX4 axis.
Ferroptosis/drug effects* ; Animals ; Stomach Neoplasms/metabolism* ; Tumor Suppressor Protein p53/metabolism* ; Mice, Nude ; Phospholipid Hydroperoxide Glutathione Peroxidase ; Drugs, Chinese Herbal/pharmacology* ; Humans ; Amino Acid Transport System y+/metabolism* ; Mice ; Cell Line, Tumor ; Cell Proliferation/drug effects* ; Xenograft Model Antitumor Assays

Objective:To investigate the possible mechanism of learning and memory damage induced by arsenic exposure through studying the effects of arsenic exposure on levels of brain-derived neurotrophic factor (BDNF) and tyrosine kinases B (TrkB) in hippocampus of offspring mice at different developmental stages.Methods:Twenty-four pregnant Kunming mice were divided into control (distilled water) group and 15, 30 and 60 mg/L sodium arsenite (NaAsO 2) groups according to random number table method, six mice in each group. The pregnant mice were exposed to NaAsO 2 until weaning. After weaning, the offspring mice were still exposed to NaAsO 2 through drinking water till postnatal day (PND) 40. Morris water maze was used to determine the effects of arsenic exposure on learning and memory ability in PND 40 mice. The body weight of the mice was measured at PND 10, 20 or 40, and brain tissues were taken after the mice were sacrificed and the hippocampus was isolated. The levels of BDNF and TrkB mRNA in the hippocampus of offspring mice were measured by Real-time PCR. Results:There was significant difference in body weight of PND 20 offspring mice among the control, 15, 30 and 60 mg/L NaAsO 2 groups [(14.42 ± 1.88), (13.50 ± 1.38), (13.00 ± 1.14), (11.75 ± 0.82) g, F = 4.000, P < 0.05], the body weight of offspring mice in 60 mg/L NaAsO 2 group decreased significantly than that in control group( P < 0.05); there was significant difference in body weight of PND 40 offspring mice among groups [(38.58 ± 2.35), (37.17 ± 1.78), (35.67 ± 1.69), (33.83 ± 1.47) g, F = 7.248, P < 0.05], the body weights of offspring mice in 30 and 60 mg/L NaAsO 2 groups were significantly lower than that in control group, and the body weight of PND 40 offspring mice in 60 mg/L NaAsO 2 group was significantly lower than that in 15 mg/L NaAsO 2 group ( P < 0.05); the results of Morris water maze showed that there were significant differences in the escape latency of offspring mice among groups since 3 - 5 days of training ( F = 3.380, 6.788, 7.240, P < 0.05), the escape latency of offspring mice in NaAsO 2 groups [(67.76 ± 6.45), (71.47 ± 12.19), (73.96 ± 10.42), (58.63 ± 9.24), (60.20 ± 3.74), (67.96 ± 15.41) s] was significantly longer than that in control group [(52.83 ± 8.33), (43.39 ± 8.98) s] since 4 - 5 days of training ( P < 0.05); on the other hand, in the probe trail, there was significant difference in time spent in the target quadrant of offspring mice among groups ( F = 5.709, P < 0.05), time spent in the target quadrant of offspring mice in 30 and 60 mg/L NaAsO 2 groups [(18.85 ± 3.97), (16.90 ± 1.62) s] was significantly less than that in control group [(24.48 ± 3.18) s, P < 0.05]; there was significant difference in BDNF mRNA levels (1.00 ± 0.05, 0.98 ± 0.06, 0.85 ± 0.06, 0.68 ± 0.03) of PND 20 mice among groups ( F = 9.368, P < 0.05), BDNF mRNA level of mice exposed to 60 mg/L NaAsO 2 was significantly lower than that in control, 15 and 30 mg/L NaAsO 2 groups ( P < 0.05); there was significant difference in BDNF mRNA levels (1.00 ± 0.03, 0.75 ± 0.02, 0.76 ± 0.03, 0.73 ± 0.06) of PND 40 mice among groups ( F = 3.998, P < 0.05), and that of PND 40 mice exposed to NaAsO 2 decreased significantly than that in control group ( P < 0.05); there was significant difference in TrkB mRNA levels (1.00 ± 0.08, 0.71 ± 0.02, 0.73 ± 0.02, 0.68 ± 0.09) of PND 20 mice among groups ( F = 16.158, P < 0.05), and that of PND 20 mice exposed to NaAsO 2 were significantly lower than that in control group ( P < 0.05). Conclusion:Arsenic exposure could decrease the mRNA levels of BDNF and TrkB in the hippocampus of offspring mice, which may affect the ability of learning and memory.

Objective To explore the prognostic factors in Guillain Barre syndrome (GBS) in children. Methods A total of 125 children with GBS were included and grouped according to their independent walking at two and six months after discharge, and their clinical data were analyzed. Results In 125 children (74 males, 51 females) the average age was 84.49±25.32 months, and 41 were under 6 years old. 102 children had a history of prodromal infections. 32 children had cranial nerve involvement and 35 had autonomic nerve involvement. 12 children need assisted respiration. At 2 and 6 months after discharge, when compared with children who could walk independently, the rates of functional score > 3, cranial nerve involvement, and neuroelectrophysiology as denervation potential were higher in children who could not walk independently, and the differences were statistically significant (P all<0.05). Conclusions The factors that affect the short-term prognosis are denervation potential in neuroelectrophysiology, cranial nerve involvement, and functional score > 3. Early identification of uniqueness in patients and subsequent development of targeted rehabilitation training should be carried out to improve the prognosis.

Objective To explore the clinical menifestation, electrophysiological characteristics and prognosis of demyelinating and axonal Guillain-Barré syndrome (GBS) in children. Method A total of 81 children with GBS were divided into demyelinating and axonal subtypes according to the results of two electrophysiological examinations. And the clinical, neuro electrophysiological characteristics and prognosis of the two groups were analyzed. Results There were 60 cases of demyelinating GBS and 21 cases of axonal GBS. In children with axonal GBS, there were 5 cases of reversible conduction block. The interval of onset to fastigium in axonal GBS was shorter than that of demyelinating subtype, and blood antiganglioside antibody was more common, and there were statistically differences (P all<0.05). The age at onset, the history of the prodromal infection, the sensory symptoms, the cranial nerve involvement, the impairment of the autonomic nervous function, the cerebrospinal fluid protein-cell separation, and the HG scores at the time of admission and during fastigium were similar between the two groups (P>0.05). Children with reversible conduction block had faster recovery than those without reversible conduction block in axonal GBS, and there was statistical differences (P<0.01). There was no difference in short-term prognosis (2 months after discharge) and long-term prognosis (1 years after discharge) between the axonal GBS and demyelinating GBS children (P>0.05). Conclusion Axonal GBS clinically progressed more rapidly than demyelinating subtype, but there was no difference in prognosis between them. Also, axonal GBS with a reversible conduction block recovered faster.

Objective:investigate the effect of β-caryophyllene(BCP)on cerebral ischemia-reperfusion(CIR)injury in mice.Methods: Mice were subjected to CIR with or without BCP(62,124,248 mg/kg).At 24 h of reperfusion,ischemic degrees were determined according to neurologic dysfunction score and cerebral infarct volume.The protein expression of Toll-like receptor(TLR)4 was measured by Western blot.Nuclear factor κB(NF-κB)p65 were measured by immunohistochemistry and Western blot.IL-1β,tumor necrosis factor-α(TNF-α)and serum high-mobility group box 1(HMGB1)levels were measured by ELISA kit.Results: Compared to the CIR group,BCP(248 mg/kg)reduced the neurological score and cerebral infarct volume.BCP reduced neuronal death in mice brain subjected to cerebral I/R.In addition,BCP also inhibited the activation of NF-κB pathway and decreased increases in TLR4,HMGB1,TNF-α,IL-1β levels by CIR(P<0.01).Conclusion: BCP protects mice brain against CIR injury,its neuroprotective mechanisms may involves HMGB1/TLR4/NF-κB pathway.

Objective To investigate the factors in diagnosis delay in Guillain-Barré syndrome (GBS) and its impact on prognosis.Methods In this study 118 GBS children including Miller-Fisher syndrome (MFS) and pharyngeal-cervical-brachial Guillain-Barré syndrome (PCB) were studied.All children included were divided into 2 groups as GBS-initially-diagnosed group (GBSid,n=76) and not-GBS-initially diagnosed group (nGBSid,n=42) based on the initial diagnosis.Analysis was performed with age at disease onset,preceding infection,Hughes functional grading (HG),the department where the instial diaghosis is done,main complain,the days from disease onset to seeing doctor,time start to treatment,the discharge time,evaluation by a neurologist.Results Among 118 GBS,90 children were of classical GBS,13 of MFS,and 6 of PCB.Atypical muscle weakness,neuropathic pain and impaired respiration function were more frequently seen in nGBSid group (P＜0.05).At the initial diagnosis,lacking of neurological evaluation was found more frequently in nGBSid group (P＜0.05).The duration from onset to the commencement of treatment was longer in nGBSid group than that in GBSid group (P＜0.05),and short term prognosis was poor in GBSid group (P＜0.05).Conclusions Atypical main complaints including neuropathic pain,the impaired respiration function and atypical muscle weakness,and lack of neurological evaluation were all associated with a delay in considering the diagnosis of GBS.The delay in diagnosis had a significant impact on short term prognosis.