Dissecting Causal Relationships Between Gut Microbiota, Blood Metabolites, and Stroke: A Mendelian Randomization Study / 대한뇌졸중학회지

Background@#and Purpose We investigated the causal relationships between the gut microbiota (GM), stroke, and potential metabolite mediators using Mendelian randomization (MR). @*Methods@#We leveraged the summary statistics of GM (n=18,340 in the MiBioGen consortium), blood metabolites (n=115,078 in the UK Biobank), and stroke (cases n=60,176 and controls n=1,310,725 in the Global Biobank Meta-Analysis Initiative) from the largest genome-wide association studies to date. We performed bidirectional MR analyses to explore the causal relationships between the GM and stroke, and two mediation analyses, two-step MR and multivariable MR, to discover potential mediating metabolites. @*Results@#Ten taxa were causally associated with stroke, and stroke led to changes in 27 taxa. In the two-step MR, Bifidobacteriales order, Bifidobacteriaceae family, Desulfovibrio genus, apolipoprotein A1 (ApoA1), phospholipids in high-density lipoprotein (HDL_PL), and the ratio of apolipoprotein B to ApoA1 (ApoB/ApoA1) were causally associated with stroke (all P<0.044). The causal associations between Bifidobacteriales order, Bifidobacteriaceae family and stroke were validated using the weighted median method in an independent cohort. The three GM taxa were all positively associated with ApoA1 and HDL_PL, whereas Desulfovibrio genus was negatively associated with ApoB/ApoA1 (all P<0.010). Additionally, the causal associations between the three GM taxa and ApoA1 remained significant after correcting for the false discovery rate (all q-values <0.027). Multivariable MR showed that the associations between Bifidobacteriales order, Bifidobacteriaceae family and stroke were mediated by ApoA1 and HDL_PL, each accounting for 6.5% (P=0.028) and 4.6% (P=0.033); the association between Desulfovibrio genus and stroke was mediated by ApoA1, HDL_PL, and ApoB/ApoA1, with mediated proportions of 7.6% (P=0.019), 4.2% (P=0.035), and 9.1% (P=0.013), respectively. @*Conclusion@#The current MR study provides evidence supporting the causal relationships between several specific GM taxa and stroke and potential mediating metabolites.

Systematic analysis of epidemiological features of norovirus causing sporadic acute gastroenteritis in China / 中华微生物学和免疫学杂志

Objective:To systematically evaluate the prevalence of norovirus causing sporadic acute gastroenteritis in China.Methods:Relevant articles on acute gastroenteritis caused by norovirus in China published between January 2010 and October 2023 were retrieved from Wanfang, CNKI and PubMed database. The articles met inclusion and exclusion criteria were enrolled in this study. Excel software and SPSS20.0 software were used for statistical analysis. The epidemiological features of sporadic cases of acute gastroenteritis caused by norovirus in China were summarized using descriptive statistical analysis.Results:A total of 500 articles were included in this study, involving 784 486 cases of acute gastroenteritis and 670 292 samples in 32 provinces and regions. Norovirus GⅡ was the predominant genogroup causing acute gastroenteritis in China in recent years, but there were significant differences in the distribution of genotypes and epidemic strains at different times. GⅡ.4 was the predominant genotype in each year, and GⅡ.4/2006b and GⅡ.4 /Sydney_2012 were the main epidemic strains. Norovirus-related diarrhea occurred throughout the year, especially between the months of October and December. The incidence of norovirus infection was high in children under five years old and varied in different regions.Conclusions:Norovirus GⅡ was the predominant genogroup causing norovirus-related sporadic acute gastroenteritis in China, but there was an obvious genetic evolutionary trend in the epidemic strains. Factors such as epidemic strains, season and geographical region should be considered when making strategies for the prevention and control of norovirus-related diarrhea and developing vaccines.

Research progress of TCM non-drug therapy in gastroesophageal reflux disease / 国际中医中药杂志

Traditional Chinese Medicine (TCM) non-drug therapy for gastroesophageal reflux mainly includes appropriate TCM techniques, such as conventional acupuncture, moxibustion, fire needle, etc. Emotional therapy, such as regulating emotion, transforming the patient's spirit and change the state of qi, the five-element music therapy, etc; exercise therapy, such as Baduanjin and Zhanzhuang, can be used alone, or in combination, or in combination with oral administration of Chinese materia medica. By reducing the probability of esophageal sphincter relaxation, inhibiting gastric acid secretion, improving esophageal motility disorder, reducing visceral hypersensitivity, immune regulation and other effects, it can alleviate the symptoms of acid reflux, heartburn and pharyngeal discomfort, and help to improve the patients' anxiety, depression and other negative emotions. It has the characteristics of simplicity and fewer adverse reactions, at the same time, according to the patient's condition and compliance to choose the appropriate therapy. The mechanism of TCM non-drug therapy in the treatment of this disease needs to be further explored, so as to better guide clinical popularization and application.

Comparison of therapeutic effects of non-vitrectomy versus vitrectomy for idiopathic epiretinal membrane / 中华眼底病杂志

Objective:To compare the efficacy of pars plana vitrectomy (PPV) and nonvitrectomizing vitreous surgery (NVS) in the treatment of idiopathic epimacular membrane (IMEM).Methods:A prospective , randomized and comparative clinical study. From April 2019 to May 2020, 21 eyes of 21 patients with IMEM diagnosed in Chongqing Aier Eye Hospital were included in the study. Among them, 11 males had 11 eyes, and 10 females had 10 eyes. Best-corrected visual acuity (BCVA), optical coherence tomography angiography (OCTA), and corneal, intraocular, and global aberration measurements were performed in all eyes. The international standard logarithmic visual acuity chart was used for BCVA examination, and the visual acuity was converted into logarithm of minimum angle of resolution (logMAR) during statistics. The iTrace visual function analyzer was used to measure the corneal, intraocular and whole ocular aberrations, and the dysfunction lens index (DLI) was calculated. Lens density in Scheimpflug images was calculated using Pentacam three-dimensional anterior segment analysis and diagnosis system. The 6 mm×6 mm area of the macular area was scanned by OCTA, which was divided by the software automatically into three concentric circles with the fovea as the center, namely the central area with a diameter of 1 mm, the inner ring area with a diameter of 1-3 mm, The outer ring area of 3-6 mm was used to measure the superficial vessel density (SVD) and superficial perfusion density (SPD) of the entire macular area, the central area, the inner ring area, and the outer ring area. The patients were divided into PPV combined with epimacular membrane (MEM) peeling group (PPV group) and NVS direct peeling MEM group (NVS group) by random number table method, 10 cases with 10 eyes and 11 cases with 11 eyes, respectively. The age of the two groups ( t=-0.72), logMAR BCVA ( t=-0.98), lens density ( t=-1.10), DLI ( t=1.15), SVD ( t=0.82) and SPD ( t=1.19) of entire macular area, corneal aberration ( t=0.45), intraocular aberration ( t=-0.22), and whole eye aberration ( t=0.83), there was no significant difference ( P>0.05). All eyes were operated on with a 27G vitrectomy system. The MEM was removed from the eyes of the NVS group under NVS condition, and the MEM was removed from the eyes of the PPV group under the condition of PPV, and the operation time was recorded at the same time. The follow-up period after surgery was 12 months. Relevant examinations were performed using the same equipment and methods before surgery. Taking the last follow-up as the time point for efficacy judgment, the BCVA, lens opacity, DLI, visual quality, SVD, SPD and MEM recurrence in the macula were compared between the two groups. The two groups were compared by paired t test. Results:The operation time of eyes in PPV group and NVS group was 20.81±3.52 and 5.70±1.30 min, respectively, and the difference was statistically significant ( t=7.23, P<0.001). At the last follow-up, the logMAR BCVA of PPV group and NVS group were 0.65±0.25 and 0.44±0.20, respectively, and the difference was statistically significant ( t=-2.16, P=0.04); compared with before operation, the BCVA of eyes of the two groups was significantly improved, and the difference was statistically significant. ( t=2.52, 4.41; P=0.033, P<0.001). The lens density and DLI of the affected eyes in the PPV group and NVS group were 10.64±1.58, 6.24±3.99 and 5.77±1.63, 7.74±1.55, respectively, and the differences were statistically significant ( t=-3.90, 2.85; P<0.05). The macular area SVD ( t=1.03), SPD ( t=1.77), corneal aberration ( t=-0.42), intraocular aberration ( t=-1.10), and whole-eye aberration ( t=-1.17) of eyes of the two groups, the difference was not statistically significant ( P>0.05). During the follow-up period, there were 2 eyes with MEM recurrence, 1 eye in the PPV group and 1 eye in the NVS group; there was no significant difference in the recurrence rate of MEM between the two groups ( χ2=0.005, P=0.94). Conclusion:Compared with PPV combined with MEM stripping, the BCVA after NVS surgery increases more, has a better protective effect on the lens, and has a shorter operation time.

Progress in norovirus research and vaccine development / 中华微生物学和免疫学杂志

Norovirus is one of the leading causes of acute non-bacterial gastroenteritis. Emergence of new genotypes due to frequent genetic recombination and antigenic drift increases the prevalence of noro-virus infection worldwide. Norovirus infection has become a global public health concern. This review fo-cused on disease burden, vaccine research, cell culture and animal models regarding norovirus infection.

Type 2 diabetes is causally associated with depression: a Mendelian randomization analysis / 医学前沿

Type 2 diabetes (T2D) has been associated with a high prevalence of depression.We aimed to determine the causal relation by performing a Mendelian randomization (MR) study using 34 T2D risk genetic variants validated in East Asians as the instrumental variable (IV). An MR analysis was performed involving 11 506 participants from a large longitudinal study. The T2D genetic risk score (GRS) was built using the 34 typical T2D common variants. We used T2D_GRS as the IV estimator and performed inverse-variance weighted (IVW) and Egger MR analysis. The T2D_GRS was found to be associated with depression with an OR of 1.21 (95% CI: 1.07-1.37) after adjustments for age, sex, body mass index, current smoking and drinking, physical activity, education, and marital status. Using T2D_GRS as the IV, we similarly found a causal relationship between genetically determined T2D and depression (OR: 1.84, 95% CI: 1.25-2.70). Though we found no association between the combined effect of the genetic IVs for T2D and depression with EggerMR(OR: 0.95, 95%CI: 0.42-2.14), we found an association for T2D and depression with IVW (OR: 1.75, 95% CI: 1.31-2.46) after excluding pleiotropic SNPs. Overall, the MR analyses provide evidence inferring a potential causal relationship between T2D and depression.

Evaluation of immune effects of virus-like particles of recombinant GⅡ. 17 norovirus / 中华微生物学和免疫学杂志

Objective To evaluate the immune effects of virus-like particles ( VLPs) assembled from the capsid protein VP1 of a recombinant norovirus ( NoV) GⅡ. 17 genotype. Methods The recombi-nant NoV GⅡ. 17 VP1 VLPs were purified, and then tested by SDS-PAGE and Western blot to analyze the purity. The size, morphology and diameter distribution of the recombinant VLPs were detected by transmis-sion electron microscopy ( TEM) and dynamic light scattering ( DLS) analyzer. The recombinant VP1 VLPs adsorbed by aluminium adjuvant were used to immunize BALB/c mice. Serum samples were collected after immunization. Specific antibody level and neutralizing antibody activity were evaluated with enzyme linked immunosorbent assay ( ELISA) and histo-blood group antigen ( HBGA)-VLP blocking test. Cross-reactivity of serum samples with GⅠ. 1 and GⅡ. 4 VP1 VLPs were detected. Moreover, cross-protection against GⅠ. 1 and GⅡ. 4 VP1 VLPs was analyzed. Results The purity of the recombinant NoV GⅡ. 17 VP1 VLP was greater than 90％ and specific bands were detected by Western blot. TEM images and DLS experiments showed that VLPs were 30-50 nm in size with good morphology and uniformity, indicating that the recombi-nant VLPs were similar to the wildtype virus. High titers of specific antibodies were detected in serum sam-ples of the immunized mice. A certain degree of cross-reactions between serum samples and VP1 VLPs of NoV GⅠ. 1 and GⅡ. 4 were observed, but no cross-protection was detected. Conclusion The recombinant GⅡ. 17 VP1 VLPs in combination with aluminum adjuvant can induce higher titers of HBGA blocking anti-bodies in mice, suggesting that it could be used as a candidate target antigen for norovirus vaccine.

The relationship between the expression of sonic hedgehog and vascular endothelial growth factor in hypoxic human retinal pigment epithelial cells / 中华眼底病杂志

Objective To study the relationship between the expression of sonic hedgehog (Shh) and vascular endothelial growth factor (VEGF) in hypoxic human retinal pigment epithelial (hRPE) cells.Methods Cultured hRPE-19 cells (3rd-6th generations) were used in this experiment.hRPE-19 cells were divided into three groups including the control group,the hypoxia experimental group (100 μmol/L CoCl2) and the inhibition group (pretreatment with 20 μmol/L cyclopamine 1 hour before hypoxia).After culturing for 4,8,12 and 24 hours,the mRNA level of Shh and VEGF genes in these cells were measured by fluorescence quantitative polymerase chain reaction,and the protein level of Shh and VEGF in the supematants were measure by enzymelinked immunosorbent assay.The relationship between the expression of Shh and VEGF was analyzed by Pearson correlation analysis.Results The control group expressed low levels of Shh and VEGF mRNA/protein.The expression of Shh and VEGF mRNA/protein in the hypoxia experimental group was significantly higher than that in the control group (F=178.364,183.732,77.456,91.572;P＜0.01).The expression of Shh and VEGF mRNA in the inhibition group was significantly lower than that in the hypoxia experimental group (F=68.745,121.834;P＜0.01).In the hypoxia experimental group,the expression of VEGF protein was positively correlated with the expression of Shh protein (r=0.942,P＜ 0.05);and the expression of VEGF and Shh mRNA was positively correlated (r=0.970,P＜0.01).However,there was no significant correlation in the expression of VEGF and Shh mRNA in the inhibition group (r=0.915,P＞ 0.05).Conclusion There is a positive correlation between the expression of Shh and VEGF in hypoxic hRPE cells.

Evaluation of digital dental models obtained from dental cone-beam computed tomography scan of alginate impressions / 대한치과교정학회지

OBJECTIVE: To investigate the dimensional accuracy of digital dental models obtained from the dental cone-beam computed tomography (CBCT) scan of alginate impressions according to the time elapse when the impressions are stored under ambient conditions. METHODS: Alginate impressions were obtained from 20 adults using 3 different alginate materials, 2 traditional alginate materials (Alginoplast and Cavex Impressional) and 1 extended-pour alginate material (Cavex ColorChange). The impressions were stored under ambient conditions, and scanned by CBCT immediately after the impressions were taken, and then at 1 hour intervals for 6 hours. After reconstructing three-dimensional digital dental models, the models were measured and the data were analyzed to determine dimensional changes according to the elapsed time. The changes within the measurement error were regarded as clinically acceptable in this study. RESULTS: All measurements showed a decreasing tendency with an increase in the elapsed time after the impressions. Although the extended-pour alginate exhibited a less decreasing tendency than the other 2 materials, there were no statistically significant differences between the materials. Changes above the measurement error occurred between the time points of 3 and 4 hours after the impressions. CONCLUSIONS: The results of this study indicate that digital dental models can be obtained simply from a CBCT scan of alginate impressions without sending them to a remote laboratory. However, when the impressions are not stored under special conditions, they should be scanned immediately, or at least within 2 to 3 hours after the impressions are taken.

Role of Shh signal transduction pathway in vascular endothelial growth factor expression under hypoxia in cultured human retinal pigment epithelial cells / 中华眼底病杂志

Objective To investigate the role of sonic hedgehog (Shh) signal transduction pathway in the expression of vascular endothelial growth factor (VEGF) under hypoxia in cultured human retinal pigment epithelial (hRPE) cells.Methods ARPE-19 were cultured and divided into normal ARPE-19 (Cont) and hypoxia group (100 μmol/L CoCl2 Cobalt Chloride +-ARPE-19);hypoxia group was further divided into CoCl2 group,cyclopamine group (CYA) and dimethyl sulfoxide (DMSO) group.20 μmol/L cyclopamine was added to the CYA group 1 hour before hypoxia,1‰ DMSO was added into DMSO group at the same time.The hRPE cells were cultured under hypoxia for 4,8,12,24 hours.The expression of Shh and VEGF were determined by Real-time fluorescent quantitate PCR (RT-PCR).The amount of VEGF in the hRPE-conditioned supernatant was measured using enzyme linked immunosorbent assay (ELISA) at 4,8,12,24 hours,respectively.Results RT-PCR tests showed that the level of Shh and VEGF of hRPE was time dependently increased (Shh:F=45.260,P=0.001;VEGF:F=264.938,P=0.001).The level of Shh and VEGF of hRPE in the group treated with cyclopamine was decreased (P＜0.01).ELISA tests showed that the amount of VEGF in hRPE supernatant was significantly increased in time-dependent manner (F =3 156.676,P =0.001),and it was down-regulated by cyclopamine under hypoxia (P＜0.01).Conclusion Shh signal transduction pathway could play a role in the VEGF expression induced by hypoxia in hRPE cells.

Spontaneous neural activity in different frequency bands in Parkinson 's disease：a fMRI study / 中华行为医学与脑科学杂志

Objective To explore the pattern of spontaneous neural activity in different frequency bands in Parkinson's disease(PD).Methods The blood oxygen level-dependent signals in 39 PD patients and 37 normal controls were acquired and the amplitude of low-frequency fluctuation ( ALFF) in five differ-ent frequecy bands ( slow-2:0.198-0.25 Hz;slow-3:0.073-0.198 Hz;slow-4:0.027-0.073 Hz;slow-5:0.01-0.027 Hz;slow-6:0-0.01Hz) was cacaulated.A repeated-measures analysis of variance and Post hoc t-test were performed to detect differences of spontaneous activity between two groups in different frequency bands. A correlation analysis was examined between Unified Parkinson’ s Disease Rating Scale ( UPDRS) motor score and ALFF in patients with PD in each frequency band to discover the relationship between disease se-verity and spontaneous neural activity.Results Compared with the normal controls,patients with PD had decreased ALFF in the putamen(-24,-3,-9) (-30,3,0) ( -21,9,6) in the slow-3,slow-4 and slow-5, and had decreased ALFF in the left precentral gyrus (-21,-24,75) (-21,-24,72) (-27,-21,72) (-15,-15,72) and right supplementary motor area (21,-24,75) (6,-3,72) (12,-6,60) (15,-24,72) in all frequency bands except for the slow-5.Increased ALFF in the cerebellum was found in all frequency bands.The ALFF in the putamen was negatively correlated with the UPDRS motor score in the slow-3,slow-5 and slow-6.Conclusion This study shows that the abnormal activities in the striatum are significant in the slow-3,slow-4and slow-5.Most frequency bands except slow-5 are helpful in detecting neural changes in mo-tor cortex.The increased activity in the cerebellum is the common findings in all frequency bands.Multiple frequency analysis may provide insight into the pathophysiological mechanisms of PD.

Application of amplitude of low frequency fluctuation to cognitive impaired patients with Parkinson's disease:a resting state fMRI study / 中华行为医学与脑科学杂志

Objective To investigate the changes of amplitude of low frequency fluctuation (ALFF) of the resting state fMRI in cognitively impaired Parkinson' s disease patients and discuss its underling neurophysiological mechanism.Methods Blood oxygen level-dependent low-frequency amplitude (ALFF) in resting-state functional magnetic resonance imaging were calculated in 16 healthy controls(HC) and 29 idiopathic Parkinson's disease patients (16 of which were patients with cognitive normal,PDCN and 13 with cognitive impairment,PDCI).The brain regions showing increased and decreased ALFF in patients were demonstrated by comparing normal subjects with 2-sample t-test with threshold of P＜ 0.05 and the analysis of the relationship between the different regions of the brain activity and cognitive function tests scores were also analyzed.Results Compared with PDCN,the PDCI patients showed decreased activity in the caudate nucleus (-3,9,12),occipital lobe (0,-78,-15) and medial temporal lobe (42,9,-27) and increased activity in the superior frontal gyrus (9,63,24).PDCI patients showed increased activity mainly in the precuneus and inferior parietal lobules compared with controls.Additionally,the regions with ALFF changes had significant correlations with the cognitive performance of patients as measured by Montreal cognitive test(Beijing Version) and neuropsychological tests (including memory,attention,visuospatial functions and executive function).Conclusion The results demonstrate that there is a specific pattern of intrinsic activity in PDCI providing insights into neurophysiological mechanisms of the Parkinson's disease dementia.