Objective To investigate the clinical value of serum hsa_circRNA_0002980 and hsa_circRNA_104348 expression in the diagnosis and prognosis evaluation of liver cancer patients.Methods From April 2020 to April 2022,a total of 105 liver cancer patients and 105 liver cirrhosis patients admitted in the hospital were selected as the liver cancer group and cirrhosis group,and another 105 healthy volunteers who underwent physical examinations in the hospital were selected as the control group.Real-time fluorescence quantitative PCR(qPCR)was applied to detect the expression of serum hsa_circRNA_0002980 and hsa_circRNA_104348.Receiver operating characteristic(ROC)curve was applied to evaluate the diagnostic value and prognostic val-ue of serum hsa_circRNA_0002980 and hsa_circRNA_104348 expression in liver cancer.Multivariate COX re-gression was performed to analyze the influencing factors of prognosis in liver cancer.Results The expression levels of serum hsa_circRNA_0002980 in the liver cancer group,liver cirrhosis group,and control group in-creased sequentially(P＜0.05),while the expression levels of serum hsa_circRNA_104348 decreased sequen-tially(P＜0.05).The levels of alanine aminotransferase and aspartate aminotransferase in the liver cancer group and the liver cirrhosis group were higher than those in the control group(P＜0.05),and the level of al-bumin was lower than that in the control group(P＜0.05).The area under the curve(AUC)for the diagnosis of liver cancer by hsa_circRNA_0002980 combined with hsa_circRNA_104348 was 0.888(95％CI:0.838-0.928),which was obviously higher than those of hsa_circRNA_0002980(Z=3.526,P＜0.001)and hsa_cir-cRNA_104348 alone(Z=2.184,P=0.029).The expression level of serum hsa_circRNA_0002980 in the poor prognosis group was lower than that in the good prognosis group(P＜0.05),and the expression level of ser-um hsa_circRNA_104348 and the proportion of TNM stage Ⅲ+Ⅳ were higher than those in the good progno-sis group(P＜0.05).The AUC for predicting prognosis in liver cancer patients by the combination of hsa_cir-cRNA_0002980 and hsa_circRNA_104348 was 0.870(95％CI:0.790-0.928),and there was no statistically significant difference compared to the AUC predicted separately by hsa_circRNA_0002980 and hsa_circRNA_104348(P＞0.05).The expression of serum hsa_circRNA_0002980,hsa_circRNA_104348 and TNM stage were influencing factors for the prognosis of liver cancer patients(P＜0.05).Conclusion The expression lev-el of hsa_circRNA_0002980 in the serum of liver cancer patients is relatively low,while the expression level of hsa_circRNA_104348 is relatively high.Both have certain clinical significance in the diagnosis and prognosis e-valuation of liver cancer.

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.

Objective:To investigate the protective effect and possible mechanism of sulforaphane (SFN) on acute liver injury in mice induced by diquat (DQ) poisoning.Methods:Forty-eight male C57BL/6 mice were divided into Control group, DQ model group (DQ group), SFN intervention group (DQ+SFN group), and SFN control group (SFN group) using a random number table method, with 12 mice in each group. Acute liver injury mice model was established by one-time intraperitoneal injection of 1 mL of 40 mg/kg DQ solution at once. SFN group was injected with 1 mL of ddH 2O. After 4 hours of molding, 0.5 mL of 5 mg/kg SFN solution was injected into the peritoneal cavity of the DQ+SFN group and SFN group, once daily for 7 consecutive days. DQ group and Control group were injected with an equal amount of ddH 2O. Then, the mice were euthanized to collect liver tissue and blood samples, and the levels of plasma biomarkers alanine aminotransferase (ALT) and aspartate aminotransferase (AST), as well as oxidative stress indicators such as superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA) in liver tissue were measured. The changes of liver structure were observed under transmission electron microscopy. The apoptosis and reactive oxygen species (ROS) level in liver tissue were observed under fluorescence microscope. Western blotting was used to detect the protein expressions of nuclear factor E2-related factor 2 (Nrf2), hemeoxygenase-1 (HO-1), Kelch-like ECH-associated protein 1 (Keap1), and cleaved caspase-9 in liver tissue. Results:Compared with the Control group, the liver mitochondria in the DQ group showed severe swelling, partial dissolution of the matrix, and cristae rupture and loss; the levels of plasma AST and ALT significantly increased, the MDA content in the liver increased, the activities of SOD and GSH decreased, the level of ROS significantly increased, the number of apoptotic cells in the liver significantly increased, the protein expressions of Nrf2 and HO-1 significantly decreased, and the protein expressions of Keap1 and cleaved caspase-9 significantly increased. Compared with the DQ group, the mitochondrial damage in the DQ+SFN group was reduced, the levels of plasma AST and ALT were significantly reduced [ALT (U/L): 58.22±4.39 vs. 79.94±3.32, AST (U/L): 177.64±8.40 vs. 219.62±11.60, both P < 0.01], the liver MDA content decreased, and the activities of SOD and GSH increased [MDA (μmol/g: 5.63±0.18 vs. 5.96±0.29, SOD (kU/g): 102.05±4.01 vs. 84.34±5.34, GSH (mmol/g): 16.32±1.40 vs. 13.12±1.84, all P < 0.05], the production of ROS in liver tissue was significantly reduced [ROS (fluorescence intensity): 115.90±10.89 vs. 190.70±10.16, P < 0.05], and apoptotic cells were significantly reduced (cell apoptosis index: 4.39±1.00 vs. 10.71±0.56, P < 0.01), the protein expressions of Nrf2 and HO-1 were significantly increased, while the protein expressions of Keap1 and cleaved caspase-9 were significantly decreased (Nrf2/β-actin: 1.15±0.04 vs. 0.93±0.05, HO-1/β-actin: 1.75±0.12 vs. 0.78±0.04, Keap1/β-actin: 1.00±0.14 vs. 1.28±0.13, cleaved caspase-9/β-actin: 1.31±0.12 vs. 1.81±0.09, all P < 0.05). However, there was no statistically significant difference in various indicators between the SFN group and the Control group. Conclusion:SFN can activate the Keap1/Nrf2 signaling pathway to alleviate DQ induced acute liver injury in mice.

Objective To explore the treatment effects and mechanism of Fangji Huangqi Xiaozhong Prescription in metabolic syndrome phenotype osteoarthritis(MS-OA)based on PPARγ/NF-κB signaling pathway.Methods SD rats were randomly divided into sham-operation group,OA group,MS-OA group,Western medicine group,and TCM high-and low-dasage groups.The modified Hulth method was used to make the OA model,and OA model was added with high-carbohydrate high-fat diet to make the MS-OA model.TCM high-and low-dosage groups were given 15.12,7.56 g/kg Fangji Huangqi Xiaozhong Prescription for gavage.The Western medicine group was given 16.2 mg/kg of losoprofen sodium by gavage,while the other groups were given physiological saline by gavage once a day for 6 consecutive weeks.Rat body mass was measured,biochemical detection of blood lipids and blood glucose was conducted,ELISA was used to detect the contents of serum TNF-α,IL-1β,IL-10 and leptin,morphological changes in cartilage tissue were observed using safranin O-fixed green and HE staining,immunohistochemical staining was used to detect expressions of Acan,ColⅩ,MMP13,TNF-α,IL-1β and PPARγ in cartilage tissue,Western blot was used to detected the expression of PPARγ,NF-κBp65 and p-NF-κBp65 protein in cartilage tissue.Results Compared with the sham-operation group,body mass and serum TC,TG,LDL-C,TNF-α,IL-1β and leptin of MS-OA group increased significantly(P<0.01),the contents of HDL-C and IL-10 decreased(P<0.01),cartilage tissue degeneration was significant,and the Mankin score increased(P<0.01),the expression of ColⅩ,MMP13,TNF-α,IL-1β,p-NF-κBp65 protein increased(P<0.05,P<0.01),and the expression of Acan and PPARγ protein decreased(P<0.01).Compared with the MS-OA group,the contents of serum TC,TG,LDL-C,TNF-α and leptin decreased in TCM high-dosage group(P<0.05,P<0.01),the content of IL-10 increased(P<0.05),the pathological damage of cartilage tissue improved,the Mankin score decreased(P<0.01),the expressions of ColⅩ,MMP13,TNF-α,IL-1β and p-NF-κBp65 protein in cartilage tissue decreased(P<0.05,P<0.01),and the protein expressions of Acan and PPARγ protein increased(P<0.01,P<0.05).Conclusion Fangji Huangqi Xiaozhong Prescription can improve lipid metabolism disorder,improve intra-articular inflammatory environment,balance cartilage metabolism,and delay cartilage degeneration in MS-OA rats.Its mechanism may be related to the regulation of PPARγ/NF-κB signaling pathway.

Objective To evaluate the effectiveness and safety of different Chinese patent medicine in improving blood lipid and microcirculation in coronary heart disease patients with phlegm-blood stasis syndrome based on network meta-analysis.Methods The randomized controlled trials(RCTs)of different Chinese patent medicine in the treatment of blood lipid and microcirculation in coronary heart disease patients with phlegm-blood stasis syndrome were collected by searching CNKI,Wanfang,VIP,SinoMed,PubMed,EMbase,Cochrane Library,and Web of science databases from the establishment of the database to April 3,2023.Literature quality evaluation and network meta-analysis were conducted using Review Manager 5.4 and Stata15.1 software.Results Thirty-seven RCTs were included,with a total sample size of 4 064 cases,involving 15 different Chinese patent medicines.The network meta-analysis showed that the efficacy of Chinese patent medicine combined with conventional Western medicine is often better than that of conventional Western medicine alone.There are no serious adverse reactions.The top three Chinese patent medicines with cumulative probability of total clinical efficacy were Guanmai Zaitong soft extract,Gualoupi Injection and Quyu Xiaoban Capsule.In terms of improving triglyceride(TG)and low-density lipoprotein(LDL-C),the top three Chinese patent medicines were Gualoupi Injection,Huxinkang Tablet and Guanxin Shutong Capsule.In terms of improving plasma viscosity and fibrinogen,the top three Chinese patent medicines were Ginkgo Damo Injection,Gualoupi Injection and Guanxin Shutong Capsule.In terms of improving endothelial function[nitric oxide(NO)and endothelin-1(ET-1)],the top three Chinese patent medicines were Ginkgo Damo Injection,Danlou Tablet and Tongmai Yuxin Pill.In terms of reducing inflammation hypersensitivity C-reactive protein(hs-CRP),the top three Chinese patent medicines were Ginkgo Damo Injection,Huxinkang Tablet and Guanxin Shutong Capsule.Conclusion The current evidence shows that the combination of TCM,which is used for the treatment of phlegm-blood stasis syndrome,with conventional Western medicine in the treatment of coronary heart disease has advantages in improving clinical efficacy,blood lipids and microcirculation.TCM especially for the treatment of phlegm-blood stasis syndrome shows more obvious advantage,such as Guanmai Zaitong soft extract and Gualoupi injection,which can be taken into consideration as part of the clinical guidelines.However,due to the limited number and quality of the included literatures,the research results still need to be verified by more high-quality,multi-center,double-blind randomized trials.The purpose is to provide more reliable evidence-based medical reference.

OBJECTIVE To optimize the water extraction process of Flos Lonicerae-Fructus Forsythuae and determine the range of water extraction process parameters.METHODS The active components were screened by network pharmacology,and the indica-tor ingredients were determined in combination with the quality markers under the relevant terms of Chinese Pharmacopoeia 2020 edition and the literature.Take extraction yield and the extraction rate of the indicative component as the critical quality attributes of the water extraction process to screen critical process parameters.The mathematical model was established by Box-Behnken experimental design to investigate the interaction between CQAs and CPPs and build the design space of the water extraction process of Flos Lonicerae-Fruc-tus Forsythuae.RESULTS The extraction percentages of phenolic acids,forsythoside A and forsythin were screened as the index components;specifications of medicinal slices,extraction time and water addition were the key process parameters.Based on the estab-lishment and optimization of the design space,the optimum water extraction process was obtained as follows:the medicinal slice of Lian-Qiao was broken into 0.8-1.2 cm,adding 12 times the amount of water in the first and extract for 30-50 min,10 times the a-mount of water in the second and extract for 25-30 min.CONCLUSION The verification results show that the measured value ob-tained by using the design space method to optimize the water extraction process is close to the predicted value,indicating that the method is stable and reliable,which can provide ideas for its further process development and quality control for the couple medicines of Flos Lonicerae-Fructus Forsythuae.

Objective:To investigate the incidence of postoperative complications in Chinese patients with gastric or colorectal cancer, and to evaluate the risk factors for postoperative complications.Methods:This was a national, multicenter, prospective, registry-based, cohort study of data obtained from the database of the Prevalence of Abdominal Complications After Gastro- enterological Surgery (PACAGE) study sponsored by the China Gastrointestinal Cancer Surgical Union. The PACAGE database prospectively collected general demographic characteristics, protocols for perioperative treatment, and variables associated with postoperative complications in patients treated for gastric or colorectal cancer in 20 medical centers from December 2018 to December 2020. The patients were grouped according to the presence or absence of postoperative complications. Postoperative complications were categorized and graded in accordance with the expert consensus on postoperative complications in gastrointestinal oncology surgery and Clavien-Dindo grading criteria. The incidence of postoperative complications of different grades are presented as bar charts. Independent risk factors for occurrence of postoperative complications were identified by multifactorial unconditional logistic regression.Results:The study cohort comprised 3926 patients with gastric or colorectal cancer, 657 (16.7%) of whom had a total of 876 postoperative complications. Serious complications (Grade III and above) occurred in 4.0% of patients (156/3926). The rate of Grade V complications was 0.2% (7/3926). The cohort included 2271 patients with gastric cancer with a postoperative complication rate of 18.1% (412/2271) and serious complication rate of 4.7% (106/2271); and 1655 with colorectal cancer, with a postoperative complication rate of 14.8% (245/1655) and serious complication rate of 3.0% (50/1655). The incidences of anastomotic leakage in patients with gastric and colorectal cancer were 3.3% (74/2271) and 3.4% (56/1655), respectively. Abdominal infection was the most frequently occurring complication, accounting for 28.7% (164/572) and 39.5% (120/304) of postoperative complications in patients with gastric and colorectal cancer, respectively. The most frequently occurring grade of postoperative complication was Grade II, accounting for 65.4% (374/572) and 56.6% (172/304) of complications in patients with gastric and colorectal cancers, respectively. Multifactorial analysis identified (1) the following independent risk factors for postoperative complications in patients in the gastric cancer group: preoperative comorbidities (OR=2.54, 95%CI: 1.51-4.28, P<0.001), neoadjuvant therapy (OR=1.42, 95%CI:1.06-1.89, P=0.020), high American Society of Anesthesiologists (ASA) scores (ASA score 2 points:OR=1.60, 95% CI: 1.23-2.07, P<0.001, ASA score ≥3 points:OR=0.43, 95% CI: 0.25-0.73, P=0.002), operative time >180 minutes (OR=1.81, 95% CI: 1.42-2.31, P<0.001), intraoperative bleeding >50 mL (OR=1.29,95%CI: 1.01-1.63, P=0.038), and distal gastrectomy compared with total gastrectomy (OR=0.65,95%CI: 0.51-0.83, P<0.001); and (2) the following independent risk factors for postoperative complications in patients in the colorectal cancer group: female (OR=0.60, 95%CI: 0.44-0.80, P<0.001), preoperative comorbidities (OR=2.73, 95%CI: 1.25-5.99, P=0.030), neoadjuvant therapy (OR=1.83, 95%CI:1.23-2.72, P=0.008), laparoscopic surgery (OR=0.47, 95%CI: 0.30-0.72, P=0.022), and abdominoperineal resection compared with low anterior resection (OR=2.74, 95%CI: 1.71-4.41, P<0.001). Conclusion:Postoperative complications associated with various types of infection were the most frequent complications in patients with gastric or colorectal cancer. Although the risk factors for postoperative complications differed between patients with gastric cancer and those with colorectal cancer, the presence of preoperative comorbidities, administration of neoadjuvant therapy, and extent of surgical resection, were the commonest factors associated with postoperative complications in patients of both categories.

Objective:To investigate the incidence of postoperative complications in Chinese patients with gastric or colorectal cancer, and to evaluate the risk factors for postoperative complications.Methods:This was a national, multicenter, prospective, registry-based, cohort study of data obtained from the database of the Prevalence of Abdominal Complications After Gastro- enterological Surgery (PACAGE) study sponsored by the China Gastrointestinal Cancer Surgical Union. The PACAGE database prospectively collected general demographic characteristics, protocols for perioperative treatment, and variables associated with postoperative complications in patients treated for gastric or colorectal cancer in 20 medical centers from December 2018 to December 2020. The patients were grouped according to the presence or absence of postoperative complications. Postoperative complications were categorized and graded in accordance with the expert consensus on postoperative complications in gastrointestinal oncology surgery and Clavien-Dindo grading criteria. The incidence of postoperative complications of different grades are presented as bar charts. Independent risk factors for occurrence of postoperative complications were identified by multifactorial unconditional logistic regression.Results:The study cohort comprised 3926 patients with gastric or colorectal cancer, 657 (16.7%) of whom had a total of 876 postoperative complications. Serious complications (Grade III and above) occurred in 4.0% of patients (156/3926). The rate of Grade V complications was 0.2% (7/3926). The cohort included 2271 patients with gastric cancer with a postoperative complication rate of 18.1% (412/2271) and serious complication rate of 4.7% (106/2271); and 1655 with colorectal cancer, with a postoperative complication rate of 14.8% (245/1655) and serious complication rate of 3.0% (50/1655). The incidences of anastomotic leakage in patients with gastric and colorectal cancer were 3.3% (74/2271) and 3.4% (56/1655), respectively. Abdominal infection was the most frequently occurring complication, accounting for 28.7% (164/572) and 39.5% (120/304) of postoperative complications in patients with gastric and colorectal cancer, respectively. The most frequently occurring grade of postoperative complication was Grade II, accounting for 65.4% (374/572) and 56.6% (172/304) of complications in patients with gastric and colorectal cancers, respectively. Multifactorial analysis identified (1) the following independent risk factors for postoperative complications in patients in the gastric cancer group: preoperative comorbidities (OR=2.54, 95%CI: 1.51-4.28, P<0.001), neoadjuvant therapy (OR=1.42, 95%CI:1.06-1.89, P=0.020), high American Society of Anesthesiologists (ASA) scores (ASA score 2 points:OR=1.60, 95% CI: 1.23-2.07, P<0.001, ASA score ≥3 points:OR=0.43, 95% CI: 0.25-0.73, P=0.002), operative time >180 minutes (OR=1.81, 95% CI: 1.42-2.31, P<0.001), intraoperative bleeding >50 mL (OR=1.29,95%CI: 1.01-1.63, P=0.038), and distal gastrectomy compared with total gastrectomy (OR=0.65,95%CI: 0.51-0.83, P<0.001); and (2) the following independent risk factors for postoperative complications in patients in the colorectal cancer group: female (OR=0.60, 95%CI: 0.44-0.80, P<0.001), preoperative comorbidities (OR=2.73, 95%CI: 1.25-5.99, P=0.030), neoadjuvant therapy (OR=1.83, 95%CI:1.23-2.72, P=0.008), laparoscopic surgery (OR=0.47, 95%CI: 0.30-0.72, P=0.022), and abdominoperineal resection compared with low anterior resection (OR=2.74, 95%CI: 1.71-4.41, P<0.001). Conclusion:Postoperative complications associated with various types of infection were the most frequent complications in patients with gastric or colorectal cancer. Although the risk factors for postoperative complications differed between patients with gastric cancer and those with colorectal cancer, the presence of preoperative comorbidities, administration of neoadjuvant therapy, and extent of surgical resection, were the commonest factors associated with postoperative complications in patients of both categories.

Coronavirus disease 2019 (COVID-19) has become a worldwide pandemic. During the rapid spread time, it is a great challenge for patients with inflammatory bowel disease (IBD) who use immunosuppressive drugs from vaccination and drug application. This article is intended to supplement and revise the recommendations of the Inflammatory Bowel Disease Group of the Chinese Society of Gastroenterology in 2020 on the "Management of patients with inflammatory bowel disease during epidemic of novel coronavirus pneumonia", mainly including the treatment and vaccination of IBD patients complicated with COVID-19. It is expected to guide clinicians in drug use, vaccination of IBD patients at an appropriate time, also help patients getting through the epidemic period of COVID-19.

Age-dependent loss of skeletal muscle mass and function is a feature of sarcopenia, and increases the risk of many aging-related metabolic diseases. Here, we report phenotypic and single-nucleus transcriptomic analyses of non-human primate skeletal muscle aging. A higher transcriptional fluctuation was observed in myonuclei relative to other interstitial cell types, indicating a higher susceptibility of skeletal muscle fiber to aging. We found a downregulation of FOXO3 in aged primate skeletal muscle, and identified FOXO3 as a hub transcription factor maintaining skeletal muscle homeostasis. Through the establishment of a complementary experimental pipeline based on a human pluripotent stem cell-derived myotube model, we revealed that silence of FOXO3 accelerates human myotube senescence, whereas genetic activation of endogenous FOXO3 alleviates human myotube aging. Altogether, based on a combination of monkey skeletal muscle and human myotube aging research models, we unraveled the pivotal role of the FOXO3 in safeguarding primate skeletal muscle from aging, providing a comprehensive resource for the development of clinical diagnosis and targeted therapeutic interventions against human skeletal muscle aging and the onset of sarcopenia along with aging-related disorders.
Animals ; Humans ; Sarcopenia/metabolism* ; Forkhead Box Protein O3/metabolism* ; Muscle, Skeletal/metabolism* ; Aging/metabolism* ; Primates/metabolism*