Objective:To explore the relationship between intestinal bacterial overgrowth (SIBO) and ulcerative colitis (UC).Methods:From December 2023 to June 2024, 85 patients with UC from the Gastroenterology Department of the Luquan branch of the Second Hospital of Hebei Medical University were enrolled. The lactulose hydrogen-methane breath test was performed to assess the prevalence of SIBO. Clinical data, including basic information, clinical manifestations, endoscopic manifestations, inflammatory indicators, current medication regimen, and past medical history, were collected. Furthermore, the body mass index (BMI), modified Mayo score, and patient-reported outcome (PRO2) score were calculated to evaluate disease activity in each patient. The Student′s t-test, Chi-square test, non-parametric test, and multiple logistic regression were used to analyze the data and explore the relationship between SIBO and UC. Results:The incidence of abdominal pain and bloating in patients who were SIBO positive with UC was higher than in those who were SIBO negative [abdominal pain: 50.0%(10/20) vs. 23.1%(15/65), χ2=5.34, P=0.021; abdominal distension: 40.0% (8/20) vs. 13.8% (9/65), χ2=5.01, P=0.025]; the difference was statistically significant ( P<0.05). Patients who were SIBO positive with UC were more likely to develop hypoproteinemia and anemia than those who were SIBO negative [hypoproteinemia: 50.0% (10/20) vs. 15.4% (10/65), χ2=8.35, P=0.004; anemia: 35.0% (7/20) vs. 9.2% (6/65), χ2=5.98, P=0.014]; the difference was statistically significant ( P<0.05). In the intestinal methanogen overgrowth (IMO) positive group, the number of patients with UC with 1-2 stool times/day was higher, and the distribution of stool times between the IMO positive and IMO negative groups was significantly different ( χ2=6.45, P=0.040). Furthermore, combined hypoproteinemia and anemia were risk factors for SIBO in patients with UC (hypoproteinemia OR=4.331, 95% CI 1.117-16.799, P=0.034; anemia OR=5.515, 95% CI 1.231-24.700, P=0.026). Conclusions:We observed a clinical overlap between SIBO and UC. SIBO could be targeted to optimize the treatment of patients with UC in the future.

BACKGROUND: Fibrosis of the connective tissue in the vaginal wall predominates in pelvic organ prolapse (POP), which is characterized by excessive fibroblast-to-myofibroblast differentiation and abnormal deposition of the extracellular matrix (ECM). Our study aimed to investigate the effect of ECM stiffness on vaginal fibroblasts and to explore the role of methyltransferase 3 (METTL3) in the development of POP. METHODS: Polyacrylamide hydrogels were applied to create an ECM microenvironment with variable stiffness to evaluate the effects of ECM stiffness on the proliferation, differentiation, and expression of ECM components in vaginal fibroblasts. METTL3 small interfering RNA and an overexpression vector were transfected into vaginal fibroblasts to evaluate the effects of METTL3 silencing and overexpression on matrix stiffness-induced vaginal fibroblast-to-myofibroblast differentiation and abnormal modulation of the ECM. Both procedures were detected by 5-ethynyl-2'-deoxyuridine (EdU) staining, Western blotting (WB), quantitative real-time polymerase chain reaction (RT-qPCR), and immunofluorescence (IF). RESULTS: Vaginal fibroblasts from POP patients exhibited increased proliferation ability, increased expression of α-smooth muscle actin (α-SMA), decreased expression of collagen I/III, and significantly decreased expression of tissue inhibitors of matrix metalloproteinases (TIMPs) in the stiff matrix ( P <0.05). Compared with those from non-POP patients, vaginal wall tissues from POP patients demonstrated a significant increase in METTL3 content ( P <0.05). However, silencing METTL3 expression in vaginal fibroblasts with high ECM stiffness resulted in decreased proliferation ability, decreased α-SMA expression, an increased ratio of collagen I/III, and increased TIMP1 and TIMP2 expression. Conversely, METTL3 overexpression significantly promoted the process of increased proliferation ability, increased α-SMA expression, decreased ratio of collagen I/III and decreased TIMP1 and TIMP2 expression in the soft matrix ( P <0.05). CONCLUSIONS Elevated ECM stiffness can promote excessive proliferation, differentiation, and abnormal ECM modulation, and the expression of METTL3 plays an important role in alleviating or aggravating matrix stiffness-induced vaginal fibroblast-to-myofibroblast differentiation and abnormal ECM modulation.
Humans ; Female ; Extracellular Matrix/metabolism* ; Cell Differentiation/genetics* ; Methyltransferases/metabolism* ; Pelvic Organ Prolapse/pathology* ; Fibroblasts/metabolism* ; Myofibroblasts/metabolism* ; Vagina/metabolism* ; Cell Proliferation/physiology* ; Cells, Cultured ; Middle Aged

Objective:To compare the efficacy and safety of LY01011,a recombinant anti-RANKL fully human monoclonal antibody injection,versus denosumab in the treatment of bone metastases from solid tumors.Methods:A randomized,double-blind,positive drug parallel-controlled,multicenter clinical trial was conducted.A total of 850 subjects were randomly assigned(1:1)to either the experimental group(424 subjects)or the control group(426 subjects).The experimental group received 13 doses of LY01011,while the control group received 3 doses of denosumab followed by 10 doses of LY01011.Results:The primary efficacy endpoint was the natural logarithmic change from baseline in urinary N-terminal telopeptide of type I collagen corrected by urinary creatinine(uNTX/uCr)at week 13.The change was-1.740(0.042 0)in the experimental group and-1.745(0.042 1)in the control group.The least-squares mean difference between groups was 0.005(90%CI:-0.088 to 0.097),indicating no statistically significant difference(P>0.05).Safety profiles,including treatment-emergent adverse events,laboratory tests,vital signs,physical examinations,and electrocardiograms,were comparable between groups(P>0.05).Conclusions:LY01011 demonstrated biosimilarity to denosumab,with favorable safety profile,tolerability,and potential for clinical application.

Objective:To explore the relationship between intestinal bacterial overgrowth (SIBO) and ulcerative colitis (UC).Methods:From December 2023 to June 2024, 85 patients with UC from the Gastroenterology Department of the Luquan branch of the Second Hospital of Hebei Medical University were enrolled. The lactulose hydrogen-methane breath test was performed to assess the prevalence of SIBO. Clinical data, including basic information, clinical manifestations, endoscopic manifestations, inflammatory indicators, current medication regimen, and past medical history, were collected. Furthermore, the body mass index (BMI), modified Mayo score, and patient-reported outcome (PRO2) score were calculated to evaluate disease activity in each patient. The Student′s t-test, Chi-square test, non-parametric test, and multiple logistic regression were used to analyze the data and explore the relationship between SIBO and UC. Results:The incidence of abdominal pain and bloating in patients who were SIBO positive with UC was higher than in those who were SIBO negative [abdominal pain: 50.0%(10/20) vs. 23.1%(15/65), χ2=5.34, P=0.021; abdominal distension: 40.0% (8/20) vs. 13.8% (9/65), χ2=5.01, P=0.025]; the difference was statistically significant ( P<0.05). Patients who were SIBO positive with UC were more likely to develop hypoproteinemia and anemia than those who were SIBO negative [hypoproteinemia: 50.0% (10/20) vs. 15.4% (10/65), χ2=8.35, P=0.004; anemia: 35.0% (7/20) vs. 9.2% (6/65), χ2=5.98, P=0.014]; the difference was statistically significant ( P<0.05). In the intestinal methanogen overgrowth (IMO) positive group, the number of patients with UC with 1-2 stool times/day was higher, and the distribution of stool times between the IMO positive and IMO negative groups was significantly different ( χ2=6.45, P=0.040). Furthermore, combined hypoproteinemia and anemia were risk factors for SIBO in patients with UC (hypoproteinemia OR=4.331, 95% CI 1.117-16.799, P=0.034; anemia OR=5.515, 95% CI 1.231-24.700, P=0.026). Conclusions:We observed a clinical overlap between SIBO and UC. SIBO could be targeted to optimize the treatment of patients with UC in the future.

Objective:To compare the efficacy and safety of LY01011,a recombinant anti-RANKL fully human monoclonal antibody injection,versus denosumab in the treatment of bone metastases from solid tumors.Methods:A randomized,double-blind,positive drug parallel-controlled,multicenter clinical trial was conducted.A total of 850 subjects were randomly assigned(1:1)to either the experimental group(424 subjects)or the control group(426 subjects).The experimental group received 13 doses of LY01011,while the control group received 3 doses of denosumab followed by 10 doses of LY01011.Results:The primary efficacy endpoint was the natural logarithmic change from baseline in urinary N-terminal telopeptide of type I collagen corrected by urinary creatinine(uNTX/uCr)at week 13.The change was-1.740(0.042 0)in the experimental group and-1.745(0.042 1)in the control group.The least-squares mean difference between groups was 0.005(90%CI:-0.088 to 0.097),indicating no statistically significant difference(P>0.05).Safety profiles,including treatment-emergent adverse events,laboratory tests,vital signs,physical examinations,and electrocardiograms,were comparable between groups(P>0.05).Conclusions:LY01011 demonstrated biosimilarity to denosumab,with favorable safety profile,tolerability,and potential for clinical application.

Objective:To construct a primary nanobody library for human papillomavirus 16(HPV16)L1 protein and obtain a nanobody specific to HPV16 L1 through selection and identification.Methods:HPV16 L1 protein was used as antigen to immunize alpaca,and a primary antibody library was constructed using phage display technology.After three rounds of screening,positive clones were identified by ELISA.The VHH sequence of the strongest positive clone was used for eukaryotic expression.The target nanobody was obtained after affinity purification,gel filtration chromatography,SDS PAGE and WB identification.The affinity between the nanobody and HPV16 L1 protein was evaluated using surface plasmon resonance(SPR)technology.The cytotoxicity of the nanobody was detected using CCK-8 assay.The neutralizing activity of nanobody against HPV16 pseudovirus was detected using a luciferase reporter gene assay.Results:The primary library was constructed with a capacity of 1.304×1010 and an abundance of 6.5×109 clones/mL.ELISA identified 36 positive clones.Protein monomer and dimers were expressed and purified,and the target nanobody(designated as"Nb")was successfully identified.The binding affinity of Nb to HPV16 L1 protein was 35.41 nmol/L.There was no significant difference in HaCat cell proliferation activity between Nb group and blank group(P>0.05).Compared to the negative group,both 0.1 and 1 μmol/L Nb inhibited pseudovirus infection in 293FT cells(all P<0.01).Conclusion:This study successfully obtained a nanobody with high purity and strong affinity that exhibited no cytotoxicity to epithelial cells and effectively inhibited HPV16 pseudovirus infection in 293FT cells.The nanobody provides a promising candidate antibody-based drug for the prevention and treatment of HPV 16 infection.

Objective:To study the effect of Long non-coding RNA(LncRNA)small nucleolar RNA host gene 12(SNHG12)regulating miR-138-5p/hypoxia inducible factor-1(HIF-1α)axis on improving the damage of hypoxia/reoxygenation(H/R)human vas-cular endothelial cells.Methods:Human umbilical vein endothelial cells(HUVECs)were cultured in vitro and randomly divided into control group,H/R model group,H/R+LncRNA SNHG12 overexpression group,H/R+miR-138-5p mimics group,H/R+co-transfec-tion group and H/R+co-transfection negative control group,each transfection group was transfected separately,and except for control group,the remaining groups were given hypoxia for 5 hours and then reoxygenated for 1 hour to induce the cell models,and then the cell viability of each group was detected by CCK-8 experiment;the cell apoptosis in each group was detected by flow cytometry experi-ment,and the apoptosis rate of each group was compared;the levels of reactive oxygen species(ROS),lactate dehydrogenase(LDH)and inflammatory factors IL-6,IL-17 and IL-18 in each group were measured by the kit;the expressions of miR-138-5p and HIF-1α mRNA in cells of each group were measured by real-time quantitative PCR(qRT-PCR)experiment;the expressions of apoptotic pro-teins caspase-9,Bcl-2-associated X protein(Bax)and HIF-1α in each group were evaluated by Western blot.Results:Compared with control group,the apoptosis rate,cellular ROS,LDH,IL-6,IL-17 and IL-18 levels,cellular HIF-1α mRNA and protein levels,cellular caspase-9,Bax and HIF-1α protein levels were increased in H/R model group(P<0.05),the cell viability and miR-138-5p level were decreased(P<0.05).Compared with H/R model group and H/R+co-transfection group,the cell viability,cell HIF-1αmRNA and protein levels were increased in H/R+LncRNA SNHG12 overexpression group(P<0.05),the apoptosis rate,cellular ROS,LDH,IL-6,IL-17 and IL-18 levels,cellular caspase-9 and Bax protein levels,and miR-138-5p level were decreased(P<0.05);the cell viability,cellular HIF-1α mRNA and protein levels were decreased in H/R+miR-138-5p mimics group(P<0.05),the apoptosis rate,cellular ROS,LDH,IL-6,IL-17 and IL-18 levels,cellular caspase-9 and Bax protein levels were increased(P<0.05).Com-pared with H/R model group,there was no significant difference in cell index levels between the H/R+co-transfection negative control group and the H/R+co-transfection group(P>0.05).Conclusion:LncRNA SNHG12 can upregulate HIF-1α expression by downregulat-ing miR-138-5p expression,inhibit H/R-induced inflammation and oxidative stress in HUVECs,and reduce cell damage and apoptosis.

Objective:To study the clinicopathologic features and the key points of differential diagnosis of appendiceal diverticulosis (AD) and low-grade mucinous neoplasm (LAMN) to avoid over-diagnosis.Methods:The clinical data, pathologic features and follow-up information of 20 patients with AD, who were diagnosed in the Peking University Third Hospital from January 2010 to November 2019 were collected and compared with 44 cases of LAMN which were diagnosed during the same period.Results:Among the 20 cases of AD, hypermucinous epithelium, filiform villi or undulating epithelium and mucosa atrophy were observed in 10 (50.0%), 4 (20.0%) and 14 (70.0%) cases, respectively, however, focally loss of lamina propria and mucosa/submucosa fibrosis were observed only in 1 (5.0%) and 4 (20.0%) cases, respectively. Extramural mucin deposits were seen in 11 (55.0%) cases, all were acellular mucin. Mucosal Schwann cell hyperplasia were present in 12 (60.0%) cases. Nine (45.0%) and 5 (25.0%) cases were associated with acute diverticulitis or acute suppurative appendicitis, respectively. In comparison with AD, LAMN cases more frequently showed hypermucinous epithelium (42/44, 95.5%), filiform villi or undulating epithelium (43/44, 97.7%), loss of lamina propria (43/44, 97.7%) and fibrosis and hyalinization of appendiceal wall (44/44, 100.0%), whereas mucosal atrophy (4/44, 9.1%) and Schwann cell hyperplasia(11/44, 25.0%) were less frequently seen ( P<0.05). Follow-up information was available for 10 AD patients and 27 LAMN patients; all were alive without evidence of recurrence. Conclusions:Epithelial hyperplasia, loss of lamina propria, fibrosis of the appendiceal wall and extramural mucin deposits may occur focally in AD and should be distinguished from LAMN. The preservation of normal appendiceal mucosa architecture, lack of diffuse appendiceal wall fibrosis and hyalinization, and no definite neoplastic epithelium are the key point for preventing over-diagnosis.

Objective To assess the short-term effects of bariatric surgery on body composition. Methods Fifty-seven patients who underwent bariatric surgery were assessed by dual-energy x-ray absorptiometry (DEXA) before surgery, and 1 and 3 months after surgery. The body composition indexes of whole body and different regions were compared. Results The body mass index (BMI) decreased by 10.61％ and 18.51％, and the lean mass (LM) by 13.22％ and 14.35％ at 1 and 3 months after surgery, respectively. The A/G far mass (FM) decreased significantly 3 months after surgery (P ＜ 0.05). The bone mineral density (BMD) of the spine increased, but that of the pelvis decreased at 1 and 3 months after the operation, and a reduction was observed in the BMD of the whole body by 1.23％ and 1.45％, respectively (P ＜ 0.05). Compared to the baseline, the bone mineral content (BMC) of the spine, pelvis, and whole body increased at 1 and 3 months post-surgery, with a statistically significant difference (P ＜ 0.05). The FM of the whole body (9.52％ and 22.77％) and four regions (legs, trunk, android, and gynoid) reduced. A significant loss of FM (P ＜ 0.05) was observed in the android region by 15.80％ and 31.86％ at the two follow-ups. Conclusion Bariatric surgery can effectively reduce the patient's BMI and FM in the short term, and promotes the redistribution of fat; however, it may be accompanied by a reduction in LM, while the BMD and BMC change trend of pelvis and whole body are opposite.

Objective To evaluate the left atrial(LA) function in patients with severe preeclampsia ( SPE) by full-volume imaging technology. Methods Forty-two patients of SPE were randomly chosen as SPE group,34 healthy pregnant women were selected as the control group. LA related function parameters including LA maximum volume( LAVmax),LA minimum volume( LAVmin),LA pre-atrium contraction volume(LAVpre),LA reservoir volume(LARV),LA passive emptying volume(LAPEV),LA contraction volume(LACV),LA expansion index(LAEI),LA passive emptying fraction(LAPEF),LA passive emptying fraction( LAAEF ) were separately required by biplane area-length method and full-volume imaging technology in antepartum and postpartum. Results Compared with control group before delivery,the parameters of SPE group before delivery such as LAVmax,LAVmin,LAVpre were higher,LAEI,LAPEF, LAAEF indexed to body surface area(BSA) were lower(all P ＜0.01).Compared with control group before delivery,the parameters of control group after delivery such as LAVmax,LAVmin,LAVpre were lower( all P ＜0.05),LAEI, LAAEF calculated as ratio to BSA were somewhat reduced,LAPEF calculated as ratio to BSA was relatively higher(all P ＞0.05).Compared with SPE group before delivery,the parameters of SPE group after delivery such as LAVmax,LAVmin,LAVpre were lower,LAEI,LAPEF,LAAEF indexed to BSA were higher( all P ＜0.01). Compared with control group after delivery,the parameters of SPE group after delivery such as LAVmax,LAVmin,LAVpre were still incresed ( all P ＜ 0.05 ), LAEI,LAPEF, LAAEF indexed to BSA were relatively lower( all P ＞0.05). Conclusions Full-volume imaging technology can quantitatively evaluate the LA function. LA reservoir function,conduit function and booster pump function are reduced in SPE before delivery,LA rereservoir function,conduit function and booster pump function are basically recovery in SPE after delivery.