Objective:To comparatively evaluate the efficacy of anti-tumor necrosis factor (TNF)-α and anti-interleukin (IL)-12/23 biologics as the first-line treatment in Crohn′s disease (CD).Methods:From January 1, 2016 to December 31, 2024, at the Department of Gastroenterology of the First Affiliated Hospital of Soochow University, the clinical data of patients with CD treated with anti-TNF-α (infliximab or adalimumab) or anti-IL-12/23 biologics (ustekinumab) as first-line treatment were retrospectively collected. All the patients were followed up for 1 year since the initiation of first-line biologic treatment, with the follow-up concluding on December 31, 2024. The primary outcomes were the clinical efficacy (including clinical response rate and clinical remission rate) of anti-TNF-α or anti-IL-12/23 treatment at week 24 and week 48, and the endoscopic efficacy(including endoscopic response rate and endoscopic remission rate) at week 48. The clinical efficacy was assessed based on Crohn′s disease activity index(CDAI). The clinical response was defined as a reduction in CDAI by ≥ 70 from baseline (week 0), and clinical remission was defined as CDAI < 150. The endoscopic efficacy was assessed based on simple endoscopic score for Crohn′s disease (SES-CD), the endoscopic response was defined as a reduction in SES-CD by ≥50% from baseline (week 0), and endoscopic remission was defined as SES-CD ≤2. Chi-square test or Fisher′s exact test was used for statistical analysis.Results:A total of 215 CD patients were enrolled, including 160 males and 55 females, with the age of (31.88±11.55) years old. Among them, 179 patients completed the clinical efficacy evaluation, 110 cases were treated with anti-TNF-α, 69 cases were treated with anti-IL-12/23. The clinical response rates of patients treated with anti-TNF-α and anti-IL-12/23 at week 24 were 95.5%(105/110) and 95.7%(66/69), respectively, and the clinical remission rates at week 24 were 86.4%(95/110) and 85.5%(59/69), respectively; the clinical response rates at week 48 were 95.5%(105/110) and 97.1%(67/69), respectively, and the clinical remission rates at week 48 were 89.1%(98/110) and 88.4%(61/69), respectively; and the differences were not statistically significant(Fisher′s exact test, χ2=0.03, Fisher′s exact test, χ2=0.02; P=1.000, 0.708, 0.872, and 0.887). A total of 76 patients completed endoscopic efficacy evaluation, among which 55 cases were treated with anti-TNF-α, and 21 cases were treated with anti-IL-12/23. The endoscopic response rates of patients treated with anti-TNF-α and anti-IL-12/23 were 74.5%(41/55) and 66.7%(14/21), respectively, and the endoscopic remission rates at week 48 were 49.1%(27/55) and 28.6%(6/21), respectively; and the differences were not statistically significant( χ2=0.47 and 2.60, P=0.492 and 0.107). Conclusion:Both anti-TNF-α and anti-IL-12/23 are effective as first-line biological therapies for CD, and there are no significant differences in both clinical and endoscopic efficacy between these 2 biologics.

Objective:To compare the role of double-balloon enteroscopy (DBE) and dual-energy CT enterography (DCTE) in evaluating the clinical characteristics of Crohn′s disease (CD).Methods:From July 1, 2016 to November 1, 2023, 72 patients with CD who underwent both DBE and DCTE (with an interval of less than 3 months) in the First Affiliated Hospital of Soochow University were enrolled in this retropective study. Among them, 4 patients underwent both DBE and DCTE twice (a total of 76 cases). The data of DBE and DCTE in the diagnosis of 76 CD cases were analyzed, including the diagnostic rate of CD, the consistency of the 2 methods in detecting the lesion location (ileocecal, colonic, ileocolonic, and upper gastrointestinal tract involvement), and the detection rates of stenosis, ulcer and the location, long ulcer (long-diameter≥2 cm), and fistula. Kappa test was performed for the consistency analysis, and Chi-square test was used for statistical analysis.Results:The diagnostic rate of CD by DBE was higher than that by DCTE (80.3% (61/76) vs. 65.8% (50/76)), and the diagnostic rate of combination of the 2 methods (89.5% (68/76)) was higher than that by DCTE alone, and the differences were statistically significant ( χ2=4.04 and 12.28, P=0.044 and <0.001). The result of Kappa consistency test showed that the consistency of CD lesion location detected by DBE and DCTE was poor (Kappa value=0.29, t=3.17, P=0.002). The detection rate of stenosis by DBE was higher than that by DCTE (46.1% (35/76) vs. 13.2% (10/76)), the detection rate of stenosis by combination of the 2 methods (52.6% (40/76)) was higher than that by DCTE alone, and the differences were statistically significant ( χ2=19.73 and 26.82, both P<0.001). There were no statistically significant differences in the detection rates of fistula among DBE, DCTE, and the combination of the 2 methods (3.9%(3/76), 2.6% (2/76), 5.3% (4/76); all P>0.05). The detection rate of ulcer by DBE was higher than that by DCTE(73.7% (56/76) vs. 7.9% (6/76)), the detection rate of ulcer by combination of the 2 methods (76.3%(58/56)) was higher than that by DCTE alone, and the differences were statistically significant ( χ2=68.10 and 72.98, both P<0.001). The detection rates of long ulcer and non-terminal ileum ulcer by DBE were both 17.9% (10/56). All the 6 cases with ulcer detected by DCTE were located in the terminal ileum, and no long ulcers were observed. Conclusions:In the diagnosis of CD, as well as in the detection of stenosis and ulcer, DBE and the combination of DBE and DCTE have more advantages over DCTE alone. The consistency between DBE and DCTE in identifying the location of lesion is poor. DBE has advantages in detecting long ulcer and non-terminal ileum ulcer.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons and the accumulation of Lewy bodies, leading to motor and nonmotor symptoms. While both genetic and environmental factors contribute to PD, recent studies highlight the crucial role of lipid metabolism disturbances in disease progression. Altered lipid homeostasis promotes protein aggregation and oxidative stress, with significant changes in lipid classes such as sphingolipids and glycerolipids observed in patients with PD. These disturbances are involved in key pathological processes, such as α-synuclein aggregation, organelle dysfunction, lipid-mediated neuroinflammation, and impaired lipid homeostasis. This review examines the relationship between lipid species and PD progression, focusing on the physiological roles of lipids in the central nervous system. It explores the mechanistic links between lipid metabolism and PD pathology, along with lipid-related genetic risk factors. Furthermore, this review discusses lipid-targeting therapeutic strategies to mitigate PD progression, emphasizing the potential of lipid modulation for effective treatment development.
Humans ; Parkinson Disease/metabolism* ; Lipid Metabolism/physiology* ; Animals ; Oxidative Stress/physiology* ; alpha-Synuclein/metabolism*

This studyobtained the proteins of virulence factors EsxA and EsxB from Mycobacterium haemophilum and explored their interactions both in vitro and in vivo.The aim was to lay a foundation for further analysis of the functional mechanisms of EsxA and EsxB,and to further the development of drugs targeting Mycobacterium haemophilum.On the basis of bioinformatics analysis of the virulence factors EsxA and EsxB from Mycobacterium haemophilum,we performed molecular cloning,using Mycobacterium haemophi-lum as a template to construct recombinant plasmids EsxA-pGl01,EsxB-pGl01,and EsxB-pET-29b.The proteins of EsxA,EsxB,and their complex were expressed with a prokaryotic system,then purified through nickel-affinity chromatography and gel filtration chromatography.Intracellular colocalization was determined through fluorescence colocalization.Prokaryotic expression systems for EsxA,EsxB,and their complex were successfully constructed,and purified proteins were obtained.Fluorescence colocalization indi-cated that EsxA and EsxB interacted in vivo.In vivo fluorescence colocalization and in vitro complex formation suggested that EsxA and EsxB interacted both intracellularly and extracellularly.Our findings lay a foundation for studying the pathogenic mechanisms of the virulence factors EsxA and EsxB in Mycobacterium haemophilum,and performing structural analysis of their complex.

This studyobtained the proteins of virulence factors EsxA and EsxB from Mycobacterium haemophilum and explored their interactions both in vitro and in vivo.The aim was to lay a foundation for further analysis of the functional mechanisms of EsxA and EsxB,and to further the development of drugs targeting Mycobacterium haemophilum.On the basis of bioinformatics analysis of the virulence factors EsxA and EsxB from Mycobacterium haemophilum,we performed molecular cloning,using Mycobacterium haemophi-lum as a template to construct recombinant plasmids EsxA-pGl01,EsxB-pGl01,and EsxB-pET-29b.The proteins of EsxA,EsxB,and their complex were expressed with a prokaryotic system,then purified through nickel-affinity chromatography and gel filtration chromatography.Intracellular colocalization was determined through fluorescence colocalization.Prokaryotic expression systems for EsxA,EsxB,and their complex were successfully constructed,and purified proteins were obtained.Fluorescence colocalization indi-cated that EsxA and EsxB interacted in vivo.In vivo fluorescence colocalization and in vitro complex formation suggested that EsxA and EsxB interacted both intracellularly and extracellularly.Our findings lay a foundation for studying the pathogenic mechanisms of the virulence factors EsxA and EsxB in Mycobacterium haemophilum,and performing structural analysis of their complex.

Objective:To comparatively evaluate the efficacy of anti-tumor necrosis factor (TNF)-α and anti-interleukin (IL)-12/23 biologics as the first-line treatment in Crohn′s disease (CD).Methods:From January 1, 2016 to December 31, 2024, at the Department of Gastroenterology of the First Affiliated Hospital of Soochow University, the clinical data of patients with CD treated with anti-TNF-α (infliximab or adalimumab) or anti-IL-12/23 biologics (ustekinumab) as first-line treatment were retrospectively collected. All the patients were followed up for 1 year since the initiation of first-line biologic treatment, with the follow-up concluding on December 31, 2024. The primary outcomes were the clinical efficacy (including clinical response rate and clinical remission rate) of anti-TNF-α or anti-IL-12/23 treatment at week 24 and week 48, and the endoscopic efficacy(including endoscopic response rate and endoscopic remission rate) at week 48. The clinical efficacy was assessed based on Crohn′s disease activity index(CDAI). The clinical response was defined as a reduction in CDAI by ≥ 70 from baseline (week 0), and clinical remission was defined as CDAI < 150. The endoscopic efficacy was assessed based on simple endoscopic score for Crohn′s disease (SES-CD), the endoscopic response was defined as a reduction in SES-CD by ≥50% from baseline (week 0), and endoscopic remission was defined as SES-CD ≤2. Chi-square test or Fisher′s exact test was used for statistical analysis.Results:A total of 215 CD patients were enrolled, including 160 males and 55 females, with the age of (31.88±11.55) years old. Among them, 179 patients completed the clinical efficacy evaluation, 110 cases were treated with anti-TNF-α, 69 cases were treated with anti-IL-12/23. The clinical response rates of patients treated with anti-TNF-α and anti-IL-12/23 at week 24 were 95.5%(105/110) and 95.7%(66/69), respectively, and the clinical remission rates at week 24 were 86.4%(95/110) and 85.5%(59/69), respectively; the clinical response rates at week 48 were 95.5%(105/110) and 97.1%(67/69), respectively, and the clinical remission rates at week 48 were 89.1%(98/110) and 88.4%(61/69), respectively; and the differences were not statistically significant(Fisher′s exact test, χ2=0.03, Fisher′s exact test, χ2=0.02; P=1.000, 0.708, 0.872, and 0.887). A total of 76 patients completed endoscopic efficacy evaluation, among which 55 cases were treated with anti-TNF-α, and 21 cases were treated with anti-IL-12/23. The endoscopic response rates of patients treated with anti-TNF-α and anti-IL-12/23 were 74.5%(41/55) and 66.7%(14/21), respectively, and the endoscopic remission rates at week 48 were 49.1%(27/55) and 28.6%(6/21), respectively; and the differences were not statistically significant( χ2=0.47 and 2.60, P=0.492 and 0.107). Conclusion:Both anti-TNF-α and anti-IL-12/23 are effective as first-line biological therapies for CD, and there are no significant differences in both clinical and endoscopic efficacy between these 2 biologics.

Objective:To compare the role of double-balloon enteroscopy (DBE) and dual-energy CT enterography (DCTE) in evaluating the clinical characteristics of Crohn′s disease (CD).Methods:From July 1, 2016 to November 1, 2023, 72 patients with CD who underwent both DBE and DCTE (with an interval of less than 3 months) in the First Affiliated Hospital of Soochow University were enrolled in this retropective study. Among them, 4 patients underwent both DBE and DCTE twice (a total of 76 cases). The data of DBE and DCTE in the diagnosis of 76 CD cases were analyzed, including the diagnostic rate of CD, the consistency of the 2 methods in detecting the lesion location (ileocecal, colonic, ileocolonic, and upper gastrointestinal tract involvement), and the detection rates of stenosis, ulcer and the location, long ulcer (long-diameter≥2 cm), and fistula. Kappa test was performed for the consistency analysis, and Chi-square test was used for statistical analysis.Results:The diagnostic rate of CD by DBE was higher than that by DCTE (80.3% (61/76) vs. 65.8% (50/76)), and the diagnostic rate of combination of the 2 methods (89.5% (68/76)) was higher than that by DCTE alone, and the differences were statistically significant ( χ2=4.04 and 12.28, P=0.044 and <0.001). The result of Kappa consistency test showed that the consistency of CD lesion location detected by DBE and DCTE was poor (Kappa value=0.29, t=3.17, P=0.002). The detection rate of stenosis by DBE was higher than that by DCTE (46.1% (35/76) vs. 13.2% (10/76)), the detection rate of stenosis by combination of the 2 methods (52.6% (40/76)) was higher than that by DCTE alone, and the differences were statistically significant ( χ2=19.73 and 26.82, both P<0.001). There were no statistically significant differences in the detection rates of fistula among DBE, DCTE, and the combination of the 2 methods (3.9%(3/76), 2.6% (2/76), 5.3% (4/76); all P>0.05). The detection rate of ulcer by DBE was higher than that by DCTE(73.7% (56/76) vs. 7.9% (6/76)), the detection rate of ulcer by combination of the 2 methods (76.3%(58/56)) was higher than that by DCTE alone, and the differences were statistically significant ( χ2=68.10 and 72.98, both P<0.001). The detection rates of long ulcer and non-terminal ileum ulcer by DBE were both 17.9% (10/56). All the 6 cases with ulcer detected by DCTE were located in the terminal ileum, and no long ulcers were observed. Conclusions:In the diagnosis of CD, as well as in the detection of stenosis and ulcer, DBE and the combination of DBE and DCTE have more advantages over DCTE alone. The consistency between DBE and DCTE in identifying the location of lesion is poor. DBE has advantages in detecting long ulcer and non-terminal ileum ulcer.

Objective:To investigate the effect of Fu-Fang-Yu-Jie(FFYJ)granules on LPS-induced inflammation model in bone marrow-derived macrophages(BMDM)and its intervention of FFYJ on nucleotide-bound oligomeric domain-like receptor protein 3(NLRP3)inflammatory signaling pathway in macrophages.Methods:Primary cells were extracted and isolated from the leg bone mar-row of C57BL/6 mice and BMDM macrophages were obtained after 7 days of induction with 50 ng/ml M-CSF.Groups included control group(Control),model group(LPS+ATP),FFYJ low dose group(FFYJ 50 μg/ml),FFYJ medium dose group(FFYJ 100 μg/ml),FFYJ high dose group(FFYJ 200 μg/ml)and positive drug dexamethasone group(DEX).BMDM in FFYJ treatment group and posi-tive drug group were pretreated for 1 hour before modeling.Lactate dehydrogenase(LDH)release assay was used to detect the level of LDH in the supernatant of each group of cells;ELISA was used to detect the level of inflammatory factors TNF-α,IL-6 and IL-1β in the supernatant of each group of cells;qRT-PCR was used to detect the levels of TNF-α,IL-6 and IL-1β in each group of cells;protein levels of NF-κB,p-NF-κB,NLRP3,Caspase-1 p45,Caspase-1 p20 and GSDMD-N in each group of cells were detected by Western blot;inverted fluorescence microscope was used to observe the cell pyroptosis of each group after Hoechst-PI staining.Results:Compared with control group,the levels of LDH,TNF-α,IL-6 and IL-1β in the supernatant of the model group were signifi-cantly higher(P<0.000 1);the mRNA levels of TNF-α,IL-6 and IL-1β in the model group were significantly higher(P<0.000 1);the protein levels of p-NF-κB,NLRP3,Caspase-1 p20 and GSDMD-N were significantly higher(P<0.05);and the number of PI-posi-tive cells was significantly higher(P<0.05).Compared with the model group,FFYJ and DEX significantly reduced the levels of LDH,TNF-α,IL-6 and IL-1β in the supernatant of BMDMs(P<0.05);down-regulated the mRNA levels of TNF-α,IL-6 and IL-1β in the cells(P<0.05);and inhibited the expressions of p-NF-κB,NLRP3,Caspase-1 p20 and GSDMD-N protein expressions(P<0.05);and significantly reduced the number of PI-positive cells(P<0.05).Conclusion:FFYJ exerts anti-inflammatory effects by inhibiting NLRP3 inflammasome activation in BMDM macrophages.

Dimethylarginine dimethylaminohydrolase 1 (DDAH1) is an important regulator of plasma asymmetric dimethylarginine (ADMA) levels, which are associated with insulin resistance in patients with nonalcoholic fatty liver disease (NAFLD). To elucidate the role of hepatic DDAH1 in the pathogenesis of NAFLD, we used hepatocyte-specific Ddah1-knockout mice (Ddah1^HKO) to examine the progress of high-fat diet (HFD)-induced NAFLD. Compared to diet-matched flox/flox littermates (Ddah1^f/f), Ddah1^HKO mice exhibited higher serum ADMA levels. After HFD feeding for 16 weeks, Ddah1^HKO mice developed more severe liver steatosis and worse insulin resistance than Ddah1^f/f mice. On the contrary, overexpression of DDAH1 attenuated the NAFLD-like phenotype in HFD-fed mice and ob/ob mice. RNA-seq analysis showed that DDAH1 affects NF-κB signaling, lipid metabolic processes, and immune system processes in fatty livers. Furthermore, DDAH1 reduces S100 calcium-binding protein A11 (S100A11) possibly via NF-κB, JNK and oxidative stress-dependent manner in fatty livers. Knockdown of hepatic S100a11 by an AAV8-shS100a11 vector alleviated hepatic steatosis and insulin resistance in HFD-fed Ddah1^HKO mice. In summary, our results suggested that the liver DDAH1/S100A11 axis has a marked effect on liver lipid metabolism in obese mice. Strategies to increase liver DDAH1 activity or decrease S100A11 expression could be a valuable approach for NAFLD therapy.

Objective:To investigate the composition characteristics of urolithiasis patients in Chongqing.Methods:From May 2017 to July 2021, clinical data of 1 972 urinary stone patients treated in the Second Affiliated Hospital of Chongqing Medical University was retrospectively analyzed. Among 1 972 patients, there were 1 323 males and 649 females, the average age was (52.7±13.8) years (aged 14-92 years). In this study, all of the patients were first divided into the central and western areas of Chongqing group ( n=1 532) and southeastern areas of Chongqing group ( n=440) according to regional differences; then according to the difference of economic development level, all patients were divided into the more developed area of Chongqing group ( n=1 491) and the less developed area of Chongqing group ( n=481). To study and analyze the influence of gender, age, region and economic development level on stone composition in patients. The distribution characteristics of urinary calculi constituents in different groups of region, gender and age were analyzed by Chi-square test, and analysis of the proportion of various urinary calculi with age were conducted by Cochran-Armitage trend test. Results:The results of stone composition analysis showed that, among the 1 972 cases, the mixed urinary stones were dominant in the urinary stones [92.9%(1 832/1 972)], in which, the most component was the calcium oxalate monohydrate+ calcium oxalate dehydrate [40.8%(805/1 972)]; among the pure stones, the most component was the calcium oxalate dehydrate [2.5%(50/1 972)]. The proportion of carbonated apatite stones [53.6%(348/649) vs 43.5%(576/1 323), P<0.05], hydroxyapatite stones [25.1%(163/649) vs 17.2%(228/1 323), P<0.05] and magnesium ammonium phosphate stones [20.6%(134/649) vs 6.3%(83/1 323), P<0.05] in female patients were significantly higher than those in male patients, but the proportion of calcium oxalate stones [91.4%(1 209/1 323) vs 80.7%(524/649), P<0.05] and uric acid stones [9.4%(125/1 323) vs 1.5%(10/649), P<0.05] in male patients were significantly higher than those in female patients. Compared with patients aged 40-70 years and ≥70 years, the proportion of carbonated apatite stones [39.6%(155/391) vs 48.4%(673/1 391), 50.5%(96/190), P<0.05], magnesium ammonium phosphate stones [6.1% (24/391) vs 12.0% (167/1 391), 13.7% (26/190), P<0.05] and uric acid stones [3.3% (13/391) vs 7.4% (103/1 391), 10.0% (19/190), P<0.05] was significantly lower for patients aged <40 years; but the proportion of calcium oxalate stones in patients aged < 40 years was significantly higher [93.6%(366/391) vs 87.2%(1 213/1 391), 81.0%(154/190), P<0.05]. In this study, there were no significant difference in stone composition between the central and western areas of Chongqing and the southeastern areas of Chongqing, and between the more developed areas of Chongqing and the less developed areas of Chongqing ( P>0.05). Conclusions:There are gender and age differences in the distribution of urinary stone components in Chongqing, but the regional and economic development level differences are not particularly obvious. Carbonated apatite stones, hydroxyapatite stones and magnesium ammonium phosphate stones were more prevalent in females, calcium oxalate stones and uric acid stones were more common in males. Calcium oxalate stones were the most common in patients aged< 40 years, carbonate apatite, magnesium ammonium phosphate and uric acid stones were more common in patients aged ≥40 years.