This review aims to provide clinical guidance for the diagnosis and treatment of ANCA-associated vasculitis(AAV)by summarizing recent advances in the research on the immunological aspects of infection and AAV.Literatures are retrieved from PubMed,CNKI,Wanfang and other databases.The search terms are set as"ANCA","vasculitis","infection"and"immunity".The existing literatures are reviewed and analyzed.Infection plays a crucial role throughout the course of AAV,affecting onset,disease activity,treatment and prognosis.Infections are not only significant triggers for the onset of AAV,but also factors that precipitate relapses.Additionally,the immunosuppression involved in AAV treatment increases susceptibility to infections,which can exacerbate AAV.Concurrent infections have become a leading cause of death in AAV patients.The interplay of infection,molecular mimicry,and genetic cross-reactivity represents a primary pathogenic mechanism in AAV.Reducing infection-induced immune responses has a posi-tive implication in the management of AAV.

Objective To observe the value of fetal MRI in diagnosis of duodenal obstruction(DO).Methods A total of 35 fetuses with suspected DO according to MRI were retrospectively included.The length and the maximum diameter of the dilated duodenum were measured,so as site(categorized in descending order from proximal to distal as descending segment,horizontal segment and ascending duodenum/proximal jejunum)and the degree of obstruction(complete or incomplete)were assessed.Taken findings of labor induction specimen,postnatal neonatal surgery or follow-up data as standards,the positive predictive value(PPV)of MRI for diagnosing fetal DO was calculated,while the correlations of the measured parameters of dilated duodenum and the confirmed obstruction site/degree were analyzed.Results Among 35 fetuses,DO was confirmed in 34 fetuses,yielding an overall PPV of 97.14％(34/35)for MRI.In 34 fetuses with confirmed DO,there were 23 with descending DO(DDO),4 with horizontal DO(HDO)and 7 with ascending DO/proximal jejunum obstruction(ADO/PJO),including 12 with complete DO and 22 with incomplete DO.PPV of MRI for diagnosing DDO,HDO and ADO/PJO was 87.50％(21/24),50.00％(2/4)and 100％(7/7),respectively,for diagnosing complete and incomplete DO was 90.00％(9/10)and 84.00％(21/25),respectively.Both the length and the maximum diameter of fetal proximal dilated duodenum showed on MRI were positively correlated with the actual obstruction site(from proximal to distal)(rs=0.736,P＜0.001;rs=0.424,P=0.011,respectively),but had no significant rank correlation with the degree of obstruction(rs=-0.216,P=0.212;rs=-0.285,P=0.097,respectively).Conclusion Fetal MRI could effectively evaluate the length and the maximum diameter of dilated duodenum hence indicating the level and degree of DO.

Objective:To investigate the effect and mechanism of Huanglian Jiedu Decoction(HLJDD)on platelet-neutrophil crosstalk in inflammatory response.Methods:The rat model of inflammatory reaction was induced by lipopolysaccharide(LPS),and HLJDD was used to intervene LPS rats.Proinflammatory factors and platelet-neutrophil cross-talk were detected.Immunofluorescence and HE staining were used to observe the platelet-neutrophil adhesion rate in lung tissue and lung histopathology.Transcriptomics was used to explore the potential signaling pathways and targets of HLJDD in platelet-neutrophil crosstalk and verified them.Results:Com-pared with the control group,the white blood cell count,platelet count,plasma TNF-α,IL-1β,SLEP,sC5b-9 and ICAM-1 levels in the model group were significantly increased,and the positive expression rates of CD62p,MPO and CD61+CD62p+MPO coincidence in the lung tissue of the model group were also significantly increased(P<0.001 or P<0.05).The inflammatory injury was severe in the model group.Compared with the model group,the white blood cell count,plasma levels of TNF-α,IL-1β,SLEP,sC5b-9 and ICAM-1 in the HLJDD group were decreased(P<0.001 or P<0.05),the positive expression rates of CD62p and MPO and the coincident posi-tive expression rates of CD61+CD62p+MPO in the lung tissue of the HLJDD group were decreased(P<0.05),and LPS-induced lung tis-sue injury was alleviated.Transcriptomics results showed that high-dose HLJDD could down-regulate differential genes on oxidative phosphorylation pathways.Conclusion:HLJDD ameliorates LPS-induced inflammatory response and reduces platelet-neutrophil cross-talk,which may be related to the down-regulation of oxidative phosphorylation.

This review aims to provide clinical guidance for the diagnosis and treatment of ANCA-associated vasculitis(AAV)by summarizing recent advances in the research on the immunological aspects of infection and AAV.Literatures are retrieved from PubMed,CNKI,Wanfang and other databases.The search terms are set as"ANCA","vasculitis","infection"and"immunity".The existing literatures are reviewed and analyzed.Infection plays a crucial role throughout the course of AAV,affecting onset,disease activity,treatment and prognosis.Infections are not only significant triggers for the onset of AAV,but also factors that precipitate relapses.Additionally,the immunosuppression involved in AAV treatment increases susceptibility to infections,which can exacerbate AAV.Concurrent infections have become a leading cause of death in AAV patients.The interplay of infection,molecular mimicry,and genetic cross-reactivity represents a primary pathogenic mechanism in AAV.Reducing infection-induced immune responses has a posi-tive implication in the management of AAV.

Objective To observe the value of fetal MRI in diagnosis of duodenal obstruction(DO).Methods A total of 35 fetuses with suspected DO according to MRI were retrospectively included.The length and the maximum diameter of the dilated duodenum were measured,so as site(categorized in descending order from proximal to distal as descending segment,horizontal segment and ascending duodenum/proximal jejunum)and the degree of obstruction(complete or incomplete)were assessed.Taken findings of labor induction specimen,postnatal neonatal surgery or follow-up data as standards,the positive predictive value(PPV)of MRI for diagnosing fetal DO was calculated,while the correlations of the measured parameters of dilated duodenum and the confirmed obstruction site/degree were analyzed.Results Among 35 fetuses,DO was confirmed in 34 fetuses,yielding an overall PPV of 97.14％(34/35)for MRI.In 34 fetuses with confirmed DO,there were 23 with descending DO(DDO),4 with horizontal DO(HDO)and 7 with ascending DO/proximal jejunum obstruction(ADO/PJO),including 12 with complete DO and 22 with incomplete DO.PPV of MRI for diagnosing DDO,HDO and ADO/PJO was 87.50％(21/24),50.00％(2/4)and 100％(7/7),respectively,for diagnosing complete and incomplete DO was 90.00％(9/10)and 84.00％(21/25),respectively.Both the length and the maximum diameter of fetal proximal dilated duodenum showed on MRI were positively correlated with the actual obstruction site(from proximal to distal)(rs=0.736,P＜0.001;rs=0.424,P=0.011,respectively),but had no significant rank correlation with the degree of obstruction(rs=-0.216,P=0.212;rs=-0.285,P=0.097,respectively).Conclusion Fetal MRI could effectively evaluate the length and the maximum diameter of dilated duodenum hence indicating the level and degree of DO.

Objective:To investigate the effect and mechanism of Huanglian Jiedu Decoction(HLJDD)on platelet-neutrophil crosstalk in inflammatory response.Methods:The rat model of inflammatory reaction was induced by lipopolysaccharide(LPS),and HLJDD was used to intervene LPS rats.Proinflammatory factors and platelet-neutrophil cross-talk were detected.Immunofluorescence and HE staining were used to observe the platelet-neutrophil adhesion rate in lung tissue and lung histopathology.Transcriptomics was used to explore the potential signaling pathways and targets of HLJDD in platelet-neutrophil crosstalk and verified them.Results:Com-pared with the control group,the white blood cell count,platelet count,plasma TNF-α,IL-1β,SLEP,sC5b-9 and ICAM-1 levels in the model group were significantly increased,and the positive expression rates of CD62p,MPO and CD61+CD62p+MPO coincidence in the lung tissue of the model group were also significantly increased(P<0.001 or P<0.05).The inflammatory injury was severe in the model group.Compared with the model group,the white blood cell count,plasma levels of TNF-α,IL-1β,SLEP,sC5b-9 and ICAM-1 in the HLJDD group were decreased(P<0.001 or P<0.05),the positive expression rates of CD62p and MPO and the coincident posi-tive expression rates of CD61+CD62p+MPO in the lung tissue of the HLJDD group were decreased(P<0.05),and LPS-induced lung tis-sue injury was alleviated.Transcriptomics results showed that high-dose HLJDD could down-regulate differential genes on oxidative phosphorylation pathways.Conclusion:HLJDD ameliorates LPS-induced inflammatory response and reduces platelet-neutrophil cross-talk,which may be related to the down-regulation of oxidative phosphorylation.

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 evaluate the value of contrast-enhanced ultrasound (CEUS) in the diagnosis of solid intraductal papilloma (sIDP) of breast by comparing with fibronenoma of breast (FA).Methods:The CEUS data of 62 cases of sIDP patients and 94 cases of FA patients that confirmed by pathology in the First Affiliated Hospital of Soochow University from October 2016 to January 2021 were retrospectively analyzed. The patients were divided into sIDP group and FA group according to the pathological results. The enhancement speed, enhancement degree, enhancement uniformity, whether the edge after enhancement was polished, whether the enhancement range was enlarged, whether there was a ring unenhanced area in the inner edge of the lesion and whether the inner edge of the unenhanced area was polished were observed in the two groups. SonoLiver software was used to perform offline analysis of the dynamic process of CEUS in the two groups respectively, the enhancement sequence diagram of the lesions was obtained. The pathological result was taken as the gold standard, univariate analysis was applied, and the parameters with statistical significance between the two groups were included in multivariate Logistic regression analysis to establish a differential diagnosis model. The diagnostic efficiency of sIDP was analyzed by ROC curve and diagnostic model.Results:Compared with the FA group, CEUS in the sIDP group mostly showed fast forward, high enhancement, and the enhancement sequence was mostly centrifugal. After CEUS, the lesion edges in the sIDP group were mostly accompanied by unenhanced areas and the inner edges of the unenhanced areas were not intact, and the differences between the two groups were statistically significant (all P<0.05). Binary Logistic regression showed that age, enhancement degree and enhancement order were independent risk factors for sIDP diagnosis. The ROC curve showed that the area under the ROC curve of age, enhancement degree and enhancement sequence combined for the diagnosis of sIDP was 0.874 (95% CI=0.812-0.922), the accuracy was 76.9%, the sensitivity was 67.7%, the specificity was 83.0%, the positive predictive value was 72.4%, and the negative predictive value was 79.6%. Conclusions:There are significant differences in age, enhancement degree and enhancement sequence between sIDP and FA patients. The three-parameter combination can improve the diagnostic efficiency of sIDP.

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.

Both natural ginsenoside F2 and unnatural ginsenoside 3β,20S-Di-O-Glc-DM were reported to exhibit anti-tumor activity. Traditional approaches for producing them rely on direct extraction from Panax ginseng, enzymatic catalysis or chemical synthesis, all of which result in low yield and high cost. Metabolic engineering of microbes has been recognized as a green and sustainable biotechnology to produce natural and unnatural products. Hence we engineered the complete biosynthetic pathways of F2 and 3β,20S-Di-O-Glc-DM in Saccharomyces cerevisiae via the CRISPR/Cas9 system. The titers of F2 and 3β,20S-Di-O-Glc-DM were increased from 1.2 to 21.0 mg/L and from 82.0 to 346.1 mg/L at shake flask level, respectively, by multistep metabolic engineering strategies. Additionally, pharmacological evaluation showed that both F2 and 3β,20S-Di-O-Glc-DM exhibited anti-pancreatic cancer activity and the activity of 3β,20S-Di-O-Glc-DM was even better. Furthermore, the titer of 3β,20S-Di-O-Glc-DM reached 2.6 g/L by fed-batch fermentation in a 3 L bioreactor. To our knowledge, this is the first report on demonstrating the anti-pancreatic cancer activity of F2 and 3β,20S-Di-O-Glc-DM, and achieving their de novo biosynthesis by the engineered yeasts. Our work presents an alternative approach to produce F2 and 3β,20S-Di-O-Glc-DM from renewable biomass, which lays a foundation for drug research and development.