Analysis of cerebral gray matter structure in multiple sclerosis and neuromyelitis optica / 解剖学报

Objective The volume and cortical thickness of gray matter in patients with multiple sclerosis (MS) and neuromyelitis optica (NMO) were compared and analyzed by voxel⁃based morphometry (VBM) and surface⁃based morphometry (SBM), and the differences in the structural changes of gray matter in the two diseases were discussed. Methods A total of 21 MS patients, 16 NMO patients and 19 healthy controls were scanned by routine MRI sequence. The data were processed and analyzed by VBM and SBM method based on the statistical parameter tool SPM12 of Matlab2014a platform and the small tool CAT12 under SPM12. Results Compared with the normal control group (NC), after Gaussian random field (GRF) correction, the gray matter volume in MS group was significantly reduced in left superior occipital, left cuneus, left calcarine, left precuneus, left postcentral, left central paracentral lobule, right cuneus, left middle frontal, left superior frontal and left superior medial frontal (P<0. 05). After family wise error (FWE) correction, the thickness of left paracentral, left superiorfrontal and left precuneus cortex in MS group was significantly reduced (P<0. 05). Compared with the NC group, after GRF correction, the gray matter volume in the left postcentral, left precentral, left inferior parietal, right precentral and right middle frontal in NMO group was significantly increased (P<0. 05). In NMO group, the volume of gray matter in left middle occipital, left superior occipital, left inferior temporal, right middle occipital, left superior frontal orbital, right middle cingulum, left anterior cingulum, right angular and left precuneus were significantly decreased (P<0. 05). Brain regions showed no significant differences in cortical thickness between NMO groups after FWE correction. Compared with the NMO group, after GRF correction, the gray matter volume in the right fusiform and right middle frontal in MS group was increased significantly(P<0. 05). In MS group, the gray matter volume of left thalamus, left pallidum, left precentral, left middle frontal, left middle temporal, right pallidum, left inferior parietal and right superior parietal were significantly decreased (P<0. 05). After FWE correction, the thickness of left inferiorparietal, left superiorparietal, left supramarginal, left paracentral, left superiorfrontal and left precuneus cortex in MS group decreased significantly (P<0. 05). Conclusion The atrophy of brain gray matter structure in MS patients mainly involves the left parietal region, while NMO patients are not sensitive to the change of brain gray matter structure. The significant difference in brain gray matter volume between MS patients and NMO patients is mainly located in the deep cerebral nucleus mass.

Comprehensive analysis of insulin products complex disulfide bonds structure by high resolution mass spectrum / 药学学报

The correct pairing of disulfide bonds maintains the correct folding mode and high-level structure formation of peptides and protein drugs, which is crucial for the quality control of products. In order to ensure that the disulfide bonds are correctly paired, disulfide bond analysis is an essential part of peptides and protein drug characterization. Mass spectrometry can be used to analyze disulfide bonds. However, insulin and its analogues have two pairs of disulfide bonds without restriction enzyme cutting site. Conventional collision-induced dissociation (CID) and high-energy induced cleavage (HCD) cannot accurately locate the complex disulfide bond. In our study, three methods were used to localize the complex disulfide, including enzyme digestion combined with key peptide fragment in source decay (ISD) fragmentation method, enzyme digestion combined with partial reduction alkylation method, intact protein source ISD and electron transfer dissociation (ETD) cleavage method, The applicability of insulin aspart, insulin lispro and insulin glargine were also investigated. This study provides a new way for the quality control of disulfide bonding mode of insulin and its analogues, and also provides a reference for the disulfide bond localization of peptides or proteins containing this complex disulfide bond.

Early-stage non-alcoholic fatty liver disease in relation to atherosclerosis and inflammation

Abstract Background and aims Non-alcoholic fatty liver disease (NAFLD) is a multisystem disease closely linked to cardiovascular disease (CVD). This study aims to investigate the connection between early-stage NAFLD and atherosclerosis, as well as the correlation between liver fibrosis and coronary heart disease while exploring underlying inflammatory mechanisms. Methods In this retrospective study, the authors analyzed data from 607 patients who underwent both coronary computed tomography angiography (CCTA) and abdominal ultrasonography (US). Logistic regression was utilized to examine the association between NAFLD and atherosclerosis, while mediation analysis was conducted to explore whether inflammatory markers mediate the link between liver fibrosis and coronary artery disease. Results Among the 607 patients included, 237 (39.0 %) were diagnosed with NAFLD through ultrasonography. After adjusting for traditional cardiovascular risk factors, ALT, and AST, NAFLD demonstrated a significant correlation with carotid intimal thickening (1.58, 95 % CI 1.04‒2.40; p= 0.034) and non-calcified plaque (1.56, 95 % CI 1.03‒2.37; p= 0.038). Additionally, fibrosis predictive markers, including FIB-4 > 1.3 (1.06, 95 % CI 2.30‒5.00; p= 0.035) and APRI (6.26, 95 % CI 1.03‒37.05; p= 0.046), independently correlated with coronary heart disease after adjusting for cardiovascular risk factors. Conversely, among systemic inflammatory markers, only the neutrophil-to-lymphocyte ratio (NLR) and systemic inflammatory response index (SIRI) are independently associated with coronary heart disease. ROC curve analysis indicated that combining predictive fibrosis markers or inflammatory markers with traditional cardiovascular risk factors enhanced the predictive accuracy for coronary heart disease. Mediation analysis revealed that NLR fully mediated the effect of liver fibrosis on coronary heart disease. Conclusion NAFLD is associated with carotid intimal thickening and non-calcified plaque, suggesting an increased cardiovascular risk. Furthermore, liver fibrosis independently increases the risk of coronary heart disease in the early-stage NAFLD population, and inflammation may play a fully mediating role in the effect of liver fibrosis on coronary heart disease. Early intervention is crucial for NAFLD patients to mitigate future major adverse cardiovascular events.

Multi-index analysis of regional brain activity in patients with Alzheimer's disease during resting state / 解剖学报

Objective To investigate the spontaneous neural activity in the brain of patients with Alzheimer' s disease (AD) used 3 indicators of resting state-functional magnetic resonance (rs-fMRI) amplitude of low frequency fluctuation (ALFF), fractional amplitude of low frequency fluctuation (fALFF) and percentage amplitude fluctuation (PerAF). Methods Totally 36 clinically diagnosed AD patients and 40 healthy volunteers were scanned by fMRI in resting state respectively. ALFF, fALFF and PerAF were used to calculate and compare the changes of brain regions between the two groups. Results Compared with the normal control group, mALFF value in AD group increased significantly in bilateral caudate nucleus, medial frontal gyrus, superior frontal gyrus, gyrus rectus, anterior cingulate gyrus, olfactive cortex, left middle frontal gyrus and inferior frontal gyrus (P<0. 05). mALFF values decreased significantly in the right middle temporal gyrus, inferior temporal gyrus, inferior occipital gyrus, middle occipital gyrus, bilateral calcarine, cuneus, lingual gyrus, superior occipital gyrus, vermis, precuneus and other regions (P<0. 05). In AD group, mfALFF value of right inferior temporal gyrus, anterior cerebellar lobe, fusiform gyrus, left superior frontal gyrus, medial frontal gyrus, middle frontal gyrus, inferior frontal gyrus, gyrus rectus and anterior cingulate gyrus increased significantly (P<0. 05); mfALFF values decreased significantly in bilateral lingual gyrus, left calcarine, cuneus, superior occipital gyrus, middle occipital gyrus and vermis (P<0. 05). In AD group, mPerAF value increased significantly in bilateral gyrus rectus, anterior cingulate gyrus, medial frontal gyrus, left superior frontal gyrus, caudate nucleus, middle frontal gyrus, inferior frontal gyrus, olfactive cortex and insula (P<0. 05); mPerAF values decreased significantly in bilateral calcarine, cuneus, superior occipital gyrus, lingual gyrus, precuneus, left fusiform gyrus, inferior occipital gyrus, right superior parietal lobule, angular gyrus, middle temporal gyrus, inferior temporal gyrus and middle occipital gyrus (P < 0. 05). Conclusion The default mode network (DMN) and visual network of AD patients are characterized by abnormal brain activity, with the most significant neural activity in the prefrontal cortex and visual cortex.

Research progress in the reprogramming of retinal Müller glia cells / 解剖学报

[Abstract] Blinding eye diseases caused by retinal degeneration have a detrimental effect on human health. Mammalian retina exhibits very limited capacity for self-repair after degenerative disease or injury. In contrast, zebrafish retina possesses a robust regenerative response that regenerates all types of retinal neurons and restores vision. Retina regeneration in zebrafish depends on a type of glia cells called Müller glia. Following retinal injury, zebrafish Müller glia undergo a reprogramming process and proliferate into multipotent progenitor cells that further differentiate into newborn retinal neurons. In recent years, significant progress has been made in the field of Müller glia-based retina regeneration. Here we summarize the mechanisms governing zebrafish retina regeneration and the recent advances in mammalian Müller glia reprogramming.

Susceptibility weighted imaging of superficial cerebellar veins / 解剖学报

[Abstract] ObjectVisualizing the superficial cerebellar vein and its tributaries on suscepxibility weighted imaging (SWI), and to construct superficial cerebellar vein network. Methods According to the inclusion criteria, 80 healthy volunteers (40 males and 40 females) were selected for 3. 0 T MRI scans to obtain conventional sequence cross-section, sagittal tomographic images, and SWI image data. Post-processing was performed on the Extended MR workspace 2. 6. 3. 4 image workstation to reconstruct minimum intensity projection(mIP) images. SPSS 21. 0 statistical software was used to analyze and process each data, and the diameter measurement result were expressed as mean ± standard deviation. Results Both SWI and mIP could image the structures of the cerebellum and its veins. The cerebellar veins were divided into deep and superficial parts. The superficial cerebellar veins were divided into two groups: the vermis and the cerebellar hemispheres. The superficial vein of the cerebellar vermis consisted of superior vermis vein [diameter: (1. 21±0. 24)mm, occurrence rate: 92. 16%], summit vein [ diameter: (0. 66 ± 0. 05) mm, occurrence rate: 95%], mountain vein [diameter: (0. 76±0. 03)mm, occurrence rate: 100%], inferior vermis vein [diameter: (1. 40±0. 27)mm, occurrence rate: 99. 02%]. The superficial cerebellar hemisphere vein consists of anterior superior cerebellar vein [diameter: (1. 09± 0. 12)mm, occurrence rate: 100%], posterior superior cerebellar vein [diameter: (0. 88±0. 13) mm, occurrence rate: 70%], anterior inferior cerebellar vein [ diameter: (1. 34 ± 0. 15) mm, occurrence rate: 100%], posterior inferior cerebellar vein [ diameter: (1. 11 ± 0. 09) mm, occurrence rate: 92. 5%]. The deep veins were divided into cerebellomesencephalic fissure group, cerebellopontine fissure group, and cerebellomedullary fissure group. Conclusion SWI can display the microstructure and venules of the cerebellum, and can construct a network of superficial cerebellar veins.

Licochalcone A inhibits osteosarcoma proliferation by Akt/ERK signaling pathway / 中国药理学通报

Aim To investigate the effect of licochalcone A (LCA) on proliferation and apoptosis of osteosarcoma HOS and U2OS cells and to explore its possible molecular mechanism. Methods The HOS and U2OS cells were cultured in vitro. MTT assay was used to detect the proliferation of the cells after being treated with different concentrations of LCA at different intervention time. Then HOS and U2OS cells were treated with 0. 1% DMSO, or different concentrations of LCA (5, 10, 20 μmol/L), and flow cytometry was used to assess the cell apoptosis. The expression of apoptosis-related protein cleaved PARP1, Bcl-2, Bax, and Akt, ERK were detected by Western blot. The antitumor effect of LCA was detected on U2OS xenograft mice in vivo. Results LCA could inhibit the proliferation of HOS and U2OS cells in a time-and dose-dependent manner. Flow cytometry showed that LCA treatment could induce cell apoptosis. Western blot results showed that LCA could inhibit the phosphorylation of Akt and ERK, increase the expression of cleaved PARP1 and Bax, and decrease the expression of Bcl-2. In the tumor-bearing mouse models, LCA significantly decreased the tumor volume (P < 0. 05) and weight (P < 0. 01). Conclusions LCA could inhibit the proliferation of HOS and U2OS and induce apoptosis possibly by inhibiting the Akt/ERK signaling pathway.

FKBP38 regulates apoptosis of dopaminergic neurons / 中国药理学通报

Aim To investigate the role of FKBP38 in inhibiting apoptosis in a rotenone-induced Parkinson's disease(PD)cell model. Methods In vivo experiments:MPTP-induced PD in vivo models were constructed,and the expressions of α-synuclein,TH and FKBP38 in brains of PD mice were detected. In vitro experiments:Dopaminergic neuron MN9D cells were stimulated with rotenone to construct an in vitro model of PD; Western blot was used to detect the expression levels of α-synuclein,TH,Tom20 and FKBP38 in PD in vitro model; FKBP38 lentivirus was transferred into MN9D cells to construct stable overexpression and FKBP38 knockdown cell lines; CCK-8 assay was used to detect the cell viability of FKBP38 overexpression and knockdown cells stimulated by rotenone; Western blot was used to detect anti-apoptotic protein Bcl-2 and apoptosis protein in PD cell model expression levels of Bax. Results The expression level of FKBP38 was significantly down-regulated in both in vitro and in vivo models of PD(P<0.01). Knockdown of FKBP38 aggravated the decline of dopaminergic neuron cell viability caused by rotenone(P<0.05),while overexpression of FKBP38 significantly ameliorated the decline of dopaminergic neuron cell viability caused by rotenone(P<0.05). Western blot results showed that overexpression of FKBP38 could significantly up-regulate the expression level of anti-apoptotic protein Bcl-2 and increase the ratio of Bcl-2/Bax in PD dopaminergic neurons(P<0.05). Conclusion In the PD cell model regulation of FKBP38 can improve the apoptosis of dopaminergic neurons.

Effects of total saponins from Trillium tschonoskii maxim on cognition impairment and mitochondrial autophagy in aging rats induced by D-Gal / 中国药理学通报

Aim To investigate the effects of total saponins from Trillium tschonoskii maxim(TST)on cognitive impairment and mitochondrial autophagy in aging rats induced by D-galactose(D-gal). Methods Male SD rats were randomly divided into normal control group,model group(D-gal,subcutaneous injection),intervention group(TST,low,medium and high dose groups by intragastric administration),with 10 rats in each group,and administered for 6 weeks. Morris water maze was used to evaluate the cognitive function. HE and Nissl staining were used to test the hippocampal and brain cortex morphology. Immunohistochemistry staining was applied to detect the localization expression of Pink1 and Parkin. Western blot was employed to detect the expressions of Pink1,Parkin,LC3-Ⅱ,p62 and Beclin1. Results Compared with the normal control group,the escape latency time was prolonged and the number of crossing platform decreased in D-gal model group(P<0.05). The number of neurons in hippocampus significantly decreased. The positive cells labeled by Pink1 and Parkin staining in hippocampus significantly decreased. The expressions of Pink1,Parkin,LC3-Ⅱ and Beclin1 were markedly reduced,while the expression of p62 was significantly raised(P<0.05). Compared with D-gal model group,the escape latency time of TST dose groups was shortened,the Times of crossing the platform was more,and the time of staying in the platform quadrant increased(P<0.05). The number of neurons in hippocampus significantly increased. The positive cells labeled by Pink1 and Parkin staining in hippocampus significantly increased. The expressions of Pink1,Parkin,LC3-Ⅱ and Beclin1 in hippocampus were apparently up-regulated,while the protein expression of p62 was evidently down-regulated(P<0.05). Conclusions TST has neuroprotective effects on the learning and memory capacities in aging rats induced by D-gal,which may be related to the increasing levels of Pink1,Parkin,LC3-Ⅱ and Beclin1 proteins and the activation of mitochondrial autophagy.

The association between Helicobacter pylori virulence factor genotypes and gastroduodenal diseases in children / 中华儿科杂志

Objective: To investigate the association between Helicobacter pylori (Hp) virulence factor genotypes and the degree and activity of gastric mucosa pathological changes in pediatric gastroduodenal diseases. Methods: This retrospective cohort study was conducted from May 2020 to October 2020. The frozen strains of Hp, which were cultured with the gastric mucosa of 68 children with gastroscopy confirmed gastroduodenal diseases who visited the children's hospital of Zhejiang University School of Medicine from April 2012 to December 2014, were resuscitated. After extracting DNA from these Hp strains, PCR amplification and agarose gel electrophoresis were performed to determine the detection rate of cytotoxin-associated protein A (cagA),vacuolating cytotoxin A (vacA)(s1a、s1b/s2,m1/m2), outer inflammatory protein A (oipA),blood group antigen binding adhesin (babA),duodenal ulcer promoting protein A (dupA) genes; oipA genes were sequenced to determine the gene status. The patients were divided into different groups according to the findings of gastroscopy and gastric mucosa pathology. The detection rates of various virulence factor genotypes among different groups were compared using χ2 tests or Fisher's exact tests. Results: The 68 Hp strains all completed genetic testing. According to the diagnostic findings of gastroscopy, the 68 cases were divided into 47 cases of superficial gastritis and 21 cases of peptic ulcer. Regarding the pathological changes of gastric mucosa, 8 cases were mild, and 60 cases were moderate and severe according to the degree of inflammation; 61 cases were active and 7 cases inactive according to the activity of inflammation. The overall detection rates of cagA, vacA, vacA s1/m2, functional oipA, babA2, and dupA virulence factor genes were 100% (68/68), 100% (68/68), 94% (64/68), 99% (67/68), 82% (56/68), and 71% (48/68), respectively. In the superficial gastritis group, their detection rates were 100% (47/47), 100% (47/47), 96% (45/47), 98% (46/47), 81% (38/47), and 70% (33/47), respectively; in the peptic ulcer group, their detection rates were 100% (21/21), 100% (21/21), 90% (19/21), 100% (21/21), 86% (18/21), and 71% (15/21), respectively. There was no statistically significant difference between the two groups (all P>0.05). In the mild gastric mucosa inflammation group, the detection rates of the above six genotypes were 8/8, 8/8, 8/8, 7/8, 7/8, and 5/8, respectively; and in the moderate to severe inflammation groups, the detection rates were 100% (60/60), 100% (60/60), 93% (56/60), 100% (60/60), 82% (49/60), and 72% (43/60), respectively, with no statistically significant difference between the two groups (all P>0.05). In the active inflammation group, the detection rate of six genotypes were 100% (61/61), 100% (61/61), 93% (57/61), 98% (60/61), 82% (50/61), and 72% (44/61), respectively; and in the inactive inflammation group, they were 7/7, 7/7, 7/7, 7/7, 6/7, and 4/7, respectively. Again, there was no statistically significant difference between the two groups (all P>0.05). There was no statistically significant difference in the detection rate of combinations of 4 or 5 virulence factor genes among the different groups (all P>0.05). Conclusions: CagA, vacA, vacA s1/m2, functional oipA, babA2, and dupA genes are not associated with superficial gastritis and peptic ulcer in children, or with the degree and activity of gastric mucosa pathological inflammation. Different gene combinations of cagA, vacA, oipA, babA2, and dupA have no significant effects on predicting the clinical outcome of Hp infection in children.

Clinicopathological features of adult Wilms tumor with BRAF V600E mutation / 中华病理学杂志

Objective: To identify BRAF V600E mutations in adult Wilms tumor (WT) with overlapping histologic features of metanephric adenoma (MA) and to investigate the clinicopathological features of adult WT. Methods: The clinical features of adult WT diagnosed at the Fudan University Shanghai Cancer Center, Shanghai, China from 2012 to 2021 were reviewed. HE-stained slides of all cases were reviewed by 2 expert pathologists. Representative tissues were selected for BRAF V600E immunohistochemical (IHC) staining and gene sequencing. Results: In adult WT with MA-like areas (cohort Ⅰ, n=6), 5 of the 6 cases were composed of epithelial-predominant and were positive for WT-1 and CD56, respectively, and all were positive for CD57. All 6 cases revealed highly variable Ki-67 indices, ranging from 1% in some areas to 60% in others. 5 of the 6 cases harbored a BRAF V600E mutation. All cases in cohort I were followed up for 23 to 71 months, and all survived. In classical adult WT without MA-like areas cohort (cohort Ⅱ, n=13), all 7 cases with available material were negative for BRAF by IHC and none of them had any BRAF mutation. Conclusions: BRAF V600E mutations are frequently present in adult WT with overlapping morphologically features of MA, but not in those without. More importantly, adult WTs with overlapping histologic features of MA may be an intermediate entity between typical MA and WT that may have a favorable prognosis and possible therapeutic targets.

Efficacy of neoadjuvant therapy on HER2-positive breast cancer: a clinicopathological analysis / 中华病理学杂志

Objective: To investigate the efficacy of neoadjuvant therapy (NAT) on HER2-positive breast cancer and to analyze their clinicopathological features. Methods: A total of 480 cases of HER2-positive breast cancer who received neoadjuvant therapy (NAT), diagnosed at the Department of Pathology of Fudan University Shanghai Cancer Center from 2015 to 2020, were retrospectively identified. Clinicopathological parameters such as age, tumor size, molecular subtype, type of targeted therapy, Ki-67 proliferation index, ER and HER2 immunohistochemical expression, and HER2 amplification status were analyzed to correlate with the efficacy of NAT. Results: Among 480 patients with HER2-positive breast cancer, 209 achieved pathology complete response (pCR) after NAT, with a pCR rate of 43.5%. Of all the cases,457 patients received chemotherapy plus trastuzumab and 23 patients received chemotherapy with trastuzumab and pertuzumab. A total of 198 cases (43.3%) achieved pCR in patients with chemotherapy plus trastuzumab, and 11 cases (47.8%) achieved pCR in patients with chemotherapy plus trastuzumab and pertuzumab. The pCR rate in the latter group was higher, but there was no statistical significance. The results showed that the pCR rate of IHC-HER2 3+patients (49%) was significantly higher than that of IHC-HER2 2+patients (26.1%, P<0.001). The higher the mean HER2 copy number in the FISH assay, the higher the pCR rate was achieved. The expression level of ER was inversely correlated with the efficacy of NAT, and the pCR rate in the ER-positive group (28.2%) was significantly lower than that in the ER-negative group (55.8%, P<0.001). The pCR rate (29.1%) of patients with luminal B type was lower than that of HER2 overexpression type (55.8%, P<0.001). In addition, higher Ki-67 proliferation index was associated with higher pCR rate (P<0.001). The pCR rate was the highest in the tumor ≤2 cm group (57.7%), while the pCR rate in the tumor >5 cm group was the lowest (31.1%). The difference between the groups was significant (P=0.005). Conclusions: HER2 copy numbers, HER2 immunohistochemical expression level, molecular subtype, ER expression level and Ki-67 proliferation index are significantly associated with pCR after NAT. In addition, fluorescence in situ hybridization results, HER2/CEP17 ratio and tumor size could also significantly affect the efficacy of NAT.

Association between maternal plasma one-carbon biomarkers during pregnancy and fetal growth in twin pregnancies / 中华妇产科杂志

Objective: To characterize the relationship between the levels of plasma methyl donor and related metabolites (including choline, betaine, methionine, dimethylglycine and homocysteine) and fetal growth in twin pregnancies. Methods: A hospital-based cohort study was used to collect clinical data of 92 pregnant women with twin pregnancies and their fetuses who were admitted to Peking University Third Hospital from March 2017 to January 2018. Fasting blood was collected from the pregnant women with twin pregnancies (median gestational age: 18.9 weeks). The levels of methyl donors and related metabolites in plasma were quantitatively analyzed by high-performance liquid chromatography combined with mass spectrometry. The generalized estimation equation was used to analyze the relationship between maternal plasma methyl donors and related metabolites levels and neonatal outcomes of twins, and the generalized additive mixed model was used to analyze the relationship between maternal plasma methyl donors and related metabolites levels and fetal growth ultrasound indicators. Results: (1) General clinical data: of the 92 women with twin pregnancies, 66 cases (72%) were dichorionic diamniotic (DCDA) twin pregnancies, and 26 cases (28%) were monochorionic diamniotic (MCDA) twin pregnancies. The comparison of the levels of five plasma methyl donors and related metabolites in twin pregnancies with different basic characteristics showed that the median levels of plasma choline and betaine in pregnant women ≥35 years old were higher than those in pregnant women <35 years old, and the differences were statistically significant (all P<0.05). (2) Correlation between plasma methyl donor and related metabolites levels and neonatal growth indicators: after adjusting for confounding factors, plasma homocysteine level in pregnant women with twins was significantly negatively correlated with neonatal birth weight (β=-47.9, 95%CI:-94.3- -1.6; P=0.043). Elevated methionine level was significantly associated with decreased risks of small for gestational age infants (SGA; OR=0.5, 95%CI: 0.3-0.9; P=0.021) and low birth weight infants (OR=0.6, 95%CI: 0.4-0.9; P=0.020). Increased homocysteine level was associated with increased risks of SGA (OR=1.5, 95%CI: 1.0-2.2; P=0.029) and inconsistent growth in twin fetuses (OR=1.9, 95%CI: 1.0-3.7; P=0.049). (3) Correlation between the levels of plasma methyl donors and related metabolites and intrauterine growth indicators of twins pregnancies: for every 1 standard deviation increase in plasma choline level in pregnant women with twin pregnancies, fetal head circumference, abdominal circumference, femoral length and estimated fetal weight in the second trimester increased by 1.9 mm, 2.6 mm, 0.5 mm and 20.1 g, respectively, and biparietal diameter, abdominal circumference and estimated fetal weight increased by 0.7 mm, 3.0 mm and 38.4 g in the third trimester, respectively, and the differences were statistically significant (all P<0.05). (4) Relationship between plasma methyl donor and related metabolites levels in pregnant women with different chorionicity and neonatal birth weight and length: the negative correlation between plasma homocysteine level and neonatal birth weight was mainly found in DCDA twin pregnancy (β=-65.9, 95%CI:-110.6- -21.1; P=0.004). The levels of choline, betaine and dimethylglycine in plasma of MCDA twin pregnancy were significantly correlated with the birth weight and length of newborns (all P<0.05). Conclusion: Homocysteine level is associated with low birth weight in twins, methionine is associated with decreased risk of SGA, and choline is associated with fetal growth in the second and third trimesters of pregnancy.

To compare the efficacy and incidence of severe hematological adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia / 中华血液学杂志

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.

Meta-analysis of the efficacy of intravitreal Ranibizumab combined with compound trabeculectomy and panretinal photocoagulation in the treatment of neovascular glaucoma / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To systematically evaluate the efficacy and safety of intravitreal ranibizumab combined with compound trabeculectomy and panretinal photocoagulation(PRP)compared with compound trabeculectomy combined with PRP in the treatment of neovascular glaucoma(NVG).METHODS: Databases including Wanfang database, China National Knowledge Infrastructure(CNKI), PubMed, EMbase, China Biomedical Document Service System(CBM), Clinicalkey, and Cochrane Library were retrieved. Literatures about intravitreal ranibizumab combined with compound trabeculectomy and PRP in the treatment of NVG in the experimental group and compound trabeculectomy and PRP in the treatment of NVG in the control group from creation of database to July 20, 2022 were searched. At the same time, relevant reference were consulted. The best corrected visual acuity, intraocular pressure, occurrence of complications and the success rate of the surgery were systematically evaluated.RESULTS: A total of 8 clinical studies were included, with 864 patients(864 eyes)with NVG. Meta-analysis showed that the intraocular pressure of patients in the experimental group was lower than that in the control group at 1wk, 1 and 3mo after surgery(1wk: MD=-4.00, 95%CI: -4.62～-3.38, P&#x0026;#x003C;0.05; 1mo: MD=-4.11, 95%CI: -4.66～-3.56, P&#x0026;#x003C;0.05; 3mo: MD=-4.58, 95%CI: -5.61～-3.55, P&#x0026;#x003C;0.05). The best corrected visual acuity of the experimental group was better than that of the control group at 1mo after surgery(MD=0.17, 95%CI: 0.11～0.23, P&#x0026;#x003C;0.05), but there was no significant difference at 1wk after surgery(MD=0.08, 95%CI: -0.13～0.29, P=0.47). The patients in the experimental group had fewer complications(OR=0.30, 95%CI: 0.18～0.52, P&#x0026;#x003C;0.05)and higher surgical success rate(OR=5.15, 95%CI: 2.78～9.53, P&#x0026;#x003C;0.05).CONCLUSION:With decreased intraocular pressure, improved visual acuity and surgical success rate, intravitreal ranibizumab combined with compound trabeculectomy and PRP was better than the compound trabeculectomy and PRP in the treatment of NVG.

The effect of overweight or obesity on the negative conversion time of SARS-CoV-2 nucleic acid / 中国热带医学

@#Abstract: Objective　To investigate the relationship between the body mass index (BMI) levels and the negative conversion time of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid in adult coronavirus disease 2019 (COVID-19) patients and the asymptomatic persons. Methods　Asymptomatic infected patients and confirmed COVID-19 patients admitted to Chengdu Public Health Clinic Center from February 2021 to November 2021 were dynamically included. The epidemiological and clinical characteristics of the objects were collected, and the SARS-CoV-2 nucleic acid testing of the objects during their hospitalization was continuously monitored, and the negative nucleic acid conversion time was recorded. The t test or Wilcoxon rank sum test, χ2 test or Fisher's exact probability method examine were used to distribute characteristics of each group of variables and the connection between different variables, respectively. Then the variables showed differences in distribution (P<0.05) between different BMI groups were included in the multivariate Cox proportional risk regression model. Results　A total of 253 subjects ranged from 18 to 63 years old, with M(P25, P75) age of 37.0 (30.0, 47.0) years old, were included in this study. The male to female ratio was 4.16 to 1. The BMI was (23.97±3.33) kg/m2. 50.59% (128/253) of the objects were overweight or obese, and 78.13% (100/128) were overweight. The negative time of SARS-CoV-2 nucleic acid conversion of all subjects ranged from 1 to 71 days, with M(P25, P75) of 7.0 (2.0, 18.0) days (P<0.001). The negative time of SARS-CoV-2 nucleic acid conversion of the normal weight or the thin, and the overweight or obese were 5.00 (2.00, 19.00) and 8.00 (2.00, 17.75) days respectively. The results of multivariate Cox's proportional hazards regression model showed that the BMI levels may not be associated with the negative conversion time of SARS-CoV-2 nucleic acid (HR=1.090, 95%CI: 0.843-1.410, P=0.510). Conclusions　Adult asymptomatic persons and confirmed COVID-19 patients are mainly middle-aged and young males, and overweight or obesity is relatively common. Overweight or obesity cannot be considered as an independent factor influencing the negative conversion time of SARS-CoV-2 nucleic acid.

Establishment of comprehensive evaluation models of physical fitness of the elderly based on machine learning / 生理学报

The present study aims to establish comprehensive evaluation models of physical fitness of the elderly based on machine learning, and provide an important basis to monitor the elderly's physique. Through stratified sampling, the elderly aged 60 years and above were selected from 10 communities in Nanchang City. The physical fitness of the elderly was measured by the comprehensive physical assessment scale based on our previous study. Fuzzy neural network (FNN), support vector machine (SVM) and random forest (RF) models for comprehensive physical evaluation of the elderly people in communities were constructed respectively. The accuracy, sensitivity and specificity of the comprehensive physical fitness evaluation models constructed by FNN, SVM and RF were above 0.85, 0.75 and 0.89, respectively, with the FNN model possessing the best prediction performance. FNN, RF and SVM models are valuable in the comprehensive evaluation and prediction of physical fitness, which can be used as tools to carry out physical evaluation of the elderly.

Development of comprehensive vitality scale for the elderly based on classical test theory and analytic hierarchy process / 生理学报

The present study aims to construct an elderly vitality index evaluation system and develop a comprehensive vitality evaluation scale for the elderly to reasonably evaluate the vitality level of the elderly in China, so as to provide a reference for promoting the realization of "active aging" and "healthy aging". Literature research and in-depth interview were used to collect the senile vitality sensitive indexes. The indexes were screened and corrected by Delphi expert consultation method, item analysis method based on classical test theory, factor analysis method, and reliability and validity analysis method. The analytic hierarchy process was used to calculate the weight of each level of indexes. An elderly vitality evaluation system including 4 first-level indexes and 24 second-level indexes was constructed. The consistency test results of all levels of indicators showed that the consistency index (CI) and consistent ratio (CR) were both less than 0.1, which met the requirements and showed satisfactory consistency. The weights of exercise vitality, nutritional vitality, psychological vitality and social vitality were 0.263, 0.141, 0.455 and 0.141, respectively. In conclusion, the comprehensive vitality scale constructed for the Chinese elderly is reliable and scientific, and can be used to evaluate the vitality of the elderly.

Advantage analysis of flow-through cell method in quality evaluation of Chinese patent medicine: a case study of Danshen Tablets / 中国中药杂志

To explore the quality consistency evaluation method for multi-component traditional Chinese medicine and establish a dissolution evaluation method suitable for the characteristics of multi-component Chinese patent medicine, this study discussed the characteristics and advantages of the flow-through cell method in the dissolution evaluation of Chinese patent medicine by comparing the impact of the small cup method and the flow-through cell method on the dissolution behavior of water-soluble and lipid-soluble major active components of Danshen Tablets. Dissolution tests were performed using the small cup method as described in the 2020 edition of the Chinese Pharmacopoeia and the newly introduced flow-through cell method(closed-loop method) with water solution containing 0.5% SDS as dissolution medium. Cumulative dissolution curves of the water-soluble component salvianolic acid B and the lipid-soluble component tanshinone Ⅱ_A in Danshen Tablets were plotted, and fitting and similarity analysis of the dissolution models was conducted to identify the characteristics and advantages of the flow-through cell method. For the small cup method, 150 mL of water containing 0.5% SDS was used as the dissolution medium, with a rotation speed of 75 r·min~(-1) and a temperature of(37±0.5) ℃, and 3 mL of samples were taken at 15, 30 min, 1, 2, and 4 h, with fresh dissolution medium added at the same temperature and volume. For the flow-through cell method, a closed-loop system was used. Danshen Tablets were placed in the flow-through cell with approximately 6.7 g of glass beads, and 150 mL of water containing 0.5% SDS was used as the dissolution medium. The flow rate was set at 20 mL·min~(-1), and the temperature and sampling were the same as the small cup method. The results showed that compared with the small cup method, the flow-through cell method had stronger discriminative power and higher sensitivity in distinguishing the dissolution behavior of the two components, and could better reflect the differences in formulation quality, especially for water-insoluble lipid-soluble components. Given that there were no essential differences in the in vitro release kinetics between the two methods, the flow-through cell method could not only replace the traditional small cup method but also better guide the formulation development and identify quality issues of formulations.

Prediction and analysis of Q-markers of Elephantopus scaber based on its UPLC fingerprint, content determination of components, and in vitro a nti-tumor activity / 中国中药杂志

This study aimed to provide scientific evidence for predicting quality markers(Q-markers) of Elephantopus scaber by establishing UPLC fingerprint of E. scaber from different geographical origins and determining the content of 13 major components, as well as conducting in vitro anti-cancer activity investigation of the main components. The chromatographic column used was Waters CORTECS UPLC C_(18)(2.1 mm×150 mm, 1.6 μm), and the mobile phase consisted of acetonitrile and 0.1% formic acid solution(gradient elution). The column temperature was set at 30 ℃, and the flow rate was 0.2 mL·min~(-1). The injection volume was 1 μL, and the detection wavelength was 240 nm. The UPLC fingerprint of E. scaber was fitted using the Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine(2012 edition) to determine common peaks, evaluate similarity, identify and determine the content of major components. The CCK-8 assay was used to explore the inhibitory effect of the main components on the proliferation of lung cancer cells. The results showed that in the established UPLC fingerprint of E. scaber, 35 common peaks were identified. Thirteen major components, including neochlorogenic acid(peak 1), chlorogenic acid(peak 2), cryptochlorogenic acid(peak 3), caffeic acid(peak 4), schaftoside(peak 6), galuteolin(peak 9), isochlorogenic acid B(peak 10), isochlorogenic acid A(peak 12), isochlorogenic acid C(peak 18), deoxyelephantopin(peak 28), isodeoxyelephantopin(peak 29), isoscabertopin(peak 31), and scabertopin(peak 32) were identified and quantified, and a quantitative analysis method was established. The results of the in vitro anti-cancer activity study showed that deoxyelephantopin, isodeoxyelephantopin, isoscabertopin, and scabertopin in E. scaber exhibited inhibition rates of lung cancer cell proliferation exceeding 80% at a concentration of 10 μmol·L~(-1), higher than the positive drug paclitaxel. These results indicate that the fingerprint of E. scaber is highly characteristic, and the quantitative analysis method is accurate and stable, providing references for the research on quality standards of E. scaber. Four sesquiterpene lactones in E. scaber show significant anti-cancer activity and can serve as Q-markers for E. scaber.