Objective To explore the application of plasma 7 microRNA (miR7) testing in the differential diagnosis of very early-stage hepatocellular carcinoma (HCC). Methods This study is a multicenter real-world study. Patients with single hepatic lesion (maximum diameter≤2 cm) who underwent plasma miR7 testing at Zhongshan Hospital, Fudan University, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Anhui Provincial Hospital, and Peking University People’s Hospital between January 2019 and December 2024 were retrospectively enrolled. Patients were divided into very early-stage HCC group and non-HCC group, and the clinical pathological characteristics of the two groups were compared. The value of plasma miR7 levels, alpha-fetoprotein (AFP), and des-gamma-carboxy prothrombin (DCP) in the differential diagnosis of very early-stage HCC was evaluated using receiver operating characteristic (ROC) curves and area under the curve (AUC). In patients with both negative AFP and DCP (AFP＜20 ng/mL, DCP＜40 mAU/mL), the diagnostic value of plasma miR7 for very early-stage HCC was analyzed. Results A total of 64 528 patients from 4 hospitals underwent miR7 testing, and 1 682 were finally included, of which 1 073 were diagnosed with very early-stage HCC and 609 were diagnosed with non-HCC. The positive rate of miR7 in HCC patients was significantly higher than that in non-HCC patients (67.9% vs 24.3%, P＜0.001). ROC curves showed that the AUCs for miR7, AFP, and DCP in distinguishing HCC patients from the non-HCC individuals were 0.718, 0.682, and 0.642, respectively. The sensitivities were 67.85%, 43.71%, and 44.45%, and the specificities were 75.70%, 92.78%, and 83.91%, respectively. The pairwise comparison of AUCs showed that the diagnostic efficacy of plasma miR7 detection was significantly better than that of AFP or DCP (P＜0.05). Although its specificity was slightly lower than AFP and DCP, the sensitivity was significantly higher. Among patients negative for both AFP and DCP, miR7 maintained an AUC of 0.728 for diagnosing very early-stage HCC, with 67.82% sensitivity and 77.73% specificity. Conclusions Plasma miR7 testing is a potential molecular marker with high sensitivity and specificity for the differential diagnosis of small hepatic nodules. In patients with very early-stage HCC lacking effective molecular markers (negative for both AFP and DCP), miR7 can serve as a novel and effective molecular marker to assist diagnosis.

Tripterygium wilfordii is widely used in the treatment of immune system disease and has a remarkable curative effect. Triptolide and Tripterygium glycosides are the most commonly used active ingredients in clinical practice， but their treatment window is narrow and there are many side effects. The damage involves the reproductive system， blood system， cardiovascular system， digestive system， etc. Based on clinical observations and literature summaries， the symptoms of adverse reactions mostly occur in the digestive system （liver and gastrointestinal tract）. Relevant scholars have launched a lot of studies of the manifestations of liver injury induced by T. wilfordii and the mechanism of liver injury. The mechanism is mainly related to liver cell apoptosis， induction of oxidative stress， immune injury， excessive autophagy of liver cells， abnormal fatty acid metabolism， and abnormal enzyme metabolism in liver tissues. This article reviewed and summarized relevant literature on gastrointestinal injury caused by T. wilfordii， but there are few studies on the manifestations and mechanisms of adverse reactions， which still need further research by scholars. In addition， this article also summarized the research on how to reduce toxicity and enhance efficacy of prescriptions prepared from T. wilfordii in the digestive system， mainly involving compatibility with western medicines （Methotrexate， Leflunomide， Iguratimod， etc.）， use along or combination with Chinese medicines （single Chinese medicine， Chinese medicine monomers， and Chinese medicine compounds）， acupuncture and moxibustion （electroacupuncture and moxibustion）， dosage form improvement （glycol plastid gel， self-dissolving microneedle， solid lipid nanoparticles， gastric floating sustained-release capsules， etc.）， processing （steaming， stir-frying， radish seed processing， money grass processing， licorice processing， etc.）， and other methods to reduce toxicity. To sum up， this article analyzed the manifestations， mechanisms， and methods of reducing toxicity and enhancing efficacy of T. wilfordii-induced liver injury and gastrointestinal injury by sorting out relevant literature， in order to provide a reference for the clinical application of T. wilfordii and some research ideas for the future in-depth study of T. wilfordii-induced digestive system injury.

Objective:To investigate the application value of fecal Syndecan-2 (SDC2) gene methylated SDC2 (m SDC2) detection in colorectal cancer (CRC) screening among urban residents in Guangzhou City. Methods:A cross-sectional study was conducted in Shitan Town, Zengcheng District, Guangzhou City from July to December 2022. A community-based screening program for CRC was conducted among residents aged 40-74 years old. m SDC2 detection was employed in the participants, and those with positive results should be recommended to receive colonoscopy examination. The positive rate of m SDC2 detection, colonoscopy compliance rate, detection rate of intestinal lesions and clinicopathological characteristics were observed. The relationship between cycle threshold (CT) value of m SDC2 and intestinal lesions was explored. Further, the cost-effectiveness of screening was evaluated. Results:A total of 8 189 fecal samples were collected from 8 877 participants with the recovery rate of 92.25%. 8 048 qualified samples were enrolled in this study, consisted of 3 182 males (39.54%) and 4 866 females (60.46%), with the average age of 56 years old (40-74 years). The positive rate of m SDC2 detection was 7.99% (643/8 048), and the compliance rate of colonoscopy was 73.10% (470/643). 20 cases (4.25%) of colorectal cancer, 109 cases (23.19%) of advanced adenoma, 145 cases (30.85%) of non-advanced adenoma, 79 cases (16.81%) of polyps were detected. The detection rate of intestinal lesions was 75.11% and indicated significant differences in gender and age. 20 CRCs included 15 of stage 0-I, 4 of stage Ⅱ-Ⅲ and 1 of unknown stage. The CT value of m SDC2 was negatively correlated with the proportion of advanced colorectal neoplasms ( χ2=16.063, P<0.001). The total cost of the screening was 4.339 5 million yuan, the screening benefit was 28.506 2 million yuan, and the benefit-cost ratio was 6.57. Conclusion:The CRC screening strategy of fecal m SDC2 detection combined with colonoscopy has high colonoscopy compliance and detection rate of intestinal lesions, which is conducive to the detection of early CRCs, and has good cost-effectiveness. This study suggests that this method may be applied to the general CRC screening in China and contribute to the prevention of CRC. The CT value of m SDC2 may have a certain suggestion on the malignant degree of intestinal tumors.

Objective:To investigate the application value of fecal Syndecan-2 (SDC2) gene methylated SDC2 (m SDC2) detection in colorectal cancer (CRC) screening among urban residents in Guangzhou City. Methods:A cross-sectional study was conducted in Shitan Town, Zengcheng District, Guangzhou City from July to December 2022. A community-based screening program for CRC was conducted among residents aged 40-74 years old. m SDC2 detection was employed in the participants, and those with positive results should be recommended to receive colonoscopy examination. The positive rate of m SDC2 detection, colonoscopy compliance rate, detection rate of intestinal lesions and clinicopathological characteristics were observed. The relationship between cycle threshold (CT) value of m SDC2 and intestinal lesions was explored. Further, the cost-effectiveness of screening was evaluated. Results:A total of 8 189 fecal samples were collected from 8 877 participants with the recovery rate of 92.25%. 8 048 qualified samples were enrolled in this study, consisted of 3 182 males (39.54%) and 4 866 females (60.46%), with the average age of 56 years old (40-74 years). The positive rate of m SDC2 detection was 7.99% (643/8 048), and the compliance rate of colonoscopy was 73.10% (470/643). 20 cases (4.25%) of colorectal cancer, 109 cases (23.19%) of advanced adenoma, 145 cases (30.85%) of non-advanced adenoma, 79 cases (16.81%) of polyps were detected. The detection rate of intestinal lesions was 75.11% and indicated significant differences in gender and age. 20 CRCs included 15 of stage 0-I, 4 of stage Ⅱ-Ⅲ and 1 of unknown stage. The CT value of m SDC2 was negatively correlated with the proportion of advanced colorectal neoplasms ( χ2=16.063, P<0.001). The total cost of the screening was 4.339 5 million yuan, the screening benefit was 28.506 2 million yuan, and the benefit-cost ratio was 6.57. Conclusion:The CRC screening strategy of fecal m SDC2 detection combined with colonoscopy has high colonoscopy compliance and detection rate of intestinal lesions, which is conducive to the detection of early CRCs, and has good cost-effectiveness. This study suggests that this method may be applied to the general CRC screening in China and contribute to the prevention of CRC. The CT value of m SDC2 may have a certain suggestion on the malignant degree of intestinal tumors.

Transglutaminase 2 (TGM2) is a ubiquitous multifunctional protein, which is related to the adhesion of different cells and tumor formation. Previous studies found that TGM2 is involved in the interaction between host cells and viruses, but the effect of TGM2 on the proliferation of influenza virus in cells has not been reported. To explore the effect of TGM2 during H1N1 subtype influenza virus infection, a stable MDCK cell line with TGM2 overexpression and a knockout cell line were constructed. The mRNA and protein expression levels of NP and NS1 as well as the virus titer were measured at 48 hours after pot-infection with H1N1 subtype influenza virus. The results showed that overexpression of TGM2 effectively inhibited the expression of NP and NS1 genes of H1N1 subtype influenza virus, while knockout of TGM2 up-regulated the expression of the NP and NS1 genes, and the expression of the NP at protein level was consistent with that at mRNA level. Virus proliferation curve showed that the titer of H1N1 subtype influenza virus decreased significantly upon TGM2 overexpression. On the contrary, the virus titer in TGM2 knockout cells reached the peak at 48 h, which further proved that TGM2 was involved in the inhibition of H1N1 subtype influenza virus proliferation in MDCK cells. By analyzing the expression of genes downstream of influenza virus response signaling pathway, we found that TGM2 may inhibit the proliferation of H1N1 subtype influenza virus by promoting the activation of JAK-STAT molecular pathway and inhibiting RIG-1 signaling pathway. The above findings are of great significance for revealing the mechanism underlying the interactions between host cells and virus and establishing a genetically engineering cell line for high-yield influenza vaccine production of influenza virus.
Animals ; Cell Proliferation ; Dogs ; Humans ; Influenza A Virus, H1N1 Subtype/genetics* ; Influenza, Human ; Madin Darby Canine Kidney Cells ; Protein Glutamine gamma Glutamyltransferase 2

To explore the mechanism of ovarian toxicity of Hook. F. (TwHF) by network pharmacology and molecular docking. The candidate toxic compounds and targets of TwHF were collected by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and the Comparative Toxicogenomics Database (CTD). Then, the potential ovarian toxic targets were obtained from CTD, and the target genes of ovarian toxicity of TwHF were analyzed using the STRING database. The protein-protein interaction (PPI) network was established by Cytoscape and analyzed by the cytoHubba plug-in to identify hub genes. Additionally, the target genes of ovarian toxicity of TwHF were subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses by using the R software. Finally, Discovery Studio software was used for molecular docking verification of the core toxic compounds and the hub genes. Nine candidate toxic compounds of TwHF and 56 potential ovarian toxic targets were identified in this study. Further network analysis showed that the core ovarian toxic compounds of TwHF were triptolide, kaempferol and tripterine, and the hub ovarian toxic genes included , , , , , , , , and . Besides, the GO and KEGG analysis indicated that TwHF caused ovarian toxicity through oxidative stress, reproductive system development and function, regulation of cell cycle, response to endogenous hormones and exogenous stimuli, apoptosis regulation and aging. The docking studies suggested that 3 core ovarian toxic compounds of TwHF were able to fit in the binding pocket of the 10 hub genes. TwHF may cause ovarian toxicity by acting on 10 hub genes and 140 signaling pathways.
Drugs, Chinese Herbal/toxicity* ; Medicine, Chinese Traditional ; Molecular Docking Simulation ; Network Pharmacology ; Protein Interaction Maps

In recent years, the clinical experts consensuses or guidelines of ankylosing spondylitis (AS)/spondyloarthritis (SpA) have been constantly updated, but to better understand and practice, patient self-participation management is one of the key points to improve the level of diagnosis and treatment. Through questionnaire survey of these patients, we screened out the most concerned issues, and established the AS/SpA patient practice guideline working group with multidisciplinary physicians and patients. Fifteen opinions, as the AS/SpA patient practice guidelines, are proposed in accordance with the relevant principles of the "WHO guidelines development manual" , and with the international normative process.

Objective:To analyze the antibody level of phospholipase A2 receptor (PLA2R) in Chinese patients with primary membrane nephropathy (PMN) and its correlation with clinical indicators, and to explore more suitable cut-off value for Chinese patients.Methods:All hospitalized patients with renal biopsy at Peking University People's Hospital from January to August 2018 were retrospectively reviewed. According to the primary disease, patients were divided into PMN group (including patients with idiopathic membranous nephropathy and atypical membranous nephropathy of unknown cause) and control group (other pathological types, including secondary membranous nephropathy patients). Their clinical and pathological characteristics were analyzed, and the level of serum PLA2R antibodies was detected using the method of enzyme-linked immunosorbent assay (ELISA). Spearman correlation was used to analyze the correlation between PMN patients' blood anti-PLA2R antibody level and clinical indicators. The risk factors of PMN were analyzed by logistic regression model, and the optimal cut-off value of PMN was analyzed by ROC curve.Results:A total of 354 patients were included in this study, including 114 patients in PMN group and 240 patients in control group. The age of PMN group was (51.7±14.1) years old and the ratio of male to female was 2.2∶1. The median concentration of PLA2R antibody in PMN group was 16.87 RU/ml [inter-quartile range ( IQR) 1.88-57.26], which was significantly higher than that in control group (1.43 RU/ml, IQR 1.20-1.62, P<0.001). In PMN group, the concentration of anti-PLA2R antibody was correlated with the 24-hour urine protein ration ( r=0.278, P=0.003) and urine erythrocyte ( r=0.190, P=0.043), but not with serum albumin ( r=-0.149, P=0.114) and serum creatinine ( r=0.136, P=0.149). The ROC curve showed that the sensitivity of distinguishing PMN from other diseases was 69.3% (95% CI 60.3%-77.0%), the specificity was 92.9%(95% CI 89.0%-95.5%), and the area under the curve was 0.859(95% CI 0.813-0.905) when the cut-off value was set as 2.28 RU/ml, which was significantly better than the cut-off value of 20.00 RU/ml (the sensitivity/specificity was 46.5%/97.5%) and 14.00 RU/ml (the sensitivity/specificity was 53.5%/97.1%). Conclusions:PLA2R antibody is one of the main pathogenic antibodies of PMN. In China, it is recommended to lower its cut-off value to 2.28 RU/ml, which can improve the sensitivity of distinguishing PMN from other pathological types without reducing specificity.

Objective To investigate the expression and clinical significance of pro-inflammation S100A9 protein in intestinal type gastric cancer.Methods We retrospectively analyzed the clinicopathological materials of the 278 patients who were diagnosed as Lauren classification intestinal gastric cancer and underwent surgical treatment between January and December 2008 at the Department of General Surgery,Zhongshan Hospital Fudan University.Immunohistochemistry was used to analyze the expression of S100A9 protein in tumor tissues and para-tumor tissues.Results High expression of S100A9 protein was associated with the depth of tumor invasion (P =0.013),lymph node metastasis (81.4％,53.9％,47.3％ vs.84.7％,69.3％,60.7％,x2 =4.220,P =0.041) and TNM stage (P =0.010).The overall survival rate of these patients with high expression of S100A9 protein was significantly lower than those with low expression of S100A9 protein.In stage Ⅲ/Ⅳ patients,the overall survival rate of these patients with high expression of S100A9 protein was significantly lower than those with low expression of S100A9 protein.Moreover,for those patients who received postoperative chemotherapy,the prognosis of the patients with high expression of S100A9 protein was poorer than those with low expression.By multivariable analysis,the expression of S100A9 protein was not an independent risk factor for the prognosis of intestinal gastric cancer patients.Conclusions High expression of S100A9 protein in intestinal gastric cancer was associated with poor prognosis.

Objective: To investigate the feasibility and safety of the medial approach "four-step method" in the laparoscopic mobilization of splenic flexure. Methods: A retrospective cohort study was performed. Clinical data of 157 colorectal cancer patients undergoing the medial approach "four-step method" in the laparoscopic mobilization of splenic flexure at Gastrointestinal Surgical Department of Guangdong Provincial People′s Hospital from July 2015 to June 2018 were retrospectively analyzed. Of 157 cases, 17 were transverse colon cancer, 94 were descending colon cancer, 25 were sigmoid cancer and 21 were rectal cancer; 89 were male and 68 were female; mean age was (61.8±10.3) years and mean body mass index was (23.2±3.7) kg/m². The medial approach "four-step method" in the laparoscopic mobilization of splenic flexure was performed as follows: (1) The root vessels were treated with the "provocation" technique to expand the Toldt′s gap. This expansion was extended from the lateral side to the peritoneum reflex of left colonic sulcus, from the caudal side to the posterior rectal space, and from the cephalad side to the lower edge of pancreas. (2) The left colonic sulcus was mobilized, converging with the posterior Toldt′s gap. Mobilization was carried out from cephalad side to descending colon flexure, freeing and cutting phrenicocolic ligament and splenocolic ligament, and from caudal side to peritoneal reflex. (3) Gastrocolic ligament was moblized. Whether to enter the great curvature of stomach omentum arch when the gastrocolic ligament was cut, that was, whether to clean the fourth group of lymph nodes, should be according to the tumor site and whether serosal layer was invaded. (4) Transverse mesocolon was moblized and transected at the lower edge of the pancreatic surface, merging with the posterior Toldt′s gap, and from lateral side to lower edge of the pancreatic body, merging with the lateral left paracolonic sulcus. Safety and short-term clinical efficacy of this surgical procedure was summarized. Results: All the patients completed this procedure. During operation, 3 cases were complicated with organ injury, including 1 case of colon injury, 1 case of spleen injury and 1 case of pancreas injury. No operative death and conversion to open surgery was found. The average operation time was (147.5±35.1) minutes, the average intra-operative blood loss was (40.8±32.7) ml and the average number of harvested lymph node was (16.1±5.8), including (4.0±2.3) of positive lymph nodes. The first exhaust time after surgery was (41.3±20.6) hours, the fluid intake time was (1.5±1.3) days, the postoperative hospital stay was (5.2±2.3) days. Eight (5.1%) cases developed postoperative complications, and all were improved and discharged after conservative treatments. According to the TNM classification system, postoperative pathology revealed that 31 patients were stage I, 51 were stage II, 53 were stage III, 22 were stage IV. Conclusion The medial approach "four-step method" is safe and feasible, which can effectively decrease the operation difficulty of the laparoscopic mobilization of the splenic flexure.