In recent years, there have been frequent adverse reactions/events associated with traditional Chinese medicine(TCM), especially liver injury related to traditional non-toxic TCM, which requires adequate attention. Liver injury related to traditional non-toxic TCM is characterized by its sporadic and insidious nature and is influenced by various factors, making its detection and identification challenging. There is an urgent need to develop a strategy and method for early detection and recognition of traditional non-toxic TCM-related liver injury. This study was based on national adverse drug reaction monitoring center big data, integrating methodologies such as reporting odds ratio(ROR), network toxicology, and computational chemistry, so as to systematically research the risk signal identification and evaluation methods for TCM-related liver injury. The optimized ROR method was used to discover potential TCM with a risk of liver injury, and network toxicology and computational chemistry were used to identify potentially high-risk TCM. Additionally, typical clinical cases were analyzed for confirmation. An integrated strategy of "discovery via big data, identification via dry/wet method, confirmation via typical cases, and precise risk prevention and control" was developed to identify the risk of TCM-related liver injury. Corydalis Rhizoma was identified as a TCM with high risk, and its toxicity-related substances and potential toxicity mechanisms were analyzed. The results revealed that liver injury is associated with components such as tetrahydropalmatine and tetrahydroberberine, with potential mechanisms related to immune-inflammatory pathways such as the tumor necrosis factor signaling pathway, interleukin-17 signaling pathway, and Th17 cell differentiation. This paper innovatively integrated real-world evidence and computational toxicology methods, offering insights and technical support for establishing a risk discovery and identification strategy for TCM-related liver injury based on real-world big data, providing innovative ideas and strategies for guiding the safe and rational use of medication in clinical practices.
Corydalis/adverse effects* ; Drugs, Chinese Herbal/adverse effects* ; Humans ; Chemical and Drug Induced Liver Injury/etiology* ; Medicine, Chinese Traditional/adverse effects* ; Rhizome/adverse effects* ; Male ; Female

Objective:To investigate the diagnostic value of serum ferritin in intestinal failure-associated liver disease. Methods:Clinical data of adult patients with short bowel syndrome admitted to the Department of General Surgery of Jinling Hospital affiliated to Nanjing University from January 2019 to December 2022 were retrospectively analyzed to determine the correlation between serum ferritin and liver enzyme profiles by linear regression,to screen the potential risk factors of liver injury by multifactorial Logistic regression analysis,and to establish a prediction model for liver fibrosis. The area under the curve was also calculated to assess the accuracy of the model. Results:A total of 106 patients with short bowel syndrome were included,of whom 55 (51.9％) had elevated serum ferritin (SF). Linear regression analysis showed a positive correlation between serum ferritin and ALT (r=0.427,P<0.001),ALP (r=0.365,P<0.001),and γ-GT (r=0.423,P<0.001),and one-way Logistic regression analysis showed that the higher the level of serum ferritin,the more pronounced the difference was (SF>ULN) The one-way logistic regression analysis showed that the higher the serum ferritin level,the more significant the difference was[SF>ULN (upper limit of normal value of serum ferritin),P=0.033;SF>1.5×ULN,P=0.018;SF>2.5×ULN,P=0.006]. Multifactorial logistic regression analysis showed that PN dependence (OR=3.366,P=0.017) and serum ferritin>2.5 ULN (OR=3.292,P=0.014)were independent risk factors for intestinal failure-associated liver disease-liver fibrosis,and the receiver operating curve (ROC) of the subjects showed area under the curve of 74.8％,95％ CI:0.652～0.844. Conclusion:Serum ferritin can be used as a reliable clinical biomarker to help identify intestinal failure-associated liver disease.

Aim To investigate the effect of quercetin on the aging model of bone marrow mesenchymal stem cells established under microgravity. Methods Using 3D gyroscope, a aging model of bone marrow mesenchymal stem cells was constructed, and after receiving quercetin and microgravity treatment, the anti-aging effect of the quercetin was evaluated by detecting related proteins and oxidation indexes. Results Compared to the control group, the expressions of age-related proteins p21, pi6, p53 and RB in the microgravity group significantly increased, while the expressions of cyclin D1 and lamin B1 significantly decreased, with statistical significance (P<0.05). In the microgravity group, mitochondrial membrane potential significantly decreased (P<0.05), ROS accumulation significantly increased (P <0.05), SOD content significantly decreased and MDA content significantly increased (P<0.05). Compared to the microgravity group, the expressions of age-related proteins p21, pi6, p53 and RB in the quercetin group significantly decreased, while the expressions of cyclin D1 and lamin B1 significantly increased, with statistical significance (P<0.05). In the quercetin group, mitochondrial membrane potential significantly increased (P<0.05), ROS accumulation significantly decreased (P<0.05), SOD content significantly increased and MDA content significantly decreased (P<0.05). Conclusions Quercetin can resist oxidation, protect mitochondrial function and normal cell cycle, thus delaying the aging of bone marrow mesenchymal stem cells induced by microgravity.

Objective Tissue uptake and distribution of nano-/microplastics was studied at a single high dose by gavage in vivo.Methods Fluorescent microspheres (100 nm, 3 μm, and 10 μm) were given once at a dose of 200 mg/(kg·body weight). The fluorescence intensity (FI) in observed organs was measured using the IVIS Spectrum at 0.5, 1, 2, and 4 h after administration. Histopathology was performed to corroborate these findings.Results In the 100 nm group, the FI of the stomach and small intestine were highest at 0.5 h, and the FI of the large intestine, excrement, lung, kidney, liver, and skeletal muscles were highest at 4 h compared with the control group (P < 0.05). In the 3 μm group, the FI only increased in the lung at 2 h (P < 0.05). In the 10 μm group, the FI increased in the large intestine and excrement at 2 h, and in the kidney at 4 h (P < 0.05). The presence of nano-/microplastics in tissues was further verified by histopathology. The peak time of nanoplastic absorption in blood was confirmed.Conclusion Nanoplastics translocated rapidly to observed organs/tissues through blood circulation;however, only small amounts of MPs could penetrate the organs.

AIM To compare the components difference between Lonicera fragrantissima Lindl.et Paxt.(LFL)and Lonicerae japonicae Flos(LJF),and to evaluate the medicinal value of LFL,so as to provide reference for the development and utilization of LFL and LJF.METHODS With 70%methanol as extraction solvent,the components were analyzed by UPLC-TOF-MS,and the contents of 20 components were determined by HPLC-QQQ-MS.The components difference was determined by multivariate statistical analysis.RESULTS A total of 52 components were identified in the buds of LFL and LJF.There were 4 different components in LJF,and the contents of 20 quantitative components were significantly different.The contents of isochlorogenic acid C,ferulic acid,luteolin and rutin in the buds of LFL were more than 2 times that of LJF,and the contents of marchanic acid and marchanin were 11.96 times and 37.23 times that of LJF respectively.Maganin,isochlorogenic acid A,maganic acid,rutin and dicomachanic acid are the key differentiating components of LFL and LJF.CONCLUSION The buds of LFL and LJF have similar species,but the content difference is obvious.The buds of LFL have important medicinal value,which need further development and utilization.

Objective:To develop a risk prediction model for the recurrence of diabetic foot ulcer (DFU) in diabetic patients and primarily validate its predictive value.Methods:Meta-analysis combined with retrospective cohort study was conducted. The Chinese and English papers on risk factors related to DFU recurrence publicly published in China Biology Medicine disc, China National Knowledge Infrastructure, Wanfang Database, VIP Database, and PubMed, Embase, Cochrane Library, and Web of Science, and the search time was from the establishment date of each database until March 31 st, 2022. The papers were screened and evaluated, the data were extracted, a meta-analysis was performed using RevMan 5.4.1 statistical software to screen risk factors for DFU recurrence, and Egger's linear regression was used to assess the publication bias of the study results. Risk factors for DFU recurrence mentioned in ≥3 studies and with statistically significant differences in the meta-analysis were selected as the independent variables to develop a logistic regression model for risk prediction of DFU recurrence. The medical records of 101 patients with DFU who met the inclusion criteria and were admitted to Affiliated Hospital of Guizhou Medical University from January 2019 to June 2022 were collected. There were 69 males and 32 females, aged (63±14) years. The receiver operating characteristic (ROC) curve of the predictive performance of the above constructed predictive model for DFU recurrence was drawn, and the area under the ROC curve, maximum Youden index, and sensitivity and specificity at the point were calculated. Dataset including data of 8 risk factors for DFU recurrence and the DFU recurrence rates of 10 000 cases was simulated using RStudio software and a scatter plot was drawn to determine two probabilities for risk division of DFU recurrence. Using the β coefficients corresponding to 8 DFU recurrence risk factors ×10 and taking the integer as the score of coefficient weight of each risk factor, the total score was obtained by summing up, and the cutoff scores for risk level division were calculated based on the total score × two probabilities for risk division of DFU recurrence. Results:Finally, 20 papers were included, including 3 case-control studies and 17 cohort studies, with a total of 4 238 cases and DFU recurrence rate of 22.7% to 71.2%. Meta-analysis showed that glycosylated hemoglobin >7.5% and with plantar ulcer, diabetic peripheral neuropathy, diabetic peripheral vascular disease, smoking, osteomyelitis, history of amputation/toe amputation, and multidrug-resistant bacterial infection were risk factors for the recurrence of DFU (with odds ratios of 3.27, 3.66, 4.05, 3.94, 1.98, 7.17, 11.96, 3.61, 95% confidence intervals of 2.79-3.84, 2.06-6.50, 2.50-6.58, 2.65-5.84, 1.65-2.38, 2.29-22.47, 4.60-31.14, 3.13-4.17, respectively, P<0.05). There were no statistically significant differences in publication biases of diabetic peripheral neuropathy, diabetic peripheral vascular disease, glycosylated hemoglobin >7.5%, plantar ulcer, smoking, multidrug-resistant bacterial infection, or osteomyelitis ( P>0.05), but there was a statistically significant difference in the publication bias of amputation/toe amputation ( t=-30.39, P<0.05). The area under the ROC curve of the predictive model was 0.81 (with 95% confidence interval of 0.71-0.91) and the maximum Youden index was 0.59, at which the sensitivity was 72% and the specificity was 86%. Ultimately, 29.0% and 44.8% were identified respectively as the cutoff for dividing the probability of low risk and medium risk, and medium risk and high risk for DFU recurrence, while the corresponding total scores of low, medium, and high risks of DFU recurrence were <37, 37-57, and 58-118, respectively. Conclusions:Eight risk factors for DFU recurrence are screened through meta-analysis and the risk prediction model for DFU recurrence is developed, which has moderate predictive accuracy and can provide guidance for healthcare workers to take interventions for patient with DFU recurrence risk.

Objective: In this study, we aimed to investigate the prevalence of low anterior resection syndrome (LARS) in patients who had survived for more than 5 years after sphincter-preserving surgery for rectal cancer and to analyze its relationship with postoperative time. Methods: This was a single-center, retrospective, cross-sectional study. The study cohort comprised patients who had survived for at least 5 years (60 months) after undergoing sphincter- preserving radical resection of pathologically diagnosed rectal adenocarcinoma within 15 cm of the anal verge in the Department of Gastrointestinal Surgery, Peking University People's Hospital from January 2005 to May 2016. Patients who had undergone local resection, had permanent stomas, recurrent intestinal infection, local recurrence, history of previous anorectal surgery, or long- term preoperative defecation disorders were excluded. A LARS questionnaire was administered by telephone interview, points being allocated for incontinence for flatus (0-7 points), incontinence for liquid stools (0-3 points), frequency of bowel movements (0-5 points), clustering of stools (0-11 points), and urgency (0-16 points). The patients were allocated to three groups based on these scores: no LARS (0-20 points), minor LARS (21-29 points), and major LARS (30-42 points). The prevalence of LARS and major LARS in patients who had survived more than 5 years after surgery, correlation between postoperative time and LARS score, and whether postoperative time was a risk factor for major LARS and LARS symptoms were analyzed. Results: The median follow-up time of the 160 patients who completed the telephone interview was 97 (60-193) months; 81 (50.6%) of them had LARS, comprising 34 (21.3%) with minor LARS and 47 (29.4%) with major LARS. Spearman correlation analysis showed no significant correlation between LARS score and postoperative time (correlation coefficient α=-0.016, P=0.832). Multivariate analysis identified anastomotic height (RR=0.850, P=0.022) and radiotherapy (RR=5.760, P<0.001) as independent risk factors for major LARS; whereas the postoperative time was not a significant risk factor (RR=1.003, P=0.598). The postoperative time was also not associated with LARS score rank and frequency of bowel movements, clustering, or urgency (P>0.05). However, the rates of incontinence for flatus (3/31, P=0.003) and incontinence for liquid stools (8/31, P=0.005) were lower in patients who had survived more than 10 years after surgery. Conclusions: Patients with rectal cancer who have survived more than 5 years after sphincter-preserving surgery still have a high prevalence of LARS. We found no evidence of major LARS symptoms resolving over time.
Humans ; Rectal Neoplasms/pathology* ; Cross-Sectional Studies ; Low Anterior Resection Syndrome ; Postoperative Complications/etiology* ; Retrospective Studies ; Flatulence/complications* ; Anal Canal/pathology* ; Diarrhea ; Quality of Life

Objective: To study the influence of steroid withdrawal protection strategy on height growth in pediatric patients after kidney transplantation. Methods: The prospective cohort study enrolled 40 stage 5 chronic kidney disease children receiving kidney transplantation from July 2017 to September 2022 at Guangzhou Women and Children's Medical Center. Based on the primary preoperative disease, patients with immune abnormality-associated glomerular diseases or unknown causes were assigned to the steroid maintenance group, in which patients received steroid tapering within 3 months after surgery to a maintenance dose of 2.5 to 5.0 mg/d. While patients with hereditary kidney disease or congenital urinary malformations were assigned to the steroid withdrawal group, in which patients had steroids tapered off within 3 months. The characteristics of height catch-up growth and clinical data were compared between the 2 groups at baseline, 6, 12, 18 and 24 months after kidney transplantation. T-test, repeated measurement of variance analysis, Mann-Whitney U test, and Fisher exact test were used for the comparison between the 2 groups. Results: Among the 40 children, 17 were males, 23 were females, 25 were in the steroid withdraw group ((7.8±2.8) years old when receiving kidney transplantation) and 15 cases were in the steroid maintenance group ((7.6±3.5) years old when receiving kidney transplantation). The study population was followed up for (26±12) months. The total dose per unit body weight of steroids in the steroid withdrawal group was lower than that in the steroid maintenance group ((0.13±0.06) vs. (0.36±0.19) mg/(kg·d), t=5.83, P<0.001). The height catch-up rate (ΔHtSDS) in the first year after kidney transplantation in the steroid withdraw and steroid maintenance groups was 1.0 (0.7, 1.4) and 0.4 (0.1, 1.0), respectively; in the second year, the ΔHtSDS in the steroid withdraw group was significantly higher than that in the steroid maintenance group (1.1 (0.2, 1.7) vs. 0.3 (0, 0.8), U=28.00, P=0.039). The HtSDS in the steroid withdrawal group at the five follow-up time points was -2.5±0.8, -2.0±0.8, -1.5±0.8, -1.3±0.9 and -0.5±0.3, respectively, while in the steroid maintenance was -2.4±1.3, -2.2±1.1, -2.0±1.0, -1.8±1.0 and -1.6±1.0, respectively. There were statistically significant differences in HtSDS at different follow-up time points in both 2 groups (F=19.81, P<0.01), but no statistical differences in overall impact between the 2 groups (F=1.13, P=0.204). The steroid treatment was interaction with the increase of follow-up time (F=3.62, P=0.009). At the 24^th month after transplantation, the HtSDS in the steroid withdrawal group was significantly higher than that in the steroid maintenance group (P=0.047). Six patients in the steroid withdrawal group experienced antibody-mediated immune rejection (AMR), while 3 did in the steroid maintenance group. Moreover, there was no significant difference in AMR between the two groups (χ²=0.06, P=0.814). Conclusion: The steroid withdrawal protection strategy favors the height catch-up growth in pediatric patients after kidney transplantation and does not increase the risk of postoperative antibody-mediated immune rejection.
Male ; Humans ; Child ; Female ; Child, Preschool ; Kidney Transplantation ; Prospective Studies ; Steroids/therapeutic use* ; Antibodies ; Body Weight

Objective: To investigate the association between Helicobacter pylori (Hp) virulence factor genotypes and the degree and activity of gastric mucosa pathological changes in pediatric gastroduodenal diseases. Methods: This retrospective cohort study was conducted from May 2020 to October 2020. The frozen strains of Hp, which were cultured with the gastric mucosa of 68 children with gastroscopy confirmed gastroduodenal diseases who visited the children's hospital of Zhejiang University School of Medicine from April 2012 to December 2014, were resuscitated. After extracting DNA from these Hp strains, PCR amplification and agarose gel electrophoresis were performed to determine the detection rate of cytotoxin-associated protein A (cagA),vacuolating cytotoxin A (vacA)(s1a、s1b/s2,m1/m2), outer inflammatory protein A (oipA),blood group antigen binding adhesin (babA),duodenal ulcer promoting protein A (dupA) genes; oipA genes were sequenced to determine the gene status. The patients were divided into different groups according to the findings of gastroscopy and gastric mucosa pathology. The detection rates of various virulence factor genotypes among different groups were compared using χ² tests or Fisher's exact tests. Results: The 68 Hp strains all completed genetic testing. According to the diagnostic findings of gastroscopy, the 68 cases were divided into 47 cases of superficial gastritis and 21 cases of peptic ulcer. Regarding the pathological changes of gastric mucosa, 8 cases were mild, and 60 cases were moderate and severe according to the degree of inflammation; 61 cases were active and 7 cases inactive according to the activity of inflammation. The overall detection rates of cagA, vacA, vacA s1/m2, functional oipA, babA2, and dupA virulence factor genes were 100% (68/68), 100% (68/68), 94% (64/68), 99% (67/68), 82% (56/68), and 71% (48/68), respectively. In the superficial gastritis group, their detection rates were 100% (47/47), 100% (47/47), 96% (45/47), 98% (46/47), 81% (38/47), and 70% (33/47), respectively; in the peptic ulcer group, their detection rates were 100% (21/21), 100% (21/21), 90% (19/21), 100% (21/21), 86% (18/21), and 71% (15/21), respectively. There was no statistically significant difference between the two groups (all P>0.05). In the mild gastric mucosa inflammation group, the detection rates of the above six genotypes were 8/8, 8/8, 8/8, 7/8, 7/8, and 5/8, respectively; and in the moderate to severe inflammation groups, the detection rates were 100% (60/60), 100% (60/60), 93% (56/60), 100% (60/60), 82% (49/60), and 72% (43/60), respectively, with no statistically significant difference between the two groups (all P>0.05). In the active inflammation group, the detection rate of six genotypes were 100% (61/61), 100% (61/61), 93% (57/61), 98% (60/61), 82% (50/61), and 72% (44/61), respectively; and in the inactive inflammation group, they were 7/7, 7/7, 7/7, 7/7, 6/7, and 4/7, respectively. Again, there was no statistically significant difference between the two groups (all P>0.05). There was no statistically significant difference in the detection rate of combinations of 4 or 5 virulence factor genes among the different groups (all P>0.05). Conclusions: CagA, vacA, vacA s1/m2, functional oipA, babA2, and dupA genes are not associated with superficial gastritis and peptic ulcer in children, or with the degree and activity of gastric mucosa pathological inflammation. Different gene combinations of cagA, vacA, oipA, babA2, and dupA have no significant effects on predicting the clinical outcome of Hp infection in children.
Humans ; Child ; Helicobacter pylori/genetics* ; Retrospective Studies ; Genotype ; Inflammation ; Gastritis ; Cytotoxins

Humans ; Ulcer/pathology* ; Herpesvirus 4, Human ; Epstein-Barr Virus Infections ; Skin Diseases