Anti-inflammatory effects and beneficial effects of the feed additive Urtica cannabina L. in zebrafish.

Urtica cannabina L. (UL) has been used clinically for centuries because of its anti-inflammatory properties. This study aimed to investigate the underlying mechanisms and anti-inflammatory effects of different UL concentrations in zebrafish. To elucidate UL's anti-inflammatory properties, two inflammation zebrafish models were designed 1) by severing the zebrafish's caudal fin to assess the repairing effect of UL on the tail inflammation, and 2) by inducing lipopolysaccharides (LPS)-mediated intestinal inflammation to assess the protective and reparative effects of UL on intestinal inflammation at the histological and genetic levels. Furthermore, the effect of UL on the LPS-induced intestinal flora changes was also assessed. After caudal fin resection, a scar formed on the tail of the zebrafish, and the area of the caudal fin increased by 1.30 times as much as that of the control group (P < 0.01). Moreover, this tail scar was alleviated after 10 mg/g UL supplementation but not after 30 mg/g UL dose. LPS decreased the feed intake and body weight of the zebrafish; however, these effects were reversed after 10 and 30 mg/g doses of UL. In addition, the LPS treatment also reduced the intestinal goblet cells by 49% in the zebrafish when compared with the control, which was significantly restored after 10 and 30 mg/g UL treatments. At the genetics level, the expression of the pro-inflammatory cytokine genes (TNF-α, IL6, and IL8) showed that 10 and 30 mg/g UL doses could rescue LPS-induced expression. The gut microbiota analysis revealed changes in the abundance of four major bacterial phyla in the 10 and 30 mg/g UL-treated groups, with an increased probiotic Bacteroidota and decreased pathogenic bacteria. These results indicate that UL strongly inhibits inflammation caused by caudal fin removal and LPS-induced inflammatory changes in the zebrafish intensity, suggesting that UL is a feed additive that could be developed to improve resistance to inflammation in livestock.

Dynamic Analysis of Stool Microbiota of Simmental Calves and Effects of Diarrhea on Their Gut Microbiota.

The objective of this study was to explore the dynamic changes in the gut microbiota of Simmental calves before weaning and to compare the microbial composition and functionality between healthy calves and those with diarrhea. Fourteen neonatal Simmental calves were divided into a healthy group (n = 8) and a diarrhea group (n = 6). Rectal stool samples were collected from each calf on days 1, 3, 5, 7, 9, 12, 15, 18, 22, 26, 30, 35, and 40. High-throughput sequencing of the 16S rRNA gene V1-V9 region was conducted to examine changes in the gut microbiota over time in both groups and to assess the influence of diarrhea on microbiota structure and function. Escherichia coli, Bacteroides fragilis, and B. vulgatus were the top three bacterial species in preweaning Simmental calves. Meanwhile, the major functions of the fecal microbiota included "metabolic pathways", "biosynthesis of secondary metabolites", "biosynthesis of antibiotics", "microbial metabolism in diverse environments", and "biosynthesis of amino acids". For calves in the healthy group, PCoA revealed that the bacterial profiles on days 1, 3, 5, 7, and 9 differed from those on days 15, 18, 22, 26, 30, 35, and 40. The profiles on day 12 clustered with both groups, indicating that microbial structure changes increased with age. When comparing the relative abundance of bacteria between healthy and diarrheic calves, the beneficial Lactobacillus johnsonii, Faecalibacterium prausnitzii, and Limosilactobacillus were significantly more abundant in the healthy group than those in the diarrhea group (p < 0.05). This study provides fundamental insights into the gut microbiota composition of Simmental calves before weaning, potentially facilitating early interventions for calf diarrhea and probiotic development.

Hypobaric hypoxia causes low fecundity in zebrafish parents and impairment of skeletal development in zebrafish embryos and rat offspring.

Hypobaric Hypoxia (HH) negatively affects the cardiovascular and respiratory systems as well as gonadal development and the therefore next generation. This study investigated the effects of HH on zebrafish and SD rats, by exposing them to a low-pressure environment at 6000 m elevation for 30 days to simulate high-altitude conditions. It was indicated that parental zebrafish reared amh under HH had increased embryo mortality, reduced hatchability, and abnormal cartilage development in the offspring. Furthermore, the HH-exposed SD rats had fewer reproductive cells and smaller litters. Moreover, the transcriptome analysis revealed the down-regulation of steroid hormone biosynthesis pathways. The expression of the gonad-associated genes (amh, pde8a, man2a2 and lhcgr), as well as the gonad and cartilage-related gene bmpr1a, were also down-regulated. In addition, Western blot analysis validated reduced bmpr1a protein expression in the ovaries of HH-treated rats. In summary, these data indicate the negative impact of HH on reproductive organs and offspring development, emphasizing the need for further research and precautions to protect future generations' health.

The c-Fos/AP-1 inhibitor inhibits sulfur mustard-induced chondrogenesis impairment in zebrafish larvae.

Sulfur mustard (SM, dichlorodiethyl sulfide) is a potent erosive chemical poison that can cause pulmonary lung, skin and eye disease complications in humans. Currently, there is no designated remedy for SM, and its operation's toxicological process remains unidentified. This work employed zebrafish as a model organism to investigate the toxic manifestations and mechanisms of exposure to SM, aiming to offer novel insights for preventing and treating this condition. The results showed that SM caused a decrease in the survival rate of the zebrafish larvae (LC50 = 2.47 mg/L), a reduction in the hatching rate, an increase in the pericardial area, and small head syndrome. However, T-5224 (a selective inhibitor of c-Fos/activator protein) attenuated the reduction in mortality (LC50 = 2.79 mg/L), the reduction in hatching rate, and the worsening of morphological changes. We discovered that SM causes cartilage developmental disorders in zebrafish larvae. The reverse transcription-quantitative polymerase chain reaction found that SM increased the expression of inflammation-related genes (IL-1ß, IL-6, and TNF-α) and significantly increased cartilage development-related gene expression (fosab, mmp9, and atf3). However, the expression of sox9a, sox9b, and Col2a1a was reduced. The protein level detection also found an increase in c-fos protein expression and a significant decrease in COL2A1 expression. However, T-5224,also and mitigated the changes in gene expression, and protein levels caused by SM exposure. The results of this study indicate that SM-induced cartilage development disorders are closely related to the c-Fos/AP-1 pathway in zebrafish.

Diagnosis of poorly differentiated adenocarcinoma of the stomach by confocal laser endomicroscopy: A case report.

BACKGROUND: In recent years, confocal laser endomicroscopy (CLE) has become a new endoscopic imaging technology at the microscopic level, which is extensively performed for real-time in vivo histological examination. CLE can be performed to distinguish benign from malignant lesions. In this study, we diagnosed using CLE an asymptomatic patient with poorly differentiated gastric adenocarcinoma. CASE SUMMARY: A 63-year-old woman was diagnosed with gastric mucosal lesions, which may be gastric cancer, in the small curvature of the stomach by gastroscopy. She consented to undergo CLE for morphological observation of the gastric mucosa. Through the combination of CLE diagnosis and postoperative pathology, the intraoperative CLE diagnosis was considered to be reliable. According to our experience, CLE can be performed as the first choice for the diagnosis of gastric cancer. CONCLUSION: CLE has several advantages over pathological diagnosis. We believe that CLE has great potential in the diagnosis of benign and malignant gastric lesions.

Understanding the toxicity mechanism of gelsemine in zebrafish.

Gelsemium elegans (GE), also known as Duanchangcao, is a plant associated with toxic symptoms related to the abdomen; however, the toxicity caused by GE remains unknown. Gelsemine (GEL) is an alkaloid extracted from GE and is one of the most toxic alkaloids. This study used zebrafish as an animal model and employed high-throughput gene sequencing to identify genes and signaling pathways related to GEL toxicity. Exposure to GEL negatively impacted heart rate, swim bladder development, and activity in zebrafish larvae. Transcriptomics data revealed the enrichment of inflammatory and phagocyte signaling pathways. RT-PCR analysis revealed a decrease in the expression of pancreas-related genes, including the pancreatic coagulation protease (Ctr) family, such as Ctrl, Ctrb 1, and Ctrc, due to GEL exposure. Furthermore, GEL exposure significantly reduced Ctrb1 protein expression while elevating trypsin and serum amylase activities in zebrafish larvae. GEL also resulted in a decrease in pancreas-associated fluorescence area and an increase in neutrophil-related fluorescence area in transgenic zebrafish. This study revealed that GEL toxicity in zebrafish larvae is related to acute pancreatic inflammation.

Inhibitory Effect of Acetaminophen on Ocular Pigmentation and its Relationship with Thyroxine in Zebrafish Embryos.

Acetaminophen (N-acetyl-p-aminophenol; APAP) is one of the most widely used analgesics. To examine the toxicity of APAP, we used zebrafish embryos as model animals to detect the effect of APAP on the thyroid system of zebrafish embryos. The zebrafish embryos were exposed to APAP from 4 h post fertilization (4 hpf) until observation. The experimental results showed that APAP caused pericardial edema and decreased pigmentation in the zebrafish embryos or larvae. The APAP treatment caused a decrease in the expression of tpo and thrß in the zebrafish at 36 and 72 hpf. The transcriptomic analysis found that APAP affected retinol metabolism, the metabolism of xenobiotics by cytochrome P450, and the tyrosine metabolism pathway. The harmful effect of APAP on zebrafish embryos might be due to its disrupting effect on the functional regulation of the thyroid hormone system.

Single and mixture toxicity of cadmium and copper to swim bladder in early life stages of Japanese medaka (Oryzias latipes).

Toxicity observed in aquatic ecosystems often cannot be explained by the action of a single pollutant. Likewise, evaluation standards formulated by a single effect cannot truly reflect the environmental quality requirements. The study of mixtures is needed to provide environmental relevance and knowledge of combined toxicity. In this study, the embryos of Japanese medaka (Oryzias latipes) were treated with individual and binary mixture of copper (Cu) and cadmium (Cd) until 12 days post-fertilization (dpf). Hatching, mortality, development, histology and gene expression were assessed. Our results showed that the highest concentration mixture of Cd (10 mg/L) and Cu (1 mg/L) affected survival, hatching time and hatching success. Occurrence of uninflated swim bladder was the highest (value) with exposure to 10 mg/L Cd. Swim bladder was commonly over-inflated in a mixture (0.1 mg/L Cd + 1.0 mg/L Cu) exposure. Individuals exposed to the mixture (0.1 Cd + 1.0 Cu mg/L) showed up to a 7.69% increase in swim bladder area compared to the control group. The mixtures containing 0.1 or 10 mg/L Cd, each with 1.0 mg/L Cu resulted in significantly increased of Pbx1b expression, higher than any Cd or Cu alone (p < 0.01). In the co-exposure group (0.1/10 Cd + 1.0 Cu mg/L), Pbx1b expression was found at 12 dpf but not 7 dpf in controls. Higher concentrations of Cd may progressively reduce Pbx1b expression, potentially explaining why 75% of individuals in the 10 mg/L Cd group failed to inflate their swim bladders. Additionally, the swim bladder proved to be a valuable bio-indicator for biological evaluation.

Incidental gall bladder cancer in the laparoscopic treatment and magnetic resonance imaging era: A single institution experience.

BACKGROUND: Incidental gall bladder cancer (IGBC) is often discovered unexpectedly in patients after cholecystectomy. Currently, magnetic resonance imaging (MRI) has been widely applied in the pre-operative diagnosis of gall bladder diseases as laparoscopic cholecystectomy developed into the preferred method. AIMS AND OBJECTIVES: This study aimed to evaluate the pre-operative MRI application and laparoscopic management in the IGBCs. MATERIALS AND METHODS: Between January 2011 and January 2020, a total of 7917 patients with gall bladder diseases treated by laparoscopy were enrolled in this study. RESULTS: Amongst 49 patients diagnosed with IGBCs, the incidence of IGBCs in polypoid lesions, biliary pancreatitis, cholecystitis, cholecystocholedocholithiasis and gall bladder stones was 0.42%, 1.19%, 0.62%, 1.20% and 0.49%, respectively. MRI evaluation showed more remarkable pre-operative imaging as compared to ultrasonographic evaluation (40.8 vs. 26.5, P < 0.05). Furthermore, 14 patients were diagnosed with gall bladder cancer through intraoperative histological examination and 11 received laparoscopic extensive resection after cholecystectomy. MRI findings with diffuse thickening of the gall bladder detected IGBCs with 6.1% sensitivity, 96.02 specificity, 0.95% positive predictive values and 99.4% negative predictive values; diffuse thickening of the gall bladder with suspicion of malignancy detected IGBCs with 12.2% sensitivity, 99.1% specificity, 7.6% positive predictive values and 99.5% negative predictive values; focal thickening of the gall bladder detected IGBCs with 16% sensitivity, 99.8% specificity, 32% positive predictive values and 99.5% negative predictive values; moreover, suspicious lesion detected IGBCs with 6.1% sensitivity, 99.6% specificity, 8.8% positive predictive values and 99.4% negative predictive values. CONCLUSIONS: Patients with biliary pancreatitis and cholecystocholedocholithiasis have a higher incidence of IGBC. MRI evaluation could provide more accurate information for the IGBCs, which should be recommended for patients accepting cholecystectomy. MRI findings exhibited an unsatisfactory sensitivity when detecting IGBCs, but they represented high specificity. Pre-operative MRI evaluation and intraoperative histological examination may help some IGBCs to achieve one-stage laparoscopic extensive resection.

Effects of Different Pellet Feed Hardness on Growth and Reproduction, Feed Utilization Rate, and Environmental Dust in Laboratory Mice / 实验动物与比较医学

Objective To study the effects of different pellet feed hardness on the growth and reproduction, feed utilization rate, and environmental dust in laboratory mice.Methods One hundred of fifty 50 3-week-old SPF-grade C57BL/6JGpt and 150 ICR laboratory mice were randomly divided into three groups, with an equal number of males and females. They were fed diets with different hardness of 18.62 kg, 23.15 kg, and 27.89 kg. Body weight, feed utilization rate, and dust levels in cages were recorded and calculated for mice aged 3-10 weeks. Forty-five 6-week-old male mice and ninety 4-week-old female mice from each strain were randomly divided into three groups and fed pellet feeds with three different hardness levels. After 2 weeks of adaptation to the same hardness feed, the mice were paired at a 1∶2 male-to-female ratio and monitored for reproductive data for 3 months.Results At the age of 4 weeks, the body weight of male C57BL/6JGpt mice in 23.15 kg group was significantly higher than that in the 18.62 kg and 27.89 kg groups (P<0.01), and the body weight of females in the 18.62 kg group was significantly higher than that in the 27.89 kg group (P<0.05). There was no significant difference in body weight among ICR mice aged 3-10 weeks across different feed hardness groups (P>0.05). For both strains, feed utilization rate for males was higher than that for females across different feed hardness groups at all weeks of age (P<0.01). Compared to the 27.89 kg group, both the 18.62 kg and 23.15 kg groups showed a significant increase in the 50-mesh dust levels in cages for both strains aged 4-8 weeks (except for 7-week-old C57BL/6JGpt mice) (P<0.05). For both C57BL/6JGpt and ICR mice, there was no significant difference in basic reproductive performance such as interval between the first litter and the monthly production index among the three feed hardness groups during the experimental period (P>0.05). However, the monthly production index of C57BL/6JGpt mice first increased and then decreased with the increase of feed hardness, while that of ICR mice increased with increasing feed hardness, though these differences were not statistically significant (P>0.05).Conclusion Different strains and genders had different tolerance to feed hardness. C57BL/6JGpt mice are more adapted to lower hardness feeds, while ICR mice are better suited to slightly higher hardness feeds.

Clinical study of modified suspension reduction method combined with percutaneous vertebroplasty in the treatment of thoracolumbar osteoporotic compression fracture / 中国骨伤

OBJECTIVE@#To investigate the clinical effect of modified suspension reduction method combined with percutaneous vertebroplasty in the treatment of osteoporotic thoracolumbar compression fractures.@*METHODS@#From February 2020 to October 2021, 92 patients with thoracolumbar osteoporotic compression fracture were treated by percutaneous vertebroplasty. According to different treatment methods, they were divided into the observation group and the control group. The observation group was treated with modified suspension reduction and then percutaneous vertebroplasty, while the control group was treated with percutaneous vertebroplasty alone. The observation group (47 cases), including 20 males and 27 females, the age ranged from 59 to 76 years old with an average of (69.74±4.50) years old, fractured vertebral bodies:T10(2 cases), T11(7 cases), T12(19 cases), L1(14 cases), L2(5 cases);the control group(45 cases), including 21 males and 24 females, the age ranged from 61 to 78 years old with an average of (71.02±3.58) years old, fractured vertebral bodies:T10(3 cases), T11(8 cases), T12(17 cases), L1(12 cases), L2(5 cases);The leakage of bone cement were observed, the visual analogue scale (VAS), Oswestry lumbar dysfunction index (ODI), anterior vertebrae height (AVH), Cobb angle of kyphosis and the amount of bone cement injected before and after operation were recorded and compared between the two groups.@*RESULTS@#All patients were followed up, ranged from 6 to10 with an average of (8.45±1.73) months. Two patients ocurred bone cement leakage in observation group and 3 patients in control group. AVH of observation group increased (P<0.05) and Cobb angle of injured vertebrae decreased (P<0.05). Cobb angle of injured vertebrae and AVH of the control group were not significantly changed (P>0.05). Cobb angle of injured vertebrae of the observation group was lower than that of control group (P<0.05) and AVH was higher than that of the control group (P<0.05). In the observation group, VAS before operation and 1 week, 3 and 6 months after operation respectively were(7.32±1.05) scores, (3.56±1.18) scores, (1.83±0.67) scores, (1.27±0.34) scores, and ODI were(40.12±14.69) scores, (23.76±10.19) scores, (20.15±6.39) scores, (13.45±3.46) scores. In the control group, VAS before operation and 1 week, 3 and 6 months after operation respectively were(7.11±5.26) scores, (3.82±0.68) scores, (1.94±0.88) scores, (1.36±0.52) scores, and ODI were(41.38±10.23) scores, (25.13±14.22) scores , (20.61±5.82) scores, (14.55±5.27) scores . The scores of VAS and ODI after operation were lower than those before operation (P<0.05), but there was no significant difference between the two groups (P<0.05).@*CONCLUSION@#Modified suspension reduction method combined with PVP surgery for osteoporotic thoracolumbar compression fractures has achieved good clinical results, which can effectively relieve lumbar back pain, restore vertebral height, correct kyphosis, improve lumbar function and patients' quality of life.

Clinical Study on Dingxuan Decoction Combined with Vestibular Function Rehabilitation Training in the Treatment of Meniere's Disease / 广州中医药大学学报

Objective To investigate the efficacy of Dingxuan Decoction combined with vestibular function rehabilitation training in the treatment of Meniere's disease and to observe its effect on clinical symptoms and blood flow of vertebral artery.Methods A total of 100 patients with Meniere's disease of liver-kidney yin deficiency complicated with wind-water upward stirring type were randomly divided into an observation group and a control group,with 50 patients in each group.The control group was given conventional treatment and vestibular function rehabilitation training,and the observation group was treated with Dingxuan Decoction on the basis of treatment for the control group.The two groups were treated for 4 weeks and then were followed up for 6 months.The changes of traditional Chinese medicine(TCM)syndrome score,Dizziness Handicap Inventory(DHI)score,Tinnitus Handicap Inventory(THI)score,hearing visual analogue scale(VAS)score and vertebral artery blood flow in the two groups were observed before and after the treatment.After treatment,the TCM syndrome efficacy,hearing improvement and follow-up results were compared between the two groups.Results(1)After 4 weeks of treatment,the total effective rate for TCM syndrome efficacy of the observation group was 86.00%(43/50),and that of the control group was 62.00%(31/50),and the intergroup comparison showed that the TCM syndrome efficacy in the observation group was significantly superior to that in the control group(P＜0.01).(2)After 4 weeks of treatment,the hearing of patients in both groups was improved,and the total effective rate for the efficacy of hearing improvement in the observation group was 76.00%(38/50),while that in the control group was 46.00%(23/50).The intergroup comparison showed that the efficacy of hearing improvement in the observation group was significantly superior to that in the control group(P＜0.01).(3)After treatment,the TCM syndrome scores,DHI score,THI score and hearing VAS scores in the two groups were all decreased compared with those before treatment(P＜0.05 or P＜0.01),and the decrease in the observation group was significantly superior to that in the control group(P＜0.01).(4)After treatment,the average blood flow velocity of the left vertebral artery(LVA)and the right vertebral artery(RVA)in the two groups were both increased compared with those before treatment(P＜0.05),and the increase in the observation group was significantly superior to that in the control group(P＜0.05 or P＜0.01).(5)The results of 6-month follow-up after treatment showed that the incidence of Meniere's disease and the frequency of attack in the observation group were significantly reduced compared with those in the control group,and the episode duration in the observation group was significantly shorter than that in the control group,the differences being all statistically significant(P＜0.05 or P＜0.01).Conclusion Dingxuan Decoction combined with vestibular function rehabilitation training exert certain effect in treating patients with Meniere's disease of liver-kidney yin deficiency complicated with wind-water upward stirring type,and the therapy is effective on improving patients'clinical symptoms and vertebral artery blood flow,reducing the risk of recurrence and improving the quality of life of the patients.

Clinical analysis of intestinal fistula associated with invasive intervention for acute pancreatitis / 中华胰腺病杂志

Objective:To analyze the clinical characteristics of invasive intervention-related intestinal fistula in patients with acute pancreatitis (AP).Methods:We retrospectively analyzed the clinical data of 177 moderately severe acute pancreatitis (MSAP) or severe acute pancreatitis (SAP) patients who received invasive intervention in Peking Union Medical College Hospital from January 2003 to December 2022. Patients were divided into fistula group and non-fistula group based on the presence or absence of fistula after or during receiving invasive interventions. The age, gender, etiology, systemic inflammatory response syndrome(SIRS), impairment of organ function, revised Atlanta classification, bedside index of severity of acute pancreatitis(BISAP), Balthazar CT classification, extra-pancreatic involvement and secondary infection of local complications, indications, timing and modalities of invasive interventions, length of hospitalization, length of intensive care and outcomes were recorded. The differences on clinical characteristics were compared between the two groups.Results:Intestinal fistulae were found in 21(11.9%) cases during or after invasive intervention, including 8 during or after percutaneous drainage and 13 during or after surgeries. 51 cases received endoscopic drainage or debridement and no intestinal fistula occurred after endoscopic management. Compared to patients without fistula, the median age was younger in the fistula group (36 vs 45 years, P=0.014), and the occurrence of SIRS (95.2% vs 59.6%, P=0.001), extra-pancreatic invasion (100.0% vs 67.3%, P=0.002), and secondary infection (71.4% vs 36.5%, P=0.002) were higher. Patients with fistula had a longer median length of hospitalization (71 vs 40 days, P=0.016) and intensive care (8 vs 0 days, P=0.002). All patients in the fistula group had peri-pancreatic, abdominal and retroperitoneal involvement seen on imaging or intraoperatively. The intestinal fistulae mainly occurred in the colon ( n=13, 61.9%) and the duodenum ( n=6, 28.6%). The confirmed diagnosis of fistulae was based on transfistula imaging ( n=11) or digestive tract imaging ( n=5). Among 13 cases with colonic fistulae, nonsurgical treatment was preferred in 9 cases, and surgeries of fistula repairmen or proximal ostomy were preferred in 4 cases. Among 8 cases with non-colonic fistulae, nonsurgical treatment was preferred in 7 cases, and only 1 case repaired the fistula immediately during the intraoperative detection. Conclusions:Intestinal fistula is an important complication of severe AP, and it is closely associated with invasive interventions. Improved invasive intervention strategies may help prevent intestinal fistula formation; timely and effective management of intestinal fistula may help avoid complications and shorten hospitalization.

Clinical and radiological characteristics analysis of 172 cases with resected pancreatic serous cystic neoplasm / 中华胰腺病杂志

Objective:To analyze the clinical and radiological features of patients with resected pancreatic serous cystic neoplasm (SCN).Methods:A retrospective analysis was conducted on the clinical and radiological data of 172 patients with pancreatic SCN who underwent surgical resection and were pathological confirmed at Peking Union Medical College Hospital from September 2014 to April 2022. These patients were categorized into two cohorts including 2014—2018 cohort ( n=84) and 2019—2022 ( n=88) for comparative analysis based on the operation time. Results:The radiological diagnostic accuracy for SCN was found to be notably low at 11.6%(20/172), which was mostly misdiagnosed as mucinous cystic neoplasms (86/172, 50.0%) and intraductal papillary mucinous neoplasms (35/172, 20.3%). No statistically significant variance was observed on the misdiagnosis rate between the two cohorts. There was a substantial increase of the number of lesions located in pancreatic body and tail (76.1% vs 53.6%, P=0.004) and a marked decrease in the number of those located in pancreatic head and neck (22.7% vs 39.3%, P=0.019) in 2019-2022 cohort, compared to the 2014-2018 cohort. Furthermore, there was a significant reduction in the occurrence of SCN calcification and peri-lesional venous alterations (22.8% vs 45.1%, P=0.006; 25.0% vs 46.4%, P=0.003), a decrease in the presence of fibrous scarring within SCN (31.8% vs 45.2%, P=0.070), and an increase in cases with dilatation of the upstream main pancreatic duct (28.2% vs 16.3%, P=0.065). The clinical characteristics and the rate of postoperative complications did not significantly differ between the two cohorts. Complication rates after pancreatoduodenectomy were significantly higher than those following distal pancreatectomy (46.4% vs 22.9%, P=0.010). The presence of clinical symptoms was significantly linked to the size of SCN and the expansion of the main pancreatic duct (45.4% vs 29.3%, P=0.032; 64.9% vs 31.2%, P<0.001). Conclusions:The accuracy of preoperative radiological diagnosis for SCN is still low, with a noted increase in the proportion of SCN exhibiting atypical radiological features in recent years. The frequency of postoperative complications is relatively high and does not have an obvious decreased trend.

Clinical analysis of 25 patients with type 2 autoimmune pancreatitis / 中华胰腺病杂志

Objective:To explore the clinical characteristics and outcomes of type 2 autoimmune pancreatitis (AIP) and compare with type 1 AIP.Methods:Clinical data of the patients diagnosed with type 2 AIP by the International Consensus on diagnostic criteria of AIP at Peking Union Medical College Hospital from January 2001 to December 2022 were retrospectively analyzed, and type 1 AIP patients diagnosed in Peking Union Medical College Hospital from January 1985 to December 2016 were collected as controls. The clinical symptoms, treatments and follow-ups were analyzed.Results:A total of 25 patients with type 2 AIP were included, of which 16 cases (64.0%) were pathologically confirmed cases (13 cases by endoscopic ultrasound puncture, 2 cases by surgery, and 1 case by interventional puncture), and 9 cases (36.0%) were suspected. The average age of onset was 40 years old. Most patients ( n=23, 92.0%) had abdominal pain along with emaciation to a various degree. Among them, 3 cases primarily presented as acute pancreatitis. Two cases were diagnosed after surgery for pancreatic masses. Eighteen cases were complicated with inflammatory bowel disease, including 16 cases with ulcerative colitis, one case with Crohn's disease, and one case with indeterminate colitis. All patients had typical imaging manifestations, including 13 cases (52.0%) with diffuse pancreatic enlargement, 12 cases (48.0%) with focal or multifocal pancreatic lesions, and 5 cases (20.0%) with simultaneous focal pancreatic masses and diffuse enlargement. All patients had normal serum IgG4 levels, anti-neutropil cytoplasmic antibodies (ANCA) positivity rate was 35.3% (6/17), and anti-nuclear antibody (ANA) positivity rate was 29.2% (7/24). Two surgical patients recovered well after surgery, and the other patients all achieved clinical and imaging relief after hormone therapy, and no recurrence was seen during follow-up. Compared with type 1 AIP, type 2 AIP had younger onset age, main manifestation as abdominal pain without jaundice, rare involvement with extra-pancreatic organs, the lesions mainly located in the intestine and normal IgG4 level with statistically significant differences. The recurrence rate of type 2 AIP was lower than that of type 1 AIP (0 vs 16%). Conclusions:Type 2 AIP has different clinical characteristics from type 1 AIP. Due to the lack of specific serum markers, the diagnosis is more difficult. It responds well to glucocorticoids and has a low recurrence rate.

Clinical characteristics analysis of primary pancreatic lymphoma / 中华胰腺病杂志

Objective:To analyze clinical characteristics of primary pancreatic lymphoma (PPL) patients.Methods:Clinical features of 22 patients diagnosed as PPL admitted to Peking Union Medical College Hospital from January 2002 to May 2023 were analyzed retrospectively.Results:The median age was 56.4±13.3 years. The median time from onset to diagnosis was 1.0 (1.0, 3.0) months. The main clinical manifestations were abdominal pain (15/22), weight loss (14/22) and jaundice (10/22). Elevated lactate dehydrogenase (LDH) was observed in 15/20 (75%) patients. Only 2 (2/9, 22.2%) patients had increased CA199 levels and 2 (2/9, 22.2%) patients had increased CEA levels. The maximum tumor diameter was 5.0 (3.8, 6.9) cm. Contrast-enhanced CT mostly showed low enhancement lesions. Major pancreatic duct dilatation were rare on CT scan (4/20). Fifteen patients were confirmed by pancreatic pathology, of which 8 were obtained by surgery, 4 were obtained by CT or ultrasound-guided percutaneous biopsy, and 3 were obtained by EUS-FNA. The main pathological type was diffuse large B-cell lymphoma (14/22). 19 patients received chemotherapy, and 6 patients died with a median follow-up of 5.0 (1.5, 35.5) months.Conclusions:PPL is rare and easy to be misdiagnosed. Elevated LDH levels, normal tumor markers, and non-dilatation of main pancreatic duct are important diagnostic clues. It is important to obtain pathology by EUS-FNA and other methods for definite diagnosis.

Aflatoxin B1-induced early developmental hepatotoxicity in larvae zebrafish.

Aflatoxin B1 (AFB1) is a ubiquitous mycotoxin that causes oxidative damage in various organs. At present, the research studies on AFB1 are primarily focused on its effects on the terrestrial environment and animals. However, its toxicity mechanism in aquatic environments and aquatic animals has not been largely explored. Thus, in this study, zebrafish was used as a model to study the toxicity mechanism of AFB1 on the liver of developing larvae. The results showed that AFB1 exposure inhibited liver development and promoted fat accumulation in the liver. Transcriptome sequencing analysis showed that AFB1 affected liver redox metabolism and oxidoreductase activity. KEGG analysis showed that AFB1 inhibited the expression of gsto1, gpx4a, mgst3a, and idh1 in the glutathione metabolizing enzyme gene pathway, resulting in hepatic oxidative stress. At the same time, AFB1 also inhibited the expression of acox1, acsl1b, pparα, fabp2, and cpt1 genes in peroxidase and PPAR metabolic pathways, inducing hepatic steatosis and lipid droplet accumulation. Antioxidant N-Acetyl-l-cysteine (NAC) preconditioning up-regulated gsto1, gpx4a and idh1 genes, and improved the AFB1-induced lipid droplet accumulation in the liver. In summary, AFB1 induced hepatic oxidative stress and steatosis, resulting in abnormal liver fat metabolism and accumulation of cellular lipid droplets. NAC could be used as a potential preventative drug to improve AFB1-induced fat accumulation.

A review of different types of volunteer programs for older adults with and without cognitive impairment.

Theoretical models and empirical evidence suggest an association between volunteering and health outcomes in older adults. However, less is known about existing programs that involve older adults engaging in formal volunteering, especially programs for older volunteers with cognitive impairment. In this review, we summarized and evaluated different types of volunteering-based programs involving older volunteers with and without cognitive impairment. After a non-systematic literature search, we presented eight example volunteer programs. Older volunteers participate in the programs in person or remotely. In five of the programs, older volunteers without cognitive impairment participate in intergenerational engagement, support and referral, home visiting, and dementia care services. The other three programs specifically recruit older volunteers with cognitive impairment and provide intergenerational engagement and individualized volunteer activities. Both strengths and challenges identified in the programs were discussed. Different types of volunteering-based programs are available for engaging older volunteers. For volunteers to remain active during the pandemic or for volunteers who live with cognitive impairment, remote programs can be a valuable alternative. Program effects on older volunteers need to be tested in more rigorously designed studies.

Development of the "hidden" multi-target-directed ligands by AChE/BuChE for the treatment of Alzheimer's disease.

Accumulation of evidences suggested that excessive amounts of AChE and BuChE in the brain of AD patients at the different stage of AD, which could hydrolyze ACh and accelerated Aß aggregation. To develop new "hidden" multifunctional agents through AChE/BuChE would be a promising strategy to treat AD. To this end, firstly, a series of chalcone derivatives with chelating property was designed and synthesized. The in vitro results showed that compound 3f indicated significant selective MAO-B inhibitory activity (IC50 = 0.67 µM) and remarkable anti-inflammatory property. It also significantly inhibited self-induced Aß1-42 aggregation and showed remarkable neuroprotective effects on Aß25-35-induced PC12 cell injury. Furthermore, compound 3f was a selective metal chelator and could inhibit Cu2+-induced Aß1-42 aggregation. Based on this, the carbamate fragment was introduced to compound 3f to obtain carbamate derivatives. The biological activity results exhibited that compound 4b showed good BBB permeability, good AChE inhibitory potency (IC50 = 5.3 µM), moderate BuChE inhibitory potency (IC50 = 12.4 µM), significant MAO-B inhibitory potency, anti-inflammation potency on LPS-induced BV-2 cells and neuroprotective effects on Aß25-35-induced PC12 cell injury. Compared with 3f, compound 4b did not show obvious chelation property. Significantly, compound 4b could be activated by AChE/BuChE following inhibition of AChE/BuChE to liberate an active multifunctional chelator 3f, which was consistent with our original intention. More importantly, compounds 3f and 4b presented favorable ADME properties and good stability in artificial gastrointestinal fluid, blood plasma and rat liver microsomes. The in vivo results suggested that compound 4b (0.0195 µg/mL) could significantly improve dyskinesia and reaction capacity of the AlCl3-induced zebrafish AD model by increasing the level of ACh. Together our data suggest that compound 4b was a promising "hidden" multifunctional agent by AChE/BuChE, and this strategy deserved further development for the treatment of AD.

The effectiveness of endoscopic ultrasonography findings to distinguish benign and malignant intraductal papillary mucinous neoplasm.

BACKGROUND AND AIMS: Accurate evaluation of intraductal papillary mucinous neoplasm (IPMN) is necessary to inform clinical decision-making. But it is still difficult to distinguish benign and malignant IPMN preoperatively. This study aims to evaluate the utility of EUS to predict the pathology of IPMN. METHODS: Patients with IPMN who underwent endoscopic ultrasound within 3 months before surgery were collected from six centers. Logistic regression model and random forest model were used to determine risk factors associated with malignant IPMN. In both models, 70% and 30% of patients were randomly assigned to the exploratory group and validation group, respectively. Sensitivity, specificity, and ROC were used in model assessment. RESULTS: Of the 115 patients, 56 (48.7%) had low-grade dysplasia (LGD), 25 (21.7%) had high-grade dysplasia (HGD), and 34 (29.6%) had invasive cancer (IC). Smoking history (OR = 6.95, 95%CI: 1.98-24.44, p = 0.002), lymphadenopathy (OR = 7.91, 95%CI: 1.60-39.07, p = 0.011), MPD > 7 mm (OR = 4.75, 95%CI: 1.56-14.47, p = 0.006) and mural nodules > 5 mm (OR = 8.79, 95%CI: 2.40-32.24, p = 0.001) were independent risk factors predicting malignant IPMN according to the logistic regression model. The sensitivity, specificity, and AUC were 0.895, 0.571, and 0.795 in the validation group. In the random forest model, the sensitivity, specificity, and AUC were 0.722, 0.823, and 0.773, respectively. In patients with mural nodules, random forest model could reach a sensitivity of 0.905 and a specificity of 0.900. CONCLUSIONS: Using random forest model based on EUS data is effective to differentiate benign and malignant IPMN in this cohort, especially in patients with mural nodules.