Objective To investigate the changes of the gray matter in patients with rheumatoid arthritis (RA) based on the voxel based morphometry (VBM).Methods 35 patients with RA and 30 healthy volunteers with age,sex and education level matched performed a high-resolution 3D-T1-weighted whole brain structural scan by GE Signa HDxt 1.5T MRI scanner.The high resolution T1WI images were preprocessed by the VBM 12 implemented in the SPM 12 software to display the gray matter structures of the RA patients and the healthy volunteers.T test was used to compare the morphological changes of gray matter between the RA patients and the volunteers.Results The gray matter volume gray matter volume in the right lentiform nucleus,left frontal lobe and left cerebellum posterior lobe significantly decreased in RA patients,and their gray matter volume had no correlation with the clinical indications.The increase of gray matter volume was not found in the RA patients.Conclusion RA patients show decreased gray matter volume in several cerebral regions,which suggests that RA can lead to the brain structural abnormalities.VBM can provide an objective imaging evidence to evaluate the cerebral morphological abnormalities of RA.

Objective:To investigate the prevalence of chronic constipation in maintenance hemodialysis (MHD) patients and analyze the risk factors of chronic constipation.Methods:Using the cross-sectional survey method, patients who received MHD in Huadu District People′s Hospital of Guangzhou from September 1, 2021 to September 30, 2021 were enrolled as the research objects. The patient′s demographic, general data and laboratory results were collected. The anxiety level and quality of life were assessed by questionnaires. The patients were divided into constipation group and non-constipation group according to whether they had chronic constipation. The Rome Ⅳ criteria was used to diagnose chronic constipation, and the differences of clinical data between the constipation group and the non-constipation group were compared. The risk factors of chronic constipation in MHD patients were analyzed by logistic regression analysis method.Results:A total of 321 MHD patients were enrolled in this study, with 168 males, 153 females and age of (59.5±13.4) years old (ranged from 29 to 87 years old). There were 160 patients (49.8%) with chronic constipation. The proportions of males, long dialysis age, taking sevelamer and lanthanum carbonate, diabetic nephropathy, and diabetes in the constipation group were higher than those in the non-constipation group, and the differences between the two groups were statistically significant (all P<0.05). The serum calcium, serum phosphorus, calcium-phosphorus product, anxiety scores, average weekly ultrafiltration volume/dry weight in the constipation group were significantly higher than those in the non-constipation group (all P<0.05), and the serum albumin, serum magnesium, urea clearance index (Kt/V) and geriatric nutritional risk index were significantly lower than those in the non-constipation group (all P<0.05). The results of logistic regression analysis showed that moderate to severe anxiety (moderate, OR=3.233, 95% CI 1.339-7.805, P=0.009; severe, OR=5.103, 95% CI 1.906-13.663, P=0.001), existed risk of nutrition (low risk, OR=3.705, 95% CI 1.440-9.533, P=0.007; moderate risk, OR=5.638, 95% CI 2.557-12.430, P<0.001; severe risk, OR=15.097, 95% CI 4.112-55.436, P<0.001), >60 years old (≤40 years old as a reference, OR=4.050, 95% CI 1.366-12.006, P=0.012), diabetes history ( OR=2.224, 95% CI 1.253-3.946, P=0.006), taking sevelamer ( OR=2.290, 95% CI 1.207-4.346, P=0.011), and calcium-phosphorus product ( OR=1.704, 95% CI 1.329-2.186, P<0.001), intact parathyroid hormone ( OR=1.013, 95% CI 1.003-1.022, P=0.007), blood urea nitrogen ( OR=1.092, 95% CI 1.002-1.189, P=0.045) and serum magnesium ( OR=0.042, 95% CI 0.006-0.294, P=0.001) were the independent influencing factors for chronic constipation in MHD patients. Conclusions:The prevalence of chronic constipation in MHD patients is 49.8%. Adequate dialysis, improving calcium and phosphorus metabolism, improving nutritional status, relieving anxiety, and increasing serum magnesium level may help to reduce the risk of chronic constipation in MHD patients.

OBJECTIVE: To assess the value of copy number variation sequencing (CNV-seq) for the diagnosis of children with intellectual disability (ID), developmental delay (DD), and autistic spectrum disorder (ASD). METHODS: Forty patients with ID/DD/ASD referred to Nanshan Maternity and Child Health Care Hospital from September 2018 to January 2022 were enrolled. G-banded karyotyping analysis was carried out for the patients. Genomic DNA was extracted from peripheral blood samples and subjected to CNV-Seq analysis to detect chromosome copy number variations (CNVs) in such patients. ClinVar, DECIPHER, OMIM and other database were searched for data annotation. RESULTS: Among the 40 patients (including 30 males and 10 females), 16, 15 and 6 were diagnosed with ID, DD and ASD, respectively. One patient had combined symptoms of ID and DD, whilst the remaining two had combined ID and ASD. Four patients were found with abnormal karyotypes, including 47,XY,+mar, 46,XY,inv(8)(p11.2q21.2), 46,XX,del(5)(p14) and 46,XX[76]/46,X,dup(X)(p21.1q12). Chromosome polymorphism was also found in two other patients. CNV-seq analysis has detected 32 CNVs in 20 patients (50.0%, 20/40). Pathogenic CNVs were found in 10 patients (25.0%), 15 CNVs of uncertain clinical significance were found in 12 patients (30.0%), and 7 likely benign CNVs were found in 4 patients (10.0%). CONCLUSION Chromosome CNVs play an important role in the pathogenesis of ID/DD/ASD. CNV-seq can detect chromosomal abnormalities including microdeletions and microduplications, which could provide a powerful tool for revealing the genetic etiology of ID/DD/ASD patients.
Pregnancy ; Child ; Male ; Humans ; Female ; DNA Copy Number Variations ; Intellectual Disability/genetics* ; Autism Spectrum Disorder/genetics* ; Developmental Disabilities/genetics* ; Abnormal Karyotype

Objective:To analyze the effect of percutaneous transluminal angioplasty (PTA) in the treatment of autogenous arteriovenous fistula (AVF) stenosis and influcing factors of restenosis/loss of function after PTA.Methods:The medical records of 104 patients with AVF stenosis treated by PTA in People′s Hospital of Huadu District from March 2019 to July 2020 and the 1-year follow-up were retrospectively analyzed. Kaplan-meier curves were used to analyze the primary patency rates at 3 months, 6 months and 1 year. COX regression was used to analyze the influencing factors of restenosis/loss of function after PTA.Results:The primary patency rates of AVF at 3, 6 and 12 months after PTA were 86.2%, 83.2% and 64.7%, respectively. Guide wire entry into the distal end of radial artery, the use of two balloons in stepwise mode, postoperative dilatation diameter, and dialysis blood flow after PTA were independent risk factors for restenosis/loss of fuction after PTA for AVF stenosis (all P<0.05). Conclusions:The guide wire into the distal end of the artery and passive use of more than two balloons are important factors affecting AVF restenosis/loss of function after PTA .

Objective:To investigate the effect of optimizing perioperative measures on reducing postoperative gastric emptying disorder in gastrointestinal reconstruction after pancreaticoduodenectomy.Methods:The clinical data of 146 patients who underwent pancreaticoduodenectomy from Jan 2019 to Dec 2020 at the Department of Hepatobiliary and Pancreatic Surgery,the First Affiliated Hospital ,Anhui Medical University were analyzed retrospectively. Among them, 78 cases underwent traditional Billroth Ⅱ gastrojejunal anastomosis for gastrointestinal reconstruction, and 68 cases in the improvement group took optimization measures. The time to first postoperative flatus, time to oral intake, postoperative hospital stay and complications were observed.Results:The operation time in the control group was (351.4±71.6) min, less than that in the improved group (368.8±97.6) min, while the time [(9.9±6.5)d vs. (7.6±6.0)d] to first oral take and postoperative hospital stay [(20.7±8.6)d vs. (17.9±7.0)d] were significantly longer than those in the improved group. The incidence of postoperative gastric emptying disorder (19.2% vs. 7.4%) was significantly higher than that in the improved group ( P<0.05). There was no significant difference in postoperative time to first flatus and postoperative gastrointestinal bleeding between the two groups (all P>0.05). Conclusions:The measures of optimizing gastrointestinal reconstruction in the perioperative period of pancreaticoduodenectomy have obvious advantages in reducing gastric emptying disorder, promoting the recovery of gastrointestinal function and shortening the length of hospital stay.

Objective To analyze the clinicopathological features of type 2 diabetes mellitus complicated with colorectal cancer (DCRC). Methods A case?control study was conducted. Inclusion criteria: (1) hospitalized patients receiving fibrocolonoscopy; (2) adenocarcinoma and mucinous adenocarcinoma diagnosed by pathology; (3) with preoperative cTNM clinical staging; (4) colorectal cancer patients undergoing surgical treatment; (5) with postoperative pTNM staging; (6) no smoking or drinking habits. Exclusion criteria: (1) familial adenomatous polyposis (FAP); (2) Lynch syndrome; (3) carcinoma of anal canal and perianal carcinoma; (4) multiple primary cancer; (5) with serious cardiocerebrovascular diseases or multiple organ failure. Clinicopathlogical data of 32 DCRC patients who were diagnosed and treated in Peking University Shougang Hospital from December 2017 to December 2018 were retrospectively collected and analyzed. Forty nondiabetic colorectal cancer (CRC) patients during the same period were selected as control group according to the sex ratio and the age difference less than 5 years. Student′s t test and χ2 test were used to compare the difference between the two groups in baseline clinicopathological data, clinical test results, tumor markers and infiltration status of T cells in tumor immune microenvironment. Results Among 32 DCRC patients, 24 were males and 8 were females with a mean age of (63.0±1.7) years; among 40 CRC patients, 30 were males and 10 were females with a mean age of (60.5 ± 1.6) years. The duration of diabetes mellitus in DCRC patients (from the diagnosis of diabetes mellitus to the diagnosis of colorectal cancer) was (9.2±1.3) years. The body mass index (BMI) of DCRC group was significantly higher than that of CRC group [(24.8±0.6) kg/m2 vs. (23.2±0.4) kg/m2, t=2.372, P=0.020]. There were no significant differences in other baseline data (sex, age, primary site of tumor, R0 resection rate, pathological stage, pathological type, differentiation degree of tumor, preoperative intestinal obstruction) between the two groups (all P>0.05). Serum triglyceride level in DCRC group was higher than that in CRC group [(2.1 ± 0.2) mmol/L vs. (1.5 ± 0.1) mmol/L, t=3.085, P=0.003], while hemoglobin [(120.3±5.2) g/L vs. (132.7±2.8) g/L, t=-2.224, P=0.029], anti? thrombin III [(94.2±3.7)% vs. (103.5±2.4)%, t=-2.197, P=0.031], and red blood cell count [(4.2±0.1)×1012/L vs. (4.5±0.1)×1012L, t=-2.055, P=0.044] were all lower than those in CRC group. The preoperative carcinoembryonic antigen (CEA) level in DCRC group was higher than that in CRC group [(50.3±21.8) μg/L vs. (5.6±1.0) μg/L, t=2.339, P=0.022]. There were no significant differences in preoperative levels of other four tumor molecular markers (CA199, CA242, CA724 and CA125) between the two groups (all P>0.05). The expression of Foxp3 [specific markers of CD4+, CD25+ regulatory T cells (Treg)] in DCRC group was higher than that in CRC group [(82.7±6.2) cell/ HPF vs. (62.6±4.9) cell/HPF, t=2.586, P=0.012]. There were no significant differences in the infiltration of CD4, CD8, PD?1 and PD?L1 positive cells between two groups (all P>0.05).Conclusions The average diabetic history of DCRC patients is nearly 10 years. They have higher BMI and serum CEA level, and more Treg cell infiltration in the tumor. Close attention should be paid to these patients in clinical practice.

Objective To analyze the clinicopathological features of type 2 diabetes mellitus complicated with colorectal cancer (DCRC). Methods A case?control study was conducted. Inclusion criteria: (1) hospitalized patients receiving fibrocolonoscopy; (2) adenocarcinoma and mucinous adenocarcinoma diagnosed by pathology; (3) with preoperative cTNM clinical staging; (4) colorectal cancer patients undergoing surgical treatment; (5) with postoperative pTNM staging; (6) no smoking or drinking habits. Exclusion criteria: (1) familial adenomatous polyposis (FAP); (2) Lynch syndrome; (3) carcinoma of anal canal and perianal carcinoma; (4) multiple primary cancer; (5) with serious cardiocerebrovascular diseases or multiple organ failure. Clinicopathlogical data of 32 DCRC patients who were diagnosed and treated in Peking University Shougang Hospital from December 2017 to December 2018 were retrospectively collected and analyzed. Forty nondiabetic colorectal cancer (CRC) patients during the same period were selected as control group according to the sex ratio and the age difference less than 5 years. Student′s t test and χ2 test were used to compare the difference between the two groups in baseline clinicopathological data, clinical test results, tumor markers and infiltration status of T cells in tumor immune microenvironment. Results Among 32 DCRC patients, 24 were males and 8 were females with a mean age of (63.0±1.7) years; among 40 CRC patients, 30 were males and 10 were females with a mean age of (60.5 ± 1.6) years. The duration of diabetes mellitus in DCRC patients (from the diagnosis of diabetes mellitus to the diagnosis of colorectal cancer) was (9.2±1.3) years. The body mass index (BMI) of DCRC group was significantly higher than that of CRC group [(24.8±0.6) kg/m2 vs. (23.2±0.4) kg/m2, t=2.372, P=0.020]. There were no significant differences in other baseline data (sex, age, primary site of tumor, R0 resection rate, pathological stage, pathological type, differentiation degree of tumor, preoperative intestinal obstruction) between the two groups (all P>0.05). Serum triglyceride level in DCRC group was higher than that in CRC group [(2.1 ± 0.2) mmol/L vs. (1.5 ± 0.1) mmol/L, t=3.085, P=0.003], while hemoglobin [(120.3±5.2) g/L vs. (132.7±2.8) g/L, t=-2.224, P=0.029], anti? thrombin III [(94.2±3.7)% vs. (103.5±2.4)%, t=-2.197, P=0.031], and red blood cell count [(4.2±0.1)×1012/L vs. (4.5±0.1)×1012L, t=-2.055, P=0.044] were all lower than those in CRC group. The preoperative carcinoembryonic antigen (CEA) level in DCRC group was higher than that in CRC group [(50.3±21.8) μg/L vs. (5.6±1.0) μg/L, t=2.339, P=0.022]. There were no significant differences in preoperative levels of other four tumor molecular markers (CA199, CA242, CA724 and CA125) between the two groups (all P>0.05). The expression of Foxp3 [specific markers of CD4+, CD25+ regulatory T cells (Treg)] in DCRC group was higher than that in CRC group [(82.7±6.2) cell/ HPF vs. (62.6±4.9) cell/HPF, t=2.586, P=0.012]. There were no significant differences in the infiltration of CD4, CD8, PD?1 and PD?L1 positive cells between two groups (all P>0.05).Conclusions The average diabetic history of DCRC patients is nearly 10 years. They have higher BMI and serum CEA level, and more Treg cell infiltration in the tumor. Close attention should be paid to these patients in clinical practice.

Eclipta prostrata L.has been used in traditional medicine and known for its liver-protective properties for centuries.Wedelolactone(WEL)and demethylwedelolactone(DWEL)are the major coumarins found in E.prostrata L.However,the comprehensive characterization of these two compounds on non-alcoholic fatty liver disease(NAFLD)still remains to be explored.Utilizing a well-established zebrafish model of thioacetamide(TAA)-induced liver injury,the present study sought to investigate the impacts and mechanisms of WEL and DWEL on NAFLD through integrative spatial metabolomics with liver-specific transcriptomics analysis.Our results showed that WEL and DWEL significantly improved liver function and reduced the accumulation of fat in the liver.The biodistributions and metabolism of these two compounds in whole-body zebrafish were successfully mapped,and the discriminatory endogenous metabolites reversely regulated by WEL and DWEL treatments were also characterized.Based on spatial metabolomics and transcriptomics,we identified that steroid biosynthesis and fatty acid metabolism are mainly involved in the hepatoprotective effects of WEL instead of DWEL.Our study unveils the distinct mechanism of WEL and DWEL in ameliorating NAFLD,and presents a"multi-omics"platform of spatial metabolomics and liver-specific transcriptomics to develop highly effective compounds for further improved therapy.

Objective To investigate whether activation of mitochondrial acetal dehydrogenase 2(ALDH2)alleviates hypoxic pulmonary hypertension by regulating the SIRT1/PGC-1α signaling pathway.Methods Thirty 8-week-old C57 BL/6 mice were randomized into control,hypoxia,and hypoxia+Alda-1(an ALDH2 activator)group(n=10),and the mice in the latter two groups,along with 10 ALDH2 knockout(ALDH2-/-)mice,were exposed to hypoxia(10%O2,90%N2)with or without daily intraperitoneal injection of Alda-1 for 4 weeks.The changes in right ventricular function and pressure(RVSP)of the mice were evaluated by echocardiography and right ventricular catheter test,and pulmonary artery pressure was estimated based on RVSP.Pulmonary vascular remodeling,right ventricular injury,myocardial α-SMA expression,distal pulmonary arteriole muscle normalization,right ventricular cross-sectional area,myocardial cell hypertrophy,and right cardiac hypertrophy index were assessed with HE staining,immunofluorescence staining and WGA staining,and the expressions of ALDH2,SIRT1,PGC-1α,P16INK4A and P21CIP1 were detected.In pulmonary artery smooth muscle cells with hypoxic exposure,the effect of Alda-1 and EX527 on cell senescence and protein expressions was evaluated using β-galactose staining and Western blotting.Results The wild-type mice with hypoxic exposure showed significantly increased RVSP,right ventricular free wall thickness and myocardial expressions of P16INK4A and P21CIP1,which were effectively lowered by treatment with Alda-1 but further increased in ALDH2-/-mice.In cultured pulmonary artery smooth muscle cells,hypoxic exposure significantly increased senescent cell percentage and cellular expressions of P16INK4A and P21CIP1,which were all lowered by treatment with Alda-1,but its effect was obviously attenuated by EX527 treatment.Conclusion ALDH2 alleviates hypoxia-induced senescence of pulmonary artery smooth muscle cells by upregulating the SIRT1/PGC-1α signaling pathway to alleviate pulmonary hypertension in mice.

Objective To investigate whether activation of mitochondrial acetal dehydrogenase 2(ALDH2)alleviates hypoxic pulmonary hypertension by regulating the SIRT1/PGC-1α signaling pathway.Methods Thirty 8-week-old C57 BL/6 mice were randomized into control,hypoxia,and hypoxia+Alda-1(an ALDH2 activator)group(n=10),and the mice in the latter two groups,along with 10 ALDH2 knockout(ALDH2-/-)mice,were exposed to hypoxia(10%O2,90%N2)with or without daily intraperitoneal injection of Alda-1 for 4 weeks.The changes in right ventricular function and pressure(RVSP)of the mice were evaluated by echocardiography and right ventricular catheter test,and pulmonary artery pressure was estimated based on RVSP.Pulmonary vascular remodeling,right ventricular injury,myocardial α-SMA expression,distal pulmonary arteriole muscle normalization,right ventricular cross-sectional area,myocardial cell hypertrophy,and right cardiac hypertrophy index were assessed with HE staining,immunofluorescence staining and WGA staining,and the expressions of ALDH2,SIRT1,PGC-1α,P16INK4A and P21CIP1 were detected.In pulmonary artery smooth muscle cells with hypoxic exposure,the effect of Alda-1 and EX527 on cell senescence and protein expressions was evaluated using β-galactose staining and Western blotting.Results The wild-type mice with hypoxic exposure showed significantly increased RVSP,right ventricular free wall thickness and myocardial expressions of P16INK4A and P21CIP1,which were effectively lowered by treatment with Alda-1 but further increased in ALDH2-/-mice.In cultured pulmonary artery smooth muscle cells,hypoxic exposure significantly increased senescent cell percentage and cellular expressions of P16INK4A and P21CIP1,which were all lowered by treatment with Alda-1,but its effect was obviously attenuated by EX527 treatment.Conclusion ALDH2 alleviates hypoxia-induced senescence of pulmonary artery smooth muscle cells by upregulating the SIRT1/PGC-1α signaling pathway to alleviate pulmonary hypertension in mice.