Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Fragile X syndrome(FXS)is caused by abnormal duplication and amplification of the FMR1 gene CGG.This article reports a pair of brothers diagnosed with FXS by genetic testing.Two patients,aged 15 and 14 years old respectively,both had clinical manifestations such as language disorders,intellectual disabilities,attention deficit disorder,autism spectrum disorder,and FXS's characteristic facial features.The proband had a rare late-onset epileptic seizure,which was well treated with levetiracetam,while his younger brother had no electroencephalogram abnormalities after repeated follow-up.This pair of cases suggests that the clinical phenotype of FXS has diversity and heterogeneity.

Objective:To investigate the differential gene expression profiling between subcutaneous fat (SF) and orbital septum fat (OF).Methods:Six samples of SF tissue were collected from patients undergoing abdomen or thigh liposuction, and six samples of OF tissue were collected from patients undergoing double eyelid or pouch surgery in Chongqing Xing Rong Plastic Surgery Hospital from May 2022 to June 2022. Transcriptional characteristics of SF and OF were compared by RNA sequencing. The gene expression differences between SF and OF were analyzed by bioinformatics methods. The differences in gene expression were verified by real-time quantitative PCR (qRT-PCR).Results:Principal component analysis (PCA) showed the SF and OF groups were obviously separated as two independent gene clusters. The volcano plot analysis displayed the upregulated genes (such as FOXL2 and FOXL2NB), or the downregulated genes (such as DEFB132 and HOXB3) in SF group compared to those in OF group. Besides, the protein-protein interaction (PPI) network revealed the top 3 upregulated hub genes in SF group (MYH7, TCAP and MYL2) and in OF group (SOX9, WNT1 and WNT2). Heatmap analysis based on the above PPI showed that the two groups of upregulated genes were clustered and separated obviously. In addition, the signaling pathway analysis revealed that cardiomyopathy, muscle contraction and AMPK pathway were enriched in the SF group, while Wnt singling and cancer-related pathway were enriched in OF group. Finally, the qRT-PCR showed that SOX9 ( P<0.001) and WNT2 ( P<0.001) were upregulated, while DEFB132 ( P<0.001) and HOXB3 ( P<0.01) were downregulated in OF group compared to SF group, respectively. Conclusions:Compared to SF group, SOX9 and WNT2 are regulated, while DEFB132 and HOXB3 are downregulated in OF group. The differentially expressed genes in OF may be the key factors mediating its unique physiological features.

Objective To investigate the mechanism by which Colony Stimulating Factor-1(CSF1)inhibits apoptosis in neurons subjected to oxygen-glucose deprivation(OGD).Methods Primary rat cortical neurons were divided into the OGD damaged neuron model group(OGD group),the rh-CSF1 intervention group(rh-CSF1 group),and control group.The sample size for each group was 3.After intervention with recombinant human CSF1(rh-CSF1),neuronal apoptosis rate and intracellular ATP content,reactive oxygen species levels,mitochondrial membrane potential,and mitochondrial DNA copy number were measured.The content of malondialdehyde within mitochondria and the activity of superoxide dismutase were also assessed.Results Intervention with rh-CSF1 increased mitochondrial membrane potential(0.55±0.03 vs.0.43±0.06,P<0.01),mitochondrial DNA copy number(0.88±0.05 vs.0.72±0.06,P<0.05),ATP content[(15.70±0.99)mmol/mg vs.(11.70±1.00)mmol/mg,P<0.01)],and superoxide dismutase[(18.47±1.38)U/mg vs.(14.78±1.81)U/mg,P<0.05)]activity in neurons injured by OGD.It also reduced levels of rectivereactive oxygen species(3.64±0.21 vs.4.45±0.33,P<0.05)and malondialdehyde within mitochondria[(2.13±0.19)mmol/mg vs.(2.78±0.20)mmol/mg,P<0.05)],and inhibited neuronal apoptosis(10.12±0.78 vs.17.04±1.23,P<0.01)Conclusion rh-CSF1 may alleviate the damage in neurons induced by OGD by improving mitochondrial function,reducing oxidative stress,and inhibiting cell apoptosis.

Background A large number of studies on fluoride-induced systemic bone damage have been reported previously, but there is little understanding of the characteristics of fluoride accumulation in jawbone. Jawbone is homologous to the other bone tissues in the body, and is an indispensable and important frame structure in the oral cavity. Objective To study fluoride accumulation and its change trends in teeth, jawbone, and femur of SD rats with chronic drinking-water-borne fluorosis. Methods A total of 144 three-week-old SD rats, half male and half female, were randomly divided into two groups, a normal control group and a fluoride group. The rats in the normal controlgroup drank purified water disinfected and filtered from Guizhou, and the water contained 0.08 mg·kg⁻¹ fluoride which was lower than the national water quality standard at 1 mg·kg⁻¹. The rats in the fluoride group were fed with sodium fluoride (NaF) solution with a concentration of 150 mg·L⁻¹. At 3, 5 and 7 months of the fluoride exposure, the levels of fluoride in urine, blood, teeth, jawbone, and femur were measured by fluoride ion electrode method. Results There was no sex difference in fluoride content in different biological samples of rats in the fluoride group and the normal control group (all P>0.05). After 3 months of fluoride exposure, the rats in the fluoride group showed dental fluorosis of grade II, and higher levels of fluoride ion in blood and urine than the normal control group (all P<0.05), indicating that the rat model of fluoride drinking-water-borne chronic fluorosis was successfully replicated. In the normal control group, the levels of fluoride in femur remained stable; at the end of 3 months, the levels of fluoride in jawbone and teeth were (1097.36±470.34) and (453.09±173.43) mg·kg⁻¹ respectively, and at the end of 7 months, the levels of fluoride in jawbone and teeth were (2113.18±634.49) and (1604.80±160.43) mg·kg⁻¹ respectively. Both jawbone and teeth showed a positive temporal effect of increasing fluoride accumulation (P<0.05). After continuous fluoride feeding, the fluoride levels in jawbone, teeth, and femur of rats in the fluoride group were (3145.02±765.82), (1550.20±77.73), and (3640.55±699.42) mg·kg⁻¹ after 3 months, and (8420.36±1728.56), (4702.08±1417.06), and (6091.99±1384.97) mg·kg⁻¹ after 7 months. The three kinds of hard tissues all showed a positive temporal effect of increasing fluoride accumulation (P<0.05), and the cumulative increas was large than that in the normal control group. Among them, jawbone fluorine increased most. At the end of 5 months, the levels of fluoride in jawbone, femur, and teeth were (6485.02±2141.98), (4914.99±1529.41), and (3365.21±1462.27) mg·kg⁻¹ respectively, and the levels of fluoride in jawbone was much higher than those in femur and teeth (P<0.05). Conclusion Hard tissues such as bones and teeth are fluorine sensitive tissues. Compared with femur, jawbone showed significantly high fluoride accumulation, while teeth show relatively lagging fluoride accumulation.

Objective:To observe the effect of fluoride on growth and development of bone microstructure of rats condyle subchondral bone (RCSB).Methods:Forty two 3-week-old SD rats (half male and half female) were fed adaptively for 1 week, and 3 females and 3 males were sacrificed and recorded as 0 month. The remaining rats were randomly divided into control group ( n = 18) and fluoride exposed group ( n = 18) according to their body weight (55 - 70 g), half male and half female. The fluoride exposed group was fed with 150 mg/L sodium fluoride (NaF) aqueous solution, and the control group was fed with tap water. The two groups of experimental animals were sacrificed at 3, 5 and 7 month, respectively, 6 rats in each group, half male and half female. The right mandibular condyle was separated, and Micro CT scanning was performed to detect the microstructure parameters of RCSB. Results:In fluoride exposed group (3 month), bone surface/tissue volume (BS/TV), bone surface/bone volume (BS/BV), trabecular thickness (Tb.Th), trabecular number (Tb.N), structure model index (SMI), connectivity, connectivity density (Conn.D) and total porosity of female rats were significantly different from those of male rats ( t = - 5.10, - 5.58, 4.52, - 4.32, - 4.03, - 2.81, - 6.71, - 3.32, P < 0.05). There was no significant difference in each index between female and male rats in fluoride exposed group (5, 7 month, P > 0.05). Conclusion:In chronic fluorine exposure bone environment, the RCSB bone microarchitecture of male and female rats is different with time, showing the tendency of fluoride injury that the bone changes of female rats are slowed and the bone changes of male rats are active.

Objective:The investigation and research on the application status of Hepatic Venous Pressure Gradient (HVPG) is very important to understand the real situation and future development of this technology in China.Methods:This study comprehensively investigated the basic situation of HVPG technology in China, including hospital distribution, hospital level, annual number of cases, catheters used, average cost, indications and existing problems.Results:According to the survey, there were 70 hospitals in China carrying out HVPG technology in 2021, distributed in 28 provinces (autonomous regions and municipalities directly under the central Government). A total of 4 398 cases of HVPG were performed in all the surveyed hospitals in 2021, of which 2 291 cases (52.1%) were tested by HVPG alone. The average cost of HVPG detection was (5 617.2±2 079.4) yuan. 96.3% of the teams completed HVPG detection with balloon method, and most of the teams used thrombectomy balloon catheter (80.3%).Conclusion:Through this investigation, the status of domestic clinical application of HVPG has been clarified, and it has been confirmed that many domestic medical institutions have mastered this technology, but it still needs to continue to promote and popularize HVPG technology in the future.

Objective:To prospectively follow up the patients with ileocecal inflammatory lesions, to explore the characteristics of Crohn′s disease(CD) at early stage, and to provide references for early diagnosis of CD.Methods:From January 2013 to December 2018, at Department of Gastroenterology, The Seventh Medical Center of PLA General Hospital, 232 patients with unexplained ileocecal inflammatory lesions under colonoscopy examination were enrolled, which were followed up for more than one year. Chi-square test and Fisher exact probability text were used to compare the patients with early CD, with non-specific enteritis and intestinal tuberculosis in abdominal symptoms (abdominal pain, diarrhea, abdominal distension, constipation, hematochezia, changes in bowel habits), accompanying symptoms (oral ulcer, arthralgia), the proportion of patients with elevated erythrocyte sedimentation rate (ESR) or elevated C-reactive protein (CRP) level, serum antineutrophilic cytoplasmic antibody (ANCA), anti-saccharomyces cerevisiae antibody (ASCA), tuberculosis infection of T cells spot test, positive rate of fecal occult blood, lesion size, morphology, involvement site under endoscopy and histopathological results. Multivariate binary logistic regression was used to analyze the related factors of early CD.Results:Among 232 patients, 155 were males and 77 were females, and the age of first diagnosis was (43.9±13.8) years old. The follow-up period (range) was 27 months (12 to 79 months). Twenty-nine cases (12.5%) were diagnosed as early CD, 45 cases (19.4%) were intestinal tuberculosis, 105 cases (45.3%) were non-specific enteritis, and 53 cases (22.8%) as undetermined. All of 29 patients with early CD had abdominal symptoms, which accounted for 16.9% (29/172) of 172 patients with ileoceccal inflammatory lesion as well as abdominal symptoms. In early CD patients, the proportions of patients with abdominal pain, elevated CRP level and ESR level, positive rate of ASCA, positive rate of tuberculosis infection T cells and percentage of patients with thickened intestinal wall were all higher than those in patients with non-specific enteritis (62.1%, 18/29 vs. 33.3%, 35/105; 13.8%, 4/29 vs. 0; 13.8%, 4/29 vs. 1.0%, 1/105; 24.1%, 7/29 vs. 1.0%, 1/105; 20.7%, 6/29 vs. 3.8%, 4/105; 95.7%, 22/23 vs. 0), and the proportion of patients without abdominal symptoms was lower than that of patients with non-specific enteritis (0 vs. 31.4%, 33/105). And the differences were statistically significant ( χ2=6.692, Fisher exact probability text, χ2=7.162, χ2=17.826, χ2=7.497, Fisher exact probability text, and Fisher exact probability text, all P<0.05). Early CD patients were more likely to have multiple lesion sites (55.2%, 16/29), and mainly deep ulcers (55.2%, 16/29) and ulcers with a long diameter of 5 to 10 mm (39.3%, 11/28). The lesions of non-specific enteritis were mostly confined to the end of ileum (75.2%, 79/105), which were mainly superficial ulcers (41.0%, 43/105) and ulcers with a long diameter less than 5 mm (69.0%, 49/71). The proportion of patients without abdominal symptoms and the positive rate of tuberculosis infection of T cells spot test of early CD patients were both lower than those of intestinal tuberculosis group (0 vs. 15.6%, 7/45 and 20.7%, 6/29 vs. 68.9%, 31/45). The positive rate of ASCA and the proportion of patients with thickened intestinal wall were higher than those of intestinal tuberculosis group (24.1%, 7/29 vs. 0 and 95.7%, 22/23 vs. 11/19), and the differences were statistically significant (Fisher exact probability text, χ2=13.713, Fisher exact probability text and χ2=6.710, all P<0.05). The results of multivariate binary logistic regression analysis showed that abdominal pain and positive ASCA were independent risk factors for early CD (odds ratio ( OR)=2.855, 95% confidence interval ( CI) 1.014 to 8.037, P=0.047; OR=10.033, 95% CI 2.274 to 44.250, P=0.002). Conclusions:Prospective follow-up for more than one year in patients with unexplained ileocecal inflammatory lesions can effectively identify and diagnose early CD. Ileocecal inflammatory lesions with abdominal symptoms are one of the early manifestations of CD. Abdominal pain and positive serum ASCA at the initial diagnosis are independent risk factors for early diagnosis of CD.