BACKGROUND:The mechanism of programmed death receptor-1(PD-1)effect on osteogenic differentiation of bone marrow mesenchymal stem cells in high glucose environment remains unclear. OBJECTIVE:To explore the effect of PD-1 on osteogenic differentiation of rat bone marrow mesenchymal stem cells in high glucose environment and its regulatory mechanism. METHODS:Rat bone marrow mesenchymal stem cells were randomly divided into normal glucose group(5.6 mmol/L),high glucose group(30 mmol/L),PD-1 overexpression group,PD-1 overexpression no-load group,PD-1 knockdown group,PD-1 knockdown no-load group,and PI3K/AKT pathway inhibitor group(PD-1 knockdown+5 μmol/L LY294002).Rat bone marrow mesenchymal stem cells were cultured in high glucose to simulate the diabetic environment in vitro.The mRNA expression of PD-1 and ligand PD-L1 and the mRNA expression of osteogenic markers Runx2 and OSX in rat bone marrow mesenchymal stem cells were detected by qRT-PCR.The osteogenic differentiation ability was observed by alkaline phosphatase staining and alizarin red staining.Cell proliferation was detected by CCK-8 assay.The protein expressions of PD-1,PD-L1,p-PI3K,and p-AKT were detected by western blot assay. RESULTS AND CONCLUSION:(1)The levels of PD-1 and PD-L1 were significantly increased in the high glucose environment in vitro,and the osteogenic differentiation ability of bone marrow mesenchymal stem cells was inhibited in the high glucose environment.(2)Knockdown of PD-1 expression could promote osteogenic differentiation of bone marrow mesenchymal stem cells,increase cell proliferation activity,and activate the PI3K/AKT pathway.(3)After addition of PI3K/AKT pathway inhibitor LY294002,the ability of bone marrow mesenchymal stem cells to differentiate into osteoblasts decreased.The results show that PD-1 is dependent on the PI3K/AKT signaling pathway to inhibit osteogenic differentiation of rat bone marrow mesenchymal stem cells under high glucose environment.

ObjectiveTo analyze the epidemiological characteristics of long COVID and to investigate its main influencing factors by examining individuals infected with SARS-CoV-2 between March and June 2022 in two communities in Shanghai, to lay the foundation for further research on the mechanism and clinical treatment of long COVID, and to provide the basis for the development of inexpensive, convenient, and feasible prevention and intervention strategies. MethodsA cross-sectional study was conducted, enrolling 6 410 individuals infected with SARS-CoV-2. Data were collected through a questionnaire survey. The incidence and common symptoms of long COVID were analyzed, along with their associations with demographic characteristics, medical history, and behavioral factors. A logistic regression model was used to identify the major factors associated with the development of long COVID symptoms. ResultsThe overall incidence rate of long COVID among the study population was 13.9%. The most commonly reported symptoms included fatigue (65.1%), attention disorders (23.1%), and cough (16.9%). The analysis showed that having underlying chronic diseases (OR=2.580, 95%CI: 2.165‒3.074), a history of allergies (OR=1.418, 95%CI: 1.003‒1.971), current smoking (OR=1.461, 95%CI: 1.013‒2.079), ever smoking (OR=2.462, 95%CI: 1.687‒3.551), a greater number of symptoms during the acute phase [1 symptom (OR=1.778, 95%CI: 1.459‒2.162), 2 symptoms (OR=2.749, 95%CI: 2.209‒3.409), ≥3 symptoms (OR=7.792, 95%CI: 6.333‒9.593)] and aggravated symptoms during the acute phase (OR=1.082, 95%CI: 1.070‒1.094) were factors associated with a higher risk of developing long COVID symptoms. Additionally, individuals who had consumed alcohol in the past year (OR=1.914, 95%CI: 1.344‒2.684) were more prone to objective long COVID symptoms. Among individuals under 50 years of age, females (OR=1.427, 95%CI: 1.052‒1.943) were more likely to develop objective long COVID symptoms. ConclusionThis study has identified the diversity of long COVID symptoms, which involve multiple organs and systems, including fatigue, attention disorders, cough, and joint pain. It has also revealed associations between long COVID and various demographic factors (e.g., age, gender), personal medical history (e.g., underlying chronic diseases, history of allergies), acute-phase characteristics (e.g., number and severity of symptoms), and behavioral factors (e.g., smoking, alcohol consumption). These findings highlight the need for further research and ongoing surveillance of long COVID and may inform the development of more targeted health management strategies for specific populations.

Humans ; Artificial Intelligence ; Lung Neoplasms/pathology* ; Mediastinum/pathology* ; Lymph Nodes/pathology* ; Neoplasm Staging ; Lymph Node Excision

Objective To investigate the association between single nucleotide polymorphisms(SNPs)of YTHDF1 rs6011668,HNRNPA2B1 rs2070601 and rs76558212 with the risk of gastric cancer.Methods A total of 457 cases with gastric cancer and 525 healthy controls were collected.The candidate SNPs were genotyped using Hi-SNP genotyping methods by multiplex rounds of PCR and high-throughput sequencing;the association between the three SNPs with the risk of gastric cancer was analyzed by test and Logistic regression.Multifactorial logistic regression and Risk Score(RS)model was used to analyze the influence of environmental and genetic factors on the risk of gastric cancer.Results YTHDF1rs6011668 TT genotype carriers had 3.075 times higher risk of gastric cancer than CC genotype carriers(95%CI:1.128～8.382,P = 0.028),and 2.961 times higher risk than CC/TC genotypes carriers(95%CI:1.091～8.033,P = 0.033).Subgroups-analysis revealed that TT genotype mainly increased the risk of gastric cancer in non-tea drinkers,pickled food eaters and fried food eaters(P<0.05).In addition,TT genotype carriers had the increased risk of gastric cancer infiltration,lymph node metastasis,distal metastasis and intermediate to advanced stages(P<0.05).The RS of the case and control groups were calculated by combining environmental and genetic factors.The higher the RS score,the higher the risk of gastric cancer was found in the RS quartile groups.Compared with the RS

Objective:To investigate the efficacy and safety of transcranial alternating current stimulation (tACS) in treating migraine without aura.Methods:A prospective study was performed. From June 2021 to June 2022, 40 migraine without aura patients treated at Vertigo Center, Department of Neurology, Second Affiliated Hospital of Zhengzhou University were enrolled; they were randomly assigned to true group ( n=20) and pseudo group ( n=20); treatment was given for 4 consecutive weeks and follow-up was given for 4 weeks. Pseudo group did not receive current stimulation, while true group received stimulation by 77.5 Hz, 15 mA alternating current through electrodes placed on the forehead and bilateral mastoid (twice/d, 40 min each time, 5 d as a course, a total of 4 courses). Efficacies and adverse reactions were assessed before treatment, and at the end of treatment and follow-up, respectively. Results:Compared with pseudo group, the average monthly migraine days, visual analog scale (VAS) scores, Pittsburgh Sleep Quality Index (PSQI), Hamilton Anxiety Scale (HAMA) scores and Hamilton Depression Scale (HAMD) scores decreased statistically in true group ( P<0.05), and Migraine-specific Quality of Life Questionnaire (MSQ) scores increased statistically in true group ( P<0.05). In true group, compared with those before treatment, the average monthly migraine days, VAS scores, PSQI, HAMA scores and HAMD scores significantly decreased, and MSQ scores increased statistically at the end of treatment and follow-up ( P<0.05). During treatment, no adverse reactions such as seizures, hearing loss, scalp burns, dizziness, or tinnitus were noted in true group and pseudo group. Conclusion:Repeated tACS can obviously reduce frequency and degree of migraine, improve quality of life in migraine without aura patients; and good safety can be recorded.

Objective:To analyze the abnormal vestibular function of Wernicke encephalopathy (WE) and to explore its diagnostic value.Methods:WE patients who visited the Vertigo Center of the Second Affiliated Hospital of Zhengzhou University from January 2018 to January 2021 were retrospectively collected. All patients were evaluated by clinical neurology. Before treatment, all patients completed video head impulse test (vHIT) and video nystagmusgraphy (VNG) in addition to cranial magnetic resonance and serum thiamine level examination.Results:All 12 patients had a history of eating defects, including 8 cases of alcoholism. All 12 patients had walking instability, 7 cases had dizziness and 8 cases had oscillopsia. Six cases had ophthalmoplegia. All 12 cases showed positive gaze nystagmus. The pathological saccades of bilateral horizontal semicircular canals were found in 12 patients by vHIT before treatment, but there was only 1 patient showing abnormality in vertical semicircular canals, the difference being statistically significant ( P<0.05). All patients could detect bilateral, horizontal, gaze-evoked nystagmus, including 3 cases with vertical nystagmus, 1 case with abnormal saccade test, 3 cases with abnormal smooth tracking test and 1 case with abnormal optokinetic test. There were abnormalities in the caloric test, including 6 cases of bilateral dysfunction and 2 cases of unilateral dysfunction. Conclusions:WE patients may have abnormal vHIT and bilateral, horizontal, gaze-evoked nystagmus, which is similar to the special abnormal signs of simultaneous damage of both peripheral and central vestibular dysfunction.Vestibular function test is valuable for diagnosis of WE, and it is suitable for patients with a history of nutritional disorders who have dizziness or walking instability and suspected WE.

Objective:To analyze the sleep quality and sleep structure of patients with obstructive sleep apnea hypopnea syndrome (OSAHS) complicated with patent foramen ovale (PFO), and to study the effect of PFO on the sleep structure of OSAHS.Methods:Fifty-six patients with OSAHS complicated with PFO, 64 patients with simple OSAHS and 62 controls were collected from December 2018 to March 2020 in Centre of Sleep Disorders, the Second Affiliated Hospital of Zhengzhou University. Pittsburgh Sleep Quality Index and polysomnography were used to compare the sleep quality and sleep structure of the three groups.Results:Compared with the control group [6/62(9.68%)], OSAHS complicated with PFO group [54/56(96.43%)] and simple OSAHS group [53/64(82.81%)] had higher incidence of poor sleep quality (χ2=112.08, P<0.0l). Furthermore, compared with the control group, the OSAHS complicated with PFO group and simple OSAHS group showed reduced sleep efficiency [PSQI total score was 0.5 (0, 1), 2 (1, 3) and 2 (1, 2) respectively, H=74.549, P<0.01] and reduced proportions of rapid eye movement (REM; 20.45%±3.49%, 12.19%±5.95% and 15.11%±7.21%,respectively, F=21.17, P<0.01) and slow wave sleep (N3; 21.24%±4.12%, 14.15%±6.08%, 17.68%±6.35%, respectively, F=29.51, P<0.01); the N1 (4.47%±2.40%, 9.50%±5.34%, 9.55%±4.61%, respectively, F=30.07, P<0.05) and N2 sleep (53.88%±4.35%, 64.09%±7.49%, 58.14%±6.67% , respectively, F=46.21, P<0.05) were prolonged; the inocturnal lowest oxyhemoglobin saturation (SpO 2) level was lower, mean SpO 2 reduction at night was higher [3.00% (0, 4.00%),6.00% (5.00%, 8.75%) and 4.00% (4.00%, 5.00%), respectively, H=72.24, P<0.05], and periodic leg movement index [16.30(4.80, 32.82), 33.30(9.26, 54.80) and 23.10(8.38, 31.83),respectively, H=17.86, P<0.05], arousal index [11.60(7.73, 17.55), 23.90(14.03, 30.45) and 15.6(11.23, 20.78), respectively, H=22.80, P<0.05] and sleep apnea and hypopnea index (AHI; 1.60±1.38, 23.90±7.27 and 16.24±4.22,respectively, F=136.97, P<0.05) increased. Compared with the simple OSAHS group, the incidence of poor sleep quality was higher, the proportions of slow wave sleep (N3, F=29.51, P=0.047) and REM ( F=21.17, P=0.012) were decreased, N2 sleep ( F=46.21, P=0.000) was prolonged, mean SpO 2 reduction at night ( Z=54.28, P=0.000), wake after sleep onset [116.00(89.88, 143.00) min vs 135.00(118.50, 168.38) min, Z=25.71, P=0.023], arousal times [14.00(8.25, 8.00) vs 17.50(9.00,23.00),respectively, Z=19.68, P=0.041], microarousal ( Z=23.57, P=0.044), and AHI ( F=136.97, P=0.000) were increased in the OSAHS complicated with PFO group. Conclusions:OSAHS complicated with PFO patients had poor sleep quality and high incidence of sleep disorders. They had sleep disorder at night, which was characterized by the decrease of REM sleep and slow wave sleep, the prolongation of N2, the decrease of nocturnal SpO 2 and the increase of awakening times, and the increase of arousal times and AHI. PFO can aggravate the sleep disorder of OSAHS.

Objective To analyze the distribution of Virchow-Robin spaces (VRS) in migraine by MRI,and to study the effects of the duration of the disease,the attack frequency and the migraine with or without aura on the number of VRS in order to provide imaging support for migraine diagnosis.Methods Fifty migraine patients were enrolled as migraine group and 50 healthy people as control group during January 2013 to December 2016 from Department of Neurology,the Second Affiliated Hospital of Zhengzhou University.The number of VRS in the fronto-parietal subcortical white matter,semioval central,and basal ganglia areas was calculated and compared between groups and within the group by performing a MRI scan of the same sequence,and the impact of the history of migraine,the attack frequency and the migraine with or without aura on the number of VRS was investigated.Results The VRS were found in 48 cases in the migraine group,accounting for 96％,significantly higher than in the control group (41 cases,accounting for 82％),the difference being statistically significant (x2 =5.00,P ＜ 0.05).In the migraine group,the sum of the number of VRS (13.00 (6.75,20.00)) was significantly higher than that of the control group (8.00 (5.00,12.00);Z=3.33,P＜ 0.01).In the migraine group the VRS numbers in the fronto-parietal subcortical white matter,semioval central and basal ganglia areas were 6.00(4.00,12.00),2.00(0.00,4.00)and 4.00 (2.00,6.00) respectively,while the numbers of VRS in the same areas of the control group were 0.00 (0.00,2.00),2.00 (0.75,4.00) and 4.00 (3.50,6.00).The total number of VRS in different areas was significantly different within the two groups (migraine group x2 =39.86,P ＜ 0.01;control group x2 =40.15,P ＜0.01).In the migraine group,the VRS was mainly located in fronto-parietal subcortical white matter,whereas in the control group the VRS was mainly distributed in the basal ganglia.The total number of VRS in the migraine with aura group (20.00 (14.50,26.00)) was more than that in the migraine without aura group (11.00 (6.00,20.00);Z =2.52,P =0.02).The numbers of VRS in the fronto-parietal subcortical white matter,semioval central and basal ganglia areas of the migraine with aura group were 12.00(9.00,14.00),2.00(2.00,6.00) and 4.00(2.50,7.50) respectively;The numbers of VRS in the same areas of the migraine without aura group were 6.00(4.00,10.00),1.00(0.00,4.00) and 4.00 (2.00,6.00) respectively;The numbers of VRS in different areas within the two groups were significantly different (with aura group x2 =16.31,P ＜0.01;without aura group x2 =29.48,P ＜0.01).There were statistically significant differences in the number of VRS among migraine without aura patients with different duration and frequency of episodes.Conclusions The incidence rate of perivascular space in migraine is high.VRS is mainly distributed in the fronto-parietal subcortical white matter,which may provide an imaging assistant basis for the diagnosis of migraine.Migraine with aura is more prone to VRS than those without aura.The disease course and the attack frequency have a certain impact on occurrence of VRS.

Migraine and cerebral small vessel disease (CSVD) are 2 common neurovascular diseases in clinical practice.Their pathogeneses are still not clear.Migraine may increase the risk of CSVD,and CSVD can also cause migraine attacks by triggering cortical spreading depression and other mechanisms.The relationship between the two diseases is mutual and complex,and is influenced by a variety of factors,but the mechanism of this potential relationship is not yet very clear.With further research,the reports about the relationship between migraine and CSVD are increasing.This article summarizes the pathophysiological mechanisms of migraine and CSVD and the correlation between both.

BACKGROUNDGreen tea has been shown to improve cholesterol metabolism in animal studies, but the molecular mechanisms underlying this function have not been fully understood. Long non-coding RNAs (lncRNAs) have recently emerged as a major class of regulatory molecules involved in a broad range of biological processes and complex diseases. Our aim was to identify important lncRNAs that might play an important role in contributing to the benefits of epigallocatechin-3-gallate (EGCG) on cholesterol metabolism.

METHODSMicroarrays was used to reveal the lncRNA and mRNA profiles in green tea polyphenol(-)-epigallocatechin gallate in cultured human liver (HepG2) hepatocytes treated with EGCG and bioinformatic analyses of the predicted target genes were performed to identify lncRNA-mRNA targeting relationships. RNA interference was used to investigate the role of lncRNAs in cholesterol metabolism.

RESULTSThe expression levels of 15 genes related to cholesterol metabolism and 285 lncRNAs were changed by EGCG treatment. Bioinformatic analysis found five matched lncRNA-mRNA pairs for five differentially expressed lncRNAs and four differentially expressed mRNA. In particular, the lncRNA AT102202 and its potential targets mRNA-3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) were identified. Using a real-time polymerase chain reaction technique, we confirmed that EGCG down-regulated mRNA expression level of the HMGCR and up-regulated expression of AT102202. After AT102202 knockdown in HepG2, we observed that the level of HMGCR expression was significantly increased relative to the scrambled small interfering RNA control (P < 0.05).

CONCLUSIONSOur results indicated that EGCG improved cholesterol metabolism and meanwhile changed the lncRNAs expression profile in HepG2 cells. LncRNAs may play an important role in the cholesterol metabolism.

Catechin ; analogs & derivatives ; metabolism ; Cell Line, Tumor ; Cholesterol ; metabolism ; Hep G2 Cells ; Humans ; RNA, Long Noncoding ; genetics